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In drug development, preclinical development (also termed preclinical studies or nonclinical studies) is a stage of research that begins before clinical trials (testing in humans) and during which important feasibility, iterative testing and drug safety data are collected, typically in laboratory animals.
The main goals of preclinical studies are to determine a starting, safe dose for first-in-human study and assess potential toxicity of the product, which typically include new medical devices, prescription drugs, and diagnostics.
Companies use stylized statistics to illustrate the risks in preclinical research, such as that on average, only one in every 5,000 compounds that enters drug discovery to the stage of preclinical development becomes an approved drug.
== Types ==
Each class of product may undergo different types of preclinical research. For instance, drugs may undergo pharmacodynamics (what the drug does to the body) (PD), pharmacokinetics (what the body does to the drug) (PK), ADME, and toxicology testing. This data allows researchers to allometrically estimate a safe starting dose of the drug for clinical trials in humans. Medical devices that do not have drug attached will not undergo these additional tests and may go directly to good laboratory practices (GLP) testing for safety of the device and its components. Some medical devices will also undergo biocompatibility testing which helps to show whether a component of the device or all components are sustainable in a living model. Most preclinical studies must adhere to GLPs in ICH Guidelines to be acceptable for submission to regulatory agencies such as the Food & Drug Administration in the United States.
Typically, both in vitro and in vivo tests will be performed. Studies of drug toxicity include which organs are targeted by that drug, as well as if there are any long-term carcinogenic effects or toxic effects causing illness.
== Animal testing ==
The information collected from these studies is vital so that safe human testing can begin. Typically, in drug development studies animal testing involves two species. The most commonly used models are murine and canine, although primate and porcine are also used.
=== Choice of species ===
The choice of species is based on which will give the best correlation to human trials. Differences in the gut, enzyme activity, circulatory system, or other considerations make certain models more appropriate based on the dosage form, site of activity, or noxious metabolites. For example, canines may not be good models for solid oral dosage forms because the characteristic carnivore intestine is underdeveloped compared to the omnivore's, and gastric emptying rates are increased. Also, rodents can not act as models for antibiotic drugs because the resulting alteration to their intestinal flora causes significant adverse effects. Depending on a drug's functional groups, it may be metabolized in similar or different ways between species, which will affect both efficacy and toxicology.
Medical device studies also use this basic premise. Most studies are performed in larger species such as dogs, pigs and sheep which allow for testing in a similar sized model as that of a human. In addition, some species are used for similarity in specific organs or organ system physiology (swine for dermatological and coronary stent studies; goats for mammary implant studies; dogs for gastric and cancer studies; etc.).
Importantly, the regulatory guidelines of FDA, EMA, and other similar international and regional authorities usually require safety testing in at least two mammalian species, including one non-rodent species, prior to human trials authorization.
=== Ethical issues ===
Animal testing in the research-based pharmaceutical industry has been reduced in recent years both for ethical and cost reasons. However, most research will still involve animal based testing for the need of similarity in anatomy and physiology that is required for diverse product development.
== No observable effect levels ==
Based on preclinical trials, no-observed-adverse-effect levels (NOAELs) on drugs are established, which are used to determine initial phase 1 clinical trial dosage levels on a mass API per mass patient basis. Generally a 1/100 uncertainty factor or "safety margin" is included to account for interspecies (1/10) and inter-individual (1/10) differences.
== See also ==
Drug development
Preclinical imaging
Phases of clinical research
== References == | Wikipedia/Preclinical_research |
Invertebrates are animals that neither develop nor retain a vertebral column (commonly known as a spine or backbone), which evolved from the notochord. It is a paraphyletic grouping including all animals excluding the chordate subphylum Vertebrata, i.e. vertebrates. Well-known phyla of invertebrates include arthropods, molluscs, annelids, echinoderms, flatworms, cnidarians, and sponges.
The majority of animal species are invertebrates; one estimate puts the figure at 97%. Many invertebrate taxa have a greater number and diversity of species than the entire subphylum of Vertebrata. Invertebrates vary widely in size, from 10 μm (0.0004 in) myxozoans to the 9–10 m (30–33 ft) colossal squid.
Some so-called invertebrates, such as the Tunicata and Cephalochordata, are actually sister chordate subphyla to Vertebrata, being more closely related to vertebrates than to other invertebrates. This makes the "invertebrates" paraphyletic, so the term has no significance in taxonomy.
== Etymology ==
The word "invertebrate" comes from the Latin word vertebra, which means a joint in general, and sometimes specifically a joint from the spinal column of a vertebrate. The jointed aspect of vertebra is derived from the concept of turning, expressed in the root verto or vorto, to turn. The prefix in- means "not" or "without".
== Taxonomic significance ==
The term invertebrates does not describe a taxon in the same way that Arthropoda, Vertebrata or Manidae do. Each of those terms describes a valid taxon, phylum, subphylum or family. "Invertebrata" is a term of convenience, not a taxon; it has very little circumscriptional significance except within the Chordata. The Vertebrata as a subphylum comprises such a small proportion of the Metazoa that to speak of the kingdom Animalia in terms of "Vertebrata" and "Invertebrata" has limited practicality. In the more formal taxonomy of Animalia other attributes that logically should precede the presence or absence of the vertebral column in constructing a cladogram, for example, the presence of a notochord. That would at least circumscribe the Chordata. However, even the notochord would be a less fundamental criterion than aspects of embryological development and symmetry or perhaps Bauplan.
Despite this, the concept of invertebrates as a taxon of animals has persisted for over a century among the laity, and within the zoological community and in its literature it remains in use as a term of convenience for animals that are not members of the Vertebrata. The following text reflects earlier scientific understanding of the term and of those animals which have constituted it. According to this understanding, invertebrates do not possess a skeleton of bone, either internal or external. They include hugely varied body plans. Many have fluid-filled, hydrostatic skeletons, like jellyfish or worms. Others have hard exoskeletons, outer shells like those of insects and crustaceans. The most familiar invertebrates include the Protozoa, Porifera, Coelenterata, Platyhelminthes, Nematoda, Annelida, Echinodermata, Mollusca and Arthropoda. Arthropoda include insects, crustaceans and arachnids.
== Number of extant species ==
By far the largest number of described invertebrate species are insects. The following table lists the number of described extant species for major invertebrate groups as estimated in the IUCN Red List of Threatened Species, 2014.3.
The IUCN estimates that 66,178 extant vertebrate species have been described, which means that over 95% of the described animal species in the world are invertebrates.
== Characteristics ==
The trait that is common to all invertebrates is the absence of a vertebral column (backbone): this creates a distinction between invertebrates and vertebrates. The distinction is one of convenience only; it is not based on any clear biologically homologous trait, any more than the common trait of having wings functionally unites insects, bats, and birds, or than not having wings unites tortoises, snails and sponges. Being animals, invertebrates are heterotrophs, and require sustenance in the form of the consumption of other organisms. With a few exceptions, such as the Porifera, invertebrates generally have bodies composed of differentiated tissues. There is also typically a digestive chamber with one or two openings to the exterior.
=== Morphology and symmetry ===
The body plans of most multicellular organisms exhibit some form of symmetry, whether radial, bilateral, or spherical. A minority, however, exhibit no symmetry. One example of asymmetric invertebrates includes all gastropod species. This is easily seen in snails and sea snails, which have helical shells. Slugs appear externally symmetrical, but their pneumostome (breathing hole) is located on the right side. Other gastropods develop external asymmetry, such as Glaucus atlanticus that develops asymmetrical cerata as they mature. The origin of gastropod asymmetry is a subject of scientific debate.
Other examples of asymmetry are found in fiddler crabs and hermit crabs. They often have one claw much larger than the other. If a male fiddler loses its large claw, it will grow another on the opposite side after moulting. Sessile animals such as sponges are asymmetrical alongside coral colonies (with the exception of the individual polyps that exhibit radial symmetry); Alpheidae claws that lack pincers; and some copepods, polyopisthocotyleans, and monogeneans which parasitize by attachment or residency within the gill chamber of their fish hosts).
==== Nervous system ====
Neurons differ in invertebrates from mammalian cells. Invertebrates cells fire in response to similar stimuli as mammals, such as tissue trauma, high temperature, or changes in pH. The first invertebrate in which a neuron cell was identified was the medicinal leech, Hirudo medicinalis.
Learning and memory using nociceptors have been described in the sea hare, Aplysia. Mollusk neurons are able to detect increasing pressures and tissue trauma.
Neurons have been identified in a wide range of invertebrate species, including annelids, molluscs, nematodes and arthropods.
==== Respiratory system ====
One type of invertebrate respiratory system is the open respiratory system composed of spiracles, tracheae, and tracheoles that terrestrial arthropods have to transport metabolic gases to and from tissues. The distribution of spiracles can vary greatly among the many orders of insects, but in general each segment of the body can have only one pair of spiracles, each of which connects to an atrium and has a relatively large tracheal tube behind it. The tracheae are invaginations of the cuticular exoskeleton that branch (anastomose) throughout the body with diameters from only a few micrometres up to 0.8 mm. The smallest tubes, tracheoles, penetrate cells and serve as sites of diffusion for water, oxygen, and carbon dioxide. Gas may be conducted through the respiratory system by means of active ventilation or passive diffusion. Unlike vertebrates, insects do not generally carry oxygen in their haemolymph.
A tracheal tube may contain ridge-like circumferential rings of taenidia in various geometries such as loops or helices. In the head, thorax, or abdomen, tracheae may also be connected to air sacs. Many insects, such as grasshoppers and bees, which actively pump the air sacs in their abdomen, are able to control the flow of air through their body. In some aquatic insects, the tracheae exchange gas through the body wall directly, in the form of a gill, or function essentially as normal, via a plastron. Despite being internal, the tracheae of arthropods are shed during moulting (ecdysis).
==== Hearing ====
=== Reproduction ===
Like vertebrates, most invertebrates reproduce at least partly through sexual reproduction. They produce specialized reproductive cells that undergo meiosis to produce smaller, motile spermatozoa or larger, non-motile ova. These fuse to form zygotes, which develop into new individuals. Others are capable of asexual reproduction, or sometimes, both methods of reproduction.
Extensive research with model invertebrate species such as Drosophila melanogaster and Caenorhabditis elegans has contributed much to our understanding of meiosis and reproduction. However, beyond the few model systems, the modes of reproduction found in invertebrates show incredible diversity. In one extreme example, it is estimated that 10% of orbatid mite species have persisted without sexual reproduction and have reproduced asexually for more than 400 million years.
==== Reproductive systems ====
=== Social interaction ===
Social behavior is widespread in invertebrates, including cockroaches, termites, aphids, thrips, ants, bees, Passalidae, Acari, spiders, and more. Social interaction is particularly salient in eusocial species but applies to other invertebrates as well.
Insects recognize information transmitted by other insects.
=== Phyla ===
The term invertebrates covers several phyla. One of these are the sponges (Porifera). They were long thought to have diverged from other animals early. They lack the complex organization found in most other phyla. Their cells are differentiated, but in most cases not organized into distinct tissues. Sponges typically feed by drawing in water through pores. Some speculate that sponges are not so primitive, but may instead be secondarily simplified. The Ctenophora and the Cnidaria, which includes sea anemones, corals, and jellyfish, are radially symmetric and have digestive chambers with a single opening, which serves as both the mouth and the anus. Both have distinct tissues, but they are not organized into organs. There are only two main germ layers, the ectoderm and endoderm, with only scattered cells between them. As such, they are sometimes called diploblastic.
The Echinodermata are radially symmetric and exclusively marine, including starfish (Asteroidea), sea urchins, (Echinoidea), brittle stars (Ophiuroidea), sea cucumbers (Holothuroidea) and feather stars (Crinoidea).
The largest animal phylum is also included within invertebrates: the Arthropoda, including insects, spiders, crabs, and their kin. All these organisms have a body divided into repeating segments, typically with paired appendages. In addition, they possess a hardened exoskeleton that is periodically shed during growth. Two smaller phyla, the Onychophora and Tardigrada, are close relatives of the arthropods and share some traits with them, excluding the hardened exoskeleton. The Nematoda, or roundworms, are perhaps the second largest animal phylum, and are also invertebrates. Roundworms are typically microscopic, and occur in nearly every environment where there is water. A number are important parasites. Smaller phyla related to them are the Kinorhyncha, Priapulida, and Loricifera. These groups have a reduced coelom, called a pseudocoelom. Other invertebrates include the Nemertea, or ribbon worms, and the Sipuncula.
Another phylum is Platyhelminthes, the flatworms. These were originally considered primitive, but it now appears they developed from more complex ancestors. Flatworms are acoelomates, lacking a body cavity, as are their closest relatives, the microscopic Gastrotricha. The Rotifera, or rotifers, are common in aqueous environments. Invertebrates also include the Acanthocephala, or spiny-headed worms, the Gnathostomulida, Micrognathozoa, and the Cycliophora.
Also included are two of the most successful animal phyla, the Mollusca and Annelida. The former, which is the second-largest animal phylum by number of described species, includes animals such as snails, clams, and squids, and the latter comprises the segmented worms, such as earthworms and leeches. These two groups have long been considered close relatives because of the common presence of trochophore larvae, but the annelids were considered closer to the arthropods because they are both segmented. Now, this is generally considered convergent evolution, owing to many morphological and genetic differences between the two phyla.
Among lesser phyla of invertebrates are the Hemichordata, or acorn worms, and the Chaetognatha, or arrow worms. Other phyla include Acoelomorpha, Brachiopoda, Bryozoa, Entoprocta, Phoronida, and Xenoturbellida.
== Classification ==
Invertebrates can be classified into several main categories, some of which are taxonomically obsolescent or debatable, but still used as terms of convenience. Each however appears in its own article at the following links.
Sponges (Porifera)
Comb jellies (Ctenophora)
Medusozoans and corals (Cnidaria)
Acoels (Xenacoelomorpha)
Flatworms (Platyhelminthes)
Bristleworms, earthworms and leeches (Annelida)
Insects, springtails, crustaceans, myriapods, chelicerates (Arthropoda)
Chitons, snails, slugs, bivalves, tusk shells, cephalopods (Mollusca)
Roundworms or threadworms (Nematoda)
Rotifers (Rotifera)
Tardigrades (Tardigrada)
Scalidophores (Scalidophora)
Lophophorates (Lophophorata)
Velvet worms (Onychophora)
Arrow worms (Chaetognatha)
Gordian worms or horsehair worms (Nematomorpha)
Ribbon worms (Nemertea)
Placozoa
Loricifera
Starfishes, sea urchins, sea cucumbers, sea lilies and brittle stars (Echinodermata)
Acorn worms, cephalodiscids and graptolites (Hemichordata)
Lancelets (Amphioxiformes)
Salps, pyrosomes, doliolids, larvaceans and sea squirts (Tunicata)
Cycliophora
== History ==
The earliest animal fossils are of invertebrates. 665-million-year-old fossils in the Trezona Formation at Trezona Bore, West Central Flinders, South Australia have been interpreted as being early sponges. Some paleontologists suggest that animals appeared much earlier, possibly as early as 1 billion years ago though they probably became multicellular in the Tonian. Trace fossils such as tracks and burrows found in the late Neoproterozoic Era indicate the presence of triploblastic worms, roughly as large (about 5 mm wide) and complex as earthworms.
Around 453 MYA, animals began diversifying, and many of the important groups of invertebrates diverged from one another. Fossils of invertebrates are found in various types of sediment from the Phanerozoic. Fossils of invertebrates are commonly used in stratigraphy.
=== Classification ===
Carl Linnaeus divided these animals into only two groups, the Insecta and the now-obsolete Vermes (worms). Jean-Baptiste Lamarck, who was appointed to the position of "Curator of Insecta and Vermes" at the Muséum National d'Histoire Naturelle in 1793, both coined the term "invertebrate" to describe such animals and divided the original two groups into ten, by splitting Arachnida and Crustacea from the Linnean Insecta, and Mollusca, Annelida, Cirripedia, Radiata, Coelenterata and Infusoria from the Linnean Vermes. They are now classified into over 30 phyla, from simple organisms such as sea sponges and flatworms to complex animals such as arthropods and molluscs.
==== Significance ====
Invertebrates are animals without a vertebral column. This has led to the conclusion that invertebrates are a group that deviates from the normal, vertebrates. This has been said to be because researchers in the past, such as Lamarck, viewed vertebrates as a "standard": in Lamarck's theory of evolution, he believed that characteristics acquired through the evolutionary process involved not only survival, but also progression toward a "higher form", to which humans and vertebrates were closer than invertebrates were. Although goal-directed evolution has been abandoned, the distinction of invertebrates and vertebrates persists to this day, even though the grouping has been noted to be "hardly natural or even very sharp." Another reason cited for this continued distinction is that Lamarck created a precedent through his classifications which is now difficult to escape from. It is also possible that some humans believe that, they themselves being vertebrates, the group deserves more attention than invertebrates. In any event, in the 1968 edition of Invertebrate Zoology, it is noted that "division of the Animal Kingdom into vertebrates and invertebrates is artificial and reflects human bias in favor of man's own relatives." The book also points out that the group lumps a vast number of species together, so that no one characteristic describes all invertebrates. In addition, some species included are only remotely related to one another, with some more related to vertebrates than other invertebrates (see Paraphyly).
== In research ==
For many centuries, invertebrates were neglected by biologists, in favor of big vertebrates and "useful" or charismatic species. Invertebrate biology was not a major field of study until the work of Linnaeus and Lamarck in the 18th century. During the 20th century, invertebrate zoology became one of the major fields of natural sciences, with prominent discoveries in the fields of medicine, genetics, palaeontology, and ecology. The study of invertebrates has also benefited law enforcement, as arthropods, and especially insects, were discovered to be a source of information for forensic investigators.
Two of the most commonly studied model organisms nowadays are invertebrates: the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans. They have long been the most intensively studied model organisms, and were among the first life-forms to be genetically sequenced. This was facilitated by the severely reduced state of their genomes, but many genes, introns, and linkages have been lost. Analysis of the starlet sea anemone genome has emphasised the importance of sponges, placozoans, and choanoflagellates, also being sequenced, in explaining the arrival of 1,500 ancestral genes unique to animals. Invertebrates are also used by scientists in the field of aquatic biomonitoring to evaluate the effects of water pollution and climate change.
== See also ==
Invertebrate zoology
Invertebrate paleontology
Marine invertebrates
Pain in invertebrates
== References ==
== Further reading ==
== External links ==
A. R. Maggenti; S. Gardner (2005). Online Dictionary of Invertebrate Zoology. Archived from the original on 26 December 2018. Retrieved 7 September 2005.
Buglife (UK)
African Invertebrates | Wikipedia/Invertebrates |
The primary motor cortex (Brodmann area 4) is a brain region that in humans is located in the dorsal portion of the frontal lobe. It is the primary region of the motor system and works in association with other motor areas including premotor cortex, the supplementary motor area, posterior parietal cortex, and several subcortical brain regions, to plan and execute voluntary movements. Primary motor cortex is defined anatomically as the region of cortex that contains large neurons known as Betz cells, which, along with other cortical neurons, send long axons down the spinal cord to synapse onto the interneuron circuitry of the spinal cord and also directly onto the alpha motor neurons in the spinal cord which connect to the muscles.
At the primary motor cortex, motor representation is orderly arranged (in an inverted fashion) from the toe (at the top of the cerebral hemisphere) to mouth (at the bottom) along a fold in the cortex called the central sulcus. However, some body parts may be controlled by partially overlapping regions of cortex. Each cerebral hemisphere of the primary motor cortex only contains a motor representation of the opposite (contralateral) side of the body. The amount of primary motor cortex devoted to a body part is not proportional to the absolute size of the body surface, but, instead, to the relative density of cutaneous motor receptors on said body part.
The density of cutaneous motor receptors on the body part is generally indicative of the necessary degree of precision of movement required at that body part. For this reason, the human hands and face have a much larger representation than the legs.
For the discovery of the primary motor cortex and its relationship to other motor cortical areas, see the main article on the motor cortex.
== Structure ==
The human primary motor cortex is located on the anterior wall of the central sulcus. It also extends anteriorly out of the sulcus partly onto the precentral gyrus. Anteriorly, the primary motor cortex is bordered by a set of areas that lie on the precentral gyrus and that are generally considered to compose the lateral premotor cortex. Posteriorly, the primary motor cortex is bordered by the primary somatosensory cortex, which lies on the posterior wall of the central sulcus. Ventrally the primary motor cortex is bordered by the insular cortex in the lateral sulcus. The primary motor cortex extends dorsally to the top of the hemisphere and then continues onto the medial wall of the hemisphere.
The location of the primary motor cortex is most obvious on histological examination due to the presence of the distinctive Betz cells. Layer V of the primary motor cortex contains giant (70-100 μm) pyramidal neurons which are the Betz cells. These neurons send long axons to the contralateral motor nuclei of the cranial nerves and to the lower motor neurons in the ventral horn of the spinal cord. These axons form a part of the corticospinal tract. The Betz cells account for only a small percentage of the corticospinal tract. By some measures, they account for about 10% of the primary motor cortex neurons projecting to the spinal cord or about 2-3% of the total cortical projection to the spinal cord. Though the Betz cells do not compose the entire motor output of the cortex, they nonetheless provide a clear marker for the primary motor cortex. This region of cortex, characterized by the presence of Betz cells, was termed area 4 by Brodmann.
=== Cellular components ===
The primary motor cortex alone has been shown to have as many as 116 different types of cells differentiated in their morphology, electrophysiological properties (including firing patterns) and gene expression profile (for example, by type of neurotransmitter released (GABA, glutamate etc.).
=== Pathway ===
As the primary motor axons travel down through the cerebral white matter, they move closer together and form part of the posterior limb of the internal capsule.
They continue down into the brainstem, where some of them, after crossing over to the contralateral side, distribute to the cranial nerve motor nuclei. (Note: a few motor fibers synapse with lower motor neurons on the same side of the brainstem).
After crossing over to the contralateral side in the medulla oblongata (pyramidal decussation), the axons travel down the spinal cord as the lateral corticospinal tract.
Fibers that do not cross over in the brainstem travel down the separate ventral corticospinal tract, and most of them cross over to the contralateral side in the spinal cord, shortly before reaching the lower motor neurons. In addition to the main corticospinal tract, Motor cortex projects to other cortical and subcortical areas, including the striatum, hypothalamus, midbrain and hindbrain, as well as the thalamus, basal ganglia, midbrain and medulla
=== Corticomotorneurons ===
Corticomotorneurons are neurons in the primary cortex which project directly to motor neurons in the ventral horn of the spinal cord. Axons of corticomotorneurons terminate on the spinal motor neurons of multiple muscles as well as on spinal interneurons. They are unique to primates and it has been suggested that their function is the adaptive control of the distal extremities (e.g. the hands) including the relatively independent control of individual fingers. Corticomotorneurons have so far only been found in the primary motor cortex and not in secondary motor areas.
=== Blood supply ===
Branches of the middle cerebral artery provide most of the arterial blood supply for the primary motor cortex.
The medial aspect (leg areas) is supplied by branches of the anterior cerebral artery.
== Function ==
=== Homunculus ===
There is a broad representation of the different body parts in the primary motor cortex in an arrangement called a motor homunculus (Latin: little person). The leg area is located close to the midline, in interior sections of the motor area folding into the medial longitudinal fissure. The lateral, convex side of the primary motor cortex is arranged from top to bottom in areas that correspond to the buttocks, torso, shoulder, elbow, wrist, fingers, thumb, eyelids, lips, and jaw. The arm and hand motor area is the largest, and occupies the part of precentral gyrus between the leg and face area.
These areas are not proportional to their size in the body with the lips, face parts, and hands represented by particularly large areas due to the comparative enrichment and density of motor receptor in these regions. Following amputation or paralysis, motor areas can shift to adopt new parts of the body.
=== Neural input from the thalamus ===
The primary motor cortex receives thalamic inputs from different thalamic nuclei. Among others:
- Ventral lateral nucleus for cerebellar afferents
- Ventral anterior nucleus for basal ganglia afferents
=== Alternative maps ===
At least two modifications to the classical somatotopic ordering of body parts have been reported in the primary motor cortex of primates.
First, the arm representation may be organized in a core and surround manner. In the monkey cortex, the digits of the hand are represented in a core area at the posterior edge of the primary motor cortex. This core area is surrounded on three sides (on the dorsal, anterior, and ventral sides) by a representation of the more proximal parts of the arm including the elbow and shoulder. In humans, the digit representation is surrounded dorsally, anteriorly, and ventrally, by a representation of the wrist.
A second modification of the classical somatotopic ordering of body parts is a double representation of the digits and wrist studied mainly in the human motor cortex. One representation lies in a posterior region called area 4p, and the other lies in an anterior region called area 4a. The posterior area can be activated by attention without any sensory feedback and has been suggested to be important for initiation of movements, while the anterior area is dependent on sensory feedback. It can also be activated by imaginary finger movements and listening to speech while making no actual movements. This anterior representation area has been suggested to be important in executing movements involving complex sensoriomotor interactions. It is possible that area 4a in humans corresponds to some parts of the caudal premotor cortex as described in the monkey cortex.
In 2009, it was reported, that there are two evolutionary distinct regions, an older one on the outer surface, and a new one found in the cleft. The older one connects to the spinal motorneurons through interneurons in the spinal cord. The newer one, found only in monkeys and apes, connects directly to the spinal motorneurons. The direct connections form after birth, are dominant over the indirect connections, and are more flexible in the circuits they can develop which allows the post-natal learning of complex fine motor skills. "The emergence of the 'new' M1 region during evolution of the primate lineage is therefore likely to have been important for the enhanced manual dexterity of the human hand."
=== Common misconceptions ===
Certain misconceptions about the primary motor cortex are common in secondary reviews, textbooks, and popular material. Three of the more common misconceptions are listed here.
==== Segregated map of the body ====
One of the most common misconceptions about the primary motor cortex is that the map of the body is cleanly segregated. Yet it is not a map of individuated muscles or even individuated body parts. The map contains considerable overlap. This overlap increases in more anterior regions of the primary motor cortex. One of the main goals in the history of work on the motor cortex was to determine just how much the different body parts are overlapped or segregated in the motor cortex. Researchers who addressed this issue found that the map of the hand, arm, and shoulder contained extensive overlap. Studies that map the precise functional connectivity from cortical neurons to muscles show that even a single neuron in the primary motor cortex can influence the activity of many muscles related to many joints. In experiments on cats and monkeys, as animals learn complex, coordinated movements, the map in the primary motor cortex becomes more overlapping, evidently learning to integrate the control of many muscles. In monkeys, when electrical stimulation is applied to the motor cortex on a behavioral timescale, it evokes complex, highly integrated movements such as reaching with the hand shaped to grasp, or bringing the hand to the mouth and opening the mouth. This type of evidence suggests that the primary motor cortex, while containing a rough map of the body, may participate in integrating muscles in meaningful ways rather than in segregating the control of individual muscle groups. It has been suggested that a deeper principle of organization may be a map of the statistical correlations in the behavioral repertoire, rather than a map of body parts. To the extent that the movement repertoire breaks down partly into the actions of separate body parts, the map contains a rough and overlapping body arrangement.
==== M1 and primary motor cortex ====
The term "M1" and the term "primary motor cortex" are often used interchangeably. However, they come from different historical traditions and refer to different divisions of cortex. Some scientists suggested that the motor cortex could be divided into a primary motor strip that was more posterior and a lateral premotor strip that was more anterior. Early researchers who originally proposed this view included Campbell, Vogt and Vogt, Foerster, and Fulton. Others suggested that the motor cortex could not be divided in that manner. Instead, in this second view, the so-called primary motor and lateral premotor strips together composed a single cortical area termed M1. A second motor area on the medial wall of the hemisphere was termed M2 or the supplementary motor area. Proponents of this view included Penfield and Woolsey. Today the distinction between the primary motor cortex and the lateral premotor cortex is generally accepted. However, the term M1 is sometimes mistakenly used to refer to the primary motor cortex. Strictly speaking M1 refers to the single map that, according to some previous researchers, encompassed both the primary motor and the lateral premotor cortex.
==== Betz cells as the final common pathway ====
The Betz cells, or giant pyramidal cells in the primary motor cortex, are sometimes mistaken to be the only or main output from the cortex to the spinal cord. This mistake is old, dating back at least to Campbell in 1905. Yet the Betz cells compose only about 2-3% of the neurons that project from the cortex to the spinal cord, and only about 10% of the neurons that project specifically from the primary motor cortex to the spinal cord. A range of cortical areas including the premotor cortex, the supplementary motor area, and even the primary somatosensory cortex, project to the spinal cord. Even when the Betz cells are damaged, the cortex can still communicate to subcortical motor structures and control movement. If the primary motor cortex with its Betz cells is damaged, a temporary paralysis results and other cortical areas can evidently take over some of the lost function.
== Clinical significance ==
Lesions of the precentral gyrus result in paralysis of the contralateral side of the body (facial palsy, arm-/leg monoparesis, hemiparesis) - see upper motor neuron.
== Movement coding ==
Evarts suggested that each neuron in the motor cortex contributes to the force in a muscle. As the neuron becomes active, it sends a signal to the spinal cord, the signal is relayed to a motorneuron, the motorneuron sends a signal to a muscle, and the muscle contracts. The more activity in the motor cortex neuron, the more muscle force.
Georgopoulos and colleagues suggested that muscle force alone was too simple a description. They trained monkeys to reach in various directions and monitored the activity of neurons in the motor cortex. They found that each neuron in the motor cortex was maximally active during a specific direction of reach, and responded less well to neighboring directions of reach. On this basis they suggested that neurons in motor cortex, by "voting" or pooling their influences into a "population code", could precisely specify a direction of reach.
The proposal that motor cortex neurons encode the direction of a reach became controversial. Scott and Kalaska showed that each motor cortex neuron was better correlated with the details of joint movement and muscle force than with the direction of the reach. Schwartz and colleagues showed that motor cortex neurons were well correlated with the speed of the hand. Strick and colleagues found that some neurons in motor cortex were active in association with muscle force and some with the spatial direction of movement. Todorov proposed that the many different correlations are the result of a muscle controller in which many movement parameters happen to be correlated with muscle force.
The code by which neurons in the primate motor cortex control the spinal cord, and thus movement, remains debated.
Some specific progress in understanding how motor cortex causes movement has also been made in the rodent model. The rodent motor cortex, like the monkey motor cortex, may contain subregions that emphasize different common types of actions. For example, one region appears to emphasize the rhythmic control of whisking. Neurons in this region project to a specific subcortical nucleus in which a pattern generator coordinates the cyclic rhythm of the whiskers. This nucleus then projects to the muscles that control the whiskers.
== Additional images ==
== See also ==
Corticospinal tract
Motor cortex
Cortical homunculus
Upper motor neuron
Brodmann area
List of regions in the human brain
== References ==
== External links ==
Overview at mcgill.ca | Wikipedia/Corticomotor_neuron |
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, terminal neurodegenerative disorder that results in the progressive loss of both upper and lower motor neurons that normally control voluntary muscle contraction. ALS is the most common form of the motor neuron diseases. ALS often presents in its early stages with gradual muscle stiffness, twitches, weakness, and wasting. Motor neuron loss typically continues until the abilities to eat, speak, move, and, lastly, breathe are all lost. While only 15% of people with ALS also fully develop frontotemporal dementia, an estimated 50% face at least some minor difficulties with thinking and behavior. Depending on which of the aforementioned symptoms develops first, ALS is classified as limb-onset (begins with weakness in the arms or legs) or bulbar-onset (begins with difficulty in speaking or swallowing).
Most cases of ALS (about 90–95%) have no known cause, and are known as sporadic ALS. However, both genetic and environmental factors are believed to be involved. The remaining 5–10% of cases have a genetic cause, often linked to a family history of the disease, and these are known as familial ALS (hereditary). About half of these genetic cases are due to disease-causing variants in one of four specific genes. The diagnosis is based on a person's signs and symptoms, with testing conducted to rule out other potential causes.
There is no known cure for ALS. The goal of treatment is to slow the disease progression, and improve symptoms. FDA-approved treatments that slow the progression of ALS include riluzole and edaravone. Non-invasive ventilation may result in both improved quality and length of life. Mechanical ventilation can prolong survival but does not stop disease progression. A feeding tube may help maintain weight and nutrition. Death is usually caused by respiratory failure. The disease can affect people of any age, but usually starts around the age of 60. The average survival from onset to death is two to four years, though this can vary, and about 10% of those affected survive longer than ten years.
Descriptions of the disease date back to at least 1824 by Charles Bell. In 1869, the connection between the symptoms and the underlying neurological problems was first described by French neurologist Jean-Martin Charcot, who in 1874 began using the term amyotrophic lateral sclerosis.
== Classification ==
ALS is a motor neuron disease, which is a group of neurological disorders that selectively affect motor neurons, the cells that control voluntary muscles of the body. Other motor neuron diseases include primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), progressive bulbar palsy, pseudobulbar palsy, and monomelic amyotrophy (MMA).
As a disease, ALS itself can be classified in a few different ways: by which part of the motor neurons are affected; by the parts of the body first affected; whether it is genetic; and by the age at which it started. Each individual diagnosed with the condition will sit at a unique place at the intersection of these complex and overlapping subtypes, which presents a challenge to diagnosis, understanding, and prognosis.
=== Subtypes of motor neuron disease ===
ALS can be classified by the types of motor neurons that are affected. To successfully control any voluntary muscle in the body, a signal must be sent from the motor cortex in the brain down the upper motor neuron as it travels down the spinal cord. There, it connects via a synapse to the lower motor neuron which connects to the muscle itself. Damage to either the upper or lower motor neuron, as it makes its way from the brain to muscle, causes different types of symptoms. Damage to the upper motor neuron typically causes spasticity including stiffness and increased tendon reflexes or clonus, while damage to the lower motor neuron typically causes weakness, muscle atrophy, and fasciculations.
Classical, or classic ALS, involves degeneration to both the upper motor neurons in the brain and the lower motor neurons in the spinal cord. Primary lateral sclerosis (PLS) involves degeneration of only the upper motor neurons, and progressive muscular atrophy (PMA) involves only the lower motor neurons. There is debate over whether PLS and PMA are separate diseases or simply variants of ALS.
Classical ALS accounts for about 70% of all cases of ALS and can be subdivided into where symptoms first appear as these are usually focused to one region of the body at initial presentation before later spread. Limb-onset ALS (also known as spinal-onset) and bulbar-onset ALS. Limb-onset ALS begins with weakness in the hands, arms, feet, and/or legs and accounts for about two-thirds of all classical ALS cases. Bulbar-onset ALS begins with weakness in the muscles of speech, chewing, and swallowing and accounts for about 25% of classical ALS cases. A rarer type of classical ALS affecting around 3% of patients is respiratory-onset, in which the initial symptoms are difficulty breathing (dyspnea) upon exertion, at rest, or while lying flat (orthopnea).
Primary lateral sclerosis (PLS) is a subtype of the overall ALS category which accounts for about 5% of all cases and only affects the upper motor neurons in the arms, legs, and bulbar region. However, more than 75% of people with apparent PLS go on to later develop lower motor neuron signs within four years of symptom onset, meaning that a definitive diagnosis of PLS cannot be made until several years have passed. PLS has a better prognosis than classical ALS, as it progresses slower, results in less functional decline, does not affect the ability to breathe, and causes less severe weight loss than classical ALS.
Progressive muscular atrophy (PMA) is another subtype that accounts for about 5% of the overall ALS category and affects lower motor neurons in the arms, legs, and bulbar region. While PMA is associated with longer survival on average than classical ALS, it is still progressive over time, eventually leading to respiratory failure and death. As with PLS developing into classical ALS, PMA can also develop into classical ALS over time if the lower motor neuron involvement progresses to include upper motor neurons, in which case the diagnosis might be changed to classic ALS.
=== Rare isolated variants of ALS ===
Isolated variants of ALS have symptoms that are limited to a single region for at least a year; they progress more slowly than classical ALS and are associated with longer survival. These regional variants of ALS can only be considered as a diagnosis should the initial symptoms fail to spread to other spinal cord regions for an extended period of time (at least 12 months). Flail arm syndrome is characterized by lower motor neuron damage affecting the arm muscles, typically starting with the upper arms symmetrically and progressing downwards to the hands. Flail leg syndrome is characterized by lower motor neuron damage leading to asymmetrical weakness and wasting in the legs starting around the feet. Isolated bulbar palsy is characterized by upper or lower motor neuron damage in the bulbar region (in the absence of limb symptoms for at least 20 months), leading to gradual onset of difficulty with speech (dysarthria) and swallowing (dysphagia).
=== Age of onset ===
ALS can also be classified based on the age of onset. People with familial ALS have an age of onset about 5 years younger than those with apparently sporadic ALS. About 10% of all cases of ALS begin before age 45 ("young-onset" ALS), and about 1% of all cases begin before age 25 ("juvenile" ALS). People who develop young-onset ALS are more likely to be male, less likely to have bulbar onset of symptoms, and more likely to have a slower progression of the disease. Juvenile ALS is more likely to be genetic in origin than adult-onset ALS; the most common genes associated with juvenile ALS are FUS, ALS2, and SETX. Although most people with juvenile ALS live longer than those with adult-onset ALS, some of them have specific mutations in FUS and SOD1 that are associated with a poor prognosis. Late onset (after age 65) is generally associated with a more rapid functional decline and shorter survival.
== Signs and symptoms ==
The disorder causes muscle weakness, atrophy, and muscle spasms throughout the body due to the degeneration of the upper motor and lower motor neurons. Sensory nerves and the autonomic nervous system are generally unaffected, meaning the majority of people with ALS maintain hearing, sight, touch, smell, and taste.
=== Initial symptoms ===
The start of ALS may be so subtle that the symptoms are overlooked. The earliest symptoms of ALS are muscle weakness or muscle atrophy, typically on one side of the body. Other presenting symptoms include trouble swallowing or breathing, cramping, or stiffness of affected muscles; muscle weakness affecting an arm or a leg; or slurred and nasal speech. The parts of the body affected by early symptoms of ALS depend on which motor neurons in the body are damaged first.
In limb-onset ALS, the first symptoms are in the arms or the legs. If the legs are affected first, people may experience awkwardness, tripping, or stumbling when walking or running; this is often marked by walking with a "dropped foot" that drags gently on the ground. If the arms are affected first, they may experience difficulty with tasks requiring manual dexterity, such as buttoning a shirt, writing, or turning a key in a lock.
In bulbar-onset ALS, the first symptoms are difficulty speaking or swallowing. Speech may become slurred, nasal in character, or quieter. There may be difficulty with swallowing and loss of tongue mobility. A smaller proportion of people experience "respiratory-onset" ALS, where the intercostal muscles that support breathing are affected first.
Over time, people experience increasing difficulty moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Symptoms of upper motor neuron involvement include tight and stiff muscles (spasticity) and exaggerated reflexes (hyperreflexia), including an overactive gag reflex. While the disease does not cause pain directly, pain is a symptom experienced by most people with ALS caused by reduced mobility. Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under the skin (fasciculations).
=== Progression ===
Although the initial site of symptoms and subsequent rate of disability progression vary from person to person, the initially affected body region is usually the most affected over time, and symptoms usually spread to a neighbouring body region. For example, symptoms starting in one arm usually spread next to either the opposite arm or to the leg on the same side. Bulbar-onset patients most typically get their next symptoms in their arms rather than legs, arm-onset patients typically spread to the legs before the bulbar region, and leg-onset patients typically spread to the arms rather than the bulbar region. Over time, regardless of where symptoms began, most people eventually lose the ability to walk or use their hands and arms independently. Less consistently, they may lose the ability to speak and to swallow food. It is the eventual development of weakness of the respiratory muscles, with the loss of ability to cough and to breathe without support, that is ultimately life-shortening in ALS.
The rate of progression can be measured using the ALS Functional Rating Scale - Revised (ALSFRS-R), a 12-item instrument survey administered as a clinical interview or self-reported questionnaire that produces a score between 48 (normal function) and 0 (severe disability). The ALSFRS-R is the most frequently used outcome measure in clinical trials and is used by doctors to track disease progression. Though the degree of variability is high and a small percentage of people have a much slower progression, on average people with ALS lose about 1 ALSFRS-R point per month. Brief periods of stabilization ("plateaus") and even small reversals in ALSFRS-R score are not uncommon, due to the fact the tool is subjective, can be affected by medication, and different forms of compensation for changes in function. However, it is rare (<1%) for these improvements to be large (i.e. greater than 4 ALSFRS-R points) or sustained (i.e. greater than 12 months). A survey-based study among clinicians showed that they rated a 20% change in the slope of the ALSFRS-R as being clinically meaningful, which is the most common threshold used to determine whether a new treatment is working in clinical trials.
=== Late-stage disease management ===
Difficulties with chewing and swallowing make eating very difficult (dysphagia) and increase the risk of choking or of aspirating food into the lungs. In later stages of the disorder, aspiration pneumonia can develop, and maintaining a healthy weight can become a significant problem that may require the insertion of a feeding tube. As the diaphragm and intercostal muscles of the rib cage that support breathing weaken, measures of lung function such as vital capacity and inspiratory pressure diminish. In respiratory-onset ALS, this may occur before significant limb weakness is apparent. Individuals affected by the disorder may ultimately lose the ability to initiate and control all voluntary movement, known as locked-in syndrome. Bladder and bowel function are usually spared, meaning urinary and fecal incontinence are uncommon, although trouble getting to a toilet can lead to difficulties. The extraocular muscles responsible for eye movement are usually spared, meaning the use of eye tracking technology to support augmentative communication is often feasible, albeit slow, and needs may change over time. Despite these challenges, many people in an advanced state of disease report satisfactory wellbeing and quality of life.
=== Prognosis, staging, and survival ===
Although respiratory support using non-invasive ventilation can ease problems with breathing and prolong survival, it does not affect the progression rate of ALS. Most people with ALS die between two and four years after the diagnosis. Around 50% of people with ALS die within 30 months of their symptoms beginning, about 20% live between five and ten years, and about 10% survive for 10 years or longer.
The most common cause of death among people with ALS is respiratory failure, often accelerated by pneumonia. Most ALS patients die at home after a period of worsening difficulty breathing, a decline in their nutritional status, or a rapid worsening of symptoms. Sudden death or acute respiratory distress are uncommon. Access to palliative care is recommended from an early stage to explore options, ensure psychosocial support for the patient and caregivers, and to discuss advance healthcare directives.
As with cancer staging, ALS has staging systems numbered between 1 and 4 that are used for research purposes in clinical trials. Two very similar staging systems emerged around a similar time, the King's staging system and Milano-Torino (MiToS) functional staging.
Providing individual patients with a precise prognosis is not currently possible, though research is underway to provide statistical models on the basis of prognostic factors including age at onset, progression rate, site of onset, and presence of frontotemporal dementia. Those with a bulbar onset have a worse prognosis than limb-onset ALS; a population-based study found that bulbar-onset ALS patients had a median survival of 2.0 years and a 10-year survival rate of 3%, while limb-onset ALS patients had a median survival of 2.6 years and a 10-year survival rate of 13%. Those with respiratory-onset ALS had a shorter median survival of 1.4 years and 0% survival at 10 years. While astrophysicist Stephen Hawking lived for 55 more years following his diagnosis, his was an unusual case.
=== Cognitive, emotional, and behavioral symptoms ===
Cognitive impairment or behavioral dysfunction is present in 30–50% of individuals with ALS, and can appear more frequently in later stages of the disease. Language dysfunction, executive dysfunction, and troubles with social cognition and verbal memory are the most commonly reported cognitive symptoms in ALS. Cognitive impairment is found more frequently in patients with C9orf72 gene repeat expansions, bulbar onset, bulbar symptoms, family history of ALS, and/or a predominantly upper motor neuron phenotype.
Emotional lability is a symptom in which patients cry, smile, yawn, or laugh, either in the absence of emotional stimuli, or when they are feeling the opposite emotion to that being expressed; it is experienced by about half of ALS patients and is more common in those with bulbar-onset ALS. While relatively benign relative to other symptoms, it can cause increased stigma and social isolation as people around the patient struggle to react appropriately to what can be frequent and inappropriate outbursts in public.
In addition to mild changes in cognition that may only emerge during neuropsychological testing, around 10–15% of individuals have signs of frontotemporal dementia (FTD). Repeating phrases or gestures, apathy, and loss of inhibition are the most frequently reported behavioral features of ALS. ALS and FTD are now considered to be part of a common disease spectrum (ALS–FTD) because of genetic, clinical, and pathological similarities. Genetically, repeat expansions in the C9orf72 gene account for about 40% of genetic ALS and 25% of genetic FTD.
Cognitive and behavioral issues are associated with a poorer prognosis as they may reduce adherence to medical advice, and deficits in empathy and social cognition which may increase caregiver burden.
== Cause ==
It is not known what causes sporadic ALS, hence it is described as an idiopathic disease. Though its exact cause is unknown, genetic and environmental factors are thought to be of roughly equal importance. The genetic factors are better understood than the environmental factors; no specific environmental factor has been definitively shown to cause ALS. A multi-step liability threshold model for ALS proposes that cellular damage accumulates over time due to genetic factors present at birth and exposure to environmental risks throughout life. ALS can strike at any age, but its likelihood increases with age. Most people who develop ALS are between the ages of 40 and 70, with an average age of 55 at the time of diagnosis. ALS is 20% more common in men than women, but this difference in sex distribution is no longer present in patients with onset after age 70.
=== Genetics and genetic testing ===
While they appear identical clinically and pathologically, ALS can be classified as being either familial or sporadic, depending on whether there is a known family history of the disease and/or whether an ALS-associated genetic mutation has been identified via genetic testing. Familial ALS is thought to account for 10–15% of cases overall and can include monogenic, oligogenic, and polygenic modes of inheritance.
There is considerable variation among clinicians on how to approach genetic testing in ALS, and only about half discuss the possibility of genetic inheritance with their patients, particularly if there is no discernible family history of the disease. In the past, genetic counseling and testing was only offered to those with obviously familial ALS. But it is increasingly recognized that cases of sporadic ALS may also be due to disease-causing de novo mutations in SOD1, or C9orf72, an incomplete family history, or incomplete penetrance, meaning that a patient's ancestors carried the gene but did not express the disease in their lifetimes. The lack of positive family history may be caused by lack of historical records, having a smaller family, older generations dying earlier of causes other than ALS, genetic non-paternity, and uncertainty over whether certain neuropsychiatric conditions (e.g. frontotemporal dementia, other forms of dementia, suicide, psychosis, schizophrenia) should be considered significant when determining a family history. There have been calls in the research community to routinely counsel and test all diagnosed ALS patients for familial ALS, particularly as there is now a licensed gene therapy (tofersen) specifically targeted to carriers of SOD-1 ALS. A shortage of genetic counselors and limited clinical capacity to see such at-risk individuals makes this challenging in practice, as does the unequal access to genetic testing around the world.
More than 40 genes have been associated with ALS, of which four account for nearly half of familial cases, and around 5% of sporadic cases: C9orf72 (40% of familial cases, 7% sporadic), SOD1 (12% of familial cases, 1–2% sporadic), FUS (4% of familial cases, 1% sporadic), and TARDBP (4% of familial cases, 1% sporadic), with the remaining genes mostly accounting for fewer than 1% of either familial or sporadic cases. ALS genes identified to date explain the cause of about 70% of familial ALS and about 15% of sporadic ALS. Overall, first-degree relatives of an individual with ALS have a ~1% risk of developing ALS themselves.
=== Environmental and other factors ===
The multi-step hypothesis suggests the disease is caused by some interaction between an individual's genetic risk factors and their cumulative lifetime of exposures to environmental factors, termed their exposome. The most consistent lifetime exposures associated with developing ALS (other than genetic mutations) include heavy metals (e.g. lead and mercury), chemicals (e.g. pesticides and solvents), electric shock, physical injury (including head injury), and smoking (in men more than women). Overall these effects are small, with each exposure in isolation only increasing the likelihood of a very rare condition by a small amount. For instance, an individual's lifetime risk of developing ALS might go from "1 in 400" without exposure to between "1 in 300" and "1 in 200" if they were exposed to heavy metals. Some industries are heavily dependent upon the use or exposure to these environmental factors, increasing employees' susceptibility. Agricultural tasks can be intertwined with as many as 5 such risk factors excluding workers' smoking preferences.
A range of other factors have weaker evidence supporting them and include participation in professional sports, having a lower body mass index, lower educational attainment, manual occupations, military service, exposure to Beta-N-methylamino-L-alanin (BMAA), and viral infections.
Although some personality traits, such as openness, agreeableness and conscientiousness appear remarkably common among patients with ALS, it remains open whether personality can increase susceptibility to ALS directly. Instead, genetic factors giving rise to personality might simultaneously predispose people to develop ALS, or the above personality traits might underlie lifestyle choices which are in turn risk factors for ALS.
== Pathophysiology ==
=== Neuropathology ===
Upon examination at autopsy, features of the disease that can be seen with the naked eye include skeletal muscle atrophy, motor cortex atrophy, sclerosis of the corticospinal and corticobulbar tracts, thinning of the hypoglossal nerves (which control the tongue), and thinning of the anterior roots of the spinal cord.
The defining feature of ALS is the death of both upper motor neurons (located in the motor cortex of the brain) and lower motor neurons (located in the brainstem and spinal cord). In ALS with frontotemporal dementia, neurons throughout the frontal and temporal lobes of the brain die as well. The pathological hallmark of ALS is the presence of inclusion bodies (abnormal aggregations of protein) known as Bunina bodies in the cytoplasm of motor neurons. In about 97% of people with ALS, the main component of the inclusion bodies is TDP-43 protein; however, in those with SOD1 or FUS mutations, the main component of the inclusion bodies is SOD1 protein or FUS protein, respectively. Prion-like propagation of misfolded proteins from cell to cell may explain why ALS starts in one area and spreads to others. The glymphatic system may also be involved in the pathogenesis of ALS.
=== Biochemistry ===
It is still not fully understood why neurons die in ALS, but this neurodegeneration is thought to involve many different cellular and molecular processes. The genes known to be involved in ALS can be grouped into three general categories based on their normal function: protein degradation, the cytoskeleton, and RNA processing. Mutant SOD1 protein forms intracellular aggregations that inhibit protein degradation. Cytoplasmic aggregations of wild-type (normal) SOD1 protein are common in sporadic ALS. It is thought that misfolded mutant SOD1 can cause misfolding and aggregation of wild-type SOD1 in neighboring neurons in a prion-like manner. Other protein degradation genes that can cause ALS when mutated include VCP, OPTN, TBK1, and SQSTM1. Three genes implicated in ALS that are important for maintaining the cytoskeleton and for axonal transport include DCTN1, PFN1, and TUBA4A.
Several ALS genes encode RNA-binding proteins. The first to be discovered was TDP-43 protein, a nuclear protein that aggregates in the cytoplasm of motor neurons in almost all cases of ALS; however, mutations in TARDBP, the gene that codes for TDP-43, are a rare cause of ALS. FUS codes for FUS, another RNA-binding protein with a similar function to TDP-43, which can cause ALS when mutated. It is thought that mutations in TARDBP and FUS increase the binding affinity of the low-complexity domain, causing their respective proteins to aggregate in the cytoplasm. Once these mutant RNA-binding proteins are misfolded and aggregated, they may be able to misfold normal proteins both within and between cells in a prion-like manner. This also leads to decreased levels of RNA-binding protein in the nucleus, which may mean that their target RNA transcripts do not undergo normal processing. Other RNA metabolism genes associated with ALS include ANG, SETX, and MATR3.
C9orf72 is the most commonly mutated gene in ALS and causes motor neuron death through a number of mechanisms. The pathogenic mutation is a hexanucleotide repeat expansion (a series of six nucleotides repeated over and over); people with up to 30 repeats are considered normal, while people with hundreds or thousands of repeats can have familial ALS, frontotemporal dementia, or sometimes sporadic ALS. The three mechanisms of disease associated with these C9orf72 repeats are deposition of RNA transcripts in the nucleus, translation of the RNA into toxic dipeptide repeat proteins in the cytoplasm, and decreased levels of the normal C9orf72 protein. Mitochondrial bioenergetic dysfunction leading to dysfunctional motor neuron axonal homeostasis (reduced axonal length and fast axonal transport of mitochondrial cargo) has been shown to occur in C9orf72-ALS using human induced pluripotent stem cell (iPSC) technologies coupled with CRISPR/Cas9 gene-editing, and human post-mortem spinal cord tissue examination.
Excitotoxicity, or nerve cell death caused by high levels of intracellular calcium due to excessive stimulation by the excitatory neurotransmitter glutamate, is a mechanism thought to be common to all forms of ALS. Motor neurons are more sensitive to excitotoxicity than other types of neurons because they have a lower calcium-buffering capacity and a type of glutamate receptor (the AMPA receptor) that is more permeable to calcium. In ALS, there are decreased levels of excitatory amino acid transporter 2 (EAAT2), which is the main transporter that removes glutamate from the synapse; this leads to increased synaptic glutamate levels and excitotoxicity. Riluzole, a drug that modestly prolongs survival in ALS, inhibits glutamate release from pre-synaptic neurons; however, it is unclear if this mechanism is responsible for its therapeutic effect.
== Diagnosis ==
No single test can provide a definite diagnosis of ALS. Instead, the diagnosis of ALS is primarily made based on a physician's clinical assessment after ruling out other diseases. Physicians often obtain the person's full medical history and conduct neurologic examinations at regular intervals to assess whether signs and symptoms such as muscle weakness, muscle atrophy, hyperreflexia, Babinski's sign, and spasticity are worsening. Many biomarkers are being studied for the condition, but as of 2023 are not in general medical use.
=== Differential diagnosis ===
Because symptoms of ALS can be similar to those of a wide variety of other, more treatable diseases or disorders, appropriate tests must be conducted to exclude the possibility of other conditions. One of these tests is electromyography (EMG), a special recording technique that detects electrical activity in muscles. Certain EMG findings can support the diagnosis of ALS. Another common test measures nerve conduction velocity (NCV). Specific abnormalities in the NCV results may suggest, for example, that the person has a form of peripheral neuropathy (damage to peripheral nerves) or myopathy (muscle disease) rather than ALS. While a magnetic resonance imaging (MRI) is often normal in people with early-stage ALS, it can reveal evidence of other problems that may be causing the symptoms, such as a spinal cord tumor, multiple sclerosis, a herniated disc in the neck, syringomyelia, or cervical spondylosis.
Based on the person's symptoms and findings from the examination and from these tests, the physician may order tests on blood and urine samples to eliminate the possibility of other diseases, as well as routine laboratory tests. In some cases, for example, if a physician suspects the person may have a myopathy rather than ALS, a muscle biopsy may be performed.
A number of infectious diseases can sometimes cause ALS-like symptoms, including human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), Lyme disease, and syphilis. Neurological disorders such as multiple sclerosis, post-polio syndrome, multifocal motor neuropathy, CIDP, spinal muscular atrophy, and spinal and bulbar muscular atrophy can also mimic certain aspects of the disease and should be considered.
ALS must be differentiated from the "ALS mimic syndromes", which are unrelated disorders that may have a similar presentation and clinical features to ALS or its variants. Because the prognosis of ALS and closely related subtypes of motor neuron disease are generally poor, neurologists may carry out investigations to evaluate and exclude other diagnostic possibilities. Disorders of the neuromuscular junction, such as myasthenia gravis (MG) and Lambert–Eaton myasthenic syndrome, may also mimic ALS, although this rarely presents diagnostic difficulty over time. Benign fasciculation syndrome and cramp fasciculation syndrome may also, occasionally, mimic some of the early symptoms of ALS. Nonetheless, the absence of other neurological features that develop inexorably with ALS means that, over time, the distinction will not present any difficulty to the experienced neurologist; where doubt remains, EMG may be helpful.
== Management ==
There is no cure for ALS. Management focuses on treating symptoms and providing supportive care, to improve quality of life and prolong survival. This care is best provided by multidisciplinary teams of healthcare professionals; attending a multidisciplinary ALS clinic is associated with longer survival, fewer hospitalizations, and improved quality of life.
Non-invasive ventilation (NIV) is the main treatment for respiratory failure in ALS. In people with normal bulbar function, it prolongs survival by about seven months and improves the quality of life. One study found that NIV is ineffective for people with poor bulbar function while another suggested that it may provide a modest survival benefit. Many people with ALS have difficulty tolerating NIV. Invasive ventilation is an option for people with advanced ALS when NIV is not enough to manage their symptoms. While invasive ventilation prolongs survival, disease progression, and functional decline continue. It may decrease the quality of life of people with ALS or their caregivers. Invasive ventilation is more commonly used in Japan than in North America or Europe.
Physical therapy can promote functional independence through aerobic, range of motion, and stretching exercises. Occupational therapy can assist with activities of daily living through adaptive equipment. Speech therapy can assist people with ALS who have difficulty speaking. Preventing weight loss and malnutrition in people with ALS improves both survival and quality of life. Initially, difficulty swallowing (dysphagia) can be managed by dietary changes and swallowing techniques. A feeding tube should be considered if someone with ALS loses 5% or more of their body weight or if they cannot safely swallow food and water. The feeding tube is usually inserted by percutaneous endoscopic gastrostomy (PEG). There is weak evidence that PEG tubes improve survival. PEG insertion is usually performed with the intent of improving quality of life.
Palliative care should begin shortly after someone is diagnosed with ALS. Discussion of end-of-life issues gives people with ALS time to reflect on their preferences for end-of-life care and can help avoid unwanted interventions or procedures. Hospice care can improve symptom management at the end of life and increase the likelihood of a peaceful death. In the final days of life, opioids can be used to treat pain and dyspnea, while benzodiazepines can be used to treat anxiety.
=== Medications ===
==== Disease-slowing treatments ====
Riluzole has been found to modestly prolong survival by about 2–3 months. It may have a greater survival benefit for those with bulbar-onset ALS. It may work by decreasing release of the excitatory neurotransmitter glutamate from pre-synaptic neurons. The most common side effects are nausea and a lack of energy (asthenia). People with ALS should begin treatment with riluzole as soon as possible following their diagnosis. Riluzole is available as a tablet, liquid, or dissolvable oral film.
Edaravone has been shown to modestly slow the decline in function in a small group of people with early-stage ALS. It may work by protecting motor neurons from oxidative stress. The most common side effects are bruising and gait disturbance. Edaravone is available as an intravenous infusion or as an oral suspension.
AMX0035 (Relyvrio) is a combination of sodium phenylbutyrate and taurursodiol, which was initially shown to prolong the survival of patients by an average of six months. Relyvrio was withdrawn by the manufacturer in April 2024 following the completion of the Phase 3 PHOENIX trial which did not show substantial benefit to ALS patients.
Tofersen (Qalsody) is an antisense oligonucleotide that was approved for medical use in the United States in April 2023, for the treatment of SOD1-associated ALS. In a study of 108 patients with SOD1-associated ALS there was a non-significant trend towards a slowing of progression, as well as a significant reduction in neurofilament light chain, a putative ALS biomarker thought to indicate neuronal damage. A follow-up study and open-label extension suggested that earlier treatment initiation had a beneficial effect on slowing disease progression. Tofersen is available as an intrathecal injection into the lumbar cistern at the base of the spine.
A 2025 phase II study published found that tetramethylpyrazine nitrone is safe for patients with ALS, but it did not show a significant advantage over placebo in the primary efficacy measure. Researchers noted that the drug may help slow the decline in grip strength, however further clinical trials are necessary to confirm its potential benefits.
==== Symptomatic treatments ====
Other medications may be used to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and phlegm. Gabapentin, pregabalin, and tricyclic antidepressants (e.g., amitriptyline) can be used for neuropathic pain, while nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and opioids can be used for nociceptive pain.
Depression can be treated with selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants, while benzodiazepines can be used for anxiety. There are no medications to treat cognitive impairment/frontotemporal dementia (FTD); however, SSRIs and antipsychotics can help treat some of the symptoms of FTD. Baclofen and tizanidine are the most commonly used oral drugs for treating spasticity; an intrathecal baclofen pump can be used for severe spasticity. Atropine, scopolamine, amitriptyline, or glycopyrrolate may be prescribed when people with ALS begin having trouble swallowing their saliva (sialorrhea).
A 2017 review concluded that mexiletine is safe and effective for treating cramps in ALS based on a randomized controlled trial from 2016.
=== Breathing support ===
==== Non-invasive ventilation ====
Non-invasive ventilation (NIV) is the primary treatment for respiratory failure in ALS and was the first treatment shown to improve both survival and quality of life. NIV uses a face or nasal mask connected to a ventilator that provides intermittent positive pressure to support breathing. Continuous positive pressure is not recommended for people with ALS because it makes breathing more difficult. Initially, NIV is used only at night because the first sign of respiratory failure is decreased gas exchange (hypoventilation) during sleep; symptoms associated with this nocturnal hypoventilation include interrupted sleep, anxiety, morning headaches, and daytime fatigue. As the disease progresses, people with ALS develop shortness of breath when lying down, during physical activity or talking, and eventually at rest. Other symptoms include poor concentration, poor memory, confusion, respiratory tract infections, and a weak cough. Respiratory failure is the most common cause of death in ALS.
It is important to monitor the respiratory function of people with ALS every three months because beginning NIV soon after the start of respiratory symptoms is associated with increased survival. This involves asking the person with ALS if they have any respiratory symptoms and measuring their respiratory function. The most commonly used measurement is upright forced vital capacity (FVC), but it is a poor detector of early respiratory failure and is not a good choice for those with bulbar symptoms, as they have difficulty maintaining a tight seal around the mouthpiece. Measuring FVC while the person is lying on their back (supine FVC) is a more accurate measure of diaphragm weakness than upright FVC. Sniff nasal inspiratory pressure (SNIP) is a rapid, convenient test of diaphragm strength that is not affected by bulbar muscle weakness. If someone with ALS has signs and symptoms of respiratory failure, they should undergo daytime blood gas analysis to look for hypoxemia (low oxygen in the blood) and hypercapnia (too much carbon dioxide in the blood). If their daytime blood gas analysis is normal, they should then have nocturnal pulse oximetry to look for hypoxemia during sleep.
Non-invasive ventilation prolongs survival longer than riluzole. A 2006 randomized controlled trial found that NIV prolongs survival by about 48 days and improves the quality of life; however, it also found that some people with ALS benefit more from this intervention than others. For those with normal or only moderately impaired bulbar function, NIV prolongs survival by about seven months and significantly improves the quality of life. For those with poor bulbar function, NIV neither prolongs survival nor improves the quality of life, though it does improve some sleep-related symptoms. Despite the clear benefits of NIV, about 25–30% of all people with ALS are unable to tolerate it, especially those with cognitive impairment or bulbar dysfunction. Results from a large 2015 cohort study suggest that NIV may prolong survival in those with bulbar weakness, so NIV should be offered to all people with ALS, even if it is likely that they will have difficulty tolerating it.
==== Invasive ventilation ====
Invasive ventilation bypasses the nose and mouth (the upper airways) by making a cut in the trachea (tracheostomy) and inserting a tube connected to a ventilator. It is an option for people with advanced ALS whose respiratory symptoms are poorly managed despite continuous NIV use. While invasive ventilation prolongs survival, especially for those younger than 60, it does not treat the underlying neurodegenerative process. The person with ALS will continue to lose motor function, making communication increasingly difficult and sometimes leading to locked-in syndrome, in which they are completely paralyzed except for their eye muscles. About half of the people with ALS who choose to undergo invasive ventilation report a decrease in their quality of life but most still consider it to be satisfactory. However, invasive ventilation imposes a heavy burden on caregivers and may decrease their quality of life. Attitudes toward invasive ventilation vary from country to country; about 30% of people with ALS in Japan choose invasive ventilation, versus less than 5% in North America and Europe.
=== Therapy ===
Physical therapy plays a large role in rehabilitation for individuals with ALS. Specifically, physical, occupational, and speech therapists can set goals and promote benefits for individuals with ALS by delaying loss of strength, maintaining endurance, limiting pain, improving speech and swallowing, preventing complications, and promoting functional independence.
Occupational therapy and special equipment such as assistive technology can also enhance people's independence and safety throughout the course of ALS. Gentle, low-impact aerobic exercise such as performing activities of daily living, walking, swimming, and stationary bicycling can strengthen unaffected muscles, improve cardiovascular health, and help people fight fatigue and depression. Range of motion and stretching exercises can help prevent painful spasticity and shortening (contracture) of muscles. Physical and occupational therapists can recommend exercises that provide these benefits without overworking muscles because muscle exhaustion can lead to a worsening of symptoms associated with ALS, rather than providing help to people with ALS. They can suggest devices such as ramps, braces, walkers, bathroom equipment (shower chairs, toilet risers, etc.), and wheelchairs that help people remain mobile. Occupational therapists can provide or recommend equipment and adaptations to enable ALS people to retain as much safety and independence in activities of daily living as possible. Since respiratory insufficiency is the primary cause of mortality, physical therapists can help improve respiratory outcomes in people with ALS by implementing pulmonary physical therapy. This includes inspiratory muscle training, lung volume recruitment training, and manual assisted cough therapy aimed at increasing respiratory muscle strength as well as increasing survival rates.
People with ALS who have difficulty speaking or swallowing may benefit from working with a speech-language pathologist. These health professionals can teach people adaptive strategies such as techniques to help them speak louder and more clearly. As ALS progresses, speech-language pathologists can recommend the use of augmentative and alternative communication such as voice amplifiers, speech-generating devices (or voice output communication devices), or low-tech communication techniques such as head-mounted laser pointers, alphabet boards or yes/no signals.
=== Nutrition ===
Preventing weight loss and malnutrition in people with ALS improves both survival and quality of life. Weight loss in ALS is often caused by muscle wasting and increased resting energy expenditure. Weight loss may also be secondary to reduced food intake since dysphagia develops in about 85% of people with ALS at some point throughout their disease course. Therefore, regular periodic assessment of the weight and swallowing ability in people with ALS is very important. Dysphagia is often initially managed via dietary changes and modified swallowing techniques. People with ALS are often instructed to avoid dry or chewy foods in their diet and instead have meals that are soft, moist, and easy to swallow. Switching to thick liquids (like fruit nectar or smoothies) or adding thickeners (to thin fluids like water and coffee) may also help people facing difficulty swallowing liquids. There is tentative evidence that high-calorie diets may prevent further weight loss and improve survival, but more research is still needed.
A feeding tube should be considered if someone with ALS loses 5% or more of their body weight or if they cannot safely swallow food and water. This can take the form of a gastrostomy tube, in which a tube is placed through the wall of the abdomen into the stomach, or (less commonly) a nasogastric tube, in which a tube is placed through the nose and down the esophagus into the stomach. A gastrostomy tube is more appropriate for long-term use than a nasogastric tube, which is uncomfortable and can cause esophageal ulcers. The feeding tube is usually inserted by a percutaneous endoscopic gastrostomy procedure (PEG). While there is weak evidence that PEG tubes improve survival in people with ALS, no randomized controlled trials (RCTs) have yet been conducted to indicate whether enteral tube feeding has benefits compared to continuation of feeding by mouth. Nevertheless, PEG tubes are still offered with the intent of improving the person's quality of life by sustaining nutrition, hydration status, and medication intake.
=== End-of-life care ===
Palliative care, which relieves symptoms and improves the quality of life without treating the underlying disease, should begin shortly after someone is diagnosed with ALS. Early discussion of end-of-life issues gives people with ALS time to reflect on their preferences for end-of-life care and can help avoid unwanted interventions or procedures. Once they have been fully informed about all aspects of various life-prolonging measures, they can fill out advance directives indicating their attitude toward noninvasive ventilation, invasive ventilation, and feeding tubes. Late in the disease course, difficulty speaking due to muscle weakness (dysarthria) and cognitive dysfunction may impair their ability to communicate their wishes regarding care. Continued failure to solicit the preferences of the person with ALS may lead to unplanned and potentially unwanted emergency interventions, such as invasive ventilation. If people with ALS or their family members are reluctant to discuss end-of-life issues, it may be useful to use the introduction of gastrostomy or noninvasive ventilation as an opportunity to bring up the subject.
Hospice care, or palliative care at the end of life, is especially important in ALS because it helps to optimize the management of symptoms and increases the likelihood of a peaceful death. It is unclear exactly when the end-of-life phase begins in ALS, but it is associated with significant difficulty moving, communicating, and, in some cases, thinking. Although many people with ALS fear choking to death (suffocating), they can be reassured that this occurs rarely, less than 1% of the time. Most patients die at home, and in the final days of life, opioids can be used to treat pain and dyspnea, while benzodiazepines can be used to treat anxiety.
== Epidemiology ==
ALS is the most common motor neuron disease in adults and the third most common neurodegenerative disease after Alzheimer's disease and Parkinson's disease. Worldwide the number of people who develop ALS yearly is estimated to be 1.9 people per 100,000 per year, while the number of people who have ALS at any given time is estimated to be about 4.5 people per 100,000. In Europe, the number of new cases a year is about 2.6 people per 100,000, while the number affected is 7–9 people per 100,000. The lifetime risk of developing ALS is 1:350 for European men and 1:400 for European women. Men have a higher risk mainly because spinal-onset ALS is more common in men than women. The number of those with ALS in the United States in 2015 was 5.2 people per 100,000, and was higher in whites, males, and people over 60 years old. The number of new cases is about 0.8 people per 100,000 per year in East Asia and about 0.7 people per 100,000 per year in South Asia. About 80% of ALS epidemiology studies have been conducted in Europe and the United States, mostly in people of northern European descent. There is not enough information to determine the rates of ALS in much of the world, including Africa, parts of Asia, India, Russia, and South America. There are several geographic clusters in the Western Pacific where the prevalence of ALS was reported to be 50–100 times higher than in the rest of the world, including Guam, the Kii Peninsula of Japan, and Western New Guinea. The incidence in these areas has decreased since the 1960s; the cause remains unknown.
People of all races and ethnic backgrounds may be affected by ALS, but it is more common in whites than in Africans, Asians, or Hispanics. In the United States in 2015, the prevalence of ALS in whites was 5.4 people per 100,000, while the prevalence in blacks was 2.3 people per 100,000. The Midwest had the highest prevalence of the four US Census regions with 5.5 people per 100,000, followed by the Northeast (5.1), the South (4.7), and the West (4.4). The Midwest and Northeast likely had a higher prevalence of ALS because they have a higher proportion of whites than the South and West. Ethnically mixed populations may be at a lower risk of developing ALS; a study in Cuba found that people of mixed ancestry were less likely to die from ALS than whites or blacks. There are also differences in the genetics of ALS between different ethnic groups; the most common ALS gene in Europe is C9orf72, followed by SOD1, TARDBP, and FUS, while the most common ALS gene in Asia is SOD1, followed by FUS, C9orf72, and TARDBP.
ALS can affect people at any age, but the peak incidence is between 50 and 75 years and decreases dramatically after 80 years. The reason for the decreased incidence in the elderly is unclear. One thought is that people who survive into their 80s may not be genetically susceptible to developing ALS; alternatively, ALS in the elderly might go undiagnosed because of comorbidities (other diseases they have), difficulty seeing a neurologist, or dying quickly from an aggressive form of ALS. In the United States in 2015, the lowest prevalence was in the 18–39 age group, while the highest prevalence was in the 70–79 age group. Sporadic ALS usually starts around the ages of 58 to 63 years, while genetic ALS starts earlier, usually around 47 to 52 years. The number of ALS cases worldwide is projected to increase from 222,801 in 2015 to 376,674 in 2040, an increase of 69%. This will largely be due to the aging of the world's population, especially in developing countries.
== History ==
Descriptions of the disease date back to at least 1824 by Charles Bell. In 1850, François-Amilcar Aran was the first to describe a disorder he named "progressive muscular atrophy", a form of ALS in which only the lower motor neurons are affected. In 1869, the connection between the symptoms and the underlying neurological problems was first described by Jean-Martin Charcot, who initially introduced the term amyotrophic lateral sclerosis in his 1874 paper. Flail arm syndrome, a regional variant of ALS, was first described by Alfred Vulpian in 1886. Flail leg syndrome, another regional variant of ALS, was first described by Pierre Marie and his student Patrikios in 1918.
=== Diagnostic criteria ===
In the 1950s, electrodiagnostic testing (EMG) and nerve conduction velocity (NCV) testing began to be used to evaluate clinically suspected ALS. In 1969 Edward H. Lambert published the first EMG/NCS diagnostic criteria for ALS, consisting of four findings he considered to strongly support the diagnosis. Since then several diagnostic criteria have been developed, which are mostly in use for research purposes for inclusion/exclusion criteria, and to stratify patients for analysis in trials. Research diagnostic criteria for ALS include the "El Escorial" in 1994, revised in 1998. In 2006, the "Awaji" criteria proposed using EMG and NCV tests to help diagnose ALS earlier, and most recently the "Gold Coast" criteria in 2019.
=== Name ===
Amyotrophic comes from Greek: a- means "no", myo- (from mûs) refers to "muscle", and trophḗ means "nourishment". Therefore, amyotrophy means "muscle malnourishment" or the wasting of muscle tissue. Lateral identifies the locations in the spinal cord of the affected motor neurons. Sclerosis means "scarring" or "hardening" and refers to the death of the motor neurons in the spinal cord.
ALS is sometimes referred to as Charcot's disease (not to be confused with Charcot–Marie–Tooth disease or Charcot joint disease), because Jean-Martin Charcot was the first to connect the clinical symptoms with the pathology seen at autopsy. The British neurologist Russell Brain coined the term motor neuron disease in 1933 to reflect his belief that ALS, progressive bulbar palsy, and progressive muscular atrophy were all different forms of the same disease. In some countries, especially the United States, ALS is called Lou Gehrig's disease after the American baseball player Lou Gehrig, who was diagnosed with ALS in 1939.
In the United States and continental Europe, the term ALS (as well as Lou Gehrig's disease in the US) refers to all forms of the disease, including "classical" ALS, progressive bulbar palsy, progressive muscular atrophy, and primary lateral sclerosis. In the United Kingdom and Australia, the term motor neuron disease refers to all forms of the disease while ALS only refers to "classical" ALS, meaning the form with both upper and lower motor neuron involvement.
== Society and culture ==
In addition to the baseball player Lou Gehrig and the theoretical physicist Stephen Hawking (who notably lived longer than any other known person with the condition), several other notable individuals have or have had ALS. Several books have been written and films have been made about patients of the disease as well. American sociology professor and ALS patient Morrie Schwartz was the subject of the memoir Tuesdays with Morrie and the film of the same name, and Stephen Hawking was the subject of the critically acclaimed biopic The Theory of Everything.
In August 2014, the "Ice Bucket Challenge" to raise money for ALS research went viral online. Participants filmed themselves filling a bucket full of ice water and pouring it onto themselves; they then nominated other individuals to do the same. Many participants donated to ALS research at the ALS Association, the ALS Therapy Development Institute, ALS Society of Canada, or Motor neuron Disease Association in the UK.
== References ==
== External links ==
Media related to Amyotrophic lateral sclerosis at Wikimedia Commons
ALS Association Official Website
ALS Therapy Development Institute
International Alliance of ALS/MND Associations
International Symposium on ALS/MND
Love S (23 March 2025). "An 'Impossible' Disease Outbreak in the Alps". The Atlantic. Archived from the original on 23 March 2025. Retrieved 31 March 2025. | Wikipedia/Motor_neuron_disease |
A micrograph is an image, captured photographically or digitally, taken through a microscope or similar device to show a magnified image of an object. This is opposed to a macrograph or photomacrograph, an image which is also taken on a microscope but is only slightly magnified, usually less than 10 times. Micrography is the practice or art of using microscopes to make photographs. A photographic micrograph is a photomicrograph, and one taken with an electron microscope is an electron micrograph.
A micrograph contains extensive details of microstructure. A wealth of information can be obtained from a simple micrograph like behavior of the material under different conditions, the phases found in the system, failure analysis, grain size estimation, elemental analysis and so on. Micrographs are widely used in all fields of microscopy.
== Types ==
=== Photomicrograph ===
A light micrograph or photomicrograph is a micrograph prepared using an optical microscope, a process referred to as photomicroscopy. At a basic level, photomicroscopy may be performed simply by connecting a camera to a microscope, thereby enabling the user to take photographs at reasonably high magnification.
Scientific use began in England in 1850 by Richard Hill Norris FRSE for his studies of blood cells.
Roman Vishniac was a pioneer in the field of photomicroscopy, specializing in the photography of living creatures in full motion. He also made major developments in light-interruption photography and color photomicroscopy.
Photomicrographs may also be obtained using a USB microscope attached directly to a home computer or laptop.
=== Electron micrograph ===
An electron micrograph is a micrograph prepared using an electron microscope.
== Magnification and micron bars ==
Micrographs usually have micron bars, or magnification ratios, or both.
Magnification is a ratio between the size of an object on a picture and its real size. Magnification can be a misleading parameter as it depends on the final size of a printed picture and therefore varies with picture size. A scale bar, or micron bar, is a line of known length displayed on a picture. The bar can be used for measurements on a picture. When the picture is resized the bar is also resized making it possible to recalculate the magnification. Ideally, all pictures destined for publication/presentation should be supplied with a scale bar; the magnification ratio is optional. All but one (limestone) of the micrographs presented on this page do not have a micron bar; supplied magnification ratios are likely incorrect, as they were not calculated for pictures at the present size.
== Micrography as art ==
The microscope has been mainly used for scientific discovery. It has also been linked to the arts since its invention in the 17th century. Early adopters of the microscope, such as Robert Hooke and Antonie van Leeuwenhoek, were excellent illustrators. Cornelius Varley's graphic microscope made sketching from a microscope easier with a camera-lucida-like mechanism. After the invention of photography in the 1820s the microscope was later combined with the camera to take pictures instead of relying on an artistic rendering.
Since the early 1970s individuals have been using the microscope as an artistic instrument. Websites and traveling art exhibits such as the Nikon Small World and Olympus Bioscapes have featured a range of images for the sole purpose of artistic enjoyment. Some collaborative groups, such as the Paper Project have also incorporated microscopic imagery into tactile art pieces as well as 3D immersive rooms and dance performances.
In 2015, photographer and gemologist Danny J. Sanchez photographed mineral and gemstone interiors in works referred to as "otherworldly".
== Photomicrography in smartphones ==
A paper published in 2009 described a method of photomicrography in a smartphone using a free-hand technique. An operator only need focus the camera through the eyepiece of a microscope and capture a photo normally. Later, adapters were designed for the purpose and sold commercially or home-made. A home-made adapter was also made using scrap materials and a Coca-Cola aluminum can.
== Gallery ==
== See also ==
Close-up
Digital microscope
Macro photography
Microphotograph
Microscopy
USB microscope
== References ==
== External links ==
Shots with a Microscope – a basic, comprehensive guide to photomicrography
Scientific photomicrographs – free scientific quality photomicrographs by Doc. RNDr. Josef Reischig, CSc.
Seeing Beyond the Human Eye Video produced by Off Book (web series)
Solomon C. Fuller bio
Charles Krebs Microscopic Images
Photomicrography by Danny J. Sanchez
Dennis Kunkel Microscopy
Andrew Paul Leonard, APL Microscopic
Cell Centered Database – Montage
Nikon Small World
Olympus Bioscapes
Other examples
Robert Berdan micrographs | Wikipedia/Micrograph |
A motor skill is a function that involves specific movements of the body's muscles to perform a certain task. These tasks could include walking, running, or riding a bike. In order to perform this skill, the body's nervous system, muscles, and brain have to all work together. The goal of motor skill is to optimize the ability to perform the skill at the rate of success, precision, and to reduce the energy consumption required for performance. Performance is an act of executing a motor skill or task. Continuous practice of a specific motor skill will result in a greatly improved performance, which leads to motor learning. Motor learning is a relatively permanent change in the ability to perform a skill as a result of continuous practice or experience.
A fundamental movement skill is a developed ability to move the body in coordinated ways to achieve consistent performance at demanding physical tasks, such as found in sports, combat or personal locomotion, especially those unique to humans, such as ice skating, skateboarding, kayaking, or horseback riding. Movement skills generally emphasize stability, balance, and a coordinated muscular progression from prime movers (legs, hips, lower back) to secondary movers (shoulders, elbow, wrist) when conducting explosive movements, such as throwing a baseball. In most physical training, development of core musculature is a central focus. In the athletic context, fundamental movement skills draw upon human physiology and sport psychology.
== Types of motor skills ==
Motor skills are movements and actions of the muscles. There are two major groups of motor skills:
Gross motor skills – require the use of large muscle groups in our legs, torso, and arms to perform tasks such as: walking, balancing, and crawling. The skill required is not extensive and therefore are usually associated with continuous tasks. Much of the development of these skills occurs during early childhood. We use our gross motor skills on a daily basis without putting much thought or effort into them. The performance level of gross motor skill remains unchanged after periods of non-use. Gross motor skills can be further divided into two subgroups: Locomotor skills, such as running, jumping, sliding, and swimming; and object-control skills such as throwing, catching, dribbling, and kicking.
Fine motor skills – require the use of smaller muscle groups to perform smaller movements. These muscles include those found in our wrists, hands, fingers, feet and in our toes. These tasks are precise in nature like: playing the piano, tying shoelaces, brushing your teeth, and flossing. Some fine motor skills may be susceptible to retention loss of over a period of time if not in use. The phrase "if you don't use it, you lose it" is a perfect way to describe these skills, they need to be continuously used. Discrete tasks such as switching gears in an automobile, grasping an object, or striking a match, usually require more fine motor skill than gross motor skills.
Both gross and fine motor skills can become weakened or damaged. Some reasons for these impairments could be caused by an injury, illness, stroke, congenital deformities (an abnormal change in the size or shape of a body part at birth), cerebral palsy, and developmental disabilities. Problems with the brain, spinal cord, peripheral nerves, muscles, or joints can also have an effect on these motor skills, and decrease control over them.
== Development ==
Motor skills develop in different parts of a body along three principles:
Cephalocaudal – the principle that development occurs from head to tail. For example, infants first learn to lift their heads on their own, followed by sitting up with assistance, then sitting up by themselves. Followed by scooting, crawling, pulling up, and then walking.
Proximodistal – the principle that movement of limbs that are closer to the body develop before the parts that are further away. For example, a baby learns to control their upper arm before their hands and fingers. Fine movements of the fingers are the last to develop in the body.
Gross to specific – a pattern in which larger muscle movements develop before finer movements. For example, a child will go from only being able to pick up large objects, to then being able to pick up an object that is small, between the thumb and fingers. The earlier movements involve larger groups of muscles, but as the child grows, finer movements become possible and specific tasks can be achieved. An example of this would be a young child learning to grasp a pencil.
In children, a critical period for the development of motor skills is preschool years (ages 3–5), as fundamental neuroanatomic structure shows significant development, elaboration, and myelination over the course of this period. Many factors contribute to the rate that children develop their motor skills. Unless afflicted with a severe disability, children are expected to develop a wide range of basic movement abilities and motor skills around a certain age. Motor development progresses in seven stages throughout an individual's life: reflexive, rudimentary, fundamental, sports skill, growth and refinement, peak performance, and regression. Development is age-related but is not age dependent. In regard to age, it is seen that typical developments are expected to attain gross motor skills used for postural control and vertical mobility by 5 years of age.
There are six aspects of development:
Qualitative – changes in movement-process results in changes in movement-outcome.
Sequential – certain motor patterns precede others.
Cumulative – current movements are built on previous ones.
Directional – cephalocaudal or proximodistal
Multifactorial – numerous-factors impact
Individual – dependent on each person
In the childhood stages of development, gender differences can greatly influence motor skills. In the article "An Investigation of Age and Gender Differences in Preschool Children's Specific Motor Skills", girls scored significantly higher than boys on visual motor and graphomotor tasks. The results from this study suggest that girls attain manual dexterity earlier than boys. Variability of results in the tests can be attributed towards the multiplicity of different assessment tools used. Furthermore, gender differences in motor skills are seen to be affected by environmental factors. In essence, "parents and teachers often encourage girls to engage in [quiet] activities requiring fine motor skills, while they promote boys' participation in dynamic movement actions". In the journal article "Gender Differences in Motor Skill Proficiency From Childhood to Adolescence" by Lisa Barrett, the evidence for gender-based motor skills is apparent. In general, boys are more skillful in object control and object manipulation skills. These tasks include throwing, kicking, and catching skills. These skills were tested and concluded that boys perform better with these tasks. There was no evidence for the difference in locomotor skill between the genders, but both are improved in the intervention of physical activity. Overall, the predominance of development was on balance skills (gross motor) in boys and manual skills (fine motor) in girls.
=== Components of development ===
Growth – increase in the size of the body or its parts as the individual progresses toward maturity (quantitative structural changes)
Maturation – refers to qualitative changes that enable one to progress to higher levels of functioning; it is primarily innate
Experience or learning – refers to factors within the environment that may alter or modify the appearance of various developmental characteristics through the process of learning
Adaptation – refers to the complex interplay or interaction between forces within the individual (nature) and the environment (nurture)
=== Influences on development ===
Stress and arousal – stress and anxiety are the result of an imbalance between the demand of a task and the capacity of the individual. In this context, arousal defines the amount of interest in the skill. The optimal performance level is moderate stress or arousal.
Fatigue – the deterioration of performance when a stressful task is continued for a long time, similar to the muscular fatigue experienced when exercising rapidly or over a long period. Fatigue is caused by over-arousal. Fatigue impacts an individual in many ways: perceptual changes in which visual acuity or awareness drops, slowing of performance (reaction times or movements speed), irregularity of timing, and disorganization of performance. A study conducted by Meret Branscheidt concluded that fatigue interferes with the learning of new motor skills. In the experiment, participants were split into two different groups. One group worked the muscles in their hands until they were physically fatigued and then had to learn a new motor task, while the second group learned the task without being fatigued. Those that were fatigued had a harder time learning these new motor skills compared to those who were not. Even in the days following, after the fatigue had subsided, they still had difficulty learning those same tasks.
Vigilance – the ability to maintain attention over time and respond appropriately to relevant stimuli. When vigilance is lost, it can result in slower responses or the failure to respond to stimuli all together. Some tasks include actions that require little work and high attention.
Gender – gender plays an important role in the development of the child. Girls are more likely to be seen performing fine stationary visual motor-skills, whereas boys predominantly exercise object-manipulation skills. While researching motor development in preschool-aged children, girls were more likely to be seen performing skills such as skipping, hopping, or skills with the use of hands only. Boys were seen to perform gross skills such as kicking or throwing a ball or swinging a bat. There are gender-specific differences in qualitative throwing performance, but not necessarily in quantitative throwing performance. Male and female athletes demonstrated similar movement patterns in humerus and forearm actions but differed in trunk, stepping, and backswing actions.
== Stages of motor learning ==
Motor learning is a change, resulting from practice. It often involves improving the accuracy of movements both simple and complex as one's environment changes. Motor learning is a relatively permanent skill as the capability to respond appropriately is acquired and retained.
The stages of motor learning are the cognitive phase, the associative phase, and the autonomous phase.
Cognitive phase – When a learner is new to a specific task, the primary thought process starts with, "What needs to be done?" Considerable cognitive activity is required so that the learner can determine appropriate strategies to adequately reflect the desired goal. Good strategies are retained and inefficient strategies are discarded. The performance is greatly improved in a short amount of time.
Associative phase – The learner has determined the most-effective way to do the task and starts to make subtle adjustments in performance. Improvements are more gradual and movements become more consistent. This phase can last for a long time. The skills in this phase are fluent, efficient, and aesthetically pleasing.
Autonomous phase – This phase may take several months to years to reach. The phase is dubbed "autonomous" because the performer can now "automatically" complete the task without having to pay any attention to performing it. Examples include walking and talking or sight reading while doing simple arithmetic.
== Law of effect ==
Motor-skill acquisition has long been defined in the scientific community as an energy-intensive form of stimulus-response (S-R) learning that results in robust neuronal modifications. In 1898, Edward Thorndike proposed the law of effect, which states that the association between some action (R) and some environmental condition (S) is enhanced when the action is followed by a satisfying outcome (O). For instance, if an infant moves his right hand and left leg in just the right way, he can perform a crawling motion, thereby producing the satisfying outcome of increasing his mobility. Because of the satisfying outcome, the association between being on all fours and these particular arm and leg motions are enhanced. Further, a dissatisfying outcome weakens the S-R association. For instance, when a toddler contracts certain muscles, resulting in a painful fall, the child will decrease the association between these muscle contractions and the environmental condition of standing on two feet.
== Feedback ==
During the learning process of a motor skill, feedback is the positive or negative response that tells the learner how well the task was completed.
Inherent feedback: after completing the skill, inherent feedback is the sensory information that tells the learner how well the task was completed. A basketball player will note that he or she made a mistake when the ball misses the hoop. Another example is a diver knowing that a mistake was made when the entry into the water is painful and undesirable.
Augmented feedback: in contrast to inherent feedback, augmented feedback is information that supplements or "augments" the inherent feedback. For example, when a person is driving over a speed limit and is pulled over by the police. Although the car did not do any harm, the policeman gives augmented feedback to the driver in order for him to drive more safely. Another example is a private tutor for a new student in a field of study. Augmented feedback decreases the amount of time to master the motor skill and increases the performance level of the prospect.
Transfer of motor skills: the gain or loss in the capability for performance in one task as a result of practice and experience on some other task. An example would be the comparison of initial skill of a tennis player and non-tennis player when playing table tennis for the first time. An example of a negative transfer is if it takes longer for a typist to adjust to a randomly assigned letter of the keyboard compared to a new typist.
Retention: the performance level of a particular skill after a period of no use.
The type of task can have an effect on how well the motor skill is retained after a period of non-use:
Continuous tasks – activities like swimming, bicycling, or running; the performance level retains proficiency even after years of non-use.
Discrete tasks – an instrument, video game, or a sport; the performance level drops significantly but will be better than a new learner. The relationship between the two tasks is that continuous tasks usually use gross motor skills and discrete tasks use fine motor skills.
== Brain structures ==
The regions of the frontal lobe responsible for motor skill include the primary motor cortex, the supplemental motor area, and the premotor cortex. The primary motor cortex is located in the precentral gyrus and is often visualized as the motor homunculus. By stimulating certain areas of the motor strip and observing where it had an effect, Penfield and Rassmussen were able to map out the motor homunculus. Areas on the body that have complex movements, such as the hands, have a bigger representation on the motor homunculus.
The supplemental motor area, which is just anterior to the primary motor cortex, is involved with postural stability and adjustment as well as coordinating sequences of movement. The premotor cortex, which is just below the supplemental motor area, integrates sensory information from the posterior parietal cortex and is involved with the sensory-guided planning of movement and begins the programming of movement.
The basal ganglia are an area of the brain where gender differences in brain physiology is evident. The basal ganglia are a group of nuclei in the brain that is responsible for a variety of functions, some of which include movement. The globus pallidus and putamen are two nuclei of the basal ganglia which are both involved in motor skills. The globes pallid-us is involved with the voluntary motor movement, while the putamen is involved with motor learning. Even after controlling for the naturally larger volume of the male brain, it was found that males have a larger volume of both the globus pallidus and putamen.
The cerebellum is an additional area of the brain important for motor skills. The cerebellum controls fine motor skills as well as balance and coordination. Although women tend to have better fine motor skills, the cerebellum has a larger volume in males than in females, even after correcting for the fact that males naturally have a larger brain volume.
Hormones are an additional factor that contributes to gender differences in motor skill. For instance, women perform better on manual dexterity tasks during times of high estradiol and progesterone levels, as opposed to when these hormones are low such as during menstruation.
An evolutionary perspective is sometimes drawn upon to explain how gender differences in motor skills may have developed, although this approach is controversial. For instance, it has been suggested that men were the hunters and provided food for the family, while women stayed at home taking care of the children and doing domestic work. Some theories of human development suggest that men's tasks involved gross motor skill such as chasing after prey, throwing spears and fighting. Women, on the other hand, used their fine motor skills the most in order to handle domestic tools and accomplish other tasks that required fine motor-control.
== See also ==
Muscle memory
Motor control
Motor skill consolidation
Motor system
Sensorimotor stage
== References ==
Sparrow, W.A. (July 1, 1983). "The efficiency of skilled performance". Journal of Motor Behavior. 15 (3): 237–261. doi:10.1080/00222895.1983.10735299. PMID 15151872.
Guthrie, E.R. (1957). Harper et Brothers, New York (ed.). "The psychology of learning". {{cite journal}}: Cite journal requires |journal= (help)
== External links ==
Section about motor learning and control in the Wikibook "Stuttering"
What's the difference between fine motor and gross motor skills? | Wikipedia/Motor_dysfunction |
A spinal interneuron, found in the spinal cord, relays signals between (afferent) sensory neurons, and (efferent) motor neurons. Different classes of spinal interneurons are involved in the process of sensory-motor integration. Most interneurons are found in the grey column, a region of grey matter in the spinal cord.
== Structure ==
The grey column of the spinal cord appears to have groups of small neurons, often referred to as spinal interneurons, that are neither primary sensory cells nor motor neurons. The versatile properties of these spinal interneurons cover a wide range of activities. Their functions include the processing of sensory input, the modulation of motor neuron activity, the coordination of activity at different spinal levels, and the relay of sensory or proprioceptive data to the brain. There has been extensive research on the identification and characterization of the spinal cord interneurons based on factors such as location, size, structure, connectivity, and function. Generally, it is difficult to characterize every aspect of the neuronal anatomy of a vertebrate's spinal cord. This difficulty is due not only to its structural complexity but also to the morphology and the connectivity of neurons. For instance, in the spinal cord of a 19-day-old rat embryo, at least 17 different subclasses of interneurons with ipsilateral axon projections were found. In addition, 18 types of commissural interneurons have been identified on the basis of morphology and location.
=== Location ===
In particular, the cell bodies of the spinal interneurons are found in the grey matter of the spinal cord, which also contains the motor neurons. In 1952, the grey matter of the cat's spinal cord was investigated, and it was shown to have ten distinct zones referred to as Rexed laminae. Eventually, the lamination pattern was also observed in several species including humans. Rexed laminae VII and VIII are locations where most of the interneurons are found.
== Development ==
In the mouse's dorsal alar plate, six progenitor domains give rise to dI1-dI6 neurons and two classes of dorsal interneurons. In addition, in the ventral half of the neural tube, four classes of (CPG) interneurons known as V0, V1, V2, and V3 neurons are generated. V0 neurons are commissural neurons that extend their axons rostrally for 2-4 spinal cord regions in the embryonic spinal cord. V3 neurons are excitatory commissural interneurons that extend caudally projecting primary axons. The V1 neurons are inhibitory interneurons with axons that project ipsilaterally and rostrally. V2 neurons, which include a population of glutamatergic V2a neurons and inhibitory V2b neurons, project ipsilaterally and caudally across multiple spinal cord regions. The class V1 neurons give rise to two local circuit inhibitory neurons known as Renshaw cells and Ia inhibitory interneurons.
== Function ==
The integration of the sensory feedback signals and central motor commands at several levels of the central nervous system plays a critical role in controlling movement. Research on cat's spinal cord has shown that at the spinal cord level sensory afferents and descending motor pathways converge onto common spinal interneurons. Human studies since the 1970s have documented how this integration of motor commands and sensory feedback signals is used to control muscle activity during movement. During locomotion, the sum of convergent inputs from the central pattern generator (CPG), sensory feedback, descending commands and other intrinsic properties turned on by different neuromodulators give rise to the activity of the interneurons. Further, this interneuronal activity was either recorded directly or inferred from the modulation of response in their postsynaptic targets, most often motoneurons. The most efficient way to gate sensory signals in reflex pathways is to control the firing level of interneurons. For example, during locomotion, the interneuronal activity is modulated via excitation or inhibition depending on the reflex pathways. Thus, different patterns of interneuronal activity will determine which pathways are open, blocked, or modulated.
=== Neurotransmitter ===
The sensory information that is transmitted to the spinal cord is modulated by a complex network of excitatory and inhibitory interneurons. Different neurotransmitters are released from different interneurons, but the two most common neurotransmitters are GABA, the primary inhibitory neurotransmitter and glutamate, the primary excitatory neurotransmitter. Acetylcholine is a neurotransmitter that often activates interneurons by binding to a receptor on the membrane.
=== Cell types ===
=== Renshaw cells ===
Renshaw cells are among the first identified interneurons. This type of interneuron projects onto α-motoneurons, where it establishes inhibition by expressing its inhibitory neurotransmitter glycine. However, some reports have indicated that Renshaw cells synthesize calcium-binding proteins calbindin-D28k and parvalbumin. Further, during spinal reflex, Renshaw cells control the activity of the spinal motoneurons. They are excited by the axon collaterals of the motor neurons. In addition, Renshaw cells make inhibitory connections to several groups of motor neurons, Ia inhibitory interneurons as well as the same motor neuron that excited them previously. Furthermore, the connection to the motor neurons establishes a negative feedback system that may regulate the firing rate of the motor neurons. Moreover, the connections to the Ia inhibitory interneurons may modulate the strength of the reciprocal inhibition to the antagonist motor neuron.
=== Ia inhibitory interneuron ===
Joints are controlled by two opposing sets of muscles called extensors and flexors that must work in synchrony to allow proper and desired movement. When a muscle spindle is stretched and the stretch reflex is activated, the opposing muscle group must be inhibited to prevent from working against the agonist muscle. The spinal interneuron called Ia inhibitory interneuron is responsible for this inhibition of the antagonist muscle. The Ia afferent of the muscle spindle enters the spinal cord, and one branch synapses on to the alpha motor neuron that causes the agonist muscle to contract. Thus, it results in creating the behavioral reflex.
At the same time, the other branch of the Ia afferent synapses on to the Ia inhibitory interneuron, which in turn synapses the alpha motor neuron of the antagonist muscle. Since Ia interneuron is inhibitory, it prevents the opposing alpha motor neuron from firing. Thus, it prevents the antagonist muscle from contracting. Without having this system of reciprocal inhibition, both groups of muscles may contract at the same time and work against each other. This results in spending a greater amount of energy as well.
In addition, the reciprocal inhibition is important for mechanism underlying voluntary movement. When the antagonist muscle relaxes during movement, this increases efficiency and speed. This prevents moving muscles from working against the contraction force of antagonist muscles. Thus, during voluntary movement, the Ia inhibitory interneurons are used to coordinate muscle contraction.
Further, the Ia inhibitory interneurons allow the higher centers to coordinate commands sent to the two muscles working opposite of each other at a single joint via a single command. The interneuron receives the input command from the corticospinal descending axons in such a way that the descending signal, which activates the contraction of one muscle, causes relaxation of the other muscles.
=== Ib inhibitory interneuron ===
The autogenic inhibition reflex is a spinal reflex phenomenon that involves the Golgi tendon organ. When tension is applied to a muscle, group Ib fibers that innervate the Golgi tendon organ are activated. These afferent fibers project onto the spinal cord and synapse with the spinal interneurons called Ib inhibitory interneurons. This spinal interneuron makes an inhibitory synapse onto the alpha motor neuron that innervates the same muscle that caused the Ib afferent to fire. As a result of this reflex, activation of the Ib afferent causes the alpha motor neuron to become inhibited. Thus, the contraction of the muscle stops. This is an example of a disynaptic reflex, in which the circuitry contains a spinal interneuron between the sensory afferent and the motor neuron.
The activities of the extensor and flexor muscles must be coordinated in the autogenic inhibition reflex. The Ib afferent branches in the spinal cord. One branch synapses the Ib inhibitory interneuron. The other branch synapses onto an excitatory interneuron. This excitatory interneuron innervates the alpha motor neuron that controls the antagonist muscle. When the agonist muscle is inhibited from contracting, the antagonist muscle contracts.
=== Excitatory interneurons mediating cutaneous inputs ===
An important reflex initiated by cutaneous receptors and pain receptors is the flexor reflex. This reflex mechanism allows for quick withdrawal of the body parts, in this case a limb, from the harmful stimulus. The signal travels to the spinal cord and a response is initiated even before it travels up to the brain centers for a conscious decision to be made. The reflex circuit involves the activation of the Group III afferents of pain receptors due to a stimulus affecting a limb, e.g. a foot. These afferents enter the spinal cord and travel up to the lumbar region, where they synapse an excitatory interneuron. This interneuron excites the alpha motor neuron that causes contraction of the thigh flexor muscle.
Also, Group III afferent travels up to L2 vertebra, where they branch onto another excitatory interneuron. This interneuron excites the alpha motor neurons, which then excite the hip flexor muscle. This synchronized communication allows for the removal of the whole leg from the painful stimulus. This is an example of the spinal cord circuitry coordinating movement at several joints simultaneously. In addition, during flexor reflex, when the knee joints and hip joints are flexed, the antagonist extensor muscles must be inhibited. This inhibitory effect is achieved when Group III afferents synapse inhibitory interneurons that in turn synapse the alpha motor neurons innervating the antagonists muscle.
The flexor reflex not only coordinates the activity of the leg being removed but also the activity of the other leg. When one leg is removed, the weight of the body needs to be distributed to the opposite leg to maintain the body's balance. Thus, the flexor reflex incorporates a crossed extension reflex. A branch of the Group III afferent synapse an excitatory interneuron, which extends its axon across the midline into the contralateral spinal cord. At that location, the interneuron excites the alpha motor neurons that innervate the extensor muscles of the opposite leg. This allows for balance and body posture to be maintained.
=== Excitatory commissural interneurons ===
A group of commissural interneurons present in lamina VIII in mid-lumbar segments mediates excitation of contralateral motoneurons by reticulospinal neurons. These neurons receive monosynaptic inputs from ipsilateral reticular formation and are not directly activated by group II afferents.
Another class of lamina VIII commissural neurons includes a group that is activated by both reticulospinal and vestibular systems. These cells can also be activated indirectly by group I and group II afferents. These cells have also been shown to be active during locomotion.
== References == | Wikipedia/Spinal_interneuron |
A descending neuron is a neuron that conveys signals from the brain to neural circuits in the spinal cord (vertebrates) or ventral nerve cord (invertebrates). As the sole conduits of information between the brain and the body, descending neurons play a key role in behavior. Their activity can initiate, maintain, modulate, and terminate behaviors such as locomotion. Because the number of descending neurons is several orders of magnitude smaller than the number of neurons in either the brain or spinal cord/ventral nerve cord, this class of cells represents a critical bottleneck in the flow of information from sensory systems to motor circuits.
== Anatomy ==
Descending neurons have their somas and dendrites (primary input zones) in the brain. Their axons traverse the neck in connectives, or tracts, and output onto neurons in the spinal cord (vertebrates) or ventral nerve cord (invertebrates).
Mammals possess hundreds of thousands of descending neurons. They can be divided functionally into two major pathways: pyramidal tracts, which originate in the motor cortex, and extrapyramidal tracts, which originate in the brainstem (see schematic). An example of the former is the corticospinal tract, which is responsible for voluntary movement of the body. An example of the latter is the reticulospinal tract, which contributes to the unconscious regulation of locomotion and posture. Reticulospinal neurons originate in the medullary reticular formation, where they receive information from upstream locomotor centers, such as the mesencephalic locomotor region and the basal ganglia.
Insects possess only several hundreds of descending neurons. Work in the fruit fly Drosophila melanogaster suggests that they are organized into three broad pathways (see schematic). Two direct pathways link specific regions in the brain to motor circuits in the ventral nerve cord controlling the legs and wings, respectively. A third pathway couples a broad array of brain regions to a large integrative region in the ventral nerve cord that may control both sets of appendages.
== Function ==
Descending neurons play an important role in initiating, maintaining, modulating, and terminating behaviors. Several descending neurons involved in controlling specific behaviors have been identified in both vertebrates and invertebrates. These include descending neurons that can initiate and terminate locomotion, modulate locomotion speed and direction, and help coordinate limbs.
While some descending neurons are sufficient to elicit specific behaviors, most behaviors are likely not controlled by single, command-like descending neurons, but instead by the combined activity of different descending neurons.
Some descending pathways form direct connections with motor neurons and premotor interneurons, including central pattern generators. But how exactly descending signals are integrated in circuits in the spinal cord (vertebrates) or ventral nerve cord (invertebrates) during behavior is not well understood.
== See also ==
Pyramidal tracts
Extrapyramidal tracts
Command neuron
Reticular formation
== References == | Wikipedia/Descending_neuron |
Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain.
The vertebrates make up the subphylum Vertebrata with some 65,000 species, by far the largest ranked grouping in the phylum Chordata. The vertebrates include mammals, birds, amphibians, and various classes of fish and reptiles. The fish include the jawless Agnatha, and the jawed Gnathostomata. The jawed fish include both the cartilaginous fish and the bony fish. Bony fish include the lobe-finned fish, which gave rise to the tetrapods, the animals with four limbs. Despite their success, vertebrates still only make up less than five percent of all described animal species.
The first vertebrates appeared in the Cambrian explosion some 518 million years ago. Jawed vertebrates evolved in the Ordovician, followed by bony fishes in the Devonian. The first amphibians appeared on land in the Carboniferous. During the Triassic, mammals and dinosaurs appeared, the latter giving rise to birds in the Jurassic. Extant species are roughly equally divided between fishes of all kinds, and tetrapods. Populations of many species have been in steep decline since 1970 because of land-use change, overexploitation of natural resources, climate change, pollution and the impact of invasive species.
== Characteristics ==
=== Unique features ===
Vertebrates belong to Chordata, a phylum characterised by five synapomorphies (unique characteristics): namely a notochord, a hollow nerve cord along the back, an endostyle (often as a thyroid gland), and pharyngeal gills arranged in pairs. Vertebrates share these characteristics with other chordates.
Vertebrates are distinguished from all other animals, including other chordates, by multiple synapomorphies: namely the vertebral column, skull of bone or cartilage, large brain divided into 3 or more sections, a muscular heart with multiple chambers; an inner ear with semicircular canals; sense organs including eyes, ears, and nose; and digestive organs including intestine, liver, pancreas, and stomach.
=== Physical ===
Vertebrates (and other chordates) belong to the Bilateria, a group of animals with mirror symmetrical bodies. They move, typically by swimming, using muscles along the back, supported by a strong but flexible skeletal structure, the spine or vertebral column. The name 'vertebrate' derives from the Latin vertebratus, 'jointed', from vertebra, 'joint', in turn from Latin vertere, 'to turn'.
As embryos, vertebrates still have a notochord; as adults, all but the jawless fishes have a vertebral column, made of bone or cartilage, instead. Vertebrate embryos have pharyngeal arches; in adult fish, these support the gills, while in adult tetrapods they develop into other structures.
In the embryo, a layer of cells along the back folds and fuses into a hollow neural tube. This develops into the spinal cord, and at its front end, the brain. The brain receives information about the world through nerves which carry signals from sense organs in the skin and body. Because the ancestors of vertebrates usually moved forwards, the front of the body encountered stimuli before the rest of the body, favouring cephalisation, the evolution of a head containing sense organs and a brain to process the sensory information.
Vertebrates have a tubular gut that extends from the mouth to the anus. The vertebral column typically continues beyond the anus to form an elongated tail.
The ancestral vertebrates, and most extant species, are aquatic and carry out gas exchange in their gills. The gills are finely-branched structures which bring the blood close to the water. They are positioned just behind the head, supported by cartilaginous or bony branchial arches. In jawed vertebrates, the first gill arch pair evolved into the jaws. In amphibians and some primitive bony fishes, the larvae have external gills, branching off from the gill arches. Oxygen is carried from the gills to the body in the blood, and carbon dioxide is returned to the gills, in a closed circulatory system driven by a chambered heart. The tetrapods have lost the gills of their fish ancestors; they have adapted the swim bladder (that fish use for buoyancy) into lungs to breathe air, and the circulatory system is adapted accordingly. At the same time, they adapted the bony fins of the lobe-finned fishes into two pairs of walking legs, carrying the weight of the body via the shoulder and pelvic girdles.
Vertebrates vary in size from the smallest frog species such as Brachycephalus pulex, with a minimum adult snout–vent length of 6.45 millimetres (0.254 in) to the blue whale, at up to 33 m (108 ft) and weighing some 150 tonnes.
=== Molecular ===
Molecular markers known as conserved signature indels in protein sequences have been identified and provide distinguishing criteria for the vertebrate subphylum. Five molecular markers are exclusively shared by all vertebrates and reliably distinguish them from all other animals; these include protein synthesis elongation factor-2, eukaryotic translation initiation factor 3, adenosine kinase and a protein related to ubiquitin carboxyl-terminal hydrolase). A specific relationship between vertebrates and tunicates is supported by two molecular markers, the proteins Rrp44 (associated with the exosome complex) and serine C-palmitoyltransferase. These are exclusively shared by species from these two subphyla, but not by cephalochordates.
== Evolutionary history ==
=== Cambrian explosion: first vertebrates ===
Vertebrates originated during the Cambrian explosion at the start of the Paleozoic, which saw a rise in animal diversity. The earliest known vertebrates belong to the Chengjiang biota and lived about 518 million years ago. These include Haikouichthys, Myllokunmingia, Zhongjianichthys, and probably Yunnanozoon. Unlike other Cambrian animals, these groups had the basic vertebrate body plan: a notochord, rudimentary vertebrae, and a well-defined head and tail, but lacked jaws. A vertebrate group of uncertain phylogeny, small eel-like conodonts, are known from microfossils of their paired tooth segments from the late Cambrian to the end of the Triassic. Zoologists have debated whether teeth mineralized first, given the hard teeth of the soft-bodied conodonts, and then bones, or vice versa, but it seems that the mineralized skeleton came first.
=== Paleozoic: from fish to amphibians ===
The first jawed vertebrates may have appeared in the late Ordovician (~445 mya) and became common in the Devonian period, often known as the "Age of Fishes". The two groups of bony fishes, Actinopterygii and Sarcopterygii, evolved and became common. By the middle of the Devonian, a lineage of sarcopterygii with both gills and air-breathing lungs adapted to life in swampy pools used their muscular paired fins to propel themselves on land. The fins, already possessing bones and joints, evolved into two pairs of walking legs. These established themselves as amphibians, terrestrial tetrapods, in the next geological period, the Carboniferous. A group of vertebrates, the amniotes, with membranes around the embryo allowing it to survive on dry land, branched from amphibious tetrapods in the Carboniferous.
=== Mesozoic: from reptiles to mammals and birds ===
At the onset of the Mesozoic, all larger vertebrate groups were devastated after the largest mass extinction in earth history. The following recovery phase saw the emergence of many new vertebrate groups that are still around today, and this time has been described as the origin of modern ecosystems. On the continents, the ancestors of modern lissamphibians, turtles, crocodilians, lizards, and mammals appeared, as well as dinosaurs, which gave rise to birds later in the Mesozoic. In the seas, various groups of marine reptiles evolved, as did new groups of fish. At the end of the Mesozoic, another extinction event extirpated dinosaurs (other than birds) and many other vertebrate groups.
=== Cenozoic: Age of Mammals ===
The Cenozoic, the current era, is sometimes called the "Age of Mammals", because of the dominance of the terrestrial environment by that group. Placental mammals have predominantly occupied the Northern Hemisphere, with marsupial mammals in the Southern Hemisphere.
== Approaches to classification ==
=== Taxonomic history ===
In 1811, Jean-Baptiste Lamarck defined the vertebrates as a taxonomic group, a phylum distinct from the invertebrates he was studying. He described them as consisting of four classes, namely fish, reptiles, birds, and mammals, but treated the cephalochordates and tunicates as molluscs. In 1866, Ernst Haeckel called both his "Craniata" (vertebrates) and his "Acrania" (cephalochordates) "Vertebrata". In 1877, Ray Lankester grouped the Craniates, cephalochordates, and "Urochordates (tunicates) as "Vertebrata". In 1880–1881, Francis Maitland Balfour placed the Vertebrata as a subphylum within the Chordates. In 2018, Naoki Irie and colleagues proposed making Vertebrata a full phylum.
=== Traditional taxonomy ===
Conventional evolutionary taxonomy groups extant vertebrates into seven classes based on traditional interpretations of gross anatomical and physiological traits. The commonly held classification lists three classes of fish and four of tetrapods. This ignores some of the natural relationships between the groupings. For example, the birds derive from a group of reptiles, so "Reptilia" excluding "Aves" is not a natural grouping; it is described as paraphyletic.
Subphylum Vertebrata
Class Agnatha (jawless fishes, paraphyletic)
Class Chondrichthyes (cartilaginous fishes)
Class Osteichthyes (bony fishes, paraphyletic)
Class Amphibia (traditional amphibians, paraphyletic)
Class Reptilia (reptiles, paraphyletic)
Class Aves (birds)
Class Mammalia (mammals)
In addition to these, there are two classes of extinct armoured fishes, Placodermi and Acanthodii, both paraphyletic.
Other ways of classifying the vertebrates have been devised, particularly with emphasis on the phylogeny of early amphibians and reptiles. An example based on work by M.J. Benton in 2004 is given here († = extinct):
Subphylum Vertebrata
Infraphylum "Agnatha" (lampreys and other jawless fishes)
Superclass †Anaspidomorphi (anaspids and relatives)
Class †Anaspida (anaspids)
Superclass Cyclostomata (cyclostomes)
Class Myxini (hagfish)
Class Petromyzontida (lampreys)
Class †Cephalaspidomorphi (cephalaspidomorphs)
Class †Conodonta (conodonts)
Class †Pteraspidomorpha (pteraspidomorphs)
Class †Thelodonti (thelodonts)
Infraphylum Gnathostomata (vertebrates with jaws)
Class †"Placodermi" (extinct armoured fishes)
Class Chondrichthyes (cartilaginous fishes)
Class †"Acanthodii" (extinct spiny "sharks")
Superclass "Osteichthyes" (bony fishes)
Class Actinopterygii (ray-finned bony fishes)
Class "Sarcopterygii" (lobe-finned fishes, cladistically including the tetrapods)
Superclass Tetrapoda (four-limbed vertebrates)
Class "Amphibia" (amphibians, some ancestral to the amniotes)—now a paraphyletic group
Class Synapsida (mammals and their extinct relatives)
Class Sauropsida (reptiles and birds)
Incertae sedis
Genus †Nuucichthys
Genus †Palaeospondylus
While this traditional taxonomy is orderly, most of the groups are paraphyletic, meaning that the structure does not accurately reflect the natural evolved grouping. For instance, descendants of the first reptiles include modern reptiles, mammals and birds; the agnathans have given rise to the jawed vertebrates; the bony fishes have given rise to the land vertebrates; a group of amphibians, the labyrinthodonts, have given rise to the reptiles (traditionally including the mammal-like synapsids), which in turn have given rise to the mammals and birds. Most scientists working with vertebrates use a classification based purely on phylogeny, organized by their known evolutionary history.
=== External phylogeny ===
The closest relatives of vertebrates have been debated over the years. It was once thought that the Cephalochordata was the sister taxon to Vertebrata. This group, Notochordata, was taken to be sister to the Tunicata. Since 2006, analysis has shown that the tunicates + vertebrates form a clade, the Olfactores, with Cephalochordata as its sister (the Olfactores hypothesis), as shown in the following phylogenetic tree.
=== Internal phylogeny ===
The internal phylogeny of the vertebrates is shown in the below tree.
The placement of hagfishes within the vertebrates has been controversial. Their lack of proper vertebrae (among other characteristics of jawless lampreys and jawed vertebrates) led authors of phylogenetic analyses based on morphology to place them outside Vertebrata. Molecular data however indicates that they are vertebrates, being most closely related to lampreys. An older view is that they are a sister group of vertebrates in the common taxon of Craniata. In 2019, Tetsuto Miyashita and colleagues reconciled the two types of analysis, supporting the Cyclostomata hypothesis using only morphological data.
== Diversity ==
=== Species by group ===
Described and extant vertebrate species are split roughly evenly but non-phylogenetically between non-tetrapod "fish" and tetrapods. The following table lists the number of described extant species for each vertebrate class as estimated in the IUCN Red List of Threatened Species, 2014.3. Paraphyletic groups are shown in quotation marks.
The IUCN estimates that 1,305,075 extant invertebrate species have been described, which means that less than 5% of the described animal species in the world are vertebrates.
=== Population trends ===
The Living Planet Index, following 16,704 populations of 4,005 species of vertebrates, shows a decline of 60% between 1970 and 2014. Since 1970, freshwater species declined 83%, and tropical populations in South and Central America declined 89%. The authors note that "An average trend in population change is not an average of total numbers of animals lost." According to WWF, this could lead to a sixth major extinction event. The five main causes of biodiversity loss are land-use change, overexploitation of natural resources, climate change, pollution and invasive species.
== Notes ==
== See also ==
Marine vertebrate – Marine animals with a vertebrate column
Taxonomy of the vertebrates (Young, 1962) – Classification of spine-possessing animals according to some authorities
== References ==
== Bibliography ==
Kardong, Kenneth V. (1998). Vertebrates: Comparative Anatomy, Function, Evolution (second ed.). USA: McGraw-Hill. pp. 747 pp. ISBN 978-0-697-28654-3.
"Vertebrata". Integrated Taxonomic Information System. Retrieved 6 August 2007.
== External links ==
Tree of Life
Tunicates and not cephalochordates are the closest living relatives of vertebrates
Vertebrate Pests chapter in United States Environmental Protection Agency and University of Florida/Institute of Food and Agricultural Sciences National Public Health Pesticide Applicator Training Manual
The Vertebrates
The Origin of Vertebrates Marc W. Kirschner, iBioSeminars, 2008. | Wikipedia/Vertebrates |
Transforming growth factor (, or TGF) is used to describe two classes of polypeptide growth factors, TGFα and TGFβ.
The name "Transforming Growth Factor" is somewhat arbitrary, since the two classes of TGFs are not structurally or genetically related to one another, and they act through different receptor mechanisms. Furthermore, they do not always induce cellular transformation, and are not the only growth factors that induce cellular transformation.
== Types ==
TGFα is upregulated in some human cancers. It is produced in macrophages, brain cells, and keratinocytes, and induces epithelial development. It belongs to the EGF family.
TGFβ exists in three known subtypes in humans, TGFβ1, TGFβ2, and TGFβ3. These are upregulated in Marfan's syndrome and some human cancers, and play crucial roles in tissue regeneration, cell differentiation, embryonic development, and regulation of the immune system. Isoforms of transforming growth factor-beta (TGF-β1) are also thought to be involved in the pathogenesis of pre-eclampsia. They belong to the transforming growth factor beta family. TGFβ receptors are single pass serine/threonine kinase receptors.
== Function ==
These proteins were originally characterized by their capacity to induce oncogenic transformation in a specific cell culture system, rat kidney fibroblasts. Application of the transforming growth factors to normal rat kidney fibroblasts induces the cultured cells to proliferate and overgrow, no longer subject to the normal inhibition caused by contact between cells.
== See also ==
Bone morphogenetic protein
TGF beta signaling pathway
Tubuloglomerular feedback
== References ==
== External links ==
Tumor growth factor (TGF) citations
Hoffmann, R.; Valencia, A. (2004). "A gene network for navigating the literature". Nature Genetics. 36 (7): 664. doi:10.1038/ng0704-664. PMID 15226743.
Transforming+Growth+Factors at the U.S. National Library of Medicine Medical Subject Headings (MeSH) | Wikipedia/Transforming_growth_factor |
Large-scale brain networks (also known as intrinsic brain networks) are collections of widespread brain regions showing functional connectivity by statistical analysis of the fMRI BOLD signal or other recording methods such as EEG, PET and MEG. An emerging paradigm in neuroscience is that cognitive tasks are performed not by individual brain regions working in isolation but by networks consisting of several discrete brain regions that are said to be "functionally connected". Functional connectivity networks may be found using algorithms such as cluster analysis, spatial independent component analysis (ICA), seed based, and others. Synchronized brain regions may also be identified using long-range synchronization of the EEG, MEG, or other dynamic brain signals.
The set of identified brain areas that are linked together in a large-scale network varies with cognitive function. When the cognitive state is not explicit (i.e., the subject is at "rest"), the large-scale brain network is a resting state network (RSN). As a physical system with graph-like properties, a large-scale brain network has both nodes and edges and cannot be identified simply by the co-activation of brain areas. In recent decades, the analysis of brain networks was made feasible by advances in imaging techniques as well as new tools from graph theory and dynamical systems.
The Organization for Human Brain Mapping has created the Workgroup for HArmonized Taxonomy of NETworks (WHATNET) group to work towards a consensus regarding network nomenclature. WHATNET conducted a survey in 2021 which showed a large degree of agreement about the name and topography of three networks: the "somato network", the "default network" and the "visual network", while other networks had less agreement. Several issues make the work of creating a common atlas for networks difficult: some of these issues are the variability of spatial and time scales, variability across individuals, and the dynamic nature of some networks.
Some large-scale brain networks are identified by their function and provide a coherent framework for understanding cognition by offering a neural model of how different cognitive functions emerge when different sets of brain regions join together as self-organized coalitions. The number and composition of the coalitions will vary with the algorithm and parameters used to identify them. In one model, there is only the default mode network and the task-positive network, but most current analyses show several networks, from a small handful to 17. The most common and stable networks are enumerated below. The regions participating in a functional network may be dynamically reconfigured.
Disruptions in activity in various networks have been implicated in neuropsychiatric disorders such as depression, Alzheimer's, autism spectrum disorder, schizophrenia, ADHD and bipolar disorder.
== Commonly identified networks ==
Because brain networks can be identified at various different resolutions and with various different neurobiological properties, there is currently no universal atlas of brain networks that fits all circumstances. Uddin, Yeo, and Spreng proposed in 2019 that the following six networks should be defined as core networks based on converging evidences from multiple studies to facilitate communication between researchers.
=== Default mode (medial frontoparietal) ===
The default mode network is active when an individual is awake and at rest. It preferentially activates when individuals focus on internally-oriented tasks such as daydreaming, envisioning the future, retrieving memories, and theory of mind. It is negatively correlated with brain systems that focus on external visual signals. It is the most widely researched network.
=== Salience (midcingulo-insular) ===
The salience network consists of several structures, including the anterior (bilateral) insula, dorsal anterior cingulate cortex, and three subcortical structures which are the ventral striatum, substantia nigra/ventral tegmental region. It plays the key role of monitoring the salience of external inputs and internal brain events. Specifically, it aids in directing attention by identifying important biological and cognitive events.
This network includes the ventral attention network, which primarily includes the temporoparietal junction and the ventral frontal cortex of the right hemisphere. These areas respond when behaviorally relevant stimuli occur unexpectedly. The ventral attention network is inhibited during focused attention in which top-down processing is being used, such as when visually searching for something. This response may prevent goal-driven attention from being distracted by non-relevant stimuli. It becomes active again when the target or relevant information about the target is found.
=== Attention (dorsal frontoparietal) ===
This network is involved in the voluntary, top-down deployment of attention. Within the dorsal attention network, the intraparietal sulcus and frontal eye fields influence the visual areas of the brain. These influencing factors allow for the orientation of attention.
=== Control (lateral frontoparietal) ===
This network initiates and modulates cognitive control and comprises 18 sub-regions of the brain. There is a strong correlation between fluid intelligence and the involvement of the fronto-parietal network with other networks.
Versions of this network have also been called the central executive (or executive control) network and the cognitive control network.
=== Sensorimotor or somatomotor (pericentral) ===
This network processes somatosensory information and coordinates motion. The auditory cortex may be included.
=== Visual (occipital) ===
This network handles visual information processing.
== Other networks ==
Different methods and data have identified several other brain networks, many of which greatly overlap or are subsets of more well-characterized core networks.
Limbic
Auditory
Right/left executive
Cerebellar
Spatial attention
Language
Lateral visual
Temporal
Visual perception/imagery
== See also ==
Complex network
Neural network (biology)
== References == | Wikipedia/Large_scale_brain_networks |
Ménière's disease (MD) is a disease of the inner ear that is characterized by potentially severe and incapacitating episodes of vertigo, tinnitus, hearing loss, and a feeling of fullness in the ear. Typically, only one ear is affected initially, but over time, both ears may become involved. Episodes generally last from 20 minutes to a few hours. The time between episodes varies. The hearing loss and ringing in the ears can become constant over time.
The cause of Ménière's disease is unclear, but likely involves both genetic and environmental factors. A number of theories exist for why it occurs, including constrictions in blood vessels, viral infections, and autoimmune reactions. About 10% of cases run in families. Symptoms are believed to occur as the result of increased fluid buildup in the labyrinth of the inner ear. Diagnosis is based on the symptoms and a hearing test. Other conditions that may produce similar symptoms include vestibular migraine and transient ischemic attack.
No cure is known. Attacks are often treated with medications to help with the nausea and anxiety. Measures to prevent attacks are overall poorly supported by the evidence. A low-salt diet, diuretics, and corticosteroids may be tried. Physical therapy may help with balance and counselling may help with anxiety. Injections into the ear or surgery may also be tried if other measures are not effective, but are associated with risks. The use of tympanostomy tubes (ventilation tubes) to improve vertigo and hearing in people with Ménière's disease is not supported by definitive evidence.
Ménière's disease was identified in the early 1800s by Prosper Menière. It affects between 0.3 and 1.9 per 1,000 people. The onset of Ménière's disease is usually around 40 to 60 years old. Females are more commonly affected than males. After 5-15 years of symptoms, episodes that include dizziness or a sensation of spinning sometimes stop and the person is left with loss of balance, poor hearing in the affected ear, and ringing or other sounds in the affected ear or ears.
== Signs and symptoms ==
Ménière's is characterized by recurrent episodes of vertigo, fluctuating hearing loss, and tinnitus; episodes may be preceded by a headache and a feeling of fullness in the ears. People may also experience additional symptoms related to irregular reactions of the autonomic nervous system. These symptoms are not symptoms of Ménière's disease per se, but rather are side effects resulting from failure of the organ of hearing and balance, and include nausea, vomiting, and sweating, which are typically symptoms of vertigo, and not of Ménière's. This includes a sensation of being pushed sharply to the floor from behind. Sudden falls without loss of consciousness (drop attacks) may be experienced by some people.
== Causes ==
The cause of Ménière's disease is unclear, but likely involves both genetic and environmental factors. A number of theories exist including constrictions in blood vessels, viral infections, and autoimmune reactions.
== Mechanism ==
The initial triggers of Ménière's disease are not fully understood, with a variety of potential inflammatory causes that lead to endolymphatic hydrops, a distension of the endolymphatic spaces in the inner ear. Endolymphatic hydrops (EH) is strongly associated with developing Ménière's disease, but not everyone with EH develops Ménière's disease: "The relationship between endolymphatic hydrops and Meniere's disease is not a simple, ideal correlation." Notably, mild EH can also occur in vestibular migraine which is an important differential diagnosis for Ménière's disease.
Additionally, in fully developed Ménière's disease, the balance system (vestibular system) and the hearing system (cochlea) of the inner ear are affected, but some cases occur where EH affects only one of the two systems enough to cause symptoms. The corresponding subtypes of the disease are called vestibular Ménière's disease, showing symptoms of vertigo, and cochlear Ménière's disease, showing symptoms of hearing loss and tinnitus.
The mechanism of Ménière's disease is not fully explained by EH, but fully developed EH may mechanically and chemically interfere with the sensory cells for balance and hearing, which can lead to temporary dysfunction and even to death of the sensory cells, which in turn can cause the typical symptoms of MD – vertigo, hearing loss, and tinnitus.
An estimated 30% of people with Ménière's disease have Eustachian tube dysfunction.
== Diagnosis ==
The diagnostic criteria as of 2015 define definite MD and probable MD as:
Definite
Two or more spontaneous episodes of vertigo, each lasting 20 minutes to 12 hours
Audiometrically documented low- to medium-frequency sensorineural hearing loss in the affected ear on at least one occasion before, during, or after one of the episodes of vertigo
Fluctuating aural symptoms (hearing, tinnitus, or fullness) in the affected ear
Not better accounted for by another vestibular diagnosis
Probable
Two or more episodes of vertigo or dizziness, each lasting 20 minutes to 24 hours
Fluctuating aural symptoms (hearing, tinnitus, or fullness) in the reported ear
Not better accounted for by another vestibular diagnosis
A common and important symptom of MD is hypersensitivity to sounds. This hypersensitivity is easily diagnosed by measuring the loudness discomfort levels (LDLs).
Symptoms of MD overlap with migraine-associated vertigo (MAV) in many ways, but when hearing loss develops in MAV, it is usually in both ears, and this is rare in MD, and hearing loss generally does not progress in MAV as it does in MD.
People who have had a transient ischemic attack (TIA) or stroke can present with symptoms similar to MD, and in people at risk magnetic resonance imaging should be conducted to exclude TIA or stroke.
Other vestibular conditions that should be excluded include vestibular paroxysmia, recurrent unilateral vestibulopathy, vestibular schwannoma, or a tumor of the endolymphatic sac.
== Management ==
No cure for Ménière's disease is known, but medications, diet, physical therapy, counseling, and some surgical approaches can be used to manage it. More than 85% of patients with Ménière's disease get better from changes in lifestyle, medical treatment, or minimally invasive surgical procedures. Those procedures include intratympanic steroid therapy, intratympanic gentamicin therapy or endolymphatic sac surgery.
=== Medications ===
During MD episodes, medications to reduce nausea are used, as are drugs to reduce the anxiety caused by vertigo. For longer-term treatment to stop progression, the evidence base is weak for all treatments. Although a causal relation between allergy and Ménière's disease is uncertain, medication to control allergies may be helpful. To assist with vertigo and balance problems, glycopyrrolate has been found to be a useful vestibular suppressant in patients with Ménière's disease.
Diuretics, such as the thiazide-like diuretic chlortalidone, are widely used to manage MD on the theory that it reduces fluid buildup (pressure) in the ear. Based on evidence from multiple but small clinical trials, diuretics appear to be useful for reducing the frequency of episodes of dizziness but do not seem to prevent hearing loss.
In cases where hearing loss and continuing severe episodes of vertigo occur, a chemical labyrinthectomy, in which a medication such as gentamicin is injected into the middle ear and kills parts of the vestibular apparatus, may be prescribed. This treatment has the risk of worsening hearing loss.
=== Diet ===
People with MD are often advised to reduce their sodium intake. Reducing salt intake, however, has not been well studied. Based on the assumption that MD is similar in nature to a migraine, some advise eliminating "migraine triggers" such as caffeine, but the evidence for this is weak. There is no high-quality evidence that changing diet by restricting salt, caffeine or alcohol improves symptoms.
=== Physical therapy ===
While use of physical therapy early after the onset of MD is probably not useful due to the fluctuating disease course, physical therapy to help retraining of the balance system appears to be useful to reduce both subjective and objective deficits in balance over the longer term.
=== Counseling ===
The psychological distress caused by the vertigo and hearing loss may worsen the condition in some people. Counseling may be useful to manage the distress, as may education and relaxation techniques.
=== Surgery ===
If symptoms do not improve with less invasive approaches and for cases where the condition is uncontrolled or persistent and affecting both ears, surgery may be considered.
==== Endolymphatic sac surgery ====
Surgery to decompress the endolymphatic sac is one surgical approach that is sometimes suggested. Three methods of surgical endolymphatic sac decompression are sometimes suggested – simple decompression, insertion of a shunt, or removal of the sac. There is some very weak evidence that all three methods may be useful for reducing dizziness, but that the level of evidence supporting these surgical procedures is low with further higher quality investigations being suggested. There is a risk in these types of surgical procedures that the shunts used in these surgeries are at risk of becoming displaced or misplaced. For those with severe cases who are eligible for endolymphatic sac decompression, a 2014 systematic review reported that in at least 75% of people, EL sac decompression was effective at controlling vertigo in the short term (>1 year of follow-up) and long term (>24 months).
==== Ventilation tubes ====
Surgical implantation of eustachian tubes (ventilation tubes) is not strongly supported by medical studies. There are some tentative evidence of benefit from tympanostomy tubes for improvement in the unsteadiness associated with the disease, conclusions about how effective this surgery is and the potential for side effects and harms is not clear.
==== Other surgical interventions ====
Destructive surgeries such as vestibular nerve labyrinthectomy are irreversible and involve removing entire functionality of most, if not all, of the affected ear; as of 2013, almost no evidence existed with which to judge whether these surgeries are effective. The inner ear itself can be surgically removed via labyrinthectomy, although hearing is always completely lost in the affected ear with this operation. The surgeon can also cut the nerve to the balance portion of the inner ear in a vestibular neurectomy. The hearing is often mostly preserved; however, the surgery involves cutting open into the lining of the brain, and a hospital stay of a few days for monitoring is required.
=== Poorly supported ===
As of 2014, betahistine is often used as it is inexpensive and safe; but evidence does not justify its use in Ménière's disease. However, recent pharmacokinetic experiments have shown that combination therapy with Monoamine oxidase inhibitors can drastically increase the bioavailability of betahistine in humans, and improve cochlear blood flow in guinea pigs.
Transtympanic micropressure pulses were investigated in two systematic reviews. Neither found evidence to justify this technique.
Intratympanic steroids were investigated in three systematic reviews. The data were found to be insufficient to decide if this therapy has positive effects.
Evidence does not support the use of alternative medicine such as acupuncture or herbal supplements.
== Prognosis ==
Ménière's disease usually starts confined to one ear; it extends to both ears in about 30% of cases. People may start out with only one symptom, but in Ménière's disease all three appear with time. Hearing loss usually fluctuates in the beginning stages and becomes more permanent in later stages. Ménière's disease has a course of 5–15 years, and people generally end up with mild disequilibrium, tinnitus, and moderate hearing loss in one ear.
As of 2020, there has been no recent major breakthrough in the pathogenesis research of Ménière's disease.
== Epidemiology ==
From 3 to 11% of diagnosed dizziness in neuro-otological clinics are due to Ménière's disease. The annual incidence rate is estimated to be about 15 cases per 100,000 people and the prevalence rate is about 218 per 100,000, and around 15% of people with Ménière's disease are older than 65. In around 9% of cases, a relative also had Ménière's disease, indicating a genetic predisposition in some cases.
The odds of Ménière's disease are greater for people of white ethnicity, with severe obesity, and women. Several conditions are often comorbid with Ménière's disease, including arthritis, psoriasis, gastroesophageal reflux disease, irritable bowel syndrome, and migraine.
== History ==
The condition is named after the French physician Prosper Menière, who in an 1861 article described the main symptoms and was the first to suggest a single disorder for all of the symptoms, in the combined organ of balance and hearing in the inner ear.
The American Academy of Otolaryngology – Head and Neck Surgery Committee on Hearing and Equilibrium set criteria for diagnosing MD, as well as defining two subcategories – cochlear (without vertigo) and vestibular (without deafness).
In 1972, the academy defined criteria for diagnosing MD as:
Fluctuating, progressive, sensorineural deafness
Episodic, characteristic definitive spells of vertigo lasting 20 minutes to 24 hours with no unconsciousness, vestibular nystagmus always present.
Tinnitus (ringing in the ears, from mild to severe) is accompanied often by ear pain and a feeling of fullness in the affected ear; usually, the tinnitus is more severe before a spell of vertigo and lessens after the vertigo attack.
Attacks are characterized by periods of remission and exacerbation.
In 1985, this list changed to alter wording, such as changing "deafness" to "hearing loss associated with tinnitus, characteristically of low frequencies" and requiring more than one attack of vertigo to diagnose. Finally in 1995, the list was again altered to allow for degrees of the disease:
Certain – Definite disease with histopathological confirmation
Definite – Requires two or more definitive episodes of vertigo with hearing loss plus tinnitus and/or aural fullness
Probable – Only one definitive episode of vertigo and the other symptoms and signs
Possible – Definitive vertigo with no associated hearing loss
In 2015, the International Classification for Vestibular Disorders Committee of the Barany Society published consensus diagnostic criteria in collaboration with the American Academy of Otolaryngology–Head and Neck Surgery, the European Academy of Otology and Neurootology, the Japan Society for Equilibrium Research, and the Korean Balance Society.
== References ==
== External links ==
Basura GJ, Adams ME, Monfared A, et al. (8 April 2020). "Clinical Practice Guideline: Ménière's Disease". Otolaryngology–Head and Neck Surgery. 162 (2 suppl): S1 – S55. doi:10.1177/0194599820909438. PMID 32267799.
Menière's Disease, Stanford Ear Institute. | Wikipedia/Ménière's_disease |
In cognitive science and neuropsychology, executive functions (collectively referred to as executive function and cognitive control) are a set of cognitive processes that support goal-directed behavior, by regulating thoughts and actions through cognitive control, selecting and successfully monitoring actions that facilitate the attainment of chosen objectives. Executive functions include basic cognitive processes such as attentional control, cognitive inhibition, inhibitory control, working memory, and cognitive flexibility. Higher-order executive functions require the simultaneous use of multiple basic executive functions and include planning and fluid intelligence (e.g., reasoning and problem-solving).
Executive functions gradually develop and change across the lifespan of an individual and can be improved at any time over the course of a person's life. Similarly, these cognitive processes can be adversely affected by a variety of events which affect an individual. Both neuropsychological tests (e.g., the Stroop test) and rating scales (e.g., the Behavior Rating Inventory of Executive Function) are used to measure executive functions. They are usually performed as part of a more comprehensive assessment to diagnose neurological and psychiatric disorders.
Cognitive control and stimulus control, which is associated with operant and classical conditioning, represent opposite processes (internal vs external or environmental, respectively) that compete over the control of an individual's elicited behaviors; in particular, inhibitory control is necessary for overriding stimulus-driven behavioral responses (stimulus control of behavior). The prefrontal cortex is necessary but not solely sufficient for executive functions; for example, the caudate nucleus and subthalamic nucleus also have a role in mediating inhibitory control.
Cognitive control is impaired in addiction, attention deficit hyperactivity disorder, autism, and a number of other central nervous system disorders. Stimulus-driven behavioral responses that are associated with a particular rewarding stimulus tend to dominate one's behavior in an addiction.
== Neuroanatomy ==
Historically, the executive functions have been seen as regulated by the prefrontal regions of the frontal lobes, but it is still a matter of ongoing debate if that really is the case. Even though articles on prefrontal lobe lesions commonly refer to disturbances of executive functions and vice versa, a review found indications for the sensitivity but not for the specificity of executive function measures to frontal lobe functioning. This means that both frontal and non-frontal brain regions are necessary for intact executive functions. Probably the frontal lobes need to participate in basically all of the executive functions, but they are not the only brain structure involved.
Neuroimaging and lesion studies have identified the functions which are most often associated with the particular regions of the prefrontal cortex and associated areas.
The dorsolateral prefrontal cortex (DLPFC) is involved with "on-line" processing of information such as integrating different dimensions of cognition and behavior. As such, this area has been found to be associated with verbal and design fluency, ability to maintain and shift set, planning, response inhibition, anticipation of conflict stimuli, working memory, organisational skills, reasoning, problem-solving, and abstract thinking.
The anterior cingulate cortex (ACC) is involved in emotional drives, experience and integration. Associated cognitive functions include inhibition of inappropriate responses, decision making and motivated behaviors. Lesions in this area can lead to low drive states such as apathy, abulia or akinetic mutism and may also result in low drive states for such basic needs as food or drink and possibly decreased interest in social or vocational activities and sex.
The orbitofrontal cortex (OFC) plays a key role in impulse control, maintenance of set, monitoring ongoing behavior and socially appropriate behaviors. The orbitofrontal cortex also has roles in representing the value of rewards based on sensory stimuli and evaluating subjective emotional experiences. Lesions can cause disinhibition, impulsivity, aggressive outbursts, sexual promiscuity and antisocial behavior.
Furthermore, in their review, Alvarez and Emory state that:The frontal lobes have multiple connections to cortical, subcortical and brain stem sites. The basis of "higher-level" cognitive functions such as inhibition, flexibility of thinking, problem solving, planning, impulse control, concept formation, abstract thinking, and creativity often arise from much simpler, "lower-level" forms of cognition and behavior. Thus, the concept of executive function must be broad enough to include anatomical structures that represent a diverse and diffuse portion of the central nervous system.The cerebellum also appears to be involved in mediating certain executive functions, as do the ventral tegmental area and the substantia nigra.
In humans, high contents of cannabinoid receptor 1 (CB1) is found in frontal neocortical areas, subserving higher cognitive and executive functions, and in the posterior cingulate, a region pivotal for consciousness and higher cognitive processing by its activation.
== Hypothesized role ==
The executive system is thought to be heavily involved in handling novel situations outside the domain of some of our 'automatic' psychological processes that could be explained by the reproduction of learned schemas or set behaviors. Psychologists Don Norman and Tim Shallice have outlined five types of situations in which routine activation of behavior would not be sufficient for optimal performance:
Those that involve planning or decision-making
Those that involve error correction or troubleshooting
Situations where responses are not well-rehearsed or contain novel sequences of actions
Dangerous or technically difficult situations
Situations that require the overcoming of a strong habitual response or resisting temptation.
A prepotent response is a response for which immediate reinforcement (positive or negative) is available or has been previously associated with that response.
Executive functions are often invoked when it is necessary to override prepotent responses that might otherwise be automatically elicited by stimuli in the external environment. For example, on being presented with a potentially rewarding stimulus, such as a tasty piece of chocolate cake, a person might have the automatic response to take a bite. However, where such behavior conflicts with internal plans (such as having decided not to eat chocolate cake while on a diet), the executive functions might be engaged to inhibit that response.
Although suppression of these prepotent responses is ordinarily considered adaptive, problems for the development of the individual and the culture arise when feelings of right and wrong are overridden by cultural expectations or when creative impulses are overridden by executive inhibitions.
== Historical perspective ==
Although research into the executive functions and their neural basis has increased markedly over recent years, the theoretical framework in which it is situated is not new. In the 1940s, the British psychologist Donald Broadbent drew a distinction between "automatic" and "controlled" processes (a distinction characterized more fully by Shiffrin and Schneider in 1977), and introduced the notion of selective attention, to which executive functions are closely allied. In 1975, the US psychologist Michael Posner used the term "cognitive control" in his book chapter entitled "Attention and cognitive control".
The work of influential researchers such as Michael Posner, Joaquin Fuster, Tim Shallice, and their colleagues in the 1980s (and later Trevor Robbins, Bob Knight, Don Stuss, and others) laid much of the groundwork for recent research into executive functions. For example, Posner proposed that there is a separate "executive" branch of the attentional system, which is responsible for focusing attention on selected aspects of the environment. The British neuropsychologist Tim Shallice similarly suggested that attention is regulated by a "supervisory system", which can override automatic responses in favour of scheduling behaviour on the basis of plans or intentions. Throughout this period, a consensus emerged that this control system is housed in the most anterior portion of the brain, the prefrontal cortex (PFC).
Psychologist Alan Baddeley had proposed a similar system as part of his model of working memory and argued that there must be a component (which he named the "central executive") that allows information to be manipulated in short-term memory (for example, when doing mental arithmetic).
== Development ==
The executive functions are among the last mental functions to reach maturity. This is due to the delayed maturation of the prefrontal cortex, which is not completely myelinated until well into a person's third decade of life. Development of executive functions tends to occur in spurts, when new skills, strategies, and forms of awareness emerge. These spurts are thought to reflect maturational events in the frontal areas of the brain. Attentional control appears to emerge in infancy and develop rapidly in early childhood. Cognitive flexibility, goal setting, and information processing usually develop rapidly during ages 7–9 and mature by age 12. Executive control typically emerges shortly after a transition period at the beginning of adolescence. It is not yet clear whether there is a single sequence of stages in which executive functions appear, or whether different environments and early life experiences can lead people to develop them in different sequences.
=== Early childhood ===
Inhibitory control and working memory act as basic executive functions that make it possible for more complex executive functions like problem-solving to develop. Inhibitory control and working memory are among the earliest executive functions to appear, with initial signs observed in infants, 7 to 12 months old. Then in the preschool years, children display a spurt in performance on tasks of inhibition and working memory, usually between the ages of 3 and 5 years. Also during this time, cognitive flexibility, goal-directed behavior, and planning begin to develop. Nevertheless, preschool children do not have fully mature executive functions and continue to make errors related to these emerging abilities – often not due to the absence of the abilities, but rather because they lack the awareness to know when and how to use particular strategies in particular contexts.
=== Preadolescence ===
Preadolescent children continue to exhibit certain growth spurts in executive functions, suggesting that this development does not necessarily occur in a linear manner, along with the preliminary maturing of particular functions as well. During preadolescence, children display major increases in verbal working memory; goal-directed behavior (with a potential spurt around 12 years of age); response inhibition and selective attention; and strategic planning and organizational skills. Additionally, between the ages of 8 and 10, cognitive flexibility in particular begins to match adult levels. However, similar to patterns in childhood development, executive functioning in preadolescents is limited because they do not reliably apply these executive functions across multiple contexts as a result of ongoing development of inhibitory control.
=== Adolescence ===
Many executive functions may begin in childhood and preadolescence, such as inhibitory control. Yet, it is during adolescence when the different brain systems become better integrated. At this time, youth implement executive functions, such as inhibitory control, more efficiently and effectively and improve throughout this time period. Just as inhibitory control emerges in childhood and improves over time, planning and goal-directed behavior also demonstrate an extended time course with ongoing growth over adolescence. Likewise, functions such as attentional control, with a potential spurt at age 15, along with working memory, continue developing at this stage.
=== Adulthood ===
The major change that occurs in the brain in adulthood is the constant myelination of neurons in the prefrontal cortex. At age 20–29, executive functioning skills are at their peak, which allows people of this age to participate in some of the most challenging mental tasks. These skills begin to decline in later adulthood. Working memory and spatial span are areas where decline is most readily noted. Cognitive flexibility, however, has a late onset of impairment and does not usually start declining until around age 70 in normally functioning adults. Impaired executive functioning has been found to be the best predictor of functional decline in the elderly.
Exercise, even at light intensity, significantly improves executive function with the strongest effects seen in children, adolescents, and individuals with ADHD. Low- to moderate-intensity exercise was particularly effective in enhancing these higher-order cognitive processes.
== Models ==
=== Top-down inhibitory control ===
Aside from facilitatory or amplificatory mechanisms of control, many authors have argued for inhibitory mechanisms in the domain of response control, memory, selective attention, theory of mind, emotion regulation, as well as social emotions such as empathy. A recent review on this topic argues that active inhibition is a valid concept in some domains of psychology/cognitive control.
=== Working memory model ===
One influential model is Baddeley's multicomponent model of working memory, which is composed of a central executive system that regulates three subsystems: the phonological loop, which maintains verbal information; the visuospatial sketchpad, which maintains visual and spatial information; and the more recently developed episodic buffer that integrates short-term and long-term memory, holding and manipulating a limited amount of information from multiple domains in temporal and spatially sequenced episodes.
Researchers have found significant positive effects of biofeedback-enhanced relaxation on memory and inhibition in children. Biofeedback is a mind-body tool where people can learn to control and regulate their body to improve and control their executive functioning skills. To measure one's processes, researchers use their heart rate and or respiratory rates. Biofeedback-relaxation includes music therapy, art, and other mindfulness activities.
Executive functioning skills are important for many reasons, including children's academic success and social emotional development. According to the study "The Efficacy of Different Interventions to Foster Children's Executive Function Skills: A Series of Meta-Analyses", researchers found that it is possible to train executive functioning skills. Researchers conducted a meta-analytic study that looked at the combined effects of prior studies in order to find the overarching effectiveness of different interventions that promote the development of executive functioning skills in children. The interventions included computerized and non-computerized training, physical exercise, art, and mindfulness exercises. However, researchers could not conclude that art activities or physical activities could improve executive functioning skills.
=== Supervisory attentional system (SAS) ===
Another conceptual model is the supervisory attentional system (SAS). In this model, contention scheduling is the process where an individual's well-established schemas automatically respond to routine situations while executive functions are used when faced with novel situations. In these new situations, attentional control will be a crucial element to help generate new schema, implement these schema, and then assess their accuracy.
=== Self-regulatory model ===
Russell Barkley proposed a widely known model of executive functioning that is based on self-regulation. Primarily derived from work examining behavioral inhibition, it views executive functions as composed of four main abilities. One element is working memory that allows individuals to resist interfering information. A second component is the management of emotional responses in order to achieve goal-directed behaviors. Thirdly, internalization of self-directed speech is used to control and sustain rule-governed behavior and to generate plans for problem-solving. Lastly, information is analyzed and synthesized into new behavioral responses to meet one's goals. Changing one's behavioral response to meet a new goal or modify an objective is a higher level skill that requires a fusion of executive functions including self-regulation, and accessing prior knowledge and experiences.
According to this model, the executive system of the human brain provides for the cross-temporal organization of behavior towards goals and the future and coordinates actions and strategies for everyday goal-directed tasks. Essentially, this system permits humans to self-regulate their behavior so as to sustain action and problem-solving toward goals specifically and the future more generally. Thus, executive function deficits pose serious problems for a person's ability to engage in self-regulation over time to attain their goals and anticipate and prepare for the future.
Teaching children self-regulation strategies is a way to improve their inhibitory control and their cognitive flexibility. These skills allow children to manage their emotional responses. These interventions include teaching children executive function-related skills that provide the steps necessary to implement them during classroom activities and educating children on how to plan their actions before acting upon them. Executive functioning skills are how the brain plans and reacts to situations. Offering new self-regulation strategies allow children to improve their executive functioning skills by practicing something new. It is also concluded that mindfulness practices are shown to be a significantly effective intervention for children to self-regulate. This includes biofeedback-enhanced relaxation. These strategies support the growth of children's executive functioning skills.
=== Problem-solving model ===
Yet another model of executive functions is a problem-solving framework where executive functions are considered a macroconstruct composed of subfunctions working in different phases to (a) represent a problem, (b) plan for a solution by selecting and ordering strategies, (c) maintain the strategies in short-term memory in order to perform them by certain rules, and then (d) evaluate the results with error detection and error correction.
=== Lezak's conceptual model ===
One of the most widespread conceptual models on executive functions is Lezak's model. This framework proposes four broad domains of volition, planning, purposive action, and effective performance as working together to accomplish global executive functioning needs. While this model may broadly appeal to clinicians and researchers to help identify and assess certain executive functioning components, it lacks a distinct theoretical basis and relatively few attempts at validation.
=== Miller and Cohen's model ===
In 2001, Earl Miller and Jonathan Cohen published their article "An integrative theory of prefrontal cortex function", in which they argue that cognitive control is the primary function of the prefrontal cortex (PFC), and that control is implemented by increasing the gain of sensory or motor neurons that are engaged by task- or goal-relevant elements of the external environment. In a key paragraph, they argue:
We assume that the PFC serves a specific function in cognitive control: the active maintenance of patterns of activity that represent goals and the means to achieve them. They provide bias signals throughout much of the rest of the brain, affecting not only visual processes but also other sensory modalities, as well as systems responsible for response execution, memory retrieval, emotional evaluation, etc. The aggregate effect of these bias signals is to guide the flow of neural activity along pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task.
Miller and Cohen draw explicitly upon an earlier theory of visual attention that conceptualises perception of visual scenes in terms of competition among multiple representations – such as colors, individuals, or objects. Selective visual attention acts to 'bias' this competition in favour of certain selected features or representations. For example, imagine that you are waiting at a busy train station for a friend who is wearing a red coat. You are able to selectively narrow the focus of your attention to search for red objects, in the hope of identifying your friend. Desimone and Duncan argue that the brain achieves this by selectively increasing the gain of neurons responsive to the color red, such that output from these neurons is more likely to reach a downstream processing stage, and, as a consequence, to guide behaviour. According to Miller and Cohen, this selective attention mechanism is in fact just a special case of cognitive control – one in which the biasing occurs in the sensory domain. According to Miller and Cohen's model, the PFC can exert control over input (sensory) or output (response) neurons, as well as over assemblies involved in memory, or emotion. Cognitive control is mediated by reciprocal PFC connectivity with the sensory and motor cortices, and with the limbic system. Within their approach, thus, the term "cognitive control" is applied to any situation where a biasing signal is used to promote task-appropriate responding, and control thus becomes a crucial component of a wide range of psychological constructs such as selective attention, error monitoring, decision-making, memory inhibition, and response inhibition.
=== Miyake and Friedman's model ===
Miyake and Friedman's theory of executive functions proposes that there are three aspects of executive functions: updating, inhibition, and shifting. A cornerstone of this theoretical framework is the understanding that individual differences in executive functions reflect both unity (i.e., common EF skills) and diversity of each component (e.g., shifting-specific). In other words, aspects of updating, inhibition, and shifting are related, yet each remains a distinct entity. First, updating is defined as the continuous monitoring and quick addition or deletion of contents within one's working memory. Second, inhibition is one's capacity to supersede responses that are prepotent in a given situation. Third, shifting is one's cognitive flexibility to switch between different tasks or mental states.
Miyake and Friedman also suggest that the current body of research in executive functions suggest four general conclusions about these skills. The first conclusion is the unity and diversity aspects of executive functions. Second, recent studies suggest that much of one's EF skills are inherited genetically, as demonstrated in twin studies. Third, clean measures of executive functions can differentiate between normal and clinical or regulatory behaviors, such as ADHD. Last, longitudinal studies demonstrate that EF skills are relatively stable throughout development.
=== Banich's "cascade of control" model ===
This model from 2009 integrates theories from other models, and involves a sequential cascade of brain regions involved in maintaining attentional sets in order to arrive at a goal. In sequence, the model assumes the involvement of the posterior dorsolateral prefrontal cortex (DLPFC), the mid-DLPFC, and the posterior and anterior dorsal anterior cingulate cortex (ACC).
The cognitive task used in the article is selecting a response in the Stroop task, among conflicting color and word responses, specifically a stimulus where the word "green" is printed in red ink. The posterior DLPFC creates an appropriate attentional set, or rules for the brain to accomplish the current goal. For the Stroop task, this involves activating the areas of the brain involved in color perception, and not those involved in word comprehension. It counteracts biases and irrelevant information, like the fact that the semantic perception of the word is more salient to most people than the color in which it is printed.
Next, the mid-DLPFC selects the representation that will fulfill the goal. The task-relevant information must be separated from other sources of information in the task. In the example, this means focusing on the ink color and not the word.
The posterior dorsal ACC is next in the cascade, and it is responsible for response selection. This is where the decision is made whether the Stroop task participant will say "green" (the written word and the incorrect answer) or "red" (the font color and correct answer).
Following the response, the anterior dorsal ACC is involved in response evaluation, deciding whether one's response were correct or incorrect. Activity in this region increases when the probability of an error is higher.
The activity of any of the areas involved in this model depends on the efficiency of the areas that came before it. If the DLPFC imposes a lot of control on the response, the ACC will require less activity.
Recent work using individual differences in cognitive style has shown exciting support for this model. Researchers had participants complete an auditory version of the Stroop task, in which either the location or semantic meaning of a directional word had to be attended to. Participants that either had a strong bias toward spatial or semantic information (different cognitive styles) were then recruited to participate in the task. As predicted, participants that had a strong bias toward spatial information had more difficulty paying attention to the semantic information and elicited increased electrophysiological activity from the ACC. A similar activity pattern was also found for participants that had a strong bias toward verbal information when they tried to attend to spatial information.
== Assessment ==
Assessment of executive functions involves gathering data from several sources and synthesizing the information to look for trends and patterns across time and settings. Apart from standardized neuropsychological tests, other measures can and should be used, such as behaviour checklists, observations, interviews, and work samples. From these, conclusions may be drawn on the use of executive functions.
There are several different kinds of instruments (e.g., performance based, self-report) that measure executive functions across development. These assessments can serve a diagnostic purpose for a number of clinical populations.
== Experimental evidence ==
The executive system has been traditionally quite hard to define, mainly due to what psychologist Paul W. Burgess calls a lack of "process-behaviour correspondence". That is, there is no single behavior that can in itself be tied to executive function, or indeed executive dysfunction. For example, it is quite obvious what reading-impaired patients cannot do, but it is not so obvious what exactly executive-impaired patients might be incapable of.
This is largely due to the nature of the executive system itself. It is mainly concerned with the dynamic, "online" co-ordination of cognitive resources, and, hence, its effect can be observed only by measuring other cognitive processes. In similar manner, it does not always fully engage outside of real-world situations. As neurologist Antonio Damasio has reported, a patient with severe day-to-day executive problems may still pass paper-and-pencil or lab-based tests of executive function.
Theories of the executive system were largely driven by observations of patients with frontal lobe damage. They exhibited disorganized actions and strategies for everyday tasks (a group of behaviors now known as dysexecutive syndrome) although they seemed to perform normally when clinical or lab-based tests were used to assess more fundamental cognitive functions such as memory, learning, language, and reasoning. It was hypothesized that, to explain this unusual behaviour, there must be an overarching system that co-ordinates other cognitive resources.
Much of the experimental evidence for the neural structures involved in executive functions comes from laboratory tasks such as the Stroop task or the Wisconsin Card Sorting Task (WCST). In the Stroop task, for example, human subjects are asked to name the color that color words are printed in when the ink color and word meaning often conflict (for example, the word "RED" in green ink). Executive functions are needed to perform this task, as the relatively overlearned and automatic behaviour (word reading) has to be inhibited in favour of a less practiced task – naming the ink color. Recent functional neuroimaging studies have shown that two parts of the PFC, the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC), are thought to be particularly important for performing this task.
=== Context-sensitivity of PFC neurons ===
Other evidence for the involvement of the PFC in executive functions comes from single-cell electrophysiology studies in non-human primates, such as the macaque monkey, which have shown that (in contrast to cells in the posterior brain) many PFC neurons are sensitive to a conjunction of a stimulus and a context. For example, PFC cells might respond to a green cue in a condition where that cue signals that a leftwards fast movement of the eyes and the head should be made, but not to a green cue in another experimental context. This is important, because the optimal deployment of executive functions is invariably context-dependent.
One example from Miller & Cohen involves a pedestrian crossing the street. In the United States, where cars drive on the right side of the road, an American learns to look left when crossing the street. However, if that American visits a country where cars drive on the left, such as the United Kingdom, then the opposite behavior would be required (looking to the right). In this case, the automatic response needs to be suppressed (or augmented) and executive functions must make the American look to the right while in the UK.
Neurologically, this behavioural repertoire clearly requires a neural system that is able to integrate the stimulus (the road) with a context (US or UK) to cue a behaviour (look left or look right). Current evidence suggests that neurons in the PFC appear to represent precisely this sort of information. Other evidence from single-cell electrophysiology in monkeys implicates ventrolateral PFC (inferior prefrontal convexity) in the control of motor responses. For example, cells that increase their firing rate to NoGo signals as well as a signal that says "don't look there!" have been identified.
=== Attentional biasing in sensory regions ===
Electrophysiology and functional neuroimaging studies involving human subjects have been used to describe the neural mechanisms underlying attentional biasing. Most studies have looked for activation at the 'sites' of biasing, such as in the visual or auditory cortices. Early studies employed event-related potentials to reveal that electrical brain responses recorded over left and right visual cortex are enhanced when the subject is instructed to attend to the appropriate (contralateral) side of space.
The advent of bloodflow-based neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) has more recently permitted the demonstration that neural activity in a number of sensory regions, including color-, motion-, and face-responsive regions of visual cortex, is enhanced when subjects are directed to attend to that dimension of a stimulus, suggestive of gain control in sensory neocortex. For example, in a typical study, Liu and coworkers presented subjects with arrays of dots moving to the left or right, presented in either red or green. Preceding each stimulus, an instruction cue indicated whether subjects should respond on the basis of the colour or the direction of the dots. Even though colour and motion were present in all stimulus arrays, fMRI activity in colour-sensitive regions (V4) was enhanced when subjects were instructed to attend to the colour, and activity in motion-sensitive regions was increased when subjects were cued to attend to the direction of motion. Several studies have also reported evidence for the biasing signal prior to stimulus onset, with the observation that regions of the frontal cortex tend to come active prior to the onset of an expected stimulus.
=== Connectivity between the PFC and sensory regions ===
Despite the growing currency of the 'biasing' model of executive functions, direct evidence for functional connectivity between the PFC and sensory regions when executive functions are used, is to date rather sparse. Indeed, the only direct evidence comes from studies in which a portion of frontal cortex is damaged, and a corresponding effect is observed far from the lesion site, in the responses of sensory neurons. However, few studies have explored whether this effect is specific to situations where executive functions are required. Other methods for measuring connectivity between distant brain regions, such as correlation in the fMRI response, have yielded indirect evidence that the frontal cortex and sensory regions communicate during a variety of processes thought to engage executive functions, such as working memory, but more research is required to establish how information flows between the PFC and the rest of the brain when executive functions are used. As an early step in this direction, an fMRI study on the flow of information processing during visuospatial reasoning has provided evidence for causal associations (inferred from the temporal order of activity) between sensory-related activity in occipital and parietal cortices and activity in posterior and anterior PFC. Such approaches can further elucidate the distribution of processing between executive functions in PFC and the rest of the brain.
=== Bilingualism and executive functions ===
A growing body of research demonstrates that bilinguals might show advantages in executive functions, specifically inhibitory control and task switching. A possible explanation for this is that speaking two languages requires controlling one's attention and choosing the correct language to speak. Across development, bilingual infants, children, and elderly show a bilingual advantage when it comes to executive functioning. The advantage does not seem to manifest in younger adults. Bimodal bilinguals, or people who speak one oral language and one sign language, do not demonstrate this bilingual advantage in executive functioning tasks. This may be because one is not required to actively inhibit one language in order to speak the other.
Bilingual individuals also seem to have an advantage in an area known as conflict processing, which occurs when there are multiple representations of one particular response (for example, a word in one language and its translation in the individual's other language). Specifically, the lateral prefrontal cortex has been shown to be involved with conflict processing. However, there are still some doubts. In a meta-analytic review, researchers concluded that bilingualism did not enhance executive functioning in adults.
== In disease or disorder ==
The study of executive function in Parkinson's disease suggests subcortical areas such as the amygdala, hippocampus and basal ganglia are important in these processes. Dopamine modulation of the prefrontal cortex is responsible for the efficacy of dopaminergic drugs on executive function, and gives rise to the Yerkes–Dodson Curve. The inverted U represents decreased executive functioning with excessive arousal (or increased catecholamine release during stress), and decreased executive functioning with insufficient arousal. The low activity polymorphism of catechol-O-methyltransferase is associated with slight increase in performance on executive function tasks in healthy persons. Executive functions are impaired in multiple disorders including anxiety disorder, major depressive disorder, bipolar disorder, attention deficit hyperactivity disorder, schizophrenia and autism. Lesions to the prefrontal cortex, such as in the case of Phineas Gage, may also result in deficits of executive function. Damage to these areas may also manifest in deficits of other areas of function, such as motivation, and social functioning.
== Future directions ==
Other important evidence for executive functions processes in the prefrontal cortex have been described. One widely cited review article emphasizes the role of the medial part of the PFC in situations where executive functions are likely to be engaged – for example, where it is important to detect errors, identify situations where stimulus conflict may arise, make decisions under uncertainty, or when a reduced probability of obtaining favourable performance outcomes is detected. This review, like many others, highlights interactions between medial and lateral PFC, whereby posterior medial frontal cortex signals the need for increased executive functions and sends this signal on to areas in dorsolateral prefrontal cortex that actually implement control. Yet there has been no compelling evidence at all that this view is correct, and, indeed, one article showed that patients with lateral PFC damage had reduced ERNs (a putative sign of dorsomedial monitoring/error-feedback) – suggesting, if anything, that the direction of flow of the control could be in the reverse direction. Another prominent theory emphasises that interactions along the perpendicular axis of the frontal cortex, arguing that a 'cascade' of interactions between anterior PFC, dorsolateral PFC, and premotor cortex guides behaviour in accordance with past context, present context, and current sensorimotor associations, respectively.
Recent research on network energy in brain functional connectivity reveals that energy is selectively allocated to relevant brain networks during cognitive tasks. Canonical networks involved in executive functions, such as the prefrontal cortex in working memory tasks, exhibit efficient network organization, requiring a smaller share of energy.
Advances in neuroimaging techniques have allowed studies of genetic links to executive functions, with the goal of using the imaging techniques as potential endophenotypes for discovering the genetic causes of executive function.
== See also ==
Cognitive neuropsychology
Executive dysfunction
Metacognition
Nonverbal learning disorder
Purkinje cell
Self-control
Conscientiousness
== References ==
== External links ==
Media related to Executive functions at Wikimedia Commons
The National Center for Learning Disabilities | Wikipedia/Executive_functions |
The lateralization of brain function (or hemispheric dominance/ lateralization) is the tendency for some neural functions or cognitive processes to be specialized to one side of the brain or the other. The median longitudinal fissure separates the human brain into two distinct cerebral hemispheres connected by the corpus callosum. Both hemispheres exhibit brain asymmetries in both structure and neuronal network composition associated with specialized function.
Lateralization of brain structures has been studied using both healthy and split-brain patients. However, there are numerous counterexamples to each generalization and each human's brain develops differently, leading to unique lateralization in individuals. This is different from specialization, as lateralization refers only to the function of one structure divided between two hemispheres. Specialization is much easier to observe as a trend, since it has a stronger anthropological history.
The best example of an established lateralization is that of Broca's and Wernicke's areas, where both are often found exclusively on the left hemisphere. Function lateralization, such as semantics, intonation, accentuation, and prosody, has since been called into question and largely been found to have a neuronal basis in both hemispheres. Another example is that each hemisphere in the brain tends to represent one side of the body. In the cerebellum, this is the ipsilateral side, but in the forebrain this is predominantly the contralateral side.
== Lateralized functions ==
=== Language and speech ===
Language functions are lateralized to the left hemisphere in 96% of right-handers and 60% of left-handers.
Meaning of words, called lexicon, is processed bilaterally which has been tested through the word superiority effect. This finding is consistent with the distributed memory and knowledge systems required for lexical entries; however, each hemisphere's lexicon is considered unique since it may be organized and accessed differently. For example, the right hemisphere lacks letter recognition, and cannot judge lexical relationships such as superordinate words or antonyms.
The permitted organization of words, called grammar, is lateralized in only one hemisphere, typically the left one. These functions include "understanding verbs, pluralizations, the possessive, and active-passive differences" and understanding changes in meaning due to word order. However, the right hemisphere is able to judge when a sentence is grammatically correct, which may indicate that patterns of speech are learned by rote rather than applied through understanding rules.
Speech production and language comprehension are specialized in Broca's and Wernicke's areas respectively, which are located in the left hemisphere for 96% of right-handers and 70% of left-handers. However, there exists some cases in which speech is produced in both hemispheres, also lateralization can shift due to plasticity over time. The emotional content of language, called emotional prosody, is right-lateralized.
In writing, studies attempting to isolate the linguistic component of written language in terms of brain lateralization could not provide enough evidence of a difference in the relative activation of the brain hemispheres between left-handed and right-handed adults.
=== Sensory processing ===
Sensory processing for the left and right sides of the body is often lateralized to the contralateral hemisphere due to nerve fiber decussation.
Because of the functional division of the left and right sides of the body, the processing of information in the sensory cortices is essentially identical. That is, the processing of visual and auditory stimuli, spatial manipulation, facial perception, and artistic ability are represented bilaterally. Numerical estimation, comparison and online calculation depend on bilateral parietal regions while exact calculation and fact retrieval are associated with left parietal regions, perhaps due to their ties to linguistic processing.
==== Vision ====
In vision, retinal ganglion cells undergo partial decussation at the optic chiasm, where axons from the nasal retinas cross to the opposite hemisphere, while axons from the temporal retinas remain on the ipsilateral side. As a result, visual input from the left visual hemifields are processed by the right hemisphere's visual cortex, while input from the right visual hemifields are processed by the left hemisphere's visual cortex.
==== Hearing ====
In hearing, spiral ganglion neurons in the vestibulocochlear nerve project to the ipsilateral cochlear nuclei in the medulla. However, second-order axons from the ventral cochlear nucleus branch to both the ipsilateral and contralateral superior olivary complexes. Consequently, hearing is strongly lateralized only at the ipsilateral cochlear nuclei, while further processing in the inferior colliculi, the medial geniculate nucleus of the thalamus, and the auditory cortex occurs bilaterally with a slight contralateral dominance. This lateralization explains why damage to one cochlear nucleus causes deafness in the ipsilateral ear, whereas damage above the cochlear nucleus typically results in only slight hearing loss.
When tasked to repeat words in a dichotic listening task, individuals tend to say words played in their right ear, a phenomenon called right-ear advantage. Since hearing is slightly contralateral dominant, this effect is consistent with the left hemisphere lateralization of language. When tasked to recall melodies in a dichotic listening task, people instead tend to have a left-ear advantage.
==== Touch ====
In the somatosensory system, sensations of touch, vibration, pressure, pain, and temperature are primarily processed in the contralateral somatosensory cortex of the brain. Mechanoreceptors responsible for touch and vibration transmit signals through the dorsal column-medial lemniscal pathway, where they decussate at the dorsal column nuclei in the medulla before ascending. Touch from the face and top of the head follows the trigeminal touch pathway, where second-order neurons decussate at the trigeminal nucleus.
Pain and temperature signals from nociceptors travel a different pathway, the spinothalamic pathway, where second-order neurons decussate earlier in the spinal cord. For pain and temperature in the face and top of the head, second-order neurons decussate at the spinal trigeminal nucleus of the brainstem. The earlier decussation of pain signals compared to touch explains Brown-Séquard syndrome, a condition in which damage to one half of the spinal cord leads to ipsilateral insensitivity to touch but contralateral insensitivity to pain and temperature.
=== Motor system ===
Voluntary movement is lateralized to the contralateral motor cortex, so the right hemisphere controls the left side of the body, while the left hemisphere controls the right side.
In the two lateral pathways, the corticospinal tract is responsible for control of distal muscles and begins at the contralateral motor cortex or contralateral somatosensory areas, and decussates between the medulla and spinal cord. The rubrospinal tract responsible for distal muscle and posture begins at the contralateral red nucleus and quickly decussates in the pons.
In the four ventromedial pathways, the vestibulospinal tract responsible for head balance begins at the ipsilateral vestibular nucleus of the medulla and splits into a bilateral and ipsilateral path. The bilateral path controls neck and back muscles for head balance, while the ipsilateral path maintains upright posture of the legs. The tectospinal tract responsible for orienting the head toward sensory stimuli begins at the contralateral superior colliculus and quickly decussates at the red nucleus. The reticulospinal tracts responsible for controlling muscles against gravity begin at the ipsilateral reticular formation and do not decussate.
=== Value systems ===
Rather than just being a series of places where different brain modules occur, there are running similarities in the kind of function seen in each side, for instance how right-side impairment of drawing ability making patients draw the parts of the subject matter with wholly incoherent relationships, or where the kind of left-side damage seen in language impairment not damaging the patient's ability to catch the significance of intonation in speech. This has led British psychiatrist Iain McGilchrist to view the two hemispheres as having different value systems, where the left hemisphere tends to reduce complex matters such as ethics to rules and measures, and the right hemisphere is disposed to the holistic and metaphorical.
== Clinical significance ==
Depression is linked with a hyperactive right hemisphere, with evidence of selective involvement in "processing negative emotions, pessimistic thoughts and unconstructive thinking styles", as well as vigilance, arousal and self-reflection, and a relatively hypoactive left hemisphere, "specifically involved in processing pleasurable experiences" and "relatively more involved in decision-making processes". Additionally, "left hemisphere lesions result in an omissive response bias or error pattern whereas right hemisphere lesions result in a commissive response bias or error pattern." The delusional misidentification syndromes, reduplicative paramnesia and Capgras delusion are also often the result of right hemisphere lesions.
=== Hemisphere damage ===
Damage to either the right or left hemisphere, and its resulting deficits provide insight into the function of the damaged area. There is truth to the idea that some brain functions reside more on one side of the brain than the other. We know this in part from what is lost when a stroke affects a particular part of the brain. Left hemisphere damage has many effects on language production and perception. Damage or lesions to the right hemisphere can result in a lack of emotional prosody or intonation when speaking. The left hemisphere is often involved with dealing of detail-oriented perception while the right hemisphere deals mostly with wholeness or an overall concept of things.
Right hemisphere damage also has grave effects on understanding discourse. People with damage to the right hemisphere have a reduced ability to generate inferences, comprehend and produce main concepts, and a reduced ability to manage alternative meanings. Furthermore, people with right hemisphere damage often exhibit discourse that is abrupt and perfunctory or verbose and excessive. They can also have pragmatic deficits in situations of turn taking, topic maintenance and shared knowledge. . Although both sides of the hemisphere has different responsibilities and tasks, they both complete each other and create a bigger picture.
Lateral brain damage can also affect visual perceptual spatial resolution. People with left hemisphere damage may have impaired perception of high resolution, or detailed, aspects of an image. People with right hemisphere damage may have impaired perception of low resolution, or big picture, aspects of an image.
=== Plasticity ===
If a specific region of the brain, or even an entire hemisphere, is injured or destroyed, its functions can sometimes be assumed by a neighboring region in the same hemisphere or the corresponding region in the other hemisphere, depending upon the area damaged and the patient's age. When injury interferes with pathways from one area to another, alternative (indirect) connections may develop to communicate information with detached areas, despite the inefficiencies.
=== Broca's aphasia ===
Broca's aphasia is a specific type of expressive aphasia and is so named due to the aphasia that results from damage or lesions to the Broca's area of the brain, that exists most commonly in the left inferior frontal hemisphere. Thus, the aphasia that develops from the lack of functioning of the Broca's area is an expressive and non-fluent aphasia. It is called 'non-fluent' due to the issues that arise because Broca's area is critical for language pronunciation and production. The area controls some motor aspects of speech production and articulation of thoughts to words and as such lesions to the area result in specific non-fluent aphasia.
=== Wernicke's aphasia ===
Wernicke's aphasia is the result of damage to the area of the brain that is commonly in the left hemisphere above the Sylvian fissure. Damage to this area causes primarily a deficit in language comprehension. While the ability to speak fluently with normal melodic intonation is spared, the language produced by a person with Wernicke's aphasia is riddled with semantic errors and may sound nonsensical to the listener. Wernicke's aphasia is characterized by phonemic paraphasias, neologism or jargon. Another characteristic of a person with Wernicke's aphasia is that they are unconcerned by the mistakes that they are making.
== Society and culture ==
=== Possible misapplication ===
The concept of "right-brained" or "left-brained" individuals is considered a widespread myth which oversimplifies the true nature of the brain's cerebral hemispheres (for a recent counter position, though, see below). Proof leading to the "mythbuster" of the left-/right-brained concept is increasing as more and more studies are brought to light. Harvard Health Publishing includes a study from the University of Utah in 2013, that exhibited brain scans revealing similarity on both sides of the brain, personality and environmental factors aside. Although certain functions show a degree of lateralization in the brain—with language predominantly processed in the left hemisphere, and spatial and nonverbal reasoning in the right—these functions are not exclusively tied to one hemisphere.
Terence Hines states that the research on brain lateralization is valid as a research program, though commercial promoters have applied it to promote subjects and products far outside the implications of the research. For example, the implications of the research have no bearing on psychological interventions such as eye movement desensitization and reprocessing (EMDR) and neurolinguistic programming, brain-training equipment, or management training.
=== Popular psychology ===
Some popularizations oversimplify the science about lateralization, by presenting the functional differences between hemispheres as being more absolute than is actually the case.: 107 Interestingly, research has shown quite opposite function of brain lateralisation, i.e. right hemisphere creatively and chaotically links between concepts and left hemisphere tends to adhere to specific date and time, although generally adhering to the pattern of left-brain as linguistic interpretation and right brain as spatio-temporal.
=== Sex differences ===
In the 19th century and to a lesser extent the 20th, it was thought that each side of the brain was associated with a specific gender: the left corresponding with masculinity and the right with femininity and each half could function independently. The right side of the brain was seen as the inferior and thought to be prominent in women, savages, children, criminals, and the insane. A prime example of this in fictional literature can be seen in Robert Louis Stevenson's Strange Case of Dr. Jekyll and Mr. Hyde.
== History ==
=== Broca ===
One of the first indications of brain function lateralization resulted from the research of French physician Pierre Paul Broca, in 1861. His research involved the male patient nicknamed "Tan", who had a speech deficit (aphasia); "tan" was one of the few words he could articulate, hence his nickname. In Tan's autopsy, Broca determined he had a syphilitic lesion in the left cerebral hemisphere. This left frontal lobe brain area (Broca's area) is an important speech production region. The motor aspects of speech production deficits caused by damage to Broca's area are known as expressive aphasia. In clinical assessment of this type of aphasia, patients have difficulty producing speech.
=== Wernicke ===
German physician Karl Wernicke continued in the vein of Broca's research by studying language deficits unlike expressive aphasia. Wernicke noted that not every deficit was in speech production; some were linguistic. He found that damage to the left posterior, superior temporal gyrus (Wernicke's area) caused language comprehension deficits rather than speech production deficits, a syndrome known as receptive aphasia.
=== Imaging ===
These seminal works on hemispheric specialization were done on patients or postmortem brains, raising questions about the potential impact of pathology on the research findings. New methods permit the in vivo comparison of the hemispheres in healthy subjects. Particularly, magnetic resonance imaging (MRI) and positron emission tomography (PET) are important because of their high spatial resolution and ability to image subcortical brain structures.
=== Movement and sensation ===
In the 1940s, neurosurgeon Wilder Penfield and his neurologist colleague Herbert Jasper developed a technique of brain mapping to help reduce side effects caused by surgery to treat epilepsy. They stimulated motor and somatosensory cortices of the brain with small electrical currents to activate discrete brain regions. They found that stimulation of one hemisphere's motor cortex produces muscle contraction on the opposite side of the body. Furthermore, the functional map of the motor and sensory cortices is fairly consistent from person to person; Penfield and Jasper's famous pictures of the motor and sensory homunculi were the result.
=== Split-brain patients ===
Research by Michael Gazzaniga and Roger Wolcott Sperry in the 1960s on split-brain patients led to an even greater understanding of functional laterality. Split-brain patients are patients who have undergone corpus callosotomy (usually as a treatment for severe epilepsy), a severing of a large part of the corpus callosum. The corpus callosum connects the two hemispheres of the brain and allows them to communicate. When these connections are cut, the two halves of the brain have a reduced capacity to communicate with each other. This led to many interesting behavioral phenomena that allowed Gazzaniga and Sperry to study the contributions of each hemisphere to various cognitive and perceptual processes. One of their main findings was that the right hemisphere was capable of rudimentary language processing, but often has no lexical or grammatical abilities. Eran Zaidel also studied such patients and found some evidence for the right hemisphere having at least some syntactic ability.
Language is primarily localized in the left hemisphere. While the left hemisphere has proven to be more optimized for language, the right hemisphere has the capacity with emotions, such as sarcasm, that can express prosody in sentences when speaking. According to Sheppard and Hillis, "The right hemisphere is critical for perceiving sarcasm (Davis et al., 2016), integrating context required for understanding metaphor, inference, and humour, as well as recognizing and expressing affective or emotional prosody—changes in pitch, rhythm, rate, and loudness that convey emotions". One of the experiments carried out by Gazzaniga involved a split-brain male patient sitting in front of a computer screen while having words and images presented on either side of the screen, and the visual stimuli would go to either the right or left visual field, and thus the left or right brain, respectively. It was observed that if the patient was presented with an image to his left visual field (right brain), he would report not seeing anything. If he was able to feel around for certain objects, he could accurately pick out the correct object, despite not having the ability to verbalize what he saw.
== Additional images ==
== See also ==
== References ==
== External links ==
Left Brain, Right Brain? Wrong
== Bibliography ==
== Further resources == | Wikipedia/Lateralization_of_brain_function |
Cognitive behavioral therapy (CBT) is a form of psychotherapy that aims to reduce symptoms of various mental health conditions, primarily depression, PTSD, and anxiety disorders.
Cognitive behavioral therapy focuses on challenging and changing cognitive distortions (thoughts, beliefs, and attitudes) and their associated behaviors in order to improve emotional regulation and help the individual develop coping strategies to address problems.
Though originally designed as an approach to treat depression, CBT is often prescribed for the evidence-informed treatment of many mental health and other conditions, including anxiety, substance use disorders, marital problems, ADHD, and eating disorders. CBT includes a number of cognitive or behavioral psychotherapies that treat defined psychopathologies using evidence-based techniques and strategies.
CBT is a common form of talk therapy based on the combination of the basic principles from behavioral and cognitive psychology. It is different from other approaches to psychotherapy, such as the psychoanalytic approach, where the therapist looks for the unconscious meaning behind the behaviors and then formulates a diagnosis. Instead, CBT is a "problem-focused" and "action-oriented" form of therapy, meaning it is used to treat specific problems related to a diagnosed mental disorder. The therapist's role is to assist the client in finding and practicing effective strategies to address the identified goals and to alleviate symptoms of the disorder. CBT is based on the belief that thought distortions and maladaptive behaviors play a role in the development and maintenance of many psychological disorders and that symptoms and associated distress can be reduced by teaching new information-processing skills and coping mechanisms.
When compared to psychoactive medications, review studies have found CBT alone to be as effective for treating less severe forms of depression, and borderline personality disorder. Some research suggests that CBT is most effective when combined with medication for treating mental disorders, such as major depressive disorder. CBT is recommended as the first line of treatment for the majority of psychological disorders in children and adolescents, including aggression and conduct disorder. Researchers have found that other bona fide therapeutic interventions were equally effective for treating certain conditions in adults. Along with interpersonal psychotherapy (IPT), CBT is recommended in treatment guidelines as a psychosocial treatment of choice. It is recommended by the American Psychiatric Association, the American Psychological Association, and the British National Health Service.
== History ==
=== Philosophy ===
Precursors of certain fundamental aspects of CBT have been identified in various ancient philosophical traditions, particularly Stoicism. Stoic philosophers, particularly Epictetus, believed logic could be used to identify and discard false beliefs that lead to destructive emotions, which has influenced the way modern cognitive-behavioral therapists identify cognitive distortions that contribute to depression and anxiety. Aaron T. Beck's original treatment manual for depression states, "The philosophical origins of cognitive therapy can be traced back to the Stoic philosophers". Another example of Stoic influence on cognitive theorists is Epictetus on Albert Ellis. A key philosophical figure who influenced the development of CBT was John Stuart Mill through his creation of Associationism, a predecessor of classical conditioning and behavioral theory.
Principles originating from Buddhism have significantly impacted the evolution of various new forms of CBT, including dialectical behavior therapy, mindfulness-based cognitive therapy, spirituality-based CBT, and compassion-focused therapy.
The modern roots of CBT can be traced to the development of behavior therapy in the early 20th century, the development of cognitive therapy in the 1960s, and the subsequent merging of the two.
=== Behavioral therapy ===
Groundbreaking work in behaviorism began with John B. Watson and Rosalie Rayner's studies of conditioning in 1920. Behaviorally-centered therapeutic approaches appeared as early as 1924 with Mary Cover Jones' work dedicated to the unlearning of fears in children. These were the antecedents of the development of Joseph Wolpe's behavioral therapy in the 1950s. It was the work of Wolpe and Watson, which was based on Ivan Pavlov's work on learning and conditioning, that influenced Hans Eysenck and Arnold Lazarus to develop new behavioral therapy techniques based on classical conditioning.
During the 1950s and 1960s, behavioral therapy became widely used by researchers in the United States, the United Kingdom, and South Africa. Their inspiration was by the behaviorist learning theory of Ivan Pavlov, John B. Watson, and Clark L. Hull.
In Britain, Joseph Wolpe, who applied the findings of animal experiments to his method of systematic desensitization, applied behavioral research to the treatment of neurotic disorders. Wolpe's therapeutic efforts were precursors to today's fear reduction techniques. British psychologist Hans Eysenck presented behavior therapy as a constructive alternative.
At the same time as Eysenck's work, B. F. Skinner and his associates were beginning to have an impact with their work on operant conditioning. Skinner's work was referred to as radical behaviorism and avoided anything related to cognition. However, Julian Rotter in 1954 and Albert Bandura in 1969 contributed to behavior therapy with their works on social learning theory by demonstrating the effects of cognition on learning and behavior modification. The work of Claire Weekes in dealing with anxiety disorders in the 1960s is also seen as a prototype of behavior therapy.
The emphasis on behavioral factors has been described as the "first wave" of CBT.
=== Cognitive therapy ===
One of the first therapists to address cognition in psychotherapy was Alfred Adler, notably with his idea of basic mistakes and how they contributed to creation of unhealthy behavioral and life goals.Abraham Low believed that someone's thoughts were best changed by changing their actions. Adler and Low influenced the work of Albert Ellis, who developed the earliest cognitive-based psychotherapy called rational emotive behavioral therapy, or REBT. The first version of REBT was announced to the public in 1956.
In the late 1950s, Aaron T. Beck was conducting free association sessions in his psychoanalytic practice. During these sessions, Beck noticed that thoughts were not as unconscious as Freud had previously theorized, and that certain types of thinking may be the culprits of emotional distress. It was from this hypothesis that Beck developed cognitive therapy, and called these thoughts "automatic thoughts". He first published his new methodology in 1967, and his first treatment manual in 1979. Beck has been referred to as "the father of cognitive behavioral therapy".
It was these two therapies, rational emotive therapy, and cognitive therapy, that started the "second wave" of CBT, which emphasized cognitive factors.
=== Merger of behavioral and cognitive therapies ===
Although the early behavioral approaches were successful in many so-called neurotic disorders, they had little success in treating depression. Behaviorism was also losing popularity due to the cognitive revolution. The therapeutic approaches of Albert Ellis and Aaron T. Beck gained popularity among behavior therapists, despite the earlier behaviorist rejection of mentalistic concepts like thoughts and cognitions. Both of these systems included behavioral elements and interventions, with the primary focus being on problems in the present.
In initial studies, cognitive therapy was often contrasted with behavioral treatments to see which was most effective. During the 1980s and 1990s, cognitive and behavioral techniques were merged into cognitive behavioral therapy. Pivotal to this merging was the successful development of treatments for panic disorder by David M. Clark in the UK and David H. Barlow in the US.
Over time, cognitive behavior therapy came to be known not only as a therapy, but as an umbrella term for all cognitive-based psychotherapies. These therapies include, but are not limited to, REBT, cognitive therapy, acceptance and commitment therapy, dialectical behavior therapy, metacognitive therapy, metacognitive training, reality therapy/choice theory, cognitive processing therapy, EMDR, and multimodal therapy.
This blending of theoretical and technical foundations from both behavior and cognitive therapies constituted the "third wave" of CBT. The most prominent therapies of this third wave are dialectical behavior therapy and acceptance and commitment therapy. Despite the increasing popularity of third-wave treatment approaches, reviews of studies reveal there may be no difference in the effectiveness compared with non-third wave CBT for the treatment of depression.
== Medical uses ==
In adults, CBT has been shown to be an effective part of treatment plans for anxiety disorders, body dysmorphic disorder, depression, eating disorders, chronic low back pain, personality disorders, psychosis, schizophrenia, substance use disorders, and bipolar disorder. It is also effective as part of treatment plans in the adjustment, depression, and anxiety associated with fibromyalgia, and as part of the treatment after spinal cord injuries.
In children or adolescents, CBT is an effective part of treatment plans for anxiety disorders, body dysmorphic disorder, depression and suicidality, eating disorders and obesity, obsessive–compulsive disorder (OCD), and post-traumatic stress disorder (PTSD), tic disorders, trichotillomania, and other repetitive behavior disorders. CBT has also been used to help improve a variety of childhood disorders, including depressive disorders and various anxiety disorders. CBT has shown to be the most effective intervention for people exposed to adverse childhood experiences in the form of abuse or neglect.
Criticism of CBT sometimes focuses on implementations (such as the UK IAPT) which may result initially in low quality therapy being offered by poorly trained practitioners. However, evidence supports the effectiveness of CBT for anxiety and depression.
Evidence suggests that the addition of hypnotherapy as an adjunct to CBT improves treatment efficacy for a variety of clinical issues.
The United Kingdom's National Institute for Health and Care Excellence (NICE) recommends CBT in the treatment plans for a number of mental health difficulties, including PTSD, OCD, bulimia nervosa, and clinical depression.
=== Depression and anxiety disorders ===
Cognitive behavioral therapy has been shown as an effective treatment for clinical depression. Among psychotherapeutic approaches for major depressive disorder, cognitive behavioral therapy and interpersonal psychotherapy are recommended by clinical practice guidelines including The American Psychiatric Association Practice (APA) Guidelines (April 2000), and the APA endorsed Veteran Affairs clinical practice guideline.
CBT has been shown to be effective in the treatment of adults with anxiety disorders. There is also evidence that using CBT to treat children and adolescents with anxiety disorders was probably more effective (in the short term) than wait list or no treatment and more effective than attention control treatment approaches. Some meta-analyses find CBT more effective than psychodynamic therapy and equal to other therapies in treating anxiety and depression. A 2013 meta-analysis suggested that CBT, interpersonal therapy, and problem-solving therapy outperformed psychodynamic psychotherapy and behavioral activation in the treatment of depression. According to a 2004 review by INSERM of three methods, cognitive behavioral therapy was either proven or presumed to be an effective therapy on several mental disorders. This included depression, panic disorder, post-traumatic stress, and other anxiety disorders.
A systematic review of CBT in depression and anxiety disorders concluded that "CBT delivered in primary care, especially including computer- or Internet-based self-help programs, is potentially more effective than usual care and could be delivered effectively by primary care therapists."
A 2024 systematic review found that exposure and response prevention (ERP), a specific form of cognitive behavioral therapy, is considered a first-line treatment for pediatric obsessive–compulsive disorder (OCD). Research indicates that ERP is effective in both in-person and remote settings, providing flexibility in treatment delivery without compromising efficacy.
In CBT you work on reducing fear by changing how you think and act. Instead of thinking of the fear object (for example, a spider) as an imminent threat or danger, you're taught to reevaluate the fear object as less threatening to your safety and well-being. Instead of avoiding or running from the fear, you're encouraged to face the fear.
==== Theoretical approaches ====
One etiological theory of depression is Aaron T. Beck's cognitive theory of depression. His theory states that depressed people think the way they do because their thinking is biased towards negative interpretations. Beck's theory rests on the aspect of cognitive behavioral therapy known as schemata. Schemata are the mental maps used to integrate new information into memories and to organize existing information in the mind. An example of a schema would be a person hearing the word "dog" and picturing different versions of the animal that they have grouped together in their mind. According to this theory, depressed people acquire a negative schema of the world in childhood and adolescence as an effect of stressful life events, and the negative schema is activated later in life when the person encounters similar situations.
Beck also described a negative cognitive triad. The cognitive triad is made up of the depressed individual's negative evaluations of themselves, the world, and the future. Beck suggested that these negative evaluations derive from the negative schemata and cognitive biases of the person. According to this theory, depressed people have views such as "I never do a good job", "It is impossible to have a good day", and "things will never get better". A negative schema helps give rise to the cognitive bias, and the cognitive bias helps fuel the negative schema. Beck further proposed that depressed people often have the following cognitive biases: arbitrary inference, selective abstraction, overgeneralization, magnification, and minimization. These cognitive biases are quick to make negative, generalized, and personal inferences of the self, thus fueling the negative schema.
On the other hand, a positive cognitive triad relates to a person's positive evaluations of themself, the world, and the future. More specifically, a positive cognitive triad requires self-esteem when viewing oneself and hope for the future. A person with a positive cognitive triad has a positive schema used for viewing themself in addition to a positive schema for the world and for the future. Cognitive behavioral research suggests a positive cognitive triad bolsters resilience, or the ability to cope with stressful events. Increased levels of resilience is associated with greater resistance to depression.
Another major theoretical approach to cognitive behavioral therapy treatment is the concept of Locus of Control outlined in Julian Rotter's Social Learning Theory. Locus of control refers to the degree to which an individual's sense of control is either internal or external. An internal locus of control exists when an individual views an outcome of a particular action as being reliant on themselves and their personal attributes whereas an external locus of control exists when an individual views other's or some outside, intangible force such as luck or fate as being responsible for the outcome of a particular action.
A basic concept in some CBT treatments used in anxiety disorders is in vivo exposure. CBT-exposure therapy refers to the direct confrontation of feared objects, activities, or situations by a patient. For example, a woman with PTSD who fears the location where she was assaulted may be assisted by her therapist in going to that location and directly confronting those fears. Likewise, a person with a social anxiety disorder who fears public speaking may be instructed to directly confront those fears by giving a speech. This "two-factor" model is often credited to O. Hobart Mowrer. Through exposure to the stimulus, this harmful conditioning can be "unlearned" (referred to as extinction and habituation).
CBT for children with phobias is normally delivered over multiple sessions, but one-session treatment has been shown to be equally effective and is cheaper.
==== Specialized forms of CBT ====
CBT-SP, an adaptation of CBT for suicide prevention (SP), was specifically designed for treating youths who are severely depressed and who have recently attempted suicide within the past 90 days, and was found to be effective, feasible, and acceptable.
Acceptance and commitment therapy (ACT) is a specialist branch of CBT (sometimes referred to as contextual CBT). ACT uses mindfulness and acceptance interventions and has been found to have a greater longevity in therapeutic outcomes. In a study with anxiety, CBT and ACT improved similarly across all outcomes from pre- to post-treatment. However, during a 12-month follow-up, ACT proved to be more effective, showing that it is a highly viable lasting treatment model for anxiety disorders.
Computerized CBT (CCBT) has been proven to be effective by randomized controlled and other trials in treating depression and anxiety disorders, including children. Some research has found similar effectiveness to an intervention of informational websites and weekly telephone calls. CCBT was found to be equally effective as face-to-face CBT in adolescent anxiety.
==== Combined with other treatments ====
Studies have provided evidence that when examining animals and humans, that glucocorticoids may lead to a more successful extinction learning during exposure therapy for anxiety disorders. For instance, glucocorticoids can prevent aversive learning episodes from being retrieved and heighten reinforcement of memory traces creating a non-fearful reaction in feared situations. A combination of glucocorticoids and exposure therapy may be a better-improved treatment for treating people with anxiety disorders.
==== Prevention ====
For anxiety disorders, use of CBT with people at risk has significantly reduced the number of episodes of generalized anxiety disorder and other anxiety symptoms, and also given significant improvements in explanatory style, hopelessness, and dysfunctional attitudes. In another study, 3% of the group receiving the CBT intervention developed generalized anxiety disorder by 12 months postintervention compared with 14% in the control group. Individuals with subthreshold levels of panic disorder significantly benefitted from use of CBT. Use of CBT was found to significantly reduce social anxiety prevalence.
For depressive disorders, a stepped-care intervention (watchful waiting, CBT and medication if appropriate) achieved a 50% lower incidence rate in a patient group aged 75 or older. Another depression study found a neutral effect compared to personal, social, and health education, and usual school provision, and included a comment on potential for increased depression scores from people who have received CBT due to greater self recognition and acknowledgement of existing symptoms of depression and negative thinking styles. A further study also saw a neutral result. A meta-study of the Coping with Depression course, a cognitive behavioral intervention delivered by a psychoeducational method, saw a 38% reduction in risk of major depression.
=== Bipolar disorder ===
Many studies show CBT, combined with pharmacotherapy, is effective in improving depressive symptoms, mania severity and psychosocial functioning with mild to moderate effects, and that it is better than medication alone.
INSERM's 2004 review found that CBT is an effective therapy for several mental disorders, including bipolar disorder. This included schizophrenia, depression, bipolar disorder, panic disorder, post-traumatic stress, anxiety disorders, bulimia, anorexia, personality disorders and alcohol dependency.
=== Psychosis ===
In long-term psychoses, CBT is used to complement medication and is adapted to meet individual needs. Interventions particularly related to these conditions include exploring reality testing, changing delusions and hallucinations, examining factors which precipitate relapse, and managing relapses. Meta-analyses confirm the effectiveness of metacognitive training (MCT) for the improvement of positive symptoms (e.g., delusions).
For people at risk of psychosis, in 2014 the UK National Institute for Health and Care Excellence (NICE) recommended preventive CBT.
=== Schizophrenia ===
INSERM's 2004 review found that CBT is an effective therapy for several mental disorders, including schizophrenia.
A Cochrane review reported CBT had "no effect on long‐term risk of relapse" and no additional effect above standard care. A 2015 systematic review investigated the effects of CBT compared with other psychosocial therapies for people with schizophrenia and determined that there is no clear advantage over other, often less expensive, interventions but acknowledged that better quality evidence is needed before firm conclusions can be drawn.
=== Addiction and substance use disorders ===
==== Pathological and problem gambling ====
CBT is also used for pathological and problem gambling. The percentage of people who problem gamble is 1–3% around the world. Cognitive behavioral therapy develops skills for relapse prevention and someone can learn to control their mind and manage high-risk cases. There is evidence of efficacy of CBT for treating pathological and problem gambling at immediate follow up, however the longer term efficacy of CBT for it is currently unknown.
==== Smoking cessation ====
CBT looks at the habit of smoking cigarettes as a learned behavior, which later evolves into a coping strategy to handle daily stressors. Since smoking is often easily accessible and quickly allows the user to feel good, it can take precedence over other coping strategies, and eventually work its way into everyday life during non-stressful events as well. CBT aims to target the function of the behavior, as it can vary between individuals, and works to inject other coping mechanisms in place of smoking. CBT also aims to support individuals with strong cravings, which are a major reported reason for relapse during treatment.
A 2008 controlled study out of Stanford University School of Medicine suggested CBT may be an effective tool to help maintain abstinence. The results of 304 random adult participants were tracked over the course of one year. During this program, some participants were provided medication, CBT, 24-hour phone support, or some combination of the three methods. At 20 weeks, the participants who received CBT had a 45% abstinence rate, versus non-CBT participants, who had a 29% abstinence rate. Overall, the study concluded that emphasizing cognitive and behavioral strategies to support smoking cessation can help individuals build tools for long term smoking abstinence.
Mental health history can affect the outcomes of treatment. Individuals with a history of depressive disorders had a lower rate of success when using CBT alone to combat smoking addiction.
A 2019 Cochrane review was unable to find sufficient evidence to differentiate effects between CBT and hypnosis for smoking cessation and highlighted that a review of the current research showed variable results for both modalities.
==== Substance use disorders ====
Studies have shown CBT to be an effective treatment for substance use disorders. For individuals with substance use disorders, CBT aims to reframe maladaptive thoughts, such as denial, minimizing and catastrophizing thought patterns, with healthier narratives. Specific techniques include identifying potential triggers and developing coping mechanisms to manage high-risk situations. Research has shown CBT to be particularly effective when combined with other therapy-based treatments or medication.
INSERM's 2004 review found that CBT is an effective therapy for several mental disorders, including alcohol dependency.
==== Internet addiction ====
Research has identified Internet addiction as a new clinical disorder that causes relational, occupational, and social problems. Cognitive behavioral therapy (CBT) has been suggested as the treatment of choice for Internet addiction, and addiction recovery in general has used CBT as part of treatment planning.
=== Eating disorders ===
Though many forms of treatment can support individuals with eating disorders, CBT is proven to be a more effective treatment than medications and interpersonal psychotherapy alone. CBT aims to combat major causes of distress such as negative cognitions surrounding body weight, shape and size. CBT therapists also work with individuals to regulate strong emotions and thoughts that lead to dangerous compensatory behaviors. CBT is the first line of treatment for bulimia nervosa, and non-specific eating disorders. While there is evidence to support the efficacy of CBT for bulimia nervosa and binging, the evidence is somewhat variable and limited by small study sizes. INSERM's 2004 review found that CBT is an effective therapy for several mental disorders, including bulimia and anorexia nervosa.
=== With autistic adults ===
Emerging evidence for cognitive behavioral interventions aimed at reducing symptoms of depression, anxiety, and obsessive-compulsive disorder in autistic adults without intellectual disability has been identified through a systematic review. While the research was focused on adults, cognitive behavioral interventions have also been beneficial to autistic children. A 2021 Cochrane review found limited evidence regarding the efficacy of CBT for obsessive-compulsive disorder in adults with Autism Spectrum Disorder stating a need for further study.
=== Dementia and mild cognitive impairment ===
A Cochrane review in 2022 found that adults with dementia and mild cognitive impairment (MCI) who experience symptoms of depression may benefit from CBT, whereas other counselling or supportive interventions might not improve symptoms significantly. Across 5 different psychometric scales, where higher scores indicate severity of depression, adults receiving CBT reported somewhat lower mood scores than those receiving usual care for dementia and MCI overall. In this review, a sub-group analysis found clinically significant benefits only among those diagnosed with dementia, rather than MCI.
The likelihood of remission from depression also appeared to be 84% higher following CBT, though the evidence for this was less certain. Anxiety, cognition and other neuropsychiatric symptoms were not significantly improved following CBT, however this review did find moderate evidence of improved quality of life and daily living activity scores in those with dementia and MCI.
=== Post-traumatic stress ===
Cognitive behavioral therapy interventions may have some benefits for people who have post-traumatic stress related to surviving rape, sexual abuse, or sexual assault. There is strong evidence that CBT-exposure therapy can reduce PTSD symptoms and lead to the loss of a PTSD diagnosis. In addition, CBT has also been shown to be effective for post-traumatic stress disorder in very young children (3 to 6 years of age). There is lower quality evidence that CBT may be more effective than other psychotherapies in reducing symptoms of posttraumatic stress disorder in children and adolescents.
=== Other uses ===
Evidence suggests a possible role for CBT in the treatment of attention deficit hyperactivity disorder (ADHD), hypochondriasis, and bipolar disorder, but more study is needed and results should be interpreted with caution. Moderate evidence from a 2024 systematic review supports the effectiveness of CBT and neurofeedback as part of psychosocial interventions for improving ADHD symptoms in children and adolescents.
CBT has been studied as an aid in the treatment of anxiety associated with stuttering. Initial studies have shown CBT to be effective in reducing social anxiety in adults who stutter, but not in reducing stuttering frequency.
There is some evidence that CBT is superior in the long-term to benzodiazepines and the nonbenzodiazepines in the treatment and management of insomnia. Computerized CBT (CCBT) has been proven to be effective by randomized controlled and other trials in treating insomnia. Some research has found similar effectiveness to an intervention of informational websites and weekly telephone calls. CCBT was found to be equally effective as face-to-face CBT in insomnia.
A Cochrane review of interventions aimed at preventing psychological stress in healthcare workers found that CBT was more effective than no intervention but no more effective than alternative stress-reduction interventions.
Cochrane Reviews have found no convincing evidence that CBT training helps foster care providers manage difficult behaviors in the youths under their care, nor was it helpful in treating people who abuse their intimate partners.
CBT has been applied in both clinical and non-clinical environments to treat disorders such as personality disorders and behavioral problems. INSERM's 2004 review found that CBT is an effective therapy for personality disorders.
CBT has been used with other researchers as well to minimize chronic pain and help relieve symptoms from those suffering from irritable bowel syndrome (IBS).
==== Individuals with medical conditions ====
In the case of people with metastatic breast cancer, data is limited but CBT and other psychosocial interventions might help with psychological outcomes and pain management. There is also some evidence that CBT may help reduce insomnia in cancer patients.
There is some evidence that using CBT for symptomatic management of non-specific chest pain is probably effective in the short term. However, the findings were limited by small trials and the evidence was considered of questionable quality. Cochrane reviews have found no evidence that CBT is effective for tinnitus, although there appears to be an effect on management of associated depression and quality of life in this condition. CBT combined with hypnosis and distraction reduces self-reported pain in children.
There is limited evidence to support CBT's use in managing the impact of multiple sclerosis, sleep disturbances related to aging, and dysmenorrhea, but more study is needed and results should be interpreted with caution.
Previously CBT has been considered as moderately effective for treating myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), however a National Institutes of Health Pathways to Prevention Workshop stated that in respect of improving treatment options for ME/CFS that the modest benefit from cognitive behavioral therapy should be studied as an adjunct to other methods. The Centres for Disease Control advice on the treatment of ME/CFS makes no reference to CBT while the National Institute for Health and Care Excellence states that cognitive behavioral therapy (CBT) has sometimes been assumed to be a cure for ME/CFS, however, it should only be offered to support people who live with ME/CFS to manage their symptoms, improve their functioning and reduce the distress associated with having a chronic illness.
=== Age ===
CBT is used to help people of all ages, but the therapy should be adjusted based on the age of the patient with whom the therapist is dealing. Older individuals in particular have certain characteristics that need to be acknowledged and the therapy altered to account for these differences thanks to age. Of the small number of studies examining CBT for the management of depression in older people, there is currently no strong support.
== Description ==
Mainstream cognitive behavioral therapy assumes that changing maladaptive thinking leads to change in behavior and affect, but recent variants emphasize changes in one's relationship to maladaptive thinking rather than changes in thinking itself.
=== Cognitive distortions ===
Therapists use CBT techniques to help people challenge their patterns and beliefs and replace errors in thinking, known as cognitive distortions with "more realistic and effective thoughts, thus decreasing emotional distress and self-defeating behavior". Cognitive distortions can be either a pseudo-discrimination belief or an overgeneralization of something. CBT techniques may also be used to help individuals take a more open, mindful, and aware posture toward cognitive distortions so as to diminish their impact.
Mainstream CBT helps individuals replace "maladaptive... coping skills, cognitions, emotions and behaviors with more adaptive ones", by challenging an individual's way of thinking and the way that they react to certain habits or behaviors, but there is still controversy about the degree to which these traditional cognitive elements account for the effects seen with CBT over and above the earlier behavioral elements such as exposure and skills training.
=== Assumptions ===
Chaloult, Ngo, Cousineau and Goulet have attempted to identify the main assumptions of cognitive therapy used in CBT based on the research literature (Beck; Walen and Wessler; Beck, Emery and Greenberg, and Auger). They describe fourteen assumptions:
Human emotions are primarily caused by people's thoughts and perceptions rather than events.
Events, thoughts, emotions, behaviors, and physiological reactions influence each other.
Dysfunctional emotions are typically caused by unrealistic thoughts. Reducing dysfunctional emotions requires becoming aware of irrational thoughts and changing them.
Human beings have an innate tendency to develop irrational thoughts. This tendency is reinforced by their environment.
People are largely responsible for their own dysfunctional emotions, as they maintain and reinforce their own beliefs.
Sustained effort is necessary to modify dysfunctional thoughts, emotions, and behaviors.
Rational thinking usually causes a decrease in the frequency, intensity, and duration of dysfunctional emotions, rather than an absence of affect or feelings.
A positive therapeutic relationship is essential to successful cognitive therapy.
Cognitive therapy is based on a teacher-student relationship, where the therapist educates the client.
Cognitive therapy uses Socratic questioning to challenge cognitive distortions.
Homework is an essential aspect of cognitive therapy. It consolidates the skills learned in therapy.
The cognitive approach is active, directed, and structured.
Cognitive therapy is generally short.
Cognitive therapy is based on predictable steps.
These steps largely involve learning about the CBT model; making links between thoughts, emotions, behaviors, and physiological reactions; noticing when dysfunctional emotions occur; learning to question the thoughts associated with these emotions; replacing irrational thoughts with others more grounded in reality; modifying behaviors based on new interpretations of events; and, in some cases, learning to recognize and change the major beliefs and attitudes underlying cognitive distortions.
Chaloult, Ngo, Cousineau and Goulet have also described the assumptions of behavioral therapy as used in CBT. They refer to the work of Agras, Prochaska and Norcross, and Kirk. The assumptions are:
Behaviors play an essential role in the onset, perpetuation and exacerbation of psychopathology.
Learning theory is key in understanding the treatment of mental illness, as behaviors can be learned and unlearned.
A rigorous evaluation (applied behavior analysis) is essential at the start of treatment. It includes identifying behaviors; precipitating, moderating, and perpetuating factors; the consequences of the behaviors; avoidance, and personal resources.
The effectiveness of the treatment is monitored throughout its duration.
Behavior therapy is scientific and the different forms of treatment are evaluated with rigorous evidence.
Behavior therapy is active, directed, and structured.
Together, these sets of assumptions cover the cognitive and behavioral aspects of CBT.
=== Phases in therapy ===
CBT can be seen as having six phases:
Assessment or psychological assessment;
Reconceptualization;
Skills acquisition;
Skills consolidation and application training;
Generalization and maintenance;
Post-treatment assessment follow-up.
These steps are based on a system created by Kanfer and Saslow. After identifying the behaviors that need changing, whether they be in excess or deficit, and treatment has occurred, the psychologist must identify whether or not the intervention succeeded. For example, "If the goal was to decrease the behavior, then there should be a decrease relative to the baseline. If the critical behavior remains at or above the baseline, then the intervention has failed."
The steps in the assessment phase include:
Identify critical behaviors;
Determine whether critical behaviors are excesses or deficits;
Evaluate critical behaviors for frequency, duration, or intensity (obtain a baseline);
If excess, attempt to decrease frequency, duration, or intensity of behaviors; if deficits, attempt to increase behaviors.
The re-conceptualization phase makes up much of the "cognitive" portion of CBT.
=== Delivery protocols ===
There are different protocols for delivering cognitive behavioral therapy, with important similarities among them. Use of the term CBT may refer to different interventions, including "self-instructions (e.g. distraction, imagery, motivational self-talk), relaxation and/or biofeedback, development of adaptive coping strategies (e.g. minimizing negative or self-defeating thoughts), changing maladaptive beliefs about pain, and goal setting". Treatment is sometimes manualized, with brief, direct, and time-limited treatments for individual psychological disorders that are specific technique-driven. CBT is used in both individual and group settings, and the techniques are often adapted for self-help applications. Some clinicians and researchers are cognitively oriented (e.g. cognitive restructuring), while others are more behaviorally oriented (e.g. in vivo exposure therapy). Interventions such as imaginal exposure therapy combine both approaches.
=== Related techniques ===
CBT may be delivered in conjunction with a variety of diverse but related techniques such as exposure therapy, stress inoculation, cognitive processing therapy, cognitive therapy, metacognitive therapy, metacognitive training, relaxation training, dialectical behavior therapy, and acceptance and commitment therapy. Some practitioners promote a form of mindful cognitive therapy which includes a greater emphasis on self-awareness as part of the therapeutic process.
== Methods of access ==
=== Therapist ===
A typical CBT program would consist of face-to-face sessions between patient and therapist, made up of 6–18 sessions of around an hour each with a gap of 1–3 weeks between sessions. This initial program might be followed by some booster sessions, for instance after one month and three months. CBT has also been found to be effective if patient and therapist type in real time to each other over computer links.
Cognitive-behavioral therapy is most closely allied with the scientist–practitioner model in which clinical practice and research are informed by a scientific perspective, clear operationalization of the problem, and an emphasis on measurement, including measuring changes in cognition and behavior and the attainment of goals. These are often met through "homework" assignments in which the patient and the therapist work together to craft an assignment to complete before the next session. The completion of these assignments – which can be as simple as a person with depression attending some kind of social event – indicates a dedication to treatment compliance and a desire to change. The therapists can then logically gauge the next step of treatment based on how thoroughly the patient completes the assignment. Effective cognitive behavioral therapy is dependent on a therapeutic alliance between the healthcare practitioner and the person seeking assistance. Unlike many other forms of psychotherapy, the patient is very involved in CBT. For example, an anxious patient may be asked to talk to a stranger as a homework assignment, but if that is too difficult, he or she can work out an easier assignment first. The therapist needs to be flexible and willing to listen to the patient rather than acting as an authority figure.
=== Computerized or Internet-delivered (CCBT) ===
Computerized cognitive behavioral therapy (CCBT) has been described by NICE as a "generic term for delivering CBT via an interactive computer interface delivered by a personal computer, internet, or interactive voice response system", instead of face-to-face with a human therapist. It is also known as internet-delivered cognitive behavioral therapy or ICBT. CCBT has potential to improve access to evidence-based therapies, and to overcome the prohibitive costs and lack of availability sometimes associated with retaining a human therapist. In this context, it is important not to confuse CBT with 'computer-based training', which nowadays is more commonly referred to as e-Learning.
Although improvements in both research quality and treatment adherence is required before advocating for the global dissemination of CCBT, it has been found in meta-studies to be cost-effective and often cheaper than usual care, including for anxiety and PTSD. Studies have shown that individuals with social anxiety and depression experienced improvement with online CBT-based methods. A study assessing an online version of CBT for people with mild-to-moderate PTSD found that the online approach was as effective as, and cheaper than, the same therapy given face-to-face. A review of current CCBT research in the treatment of OCD in children found this interface to hold great potential for future treatment of OCD in youths and adolescent populations. Additionally, most internet interventions for post-traumatic stress disorder use CCBT. CCBT is also predisposed to treating mood disorders amongst non-heterosexual populations, who may avoid face-to-face therapy from fear of stigma. However presently CCBT programs seldom cater to these populations.
In February 2006 NICE recommended that CCBT be made available for use within the NHS across England and Wales for patients presenting with mild-to-moderate depression, rather than immediately opting for antidepressant medication, and CCBT is made available by some health systems. The 2009 NICE guideline recognized that there are likely to be a number of computerized CBT products that are useful to patients, but removed endorsement of any specific product.
=== Smartphone app-delivered ===
Another new method of access is the use of mobile app or smartphone applications to deliver self-help or guided CBT. Technology companies are developing mobile-based artificial intelligence chatbot applications in delivering CBT as an early intervention to support mental health, to build psychological resilience, and to promote emotional well-being. Artificial intelligence (AI) text-based conversational application delivered securely and privately over smartphone devices have the ability to scale globally and offer contextual and always-available support. Active research is underway including real-world data studies that measure effectiveness and engagement of text-based smartphone chatbot apps for delivery of CBT using a text-based conversational interface. Recent market research and analysis of over 500 online mental healthcare solutions identified 3 key challenges in this market: quality of the content, guidance of the user and personalisation.
A study compared CBT alone with a mindfulness-based therapy combined with CBT, both delivered via an app. It found that mindfulness-based self-help reduced the severity of depression more than CBT self-help in the short-term. Overall, NHS costs for the mindfulness approach were £500 less per person than for CBT.
=== Reading self-help materials ===
Enabling patients to read self-help CBT guides has been shown to be effective by some studies. However one study found a negative effect in patients who tended to ruminate, and another meta-analysis found that the benefit was only significant when the self-help was guided (e.g. by a medical professional).
=== Group educational course ===
Patient participation in group courses has been shown to be effective. In a meta-analysis reviewing evidence-based treatment of OCD in children, individual CBT was found to be more efficacious than group CBT.
== Types ==
=== Brief cognitive behavioral therapy ===
Brief cognitive behavioral therapy (BCBT) is a form of CBT which has been developed for situations in which there are time constraints on the therapy sessions and specifically for those struggling with suicidal ideation and/or making suicide attempts. BCBT was based on Rudd's proposed "suicidal mode", an elaboration of Beck's modal theory. BCBT takes place over a couple of sessions that can last up to 12 accumulated hours by design. This technique was first implemented and developed with soldiers on active duty by Dr. M. David Rudd to prevent suicide.
Breakdown of treatment
Orientation
Commitment to treatment
Crisis response and safety planning
Means restriction
Survival kit
Reasons for living card
Model of suicidality
Treatment journal
Lessons learned
Skill focus
Skill development worksheets
Coping cards
Demonstration
Practice
Skill refinement
Relapse prevention
Skill generalization
Skill refinement
=== Cognitive emotional behavioral therapy ===
Cognitive emotional behavioral therapy (CEBT) is a form of CBT developed initially for individuals with eating disorders but now used with a range of problems including anxiety, depression, obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD) and anger problems. It combines aspects of CBT and dialectical behavioral therapy and aims to improve understanding and tolerance of emotions in order to facilitate the therapeutic process. It is frequently used as a "pretreatment" to prepare and better equip individuals for longer-term therapy.
=== Structured cognitive behavioral training ===
Structured cognitive-behavioral training (SCBT) is a cognitive-based process with core philosophies that draw heavily from CBT. Like CBT, SCBT asserts that behavior is inextricably related to beliefs, thoughts, and emotions. SCBT also builds on core CBT philosophy by incorporating other well-known modalities in the fields of behavioral health and psychology: most notably, Albert Ellis's rational emotive behavior therapy. SCBT differs from CBT in two distinct ways. First, SCBT is delivered in a highly regimented format. Second, SCBT is a predetermined and finite training process that becomes personalized by the input of the participant. SCBT is designed to bring a participant to a specific result in a specific period of time. SCBT has been used to challenge addictive behavior, particularly with substances such as tobacco, alcohol and food, and to manage diabetes and subdue stress and anxiety. SCBT has also been used in the field of criminal psychology in the effort to reduce recidivism.
=== Moral reconation therapy ===
Moral reconation therapy, a type of CBT used to help felons overcome antisocial personality disorder (ASPD), slightly decreases the risk of further offending. It is generally implemented in a group format because of the risk of offenders with ASPD being given one-on-one therapy reinforces narcissistic behavioral characteristics, and can be used in correctional or outpatient settings. Groups usually meet weekly for two to six months.
=== Stress inoculation training ===
This type of therapy uses a blend of cognitive, behavioral, and certain humanistic training techniques to target the stressors of the client. This is usually used to help clients better cope with their stress or anxiety after stressful events. This is a three-phase process that trains the client to use skills that they already have to better adapt to their current stressors. The first phase is an interview phase that includes psychological testing, client self-monitoring, and a variety of reading materials. This allows the therapist to individually tailor the training process to the client. Clients learn how to categorize problems into emotion-focused or problem-focused so that they can better treat their negative situations. This phase ultimately prepares the client to eventually confront and reflect upon their current reactions to stressors, before looking at ways to change their reactions and emotions to their stressors. The focus is conceptualization.
The second phase emphasizes the aspect of skills acquisition and rehearsal that continues from the earlier phase of conceptualization. The client is taught skills that help them cope with their stressors. These skills are then practiced in the space of therapy. These skills involve self-regulation, problem-solving, interpersonal communication skills, etc.
The third and final phase is the application and following through of the skills learned in the training process. This gives the client opportunities to apply their learned skills to a wide range of stressors. Activities include role-playing, imagery, modeling, etc. In the end, the client will have been trained on a preventive basis to inoculate personal, chronic, and future stressors by breaking down their stressors into problems they will address in long-term, short-term, and intermediate coping goals.
=== Activity-guided CBT: Group-knitting ===
A recently developed group therapy model, based on CBT, integrates knitting into the therapeutic process and has been proven to yield reliable and promising results. The foundation for this novel approach to CBT is the frequently emphasized notion that therapy success depends on how embedded the therapy method is in the patients' natural routine. Similar to standard group-based CBT, patients meet once a week in a group of 10 to 15 patients and knit together under the instruction of a trained psychologist or mental health professional. Central for the therapy is the patient's imaginative ability to assign each part of the wool to a certain thought. During the therapy, the wool is carefully knitted, creating a knitted piece of any form. This therapeutic process teaches the patient to meaningfully align thought, by (physically) creating a coherent knitted piece. Moreover, since CBT emphasizes the behavior as a result of cognition, the knitting illustrates how thoughts (which are tried to be imaginary tight to the wool) materialize into the reality surrounding us.
=== Mindfulness-based cognitive behavioral hypnotherapy ===
Mindfulness-based cognitive behavioral hypnotherapy (MCBH) is a form of CBT that focuses on awareness in a reflective approach, addressing subconscious tendencies. It is more the process that contains three phases for achieving wanted goals and integrates the principles of mindfulness and cognitive-behavioral techniques with the transformative potential of hypnotherapy.
=== Unified Protocol ===
The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) is a form of CBT, developed by David H. Barlow and researchers at Boston University, that can be applied to a range of anxiety disorders. The rationale is that anxiety and depression disorders often occur together due to common underlying causes and can efficiently be treated together.
The UP includes a common set of components:
Psycho-education
Cognitive reappraisal
Emotion regulation
Changing behaviour
The UP has been shown to produce equivalent results to single-diagnosis protocols for specific disorders, such as OCD and social anxiety disorder.
Several studies have shown that the UP is easier to disseminate as compared to single-diagnosis protocols.
Culturally adapted CBT
The study of psychotherapy across races, religions, and cultures, or "ethno-psycho-therapy", is a relatively new discipline
== Criticisms ==
=== Relative effectiveness ===
The research conducted for CBT has been a topic of sustained controversy. While some researchers write that CBT is more effective than other treatments, many other researchers and practitioners have questioned the validity of such claims. For example, one study determined CBT to be superior to other treatments in treating anxiety and depression. However, researchers responding directly to that study conducted a re-analysis and found no evidence of CBT being superior to other bona fide treatments and conducted an analysis of thirteen other CBT clinical trials and determined that they failed to provide evidence of CBT superiority. In cases where CBT has been reported to be statistically better than other psychological interventions in terms of primary outcome measures, effect sizes were small and suggested that those differences were clinically meaningless and insignificant. Moreover, on secondary outcomes (i.e., measures of general functioning) no significant differences have been typically found between CBT and other treatments.
A major criticism has been that clinical studies of CBT efficacy (or any psychotherapy) are not double-blind (i.e., either the subjects or the therapists in psychotherapy studies are not blind to the type of treatment). They may be single-blinded, i.e. the rater may not know the treatment the patient received, but neither the patients nor the therapists are blinded to the type of therapy given (two out of three of the persons involved in the trial, i.e., all of the persons involved in the treatment, are unblinded). The patient is an active participant in correcting negative distorted thoughts, thus quite aware of the treatment group they are in.
The importance of double-blinding was shown in a meta-analysis that examined the effectiveness of CBT when placebo control and blindness were factored in. Pooled data from published trials of CBT in schizophrenia, major depressive disorder (MDD), and bipolar disorder that used controls for non-specific effects of intervention were analyzed. This study concluded that CBT is no better than non-specific control interventions in the treatment of schizophrenia and does not reduce relapse rates; treatment effects are small in treatment studies of MDD, and it is not an effective treatment strategy for prevention of relapse in bipolar disorder. For MDD, the authors note that the pooled effect size was very low.
=== Declining effectiveness ===
Additionally, a 2015 meta-analysis revealed that the positive effects of CBT on depression have been declining since 1977. The overall results showed two different declines in effect sizes: 1) an overall decline between 1977 and 2014, and 2) a steeper decline between 1995 and 2014. Additional sub-analysis revealed that CBT studies where therapists in the test group were instructed to adhere to the Beck CBT manual had a steeper decline in effect sizes since 1977 than studies where therapists in the test group were instructed to use CBT without a manual. The authors reported that they were unsure why the effects were declining but did list inadequate therapist training, failure to adhere to a manual, lack of therapist experience, and patients' hope and faith in its efficacy waning as potential reasons. The authors did mention that the current study was limited to depressive disorders only.
=== High drop-out rates ===
Furthermore, other researchers write that CBT studies have high drop-out rates compared to other treatments. One meta-analysis found that CBT drop-out rates were 17% higher than those of other therapies. This high drop-out rate is also evident in the treatment of several disorders, particularly the eating disorder anorexia nervosa, which is commonly treated with CBT. Those treated with CBT have a high chance of dropping out of therapy before completion and reverting to their anorexia behaviors.
Other researchers analyzing treatments for youths who self-injure found similar drop-out rates in CBT and DBT groups. In this study, the researchers analyzed several clinical trials that measured the efficacy of CBT administered to youths who self-injure. The researchers concluded that none of them were found to be efficacious.
=== Philosophical concerns with CBT methods ===
The methods employed in CBT research have not been the only criticisms; some individuals have called its theory and therapy into question.
Slife and Williams write that one of the hidden assumptions in CBT is that of determinism, or the absence of free will. They argue that CBT holds that external stimuli from the environment enter the mind, causing different thoughts that cause emotional states: nowhere in CBT theory is agency, or free will, accounted for.
Another criticism of CBT theory, especially as applied to major depressive disorder (MDD), is that it confounds the symptoms of the disorder with its causes.
=== Side effects ===
CBT is generally regarded as having very few if any side effects. Calls have been made by some for more appraisal of possible side effects of CBT. Many randomized trials of psychological interventions like CBT do not monitor potential harms to the patient. In contrast, randomized trials of pharmacological interventions are much more likely to take adverse effects into consideration.
A 2017 meta-analysis revealed that adverse events are not common in children receiving CBT and, furthermore, that CBT is associated with fewer dropouts than either placebo or medications. Nevertheless, CBT therapists do sometimes report 'unwanted events' and side effects in their outpatients with "negative wellbeing/distress" being the most frequent.
=== Socio-political concerns ===
The writer and group analyst Farhad Dalal questions the socio-political assumptions behind the introduction of CBT. According to one reviewer, Dalal connects the rise of CBT with "the parallel rise of neoliberalism, with its focus on marketization, efficiency, quantification and managerialism", and he questions the scientific basis of CBT, suggesting that "the 'science' of psychological treatment is often less a scientific than a political contest". In his book, Dalal also questions the ethical basis of CBT.
== Society and culture ==
The UK's National Health Service announced in 2008 that more therapists would be trained to provide CBT at government expense as part of an initiative called Improving Access to Psychological Therapies (IAPT). The NICE said that CBT would become the mainstay of treatment for non-severe depression, with medication used only in cases where CBT had failed. Therapists complained that the data does not fully support the attention and funding CBT receives. Psychotherapist and professor Andrew Samuels stated that this constitutes "a coup, a power play by a community that has suddenly found itself on the brink of corralling an enormous amount of money ... Everyone has been seduced by CBT's apparent cheapness."
The UK Council for Psychotherapy issued a press release in 2012 saying that the IAPT's policies were undermining traditional psychotherapy and criticized proposals that would limit some approved therapies to CBT, claiming that they restricted patients to "a watered-down version of cognitive behavioural therapy (CBT), often delivered by very lightly trained staff".
== References ==
== Further reading ==
== External links ==
Association for Behavioral and Cognitive Therapies (ABCT)
British Association for Behavioural and Cognitive Psychotherapies
National Association of Cognitive-Behavioral Therapists
International Association of Cognitive Psychotherapy
Information on Research-based CBT Treatments | Wikipedia/Cognitive_behaviour_therapy |
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, terminal neurodegenerative disorder that results in the progressive loss of both upper and lower motor neurons that normally control voluntary muscle contraction. ALS is the most common form of the motor neuron diseases. ALS often presents in its early stages with gradual muscle stiffness, twitches, weakness, and wasting. Motor neuron loss typically continues until the abilities to eat, speak, move, and, lastly, breathe are all lost. While only 15% of people with ALS also fully develop frontotemporal dementia, an estimated 50% face at least some minor difficulties with thinking and behavior. Depending on which of the aforementioned symptoms develops first, ALS is classified as limb-onset (begins with weakness in the arms or legs) or bulbar-onset (begins with difficulty in speaking or swallowing).
Most cases of ALS (about 90–95%) have no known cause, and are known as sporadic ALS. However, both genetic and environmental factors are believed to be involved. The remaining 5–10% of cases have a genetic cause, often linked to a family history of the disease, and these are known as familial ALS (hereditary). About half of these genetic cases are due to disease-causing variants in one of four specific genes. The diagnosis is based on a person's signs and symptoms, with testing conducted to rule out other potential causes.
There is no known cure for ALS. The goal of treatment is to slow the disease progression, and improve symptoms. FDA-approved treatments that slow the progression of ALS include riluzole and edaravone. Non-invasive ventilation may result in both improved quality and length of life. Mechanical ventilation can prolong survival but does not stop disease progression. A feeding tube may help maintain weight and nutrition. Death is usually caused by respiratory failure. The disease can affect people of any age, but usually starts around the age of 60. The average survival from onset to death is two to four years, though this can vary, and about 10% of those affected survive longer than ten years.
Descriptions of the disease date back to at least 1824 by Charles Bell. In 1869, the connection between the symptoms and the underlying neurological problems was first described by French neurologist Jean-Martin Charcot, who in 1874 began using the term amyotrophic lateral sclerosis.
== Classification ==
ALS is a motor neuron disease, which is a group of neurological disorders that selectively affect motor neurons, the cells that control voluntary muscles of the body. Other motor neuron diseases include primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), progressive bulbar palsy, pseudobulbar palsy, and monomelic amyotrophy (MMA).
As a disease, ALS itself can be classified in a few different ways: by which part of the motor neurons are affected; by the parts of the body first affected; whether it is genetic; and by the age at which it started. Each individual diagnosed with the condition will sit at a unique place at the intersection of these complex and overlapping subtypes, which presents a challenge to diagnosis, understanding, and prognosis.
=== Subtypes of motor neuron disease ===
ALS can be classified by the types of motor neurons that are affected. To successfully control any voluntary muscle in the body, a signal must be sent from the motor cortex in the brain down the upper motor neuron as it travels down the spinal cord. There, it connects via a synapse to the lower motor neuron which connects to the muscle itself. Damage to either the upper or lower motor neuron, as it makes its way from the brain to muscle, causes different types of symptoms. Damage to the upper motor neuron typically causes spasticity including stiffness and increased tendon reflexes or clonus, while damage to the lower motor neuron typically causes weakness, muscle atrophy, and fasciculations.
Classical, or classic ALS, involves degeneration to both the upper motor neurons in the brain and the lower motor neurons in the spinal cord. Primary lateral sclerosis (PLS) involves degeneration of only the upper motor neurons, and progressive muscular atrophy (PMA) involves only the lower motor neurons. There is debate over whether PLS and PMA are separate diseases or simply variants of ALS.
Classical ALS accounts for about 70% of all cases of ALS and can be subdivided into where symptoms first appear as these are usually focused to one region of the body at initial presentation before later spread. Limb-onset ALS (also known as spinal-onset) and bulbar-onset ALS. Limb-onset ALS begins with weakness in the hands, arms, feet, and/or legs and accounts for about two-thirds of all classical ALS cases. Bulbar-onset ALS begins with weakness in the muscles of speech, chewing, and swallowing and accounts for about 25% of classical ALS cases. A rarer type of classical ALS affecting around 3% of patients is respiratory-onset, in which the initial symptoms are difficulty breathing (dyspnea) upon exertion, at rest, or while lying flat (orthopnea).
Primary lateral sclerosis (PLS) is a subtype of the overall ALS category which accounts for about 5% of all cases and only affects the upper motor neurons in the arms, legs, and bulbar region. However, more than 75% of people with apparent PLS go on to later develop lower motor neuron signs within four years of symptom onset, meaning that a definitive diagnosis of PLS cannot be made until several years have passed. PLS has a better prognosis than classical ALS, as it progresses slower, results in less functional decline, does not affect the ability to breathe, and causes less severe weight loss than classical ALS.
Progressive muscular atrophy (PMA) is another subtype that accounts for about 5% of the overall ALS category and affects lower motor neurons in the arms, legs, and bulbar region. While PMA is associated with longer survival on average than classical ALS, it is still progressive over time, eventually leading to respiratory failure and death. As with PLS developing into classical ALS, PMA can also develop into classical ALS over time if the lower motor neuron involvement progresses to include upper motor neurons, in which case the diagnosis might be changed to classic ALS.
=== Rare isolated variants of ALS ===
Isolated variants of ALS have symptoms that are limited to a single region for at least a year; they progress more slowly than classical ALS and are associated with longer survival. These regional variants of ALS can only be considered as a diagnosis should the initial symptoms fail to spread to other spinal cord regions for an extended period of time (at least 12 months). Flail arm syndrome is characterized by lower motor neuron damage affecting the arm muscles, typically starting with the upper arms symmetrically and progressing downwards to the hands. Flail leg syndrome is characterized by lower motor neuron damage leading to asymmetrical weakness and wasting in the legs starting around the feet. Isolated bulbar palsy is characterized by upper or lower motor neuron damage in the bulbar region (in the absence of limb symptoms for at least 20 months), leading to gradual onset of difficulty with speech (dysarthria) and swallowing (dysphagia).
=== Age of onset ===
ALS can also be classified based on the age of onset. People with familial ALS have an age of onset about 5 years younger than those with apparently sporadic ALS. About 10% of all cases of ALS begin before age 45 ("young-onset" ALS), and about 1% of all cases begin before age 25 ("juvenile" ALS). People who develop young-onset ALS are more likely to be male, less likely to have bulbar onset of symptoms, and more likely to have a slower progression of the disease. Juvenile ALS is more likely to be genetic in origin than adult-onset ALS; the most common genes associated with juvenile ALS are FUS, ALS2, and SETX. Although most people with juvenile ALS live longer than those with adult-onset ALS, some of them have specific mutations in FUS and SOD1 that are associated with a poor prognosis. Late onset (after age 65) is generally associated with a more rapid functional decline and shorter survival.
== Signs and symptoms ==
The disorder causes muscle weakness, atrophy, and muscle spasms throughout the body due to the degeneration of the upper motor and lower motor neurons. Sensory nerves and the autonomic nervous system are generally unaffected, meaning the majority of people with ALS maintain hearing, sight, touch, smell, and taste.
=== Initial symptoms ===
The start of ALS may be so subtle that the symptoms are overlooked. The earliest symptoms of ALS are muscle weakness or muscle atrophy, typically on one side of the body. Other presenting symptoms include trouble swallowing or breathing, cramping, or stiffness of affected muscles; muscle weakness affecting an arm or a leg; or slurred and nasal speech. The parts of the body affected by early symptoms of ALS depend on which motor neurons in the body are damaged first.
In limb-onset ALS, the first symptoms are in the arms or the legs. If the legs are affected first, people may experience awkwardness, tripping, or stumbling when walking or running; this is often marked by walking with a "dropped foot" that drags gently on the ground. If the arms are affected first, they may experience difficulty with tasks requiring manual dexterity, such as buttoning a shirt, writing, or turning a key in a lock.
In bulbar-onset ALS, the first symptoms are difficulty speaking or swallowing. Speech may become slurred, nasal in character, or quieter. There may be difficulty with swallowing and loss of tongue mobility. A smaller proportion of people experience "respiratory-onset" ALS, where the intercostal muscles that support breathing are affected first.
Over time, people experience increasing difficulty moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Symptoms of upper motor neuron involvement include tight and stiff muscles (spasticity) and exaggerated reflexes (hyperreflexia), including an overactive gag reflex. While the disease does not cause pain directly, pain is a symptom experienced by most people with ALS caused by reduced mobility. Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under the skin (fasciculations).
=== Progression ===
Although the initial site of symptoms and subsequent rate of disability progression vary from person to person, the initially affected body region is usually the most affected over time, and symptoms usually spread to a neighbouring body region. For example, symptoms starting in one arm usually spread next to either the opposite arm or to the leg on the same side. Bulbar-onset patients most typically get their next symptoms in their arms rather than legs, arm-onset patients typically spread to the legs before the bulbar region, and leg-onset patients typically spread to the arms rather than the bulbar region. Over time, regardless of where symptoms began, most people eventually lose the ability to walk or use their hands and arms independently. Less consistently, they may lose the ability to speak and to swallow food. It is the eventual development of weakness of the respiratory muscles, with the loss of ability to cough and to breathe without support, that is ultimately life-shortening in ALS.
The rate of progression can be measured using the ALS Functional Rating Scale - Revised (ALSFRS-R), a 12-item instrument survey administered as a clinical interview or self-reported questionnaire that produces a score between 48 (normal function) and 0 (severe disability). The ALSFRS-R is the most frequently used outcome measure in clinical trials and is used by doctors to track disease progression. Though the degree of variability is high and a small percentage of people have a much slower progression, on average people with ALS lose about 1 ALSFRS-R point per month. Brief periods of stabilization ("plateaus") and even small reversals in ALSFRS-R score are not uncommon, due to the fact the tool is subjective, can be affected by medication, and different forms of compensation for changes in function. However, it is rare (<1%) for these improvements to be large (i.e. greater than 4 ALSFRS-R points) or sustained (i.e. greater than 12 months). A survey-based study among clinicians showed that they rated a 20% change in the slope of the ALSFRS-R as being clinically meaningful, which is the most common threshold used to determine whether a new treatment is working in clinical trials.
=== Late-stage disease management ===
Difficulties with chewing and swallowing make eating very difficult (dysphagia) and increase the risk of choking or of aspirating food into the lungs. In later stages of the disorder, aspiration pneumonia can develop, and maintaining a healthy weight can become a significant problem that may require the insertion of a feeding tube. As the diaphragm and intercostal muscles of the rib cage that support breathing weaken, measures of lung function such as vital capacity and inspiratory pressure diminish. In respiratory-onset ALS, this may occur before significant limb weakness is apparent. Individuals affected by the disorder may ultimately lose the ability to initiate and control all voluntary movement, known as locked-in syndrome. Bladder and bowel function are usually spared, meaning urinary and fecal incontinence are uncommon, although trouble getting to a toilet can lead to difficulties. The extraocular muscles responsible for eye movement are usually spared, meaning the use of eye tracking technology to support augmentative communication is often feasible, albeit slow, and needs may change over time. Despite these challenges, many people in an advanced state of disease report satisfactory wellbeing and quality of life.
=== Prognosis, staging, and survival ===
Although respiratory support using non-invasive ventilation can ease problems with breathing and prolong survival, it does not affect the progression rate of ALS. Most people with ALS die between two and four years after the diagnosis. Around 50% of people with ALS die within 30 months of their symptoms beginning, about 20% live between five and ten years, and about 10% survive for 10 years or longer.
The most common cause of death among people with ALS is respiratory failure, often accelerated by pneumonia. Most ALS patients die at home after a period of worsening difficulty breathing, a decline in their nutritional status, or a rapid worsening of symptoms. Sudden death or acute respiratory distress are uncommon. Access to palliative care is recommended from an early stage to explore options, ensure psychosocial support for the patient and caregivers, and to discuss advance healthcare directives.
As with cancer staging, ALS has staging systems numbered between 1 and 4 that are used for research purposes in clinical trials. Two very similar staging systems emerged around a similar time, the King's staging system and Milano-Torino (MiToS) functional staging.
Providing individual patients with a precise prognosis is not currently possible, though research is underway to provide statistical models on the basis of prognostic factors including age at onset, progression rate, site of onset, and presence of frontotemporal dementia. Those with a bulbar onset have a worse prognosis than limb-onset ALS; a population-based study found that bulbar-onset ALS patients had a median survival of 2.0 years and a 10-year survival rate of 3%, while limb-onset ALS patients had a median survival of 2.6 years and a 10-year survival rate of 13%. Those with respiratory-onset ALS had a shorter median survival of 1.4 years and 0% survival at 10 years. While astrophysicist Stephen Hawking lived for 55 more years following his diagnosis, his was an unusual case.
=== Cognitive, emotional, and behavioral symptoms ===
Cognitive impairment or behavioral dysfunction is present in 30–50% of individuals with ALS, and can appear more frequently in later stages of the disease. Language dysfunction, executive dysfunction, and troubles with social cognition and verbal memory are the most commonly reported cognitive symptoms in ALS. Cognitive impairment is found more frequently in patients with C9orf72 gene repeat expansions, bulbar onset, bulbar symptoms, family history of ALS, and/or a predominantly upper motor neuron phenotype.
Emotional lability is a symptom in which patients cry, smile, yawn, or laugh, either in the absence of emotional stimuli, or when they are feeling the opposite emotion to that being expressed; it is experienced by about half of ALS patients and is more common in those with bulbar-onset ALS. While relatively benign relative to other symptoms, it can cause increased stigma and social isolation as people around the patient struggle to react appropriately to what can be frequent and inappropriate outbursts in public.
In addition to mild changes in cognition that may only emerge during neuropsychological testing, around 10–15% of individuals have signs of frontotemporal dementia (FTD). Repeating phrases or gestures, apathy, and loss of inhibition are the most frequently reported behavioral features of ALS. ALS and FTD are now considered to be part of a common disease spectrum (ALS–FTD) because of genetic, clinical, and pathological similarities. Genetically, repeat expansions in the C9orf72 gene account for about 40% of genetic ALS and 25% of genetic FTD.
Cognitive and behavioral issues are associated with a poorer prognosis as they may reduce adherence to medical advice, and deficits in empathy and social cognition which may increase caregiver burden.
== Cause ==
It is not known what causes sporadic ALS, hence it is described as an idiopathic disease. Though its exact cause is unknown, genetic and environmental factors are thought to be of roughly equal importance. The genetic factors are better understood than the environmental factors; no specific environmental factor has been definitively shown to cause ALS. A multi-step liability threshold model for ALS proposes that cellular damage accumulates over time due to genetic factors present at birth and exposure to environmental risks throughout life. ALS can strike at any age, but its likelihood increases with age. Most people who develop ALS are between the ages of 40 and 70, with an average age of 55 at the time of diagnosis. ALS is 20% more common in men than women, but this difference in sex distribution is no longer present in patients with onset after age 70.
=== Genetics and genetic testing ===
While they appear identical clinically and pathologically, ALS can be classified as being either familial or sporadic, depending on whether there is a known family history of the disease and/or whether an ALS-associated genetic mutation has been identified via genetic testing. Familial ALS is thought to account for 10–15% of cases overall and can include monogenic, oligogenic, and polygenic modes of inheritance.
There is considerable variation among clinicians on how to approach genetic testing in ALS, and only about half discuss the possibility of genetic inheritance with their patients, particularly if there is no discernible family history of the disease. In the past, genetic counseling and testing was only offered to those with obviously familial ALS. But it is increasingly recognized that cases of sporadic ALS may also be due to disease-causing de novo mutations in SOD1, or C9orf72, an incomplete family history, or incomplete penetrance, meaning that a patient's ancestors carried the gene but did not express the disease in their lifetimes. The lack of positive family history may be caused by lack of historical records, having a smaller family, older generations dying earlier of causes other than ALS, genetic non-paternity, and uncertainty over whether certain neuropsychiatric conditions (e.g. frontotemporal dementia, other forms of dementia, suicide, psychosis, schizophrenia) should be considered significant when determining a family history. There have been calls in the research community to routinely counsel and test all diagnosed ALS patients for familial ALS, particularly as there is now a licensed gene therapy (tofersen) specifically targeted to carriers of SOD-1 ALS. A shortage of genetic counselors and limited clinical capacity to see such at-risk individuals makes this challenging in practice, as does the unequal access to genetic testing around the world.
More than 40 genes have been associated with ALS, of which four account for nearly half of familial cases, and around 5% of sporadic cases: C9orf72 (40% of familial cases, 7% sporadic), SOD1 (12% of familial cases, 1–2% sporadic), FUS (4% of familial cases, 1% sporadic), and TARDBP (4% of familial cases, 1% sporadic), with the remaining genes mostly accounting for fewer than 1% of either familial or sporadic cases. ALS genes identified to date explain the cause of about 70% of familial ALS and about 15% of sporadic ALS. Overall, first-degree relatives of an individual with ALS have a ~1% risk of developing ALS themselves.
=== Environmental and other factors ===
The multi-step hypothesis suggests the disease is caused by some interaction between an individual's genetic risk factors and their cumulative lifetime of exposures to environmental factors, termed their exposome. The most consistent lifetime exposures associated with developing ALS (other than genetic mutations) include heavy metals (e.g. lead and mercury), chemicals (e.g. pesticides and solvents), electric shock, physical injury (including head injury), and smoking (in men more than women). Overall these effects are small, with each exposure in isolation only increasing the likelihood of a very rare condition by a small amount. For instance, an individual's lifetime risk of developing ALS might go from "1 in 400" without exposure to between "1 in 300" and "1 in 200" if they were exposed to heavy metals. Some industries are heavily dependent upon the use or exposure to these environmental factors, increasing employees' susceptibility. Agricultural tasks can be intertwined with as many as 5 such risk factors excluding workers' smoking preferences.
A range of other factors have weaker evidence supporting them and include participation in professional sports, having a lower body mass index, lower educational attainment, manual occupations, military service, exposure to Beta-N-methylamino-L-alanin (BMAA), and viral infections.
Although some personality traits, such as openness, agreeableness and conscientiousness appear remarkably common among patients with ALS, it remains open whether personality can increase susceptibility to ALS directly. Instead, genetic factors giving rise to personality might simultaneously predispose people to develop ALS, or the above personality traits might underlie lifestyle choices which are in turn risk factors for ALS.
== Pathophysiology ==
=== Neuropathology ===
Upon examination at autopsy, features of the disease that can be seen with the naked eye include skeletal muscle atrophy, motor cortex atrophy, sclerosis of the corticospinal and corticobulbar tracts, thinning of the hypoglossal nerves (which control the tongue), and thinning of the anterior roots of the spinal cord.
The defining feature of ALS is the death of both upper motor neurons (located in the motor cortex of the brain) and lower motor neurons (located in the brainstem and spinal cord). In ALS with frontotemporal dementia, neurons throughout the frontal and temporal lobes of the brain die as well. The pathological hallmark of ALS is the presence of inclusion bodies (abnormal aggregations of protein) known as Bunina bodies in the cytoplasm of motor neurons. In about 97% of people with ALS, the main component of the inclusion bodies is TDP-43 protein; however, in those with SOD1 or FUS mutations, the main component of the inclusion bodies is SOD1 protein or FUS protein, respectively. Prion-like propagation of misfolded proteins from cell to cell may explain why ALS starts in one area and spreads to others. The glymphatic system may also be involved in the pathogenesis of ALS.
=== Biochemistry ===
It is still not fully understood why neurons die in ALS, but this neurodegeneration is thought to involve many different cellular and molecular processes. The genes known to be involved in ALS can be grouped into three general categories based on their normal function: protein degradation, the cytoskeleton, and RNA processing. Mutant SOD1 protein forms intracellular aggregations that inhibit protein degradation. Cytoplasmic aggregations of wild-type (normal) SOD1 protein are common in sporadic ALS. It is thought that misfolded mutant SOD1 can cause misfolding and aggregation of wild-type SOD1 in neighboring neurons in a prion-like manner. Other protein degradation genes that can cause ALS when mutated include VCP, OPTN, TBK1, and SQSTM1. Three genes implicated in ALS that are important for maintaining the cytoskeleton and for axonal transport include DCTN1, PFN1, and TUBA4A.
Several ALS genes encode RNA-binding proteins. The first to be discovered was TDP-43 protein, a nuclear protein that aggregates in the cytoplasm of motor neurons in almost all cases of ALS; however, mutations in TARDBP, the gene that codes for TDP-43, are a rare cause of ALS. FUS codes for FUS, another RNA-binding protein with a similar function to TDP-43, which can cause ALS when mutated. It is thought that mutations in TARDBP and FUS increase the binding affinity of the low-complexity domain, causing their respective proteins to aggregate in the cytoplasm. Once these mutant RNA-binding proteins are misfolded and aggregated, they may be able to misfold normal proteins both within and between cells in a prion-like manner. This also leads to decreased levels of RNA-binding protein in the nucleus, which may mean that their target RNA transcripts do not undergo normal processing. Other RNA metabolism genes associated with ALS include ANG, SETX, and MATR3.
C9orf72 is the most commonly mutated gene in ALS and causes motor neuron death through a number of mechanisms. The pathogenic mutation is a hexanucleotide repeat expansion (a series of six nucleotides repeated over and over); people with up to 30 repeats are considered normal, while people with hundreds or thousands of repeats can have familial ALS, frontotemporal dementia, or sometimes sporadic ALS. The three mechanisms of disease associated with these C9orf72 repeats are deposition of RNA transcripts in the nucleus, translation of the RNA into toxic dipeptide repeat proteins in the cytoplasm, and decreased levels of the normal C9orf72 protein. Mitochondrial bioenergetic dysfunction leading to dysfunctional motor neuron axonal homeostasis (reduced axonal length and fast axonal transport of mitochondrial cargo) has been shown to occur in C9orf72-ALS using human induced pluripotent stem cell (iPSC) technologies coupled with CRISPR/Cas9 gene-editing, and human post-mortem spinal cord tissue examination.
Excitotoxicity, or nerve cell death caused by high levels of intracellular calcium due to excessive stimulation by the excitatory neurotransmitter glutamate, is a mechanism thought to be common to all forms of ALS. Motor neurons are more sensitive to excitotoxicity than other types of neurons because they have a lower calcium-buffering capacity and a type of glutamate receptor (the AMPA receptor) that is more permeable to calcium. In ALS, there are decreased levels of excitatory amino acid transporter 2 (EAAT2), which is the main transporter that removes glutamate from the synapse; this leads to increased synaptic glutamate levels and excitotoxicity. Riluzole, a drug that modestly prolongs survival in ALS, inhibits glutamate release from pre-synaptic neurons; however, it is unclear if this mechanism is responsible for its therapeutic effect.
== Diagnosis ==
No single test can provide a definite diagnosis of ALS. Instead, the diagnosis of ALS is primarily made based on a physician's clinical assessment after ruling out other diseases. Physicians often obtain the person's full medical history and conduct neurologic examinations at regular intervals to assess whether signs and symptoms such as muscle weakness, muscle atrophy, hyperreflexia, Babinski's sign, and spasticity are worsening. Many biomarkers are being studied for the condition, but as of 2023 are not in general medical use.
=== Differential diagnosis ===
Because symptoms of ALS can be similar to those of a wide variety of other, more treatable diseases or disorders, appropriate tests must be conducted to exclude the possibility of other conditions. One of these tests is electromyography (EMG), a special recording technique that detects electrical activity in muscles. Certain EMG findings can support the diagnosis of ALS. Another common test measures nerve conduction velocity (NCV). Specific abnormalities in the NCV results may suggest, for example, that the person has a form of peripheral neuropathy (damage to peripheral nerves) or myopathy (muscle disease) rather than ALS. While a magnetic resonance imaging (MRI) is often normal in people with early-stage ALS, it can reveal evidence of other problems that may be causing the symptoms, such as a spinal cord tumor, multiple sclerosis, a herniated disc in the neck, syringomyelia, or cervical spondylosis.
Based on the person's symptoms and findings from the examination and from these tests, the physician may order tests on blood and urine samples to eliminate the possibility of other diseases, as well as routine laboratory tests. In some cases, for example, if a physician suspects the person may have a myopathy rather than ALS, a muscle biopsy may be performed.
A number of infectious diseases can sometimes cause ALS-like symptoms, including human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), Lyme disease, and syphilis. Neurological disorders such as multiple sclerosis, post-polio syndrome, multifocal motor neuropathy, CIDP, spinal muscular atrophy, and spinal and bulbar muscular atrophy can also mimic certain aspects of the disease and should be considered.
ALS must be differentiated from the "ALS mimic syndromes", which are unrelated disorders that may have a similar presentation and clinical features to ALS or its variants. Because the prognosis of ALS and closely related subtypes of motor neuron disease are generally poor, neurologists may carry out investigations to evaluate and exclude other diagnostic possibilities. Disorders of the neuromuscular junction, such as myasthenia gravis (MG) and Lambert–Eaton myasthenic syndrome, may also mimic ALS, although this rarely presents diagnostic difficulty over time. Benign fasciculation syndrome and cramp fasciculation syndrome may also, occasionally, mimic some of the early symptoms of ALS. Nonetheless, the absence of other neurological features that develop inexorably with ALS means that, over time, the distinction will not present any difficulty to the experienced neurologist; where doubt remains, EMG may be helpful.
== Management ==
There is no cure for ALS. Management focuses on treating symptoms and providing supportive care, to improve quality of life and prolong survival. This care is best provided by multidisciplinary teams of healthcare professionals; attending a multidisciplinary ALS clinic is associated with longer survival, fewer hospitalizations, and improved quality of life.
Non-invasive ventilation (NIV) is the main treatment for respiratory failure in ALS. In people with normal bulbar function, it prolongs survival by about seven months and improves the quality of life. One study found that NIV is ineffective for people with poor bulbar function while another suggested that it may provide a modest survival benefit. Many people with ALS have difficulty tolerating NIV. Invasive ventilation is an option for people with advanced ALS when NIV is not enough to manage their symptoms. While invasive ventilation prolongs survival, disease progression, and functional decline continue. It may decrease the quality of life of people with ALS or their caregivers. Invasive ventilation is more commonly used in Japan than in North America or Europe.
Physical therapy can promote functional independence through aerobic, range of motion, and stretching exercises. Occupational therapy can assist with activities of daily living through adaptive equipment. Speech therapy can assist people with ALS who have difficulty speaking. Preventing weight loss and malnutrition in people with ALS improves both survival and quality of life. Initially, difficulty swallowing (dysphagia) can be managed by dietary changes and swallowing techniques. A feeding tube should be considered if someone with ALS loses 5% or more of their body weight or if they cannot safely swallow food and water. The feeding tube is usually inserted by percutaneous endoscopic gastrostomy (PEG). There is weak evidence that PEG tubes improve survival. PEG insertion is usually performed with the intent of improving quality of life.
Palliative care should begin shortly after someone is diagnosed with ALS. Discussion of end-of-life issues gives people with ALS time to reflect on their preferences for end-of-life care and can help avoid unwanted interventions or procedures. Hospice care can improve symptom management at the end of life and increase the likelihood of a peaceful death. In the final days of life, opioids can be used to treat pain and dyspnea, while benzodiazepines can be used to treat anxiety.
=== Medications ===
==== Disease-slowing treatments ====
Riluzole has been found to modestly prolong survival by about 2–3 months. It may have a greater survival benefit for those with bulbar-onset ALS. It may work by decreasing release of the excitatory neurotransmitter glutamate from pre-synaptic neurons. The most common side effects are nausea and a lack of energy (asthenia). People with ALS should begin treatment with riluzole as soon as possible following their diagnosis. Riluzole is available as a tablet, liquid, or dissolvable oral film.
Edaravone has been shown to modestly slow the decline in function in a small group of people with early-stage ALS. It may work by protecting motor neurons from oxidative stress. The most common side effects are bruising and gait disturbance. Edaravone is available as an intravenous infusion or as an oral suspension.
AMX0035 (Relyvrio) is a combination of sodium phenylbutyrate and taurursodiol, which was initially shown to prolong the survival of patients by an average of six months. Relyvrio was withdrawn by the manufacturer in April 2024 following the completion of the Phase 3 PHOENIX trial which did not show substantial benefit to ALS patients.
Tofersen (Qalsody) is an antisense oligonucleotide that was approved for medical use in the United States in April 2023, for the treatment of SOD1-associated ALS. In a study of 108 patients with SOD1-associated ALS there was a non-significant trend towards a slowing of progression, as well as a significant reduction in neurofilament light chain, a putative ALS biomarker thought to indicate neuronal damage. A follow-up study and open-label extension suggested that earlier treatment initiation had a beneficial effect on slowing disease progression. Tofersen is available as an intrathecal injection into the lumbar cistern at the base of the spine.
A 2025 phase II study published found that tetramethylpyrazine nitrone is safe for patients with ALS, but it did not show a significant advantage over placebo in the primary efficacy measure. Researchers noted that the drug may help slow the decline in grip strength, however further clinical trials are necessary to confirm its potential benefits.
==== Symptomatic treatments ====
Other medications may be used to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and phlegm. Gabapentin, pregabalin, and tricyclic antidepressants (e.g., amitriptyline) can be used for neuropathic pain, while nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and opioids can be used for nociceptive pain.
Depression can be treated with selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants, while benzodiazepines can be used for anxiety. There are no medications to treat cognitive impairment/frontotemporal dementia (FTD); however, SSRIs and antipsychotics can help treat some of the symptoms of FTD. Baclofen and tizanidine are the most commonly used oral drugs for treating spasticity; an intrathecal baclofen pump can be used for severe spasticity. Atropine, scopolamine, amitriptyline, or glycopyrrolate may be prescribed when people with ALS begin having trouble swallowing their saliva (sialorrhea).
A 2017 review concluded that mexiletine is safe and effective for treating cramps in ALS based on a randomized controlled trial from 2016.
=== Breathing support ===
==== Non-invasive ventilation ====
Non-invasive ventilation (NIV) is the primary treatment for respiratory failure in ALS and was the first treatment shown to improve both survival and quality of life. NIV uses a face or nasal mask connected to a ventilator that provides intermittent positive pressure to support breathing. Continuous positive pressure is not recommended for people with ALS because it makes breathing more difficult. Initially, NIV is used only at night because the first sign of respiratory failure is decreased gas exchange (hypoventilation) during sleep; symptoms associated with this nocturnal hypoventilation include interrupted sleep, anxiety, morning headaches, and daytime fatigue. As the disease progresses, people with ALS develop shortness of breath when lying down, during physical activity or talking, and eventually at rest. Other symptoms include poor concentration, poor memory, confusion, respiratory tract infections, and a weak cough. Respiratory failure is the most common cause of death in ALS.
It is important to monitor the respiratory function of people with ALS every three months because beginning NIV soon after the start of respiratory symptoms is associated with increased survival. This involves asking the person with ALS if they have any respiratory symptoms and measuring their respiratory function. The most commonly used measurement is upright forced vital capacity (FVC), but it is a poor detector of early respiratory failure and is not a good choice for those with bulbar symptoms, as they have difficulty maintaining a tight seal around the mouthpiece. Measuring FVC while the person is lying on their back (supine FVC) is a more accurate measure of diaphragm weakness than upright FVC. Sniff nasal inspiratory pressure (SNIP) is a rapid, convenient test of diaphragm strength that is not affected by bulbar muscle weakness. If someone with ALS has signs and symptoms of respiratory failure, they should undergo daytime blood gas analysis to look for hypoxemia (low oxygen in the blood) and hypercapnia (too much carbon dioxide in the blood). If their daytime blood gas analysis is normal, they should then have nocturnal pulse oximetry to look for hypoxemia during sleep.
Non-invasive ventilation prolongs survival longer than riluzole. A 2006 randomized controlled trial found that NIV prolongs survival by about 48 days and improves the quality of life; however, it also found that some people with ALS benefit more from this intervention than others. For those with normal or only moderately impaired bulbar function, NIV prolongs survival by about seven months and significantly improves the quality of life. For those with poor bulbar function, NIV neither prolongs survival nor improves the quality of life, though it does improve some sleep-related symptoms. Despite the clear benefits of NIV, about 25–30% of all people with ALS are unable to tolerate it, especially those with cognitive impairment or bulbar dysfunction. Results from a large 2015 cohort study suggest that NIV may prolong survival in those with bulbar weakness, so NIV should be offered to all people with ALS, even if it is likely that they will have difficulty tolerating it.
==== Invasive ventilation ====
Invasive ventilation bypasses the nose and mouth (the upper airways) by making a cut in the trachea (tracheostomy) and inserting a tube connected to a ventilator. It is an option for people with advanced ALS whose respiratory symptoms are poorly managed despite continuous NIV use. While invasive ventilation prolongs survival, especially for those younger than 60, it does not treat the underlying neurodegenerative process. The person with ALS will continue to lose motor function, making communication increasingly difficult and sometimes leading to locked-in syndrome, in which they are completely paralyzed except for their eye muscles. About half of the people with ALS who choose to undergo invasive ventilation report a decrease in their quality of life but most still consider it to be satisfactory. However, invasive ventilation imposes a heavy burden on caregivers and may decrease their quality of life. Attitudes toward invasive ventilation vary from country to country; about 30% of people with ALS in Japan choose invasive ventilation, versus less than 5% in North America and Europe.
=== Therapy ===
Physical therapy plays a large role in rehabilitation for individuals with ALS. Specifically, physical, occupational, and speech therapists can set goals and promote benefits for individuals with ALS by delaying loss of strength, maintaining endurance, limiting pain, improving speech and swallowing, preventing complications, and promoting functional independence.
Occupational therapy and special equipment such as assistive technology can also enhance people's independence and safety throughout the course of ALS. Gentle, low-impact aerobic exercise such as performing activities of daily living, walking, swimming, and stationary bicycling can strengthen unaffected muscles, improve cardiovascular health, and help people fight fatigue and depression. Range of motion and stretching exercises can help prevent painful spasticity and shortening (contracture) of muscles. Physical and occupational therapists can recommend exercises that provide these benefits without overworking muscles because muscle exhaustion can lead to a worsening of symptoms associated with ALS, rather than providing help to people with ALS. They can suggest devices such as ramps, braces, walkers, bathroom equipment (shower chairs, toilet risers, etc.), and wheelchairs that help people remain mobile. Occupational therapists can provide or recommend equipment and adaptations to enable ALS people to retain as much safety and independence in activities of daily living as possible. Since respiratory insufficiency is the primary cause of mortality, physical therapists can help improve respiratory outcomes in people with ALS by implementing pulmonary physical therapy. This includes inspiratory muscle training, lung volume recruitment training, and manual assisted cough therapy aimed at increasing respiratory muscle strength as well as increasing survival rates.
People with ALS who have difficulty speaking or swallowing may benefit from working with a speech-language pathologist. These health professionals can teach people adaptive strategies such as techniques to help them speak louder and more clearly. As ALS progresses, speech-language pathologists can recommend the use of augmentative and alternative communication such as voice amplifiers, speech-generating devices (or voice output communication devices), or low-tech communication techniques such as head-mounted laser pointers, alphabet boards or yes/no signals.
=== Nutrition ===
Preventing weight loss and malnutrition in people with ALS improves both survival and quality of life. Weight loss in ALS is often caused by muscle wasting and increased resting energy expenditure. Weight loss may also be secondary to reduced food intake since dysphagia develops in about 85% of people with ALS at some point throughout their disease course. Therefore, regular periodic assessment of the weight and swallowing ability in people with ALS is very important. Dysphagia is often initially managed via dietary changes and modified swallowing techniques. People with ALS are often instructed to avoid dry or chewy foods in their diet and instead have meals that are soft, moist, and easy to swallow. Switching to thick liquids (like fruit nectar or smoothies) or adding thickeners (to thin fluids like water and coffee) may also help people facing difficulty swallowing liquids. There is tentative evidence that high-calorie diets may prevent further weight loss and improve survival, but more research is still needed.
A feeding tube should be considered if someone with ALS loses 5% or more of their body weight or if they cannot safely swallow food and water. This can take the form of a gastrostomy tube, in which a tube is placed through the wall of the abdomen into the stomach, or (less commonly) a nasogastric tube, in which a tube is placed through the nose and down the esophagus into the stomach. A gastrostomy tube is more appropriate for long-term use than a nasogastric tube, which is uncomfortable and can cause esophageal ulcers. The feeding tube is usually inserted by a percutaneous endoscopic gastrostomy procedure (PEG). While there is weak evidence that PEG tubes improve survival in people with ALS, no randomized controlled trials (RCTs) have yet been conducted to indicate whether enteral tube feeding has benefits compared to continuation of feeding by mouth. Nevertheless, PEG tubes are still offered with the intent of improving the person's quality of life by sustaining nutrition, hydration status, and medication intake.
=== End-of-life care ===
Palliative care, which relieves symptoms and improves the quality of life without treating the underlying disease, should begin shortly after someone is diagnosed with ALS. Early discussion of end-of-life issues gives people with ALS time to reflect on their preferences for end-of-life care and can help avoid unwanted interventions or procedures. Once they have been fully informed about all aspects of various life-prolonging measures, they can fill out advance directives indicating their attitude toward noninvasive ventilation, invasive ventilation, and feeding tubes. Late in the disease course, difficulty speaking due to muscle weakness (dysarthria) and cognitive dysfunction may impair their ability to communicate their wishes regarding care. Continued failure to solicit the preferences of the person with ALS may lead to unplanned and potentially unwanted emergency interventions, such as invasive ventilation. If people with ALS or their family members are reluctant to discuss end-of-life issues, it may be useful to use the introduction of gastrostomy or noninvasive ventilation as an opportunity to bring up the subject.
Hospice care, or palliative care at the end of life, is especially important in ALS because it helps to optimize the management of symptoms and increases the likelihood of a peaceful death. It is unclear exactly when the end-of-life phase begins in ALS, but it is associated with significant difficulty moving, communicating, and, in some cases, thinking. Although many people with ALS fear choking to death (suffocating), they can be reassured that this occurs rarely, less than 1% of the time. Most patients die at home, and in the final days of life, opioids can be used to treat pain and dyspnea, while benzodiazepines can be used to treat anxiety.
== Epidemiology ==
ALS is the most common motor neuron disease in adults and the third most common neurodegenerative disease after Alzheimer's disease and Parkinson's disease. Worldwide the number of people who develop ALS yearly is estimated to be 1.9 people per 100,000 per year, while the number of people who have ALS at any given time is estimated to be about 4.5 people per 100,000. In Europe, the number of new cases a year is about 2.6 people per 100,000, while the number affected is 7–9 people per 100,000. The lifetime risk of developing ALS is 1:350 for European men and 1:400 for European women. Men have a higher risk mainly because spinal-onset ALS is more common in men than women. The number of those with ALS in the United States in 2015 was 5.2 people per 100,000, and was higher in whites, males, and people over 60 years old. The number of new cases is about 0.8 people per 100,000 per year in East Asia and about 0.7 people per 100,000 per year in South Asia. About 80% of ALS epidemiology studies have been conducted in Europe and the United States, mostly in people of northern European descent. There is not enough information to determine the rates of ALS in much of the world, including Africa, parts of Asia, India, Russia, and South America. There are several geographic clusters in the Western Pacific where the prevalence of ALS was reported to be 50–100 times higher than in the rest of the world, including Guam, the Kii Peninsula of Japan, and Western New Guinea. The incidence in these areas has decreased since the 1960s; the cause remains unknown.
People of all races and ethnic backgrounds may be affected by ALS, but it is more common in whites than in Africans, Asians, or Hispanics. In the United States in 2015, the prevalence of ALS in whites was 5.4 people per 100,000, while the prevalence in blacks was 2.3 people per 100,000. The Midwest had the highest prevalence of the four US Census regions with 5.5 people per 100,000, followed by the Northeast (5.1), the South (4.7), and the West (4.4). The Midwest and Northeast likely had a higher prevalence of ALS because they have a higher proportion of whites than the South and West. Ethnically mixed populations may be at a lower risk of developing ALS; a study in Cuba found that people of mixed ancestry were less likely to die from ALS than whites or blacks. There are also differences in the genetics of ALS between different ethnic groups; the most common ALS gene in Europe is C9orf72, followed by SOD1, TARDBP, and FUS, while the most common ALS gene in Asia is SOD1, followed by FUS, C9orf72, and TARDBP.
ALS can affect people at any age, but the peak incidence is between 50 and 75 years and decreases dramatically after 80 years. The reason for the decreased incidence in the elderly is unclear. One thought is that people who survive into their 80s may not be genetically susceptible to developing ALS; alternatively, ALS in the elderly might go undiagnosed because of comorbidities (other diseases they have), difficulty seeing a neurologist, or dying quickly from an aggressive form of ALS. In the United States in 2015, the lowest prevalence was in the 18–39 age group, while the highest prevalence was in the 70–79 age group. Sporadic ALS usually starts around the ages of 58 to 63 years, while genetic ALS starts earlier, usually around 47 to 52 years. The number of ALS cases worldwide is projected to increase from 222,801 in 2015 to 376,674 in 2040, an increase of 69%. This will largely be due to the aging of the world's population, especially in developing countries.
== History ==
Descriptions of the disease date back to at least 1824 by Charles Bell. In 1850, François-Amilcar Aran was the first to describe a disorder he named "progressive muscular atrophy", a form of ALS in which only the lower motor neurons are affected. In 1869, the connection between the symptoms and the underlying neurological problems was first described by Jean-Martin Charcot, who initially introduced the term amyotrophic lateral sclerosis in his 1874 paper. Flail arm syndrome, a regional variant of ALS, was first described by Alfred Vulpian in 1886. Flail leg syndrome, another regional variant of ALS, was first described by Pierre Marie and his student Patrikios in 1918.
=== Diagnostic criteria ===
In the 1950s, electrodiagnostic testing (EMG) and nerve conduction velocity (NCV) testing began to be used to evaluate clinically suspected ALS. In 1969 Edward H. Lambert published the first EMG/NCS diagnostic criteria for ALS, consisting of four findings he considered to strongly support the diagnosis. Since then several diagnostic criteria have been developed, which are mostly in use for research purposes for inclusion/exclusion criteria, and to stratify patients for analysis in trials. Research diagnostic criteria for ALS include the "El Escorial" in 1994, revised in 1998. In 2006, the "Awaji" criteria proposed using EMG and NCV tests to help diagnose ALS earlier, and most recently the "Gold Coast" criteria in 2019.
=== Name ===
Amyotrophic comes from Greek: a- means "no", myo- (from mûs) refers to "muscle", and trophḗ means "nourishment". Therefore, amyotrophy means "muscle malnourishment" or the wasting of muscle tissue. Lateral identifies the locations in the spinal cord of the affected motor neurons. Sclerosis means "scarring" or "hardening" and refers to the death of the motor neurons in the spinal cord.
ALS is sometimes referred to as Charcot's disease (not to be confused with Charcot–Marie–Tooth disease or Charcot joint disease), because Jean-Martin Charcot was the first to connect the clinical symptoms with the pathology seen at autopsy. The British neurologist Russell Brain coined the term motor neuron disease in 1933 to reflect his belief that ALS, progressive bulbar palsy, and progressive muscular atrophy were all different forms of the same disease. In some countries, especially the United States, ALS is called Lou Gehrig's disease after the American baseball player Lou Gehrig, who was diagnosed with ALS in 1939.
In the United States and continental Europe, the term ALS (as well as Lou Gehrig's disease in the US) refers to all forms of the disease, including "classical" ALS, progressive bulbar palsy, progressive muscular atrophy, and primary lateral sclerosis. In the United Kingdom and Australia, the term motor neuron disease refers to all forms of the disease while ALS only refers to "classical" ALS, meaning the form with both upper and lower motor neuron involvement.
== Society and culture ==
In addition to the baseball player Lou Gehrig and the theoretical physicist Stephen Hawking (who notably lived longer than any other known person with the condition), several other notable individuals have or have had ALS. Several books have been written and films have been made about patients of the disease as well. American sociology professor and ALS patient Morrie Schwartz was the subject of the memoir Tuesdays with Morrie and the film of the same name, and Stephen Hawking was the subject of the critically acclaimed biopic The Theory of Everything.
In August 2014, the "Ice Bucket Challenge" to raise money for ALS research went viral online. Participants filmed themselves filling a bucket full of ice water and pouring it onto themselves; they then nominated other individuals to do the same. Many participants donated to ALS research at the ALS Association, the ALS Therapy Development Institute, ALS Society of Canada, or Motor neuron Disease Association in the UK.
== References ==
== External links ==
Media related to Amyotrophic lateral sclerosis at Wikimedia Commons
ALS Association Official Website
ALS Therapy Development Institute
International Alliance of ALS/MND Associations
International Symposium on ALS/MND
Love S (23 March 2025). "An 'Impossible' Disease Outbreak in the Alps". The Atlantic. Archived from the original on 23 March 2025. Retrieved 31 March 2025. | Wikipedia/Motor_neurone_disease |
Gastrointestinal diseases (abbrev. GI diseases or GI illnesses) refer to diseases involving the gastrointestinal tract, namely the esophagus, stomach, small intestine, large intestine and rectum; and the accessory organs of digestion, the liver, gallbladder, and pancreas.
== Oral disease ==
The oral cavity is part of the gastrointestinal system and as such the presence of alterations in this district can be the first sign of both systemic and gastrointestinal diseases. By far the most common oral conditions are plaque-induced diseases (e.g., gingivitis, periodontitis, dental caries). Oral symptoms can be similar to lesions occurring elsewhere in the digestive tract, with a pattern of swelling, inflammation, ulcers, and fissures. If these signs are present, then patients are more likely to also have anal and esophageal lesions and experience other extra-intestinal disease manifestations. Some diseases which involve other parts of the GI tract can manifest in the mouth, alone or in combination, including:
Gastroesophageal reflux disease can cause acid erosion of the teeth and halitosis.
Gardner's syndrome can be associated with failure of tooth eruption, supernumerary teeth, and dentigerous cysts.
Peutz–Jeghers syndrome can cause dark spots on the oral mucosa or on the lips or the skin around the mouth.
Several GI diseases, especially those associated with malabsorption, can cause recurrent mouth ulcers, atrophic glossitis, and angular cheilitis (e.g., Crohn's disease is sometimes termed orofacial granulomatosis when it involves the mouth alone).
Sideropenic dysphagia can cause glossitis, angular cheilitis.
== Oesophageal disease ==
Oesophageal diseases include a spectrum of disorders affecting the oesophagus. The most common condition of the oesophagus in Western countries is gastroesophageal reflux disease, which in chronic forms is thought to result in changes to the epithelium of the oesophagus, known as Barrett's oesophagus.: 863–865
Acute disease might include infections such as oesophagitis, trauma caused by the ingestion of corrosive substances, or rupture of veins such as oesophageal varices, Boerhaave syndrome or Mallory-Weiss tears. Chronic diseases might include congenital diseases such as Zenker's diverticulum and esophageal webbing, and oesophageal motility disorders including the nutcracker oesophagus, achalasia, diffuse oesophageal spasm, and oesophageal stricture.: 853, 863–868
Oesophageal disease may result in a sore throat, throwing up blood, difficulty swallowing or vomiting. Chronic or congenital diseases might be investigated using barium swallows, endoscopy and biopsy, whereas acute diseases such as reflux may be investigated and diagnosed based on symptoms and a medical history alone.: 863–867
== Gastric disease ==
Gastric diseases refer to diseases affecting the stomach. Inflammation of the stomach by infection from any cause is called gastritis, and when including other parts of the gastrointestinal tract called gastroenteritis. When gastritis persists in a chronic state, it is associated with several diseases, including atrophic gastritis, pyloric stenosis, and gastric cancer. Another common condition is gastric ulceration, peptic ulcers. Ulceration erodes the gastric mucosa, which protects the tissue of the stomach from the stomach acids. Peptic ulcers are most commonly caused by a bacterial Helicobacter pylori infection. Epstein–Barr virus infection is another factor to induce gastric cancer.
As well as peptic ulcers, vomiting blood may result from abnormal arteries or veins that have ruptured, including Dieulafoy's lesion and Gastric antral vascular ectasia. Congenital disorders of the stomach include pernicious anaemia, in which a targeted immune response against parietal cells results in an inability to absorb vitamin B12. Other common symptoms that stomach disease might cause include indigestion or dyspepsia, vomiting, and in chronic disease, digestive problems leading to forms of malnutrition. : 850–853 In addition to routine tests, an endoscopy might be used to examine or take a biopsy from the stomach. : 848
== Intestinal disease ==
The small and large intestines may be affected by infectious, autoimmune, and physiological states. Inflammation of the intestines is called enterocolitis, which may lead to diarrhea.
Acute conditions affecting the bowels include infectious diarrhea and mesenteric ischaemia. Causes of constipation may include faecal impaction and bowel obstruction, which may in turn be caused by ileus, intussusception, volvulus. Inflammatory bowel disease is a condition of unknown aetiology, classified as either Crohn's disease or ulcerative colitis, that can affect the intestines and other parts of the gastrointestinal tract. Other causes of illness include intestinal pseudoobstruction, and necrotizing enterocolitis.: 850–862, 895–903
Diseases of the intestine may cause vomiting, diarrhoea or constipation, and altered stool, such as with blood in stool. Colonoscopy may be used to examine the large intestine, and a person's stool may be sent for culture and microscopy. Infectious disease may be treated with targeted antibiotics, and inflammatory bowel disease with immunosuppression. Surgery may also be used to treat some causes of bowel obstruction.: 850–862
The normal thickness of the small intestinal wall is 3–5 mm, and 1–5 mm in the large intestine. Focal, irregular and asymmetrical gastrointestinal wall thickening on CT scan suggests a malignancy. Segmental or diffuse gastrointestinal wall thickening is most often due to ischemic, inflammatory or infectious disease. Though less common, medications such as ACE inhibitors can cause angioedema and small bowel thickening.
=== Small intestine ===
The small intestine consists of the duodenum, jejunum and ileum. Inflammation of the small intestine is called enteritis, which if localised to just part is called duodenitis, jejunitis and ileitis, respectively. Peptic ulcers are also common in the duodenum.: 879–884
Chronic diseases of malabsorption may affect the small intestine, including the autoimmune coeliac disease, infective tropical sprue, and congenital or surgical short bowel syndrome. Other rarer diseases affecting the small intestine include Curling's ulcer, blind loop syndrome, Milroy disease and Whipple's disease. Tumours of the small intestine include gastrointestinal stromal tumours, lipomas, hamartomas and carcinoid syndromes.: 879–887
Diseases of the small intestine may present with symptoms such as diarrhoea, malnutrition, fatigue and weight loss. Investigations pursued may include blood tests to monitor nutrition, such as iron levels, folate and calcium, endoscopy and biopsy of the duodenum, and barium swallow. Treatments may include renutrition and antibiotics for infections.: 879–887
=== Large intestine ===
Diseases that affect the large intestine may affect it in whole or in part. Appendicitis is one such disease, caused by inflammation of the appendix. Generalised inflammation of the large intestine is referred to as colitis, which when caused by the bacteria Clostridioides difficile is referred to as pseudomembranous colitis. Diverticulitis is a common cause of abdominal pain resulting from outpouchings that particularly affect the colon. Functional colonic diseases refer to disorders without a known cause, including irritable bowel syndrome and intestinal pseudoobstruction. Constipation may result from lifestyle factors, impaction of a rigid stool in the rectum, or in neonates, Hirschprung's disease.: 913–915
Diseases affecting the large intestine may cause blood to be passed with stool, may cause constipation, or may result in abdominal pain or a fever. Tests that specifically examine the function of the large intestine include barium swallows, abdominal x-rays, and colonoscopy.: 913–915
=== Rectum and anus ===
Diseases affecting the rectum and anus are extremely common, especially in older adults. Hemorrhoids, vascular outpouchings of skin, are very common, as is pruritus ani, referring to anal itchiness. Other conditions, such as anal cancer may be associated with ulcerative colitis or with sexually transmitted infections such as HIV. Inflammation of the rectum is known as proctitis, one cause of which is radiation damage associated with radiotherapy to other sites such as the prostate. Faecal incontinence can result from mechanical and neurological problems, and when associated with a lack of voluntary voiding ability is described as encopresis. Pain on passing stool may result from anal abscesses, small inflamed nodules, anal fissures, and anal fistulas.: 915–916
Rectal and anal disease may be asymptomatic, or may present with pain when passing stools, fresh blood in stool, a feeling of incomplete emptying, or pencil-thin stools. In addition to regular tests, medical tests used to investigate the anus and rectum include the digital rectal exam and proctoscopy.
== Accessory digestive gland disease ==
=== Hepatic ===
Hepatic diseases refers to those affecting the liver. Hepatitis refers to inflammation of liver tissue, and may be acute or chronic. Infectious viral hepatitis, such as hepatitis A, B and C, affect in excess of (X) million people worldwide. Liver disease may also be a result of lifestyle factors, such as fatty liver and NASH. Alcoholic liver disease may also develop as a result of chronic alcohol use, which may also cause alcoholic hepatitis. Cirrhosis may develop as a result of chronic hepatic fibrosis in a chronically inflamed liver, such as one affected by alcohol or viral hepatitis.: 947–958
Liver abscesses are often acute conditions, with common causes being pyogenic and amoebic. Chronic liver disease, such as cirrhosis, may be a cause of liver failure, a state where the liver is unable to compensate for chronic damage, and unable to meet the metabolic demands of the body. In the acute setting, this may be a cause of hepatic encephalopathy and hepatorenal syndrome. Other causes of chronic liver disease are genetic or autoimmune disease, such as hemochromatosis, Wilson's disease, autoimmune hepatitis, and primary biliary cirrhosis.: 959–963, 971
Acute liver disease rarely results in pain, but may result in jaundice. Infectious liver disease may cause a fever. Chronic liver disease may result in a buildup of fluid in the abdomen, yellowing of the skin or eyes, easy bruising, immunosuppression, and feminization. Portal hypertension is often present, and this may lead to the development of prominent veins in many parts of the body, such as oesophageal varices, and haemorrhoids.: 959–963, 971–973
In order to investigate liver disease, a medical history, including regarding a person's family history, travel to risk-prone areas, alcohol use and food consumption, may be taken. A medical examination may be conducted to investigate for symptoms of liver disease. Blood tests may be used, particularly liver function tests, and other blood tests may be used to investigate the presence of the Hepatitis viruses in the blood, and ultrasound used. If ascites is present, abdominal fluid may be tested for protein levels.: 921, 926–927
=== Pancreatic ===
Pancreatic diseases that affect digestion refers to disorders affecting the exocrine pancreas, which is a part of the pancreas involved in digestion.
One of the most common conditions of the exocrine pancreas is acute pancreatitis, which in the majority of cases relates to gallstones that have impacted in the pancreatic part of the biliary tree, or due to acute or chronic hazardous alcohol use or as a side-effect of ERCP. Other forms of pancreatitis include chronic and hereditary forms. Chronic pancreatitis may predispose to pancreatic cancer and is strongly linked to alcohol use. Other rarer diseases affecting the pancreas may include pancreatic pseudocysts, exocrine pancreatic insufficiency, and pancreatic fistulas.: 888–891
Pancreatic disease may present with or without symptoms. When symptoms occur, such as in acute pancreatitis, a person may experience acute-onset, severe mid-abdominal pain, nausea and vomiting. In severe cases, pancreatitis may lead to rapid blood loss and systemic inflammatory response syndrome. When the pancreas is unable to secrete digestive enzymes, such as with a pancreatic cancer occluding the pancreatic duct, result in jaundice. Pancreatic disease might be investigated using abdominal x-rays, MRCP or ERCP, CT scans, and through blood tests such as measurement of the amylase and lipase enzymes.: 888–894
=== Gallbladder and biliary tract ===
Diseases of the hepatobiliary system affect the biliary tract (also known as the biliary tree), which secretes bile in order to aid digestion of fats. Diseases of the gallbladder and bile ducts are commonly diet-related, and may include the formation of gallstones that impact in the gallbladder (cholecystolithiasis) or in the common bile duct (choledocholithiasis).: 977–978
Gallstones are a common cause of inflammation of the gallbladder, called cholecystitis. Inflammation of the biliary duct is called cholangitis, which may be associated with autoimmune disease, such as primary sclerosing cholangitis, or a result of bacterial infection, such as ascending cholangitis.: 977–978, 963–968
Disease of the biliary tree may cause pain in the upper right abdomen, particularly when pressed. Disease might be investigated using ultrasound or ERCP, and might be treated with drugs such as antibiotics or UDCA, or by the surgical removal of the gallbladder.: 977–979
=== Cancer ===
The Wikipedia article "Gastrointestinal cancer" describes the specific malignant conditions of the gastrointestinal tract. In general, a significant factor in the etiology of gastrointestinal cancers appears to be excessive exposure of the digestive organs to bile acids.
== See also ==
Functional gastrointestinal disorder
Gastrointestinal malformations
Gastrointestinal bleeding
Neurotherapy
== References ==
== External links == | Wikipedia/Digestive_disease |
Bariatric surgery (also known as metabolic surgery or weight loss surgery) is a surgical procedure used to manage obesity and obesity-related conditions. Long term weight loss with bariatric surgery may be achieved through alteration of gut hormones, physical reduction of stomach size (stomach reduction surgery), reduction of nutrient absorption, or a combination of these. Standard of care procedures include Roux en-Y bypass, sleeve gastrectomy, and biliopancreatic diversion with duodenal switch, from which weight loss is largely achieved by altering gut hormone levels responsible for hunger and satiety, leading to a new hormonal weight set point.
In morbidly obese people, bariatric surgery is the most effective treatment for weight loss and reducing complications. A 2021 meta-analysis found that bariatric surgery was associated with reduction in all-cause mortality among obese adults with or without type 2 diabetes. This meta-analysis also found that median life-expectancy was 9.3 years longer for obese adults with diabetes who received bariatric surgery as compared to routine (non-surgical) care, whereas the life expectancy gain was 5.1 years longer for obese adults without diabetes. The risk of death in the period following surgery is less than 1 in 1,000. Bariatric surgery may also lower disease risk, including improvement in cardiovascular disease risk factors, fatty liver disease, and diabetes management.
Stomach reduction surgery is frequently used for cases where traditional weight loss approaches, consisting of diet and physical activity, have proven insufficient, or when obesity already significantly affects well-being and general health. The weight-loss procedure involves reducing food intake. Some individuals might suppress bodily functions to reduce the absorption of carbohydrates, fats, calories, and proteins. The outcome is a significant reduction in BMI. The efficacy of stomach reduction surgery varies depending on the specific type of procedure. There are two primary divisions of surgery, specifically gastric sleeve surgery and gastric bypass surgery.
As of October 2022, the American Society of Metabolic and Bariatric Surgery and International Federation for the Surgery of Obesity recommended consideration of bariatric surgery for adults meeting two specific criteria: people with a body mass index (BMI) of more than 35 whether or not they have an obesity-associated condition, and people with a BMI of 30–35 who have metabolic syndrome. However, these designated BMI ranges do not hold the same meaning in particular populations, such as among Asian individuals, for whom bariatric surgery may be considered when a BMI is more than 27.5. Similarly, the American Academy of Pediatrics recommends bariatric surgery for adolescents 13 and older with a BMI greater than 120% of the 95th percentile for age and sex.
== Medical uses ==
Bariatric surgery has proven to be the most effective obesity treatment option for enduring weight loss. Along with this weight reduction, the procedure reduces risk of cardiovascular diseases, type 2 diabetes, fatty liver disease, depression syndromes, among others. While often effective, numerous barriers to shared decision making between the medical provider and person affected include lack of insurance coverage or understanding how it functions, a lack of knowledge about procedures, conflicts with organizational priorities and care coordination, and tools supporting people who need the surgery.
=== Eligibility and guidelines ===
Historically, eligibility for bariatric surgery was defined as a BMI greater than 40, or a BMI more than 35 with an obesity-associated comorbidity, as based on the 1991 NIH Consensus Statement. In the three decades that followed, obesity rates continued to rise, laparoscopic surgical techniques made the procedure safer, and high-quality research showed effectiveness at improving health among various conditions. In October 2022, ASMBS/IFSO revised the eligibility criteria, which include all adult patients with a BMI greater than 35, and those with a BMI more than 30 with metabolic syndrome. However, BMI is a limited measurement, for which factors such as ethnicity are not used in the BMI calculation. Eligibility criteria for bariatric surgery are modified for people who identify as a part of the Asian population with a BMI of more than 27.5.
Stomach reduction surgeries were highly recommended for patients who meet these criteria: BMI>40 (type 3 obesity), BMI>35 (type 2 obesity), with specific comorbid conditions such as type 2 diabetes, hypertension, dyslipidemia, etc.
As of 2019, the American Academy of Pediatrics recommended bariatric surgery without age-based eligibility limits under the following indications: BMI more than 35 with severe comorbidity, such as obstructive sleep apnea (Apnea-Hypopnea Index above 0.5), type 2 diabetes, idiopathic intracranial hypertension, nonalcoholic steatohepatitis, Blount disease, slipped capital femoral epiphysis, gastroesophageal reflux disease, and idiopathic hypertension or a BMI above 40 without comorbidities. Surgery is contraindicated with a medically correctable cause of obesity, substance abuse, concurrent or planned pregnancy, eating disorder, or inability to adhere to postoperative recommendations and mandatory lifestyle changes.
When counseling a patient on bariatric procedures, providers take an interdisciplinary approach. Psychiatric screening is also critical for determining postoperative success. People with a BMI of 40 or greater have a 5-fold risk of depression, and half of bariatric surgery candidates are depressed. Among bariatric surgery candidates and those who undergo bariatric surgery, mental health-related conditions including anxiety disorders, eating disorders, and substance use are also more commonly reported.
==== Age ====
Elderly patients will face higher postoperative complications due to frailty of elderly patients. The adolescents who performed stomach reduction surgery showed better results and there is no negative impact on linear/puberty growth.
=== Contraindications ===
Stomach reduction surgery is not suitable for people with the following conditions:
History of severe gastrointestinal disease:
Crohn's disease–RYGB surgery limited.
Active peptic ulcers disease.
Esophagitis in severe stage.
Severe cardiovascular disease
Heart failure
Coronary artery disease
Portal hypertension
Cancer: active cancer diagnosis
Pregnancy: pregnant (within 12-18 month)
Psychiatric: lower level of mental capacity or untreated mental disorders
Blood clotting: Coagulopathy issue
=== Weight loss ===
In adults, malabsorptive procedures lead to more weight loss than restrictive procedures, but they have a higher risk profile. Gastric banding is the least invasive, so it may offer fewer complications, while gastric bypass may offer the highest initial and most sustainable weight loss. A single protocol is not superior to the other. In one 2019 systematic review, estimated weight loss (EWL) for each surgical protocol is as follows: 56.7% for gastric bypass, 45.9% for gastric banding, 74.1% for biliopancreatic bypass +/- duodenal switch and 58.3% for sleeve gastrectomy. Most patients do remain obese (BMI 25-35) following surgery despite significant weight loss, and patients with BMI over 40 tended to lose more weight than those with BMI under 40.
Concerning metabolic syndrome, bariatric surgery patients were able to achieve remission 2.4 times as often as those who underwent nonsurgical treatment. No significant difference was noted for changes in cholesterol, or LDL, but HDL did increase in the surgical groups, and reduction in blood pressure was variable between studies.
=== Type 2 diabetes mellitus ===
Studies of bariatric surgery for type 2 diabetes (T2DM) within the obese population show that 58% prioritize the improvement of diabetes, while 33% pursued surgery for weight loss alone. While weight loss is essential in T2DM management, sustaining improvements long-term is challenging; 50% to 90% of people struggle to achieve adequate diabetes control, suggesting the need for alternative interventions. In this context, studies have reported an 85–90% resolution of T2DM after bariatric surgery, measured by reductions in fasting plasma glucose and HbA1C levels, and remission rates of up to 74% two years post-surgery. Bariatric surgery is considered for individuals with new-onset T2DM and obesity, although the level of improvement may be slightly less.
The relative risk reductions associated with bariatric surgery are 61%, 64%, and 77% for the development of T2DM, hypertension, and dyslipidemia, respectively, highlighting the efficacy of bariatric surgery in prevention as well as resolution of chronic obesity. Predictors for post-operative diabetes resolution include the current method of diabetes control, adequate blood sugar control, age, duration of diabetes, and waist circumference.
Bariatric surgery likewise plays a role in the reduction of medication use. During postoperative follow-up, 76% of people discontinued the use of insulin, while 62% no longer required T2DM medications at all.
=== Reduced mortality and morbidity ===
A 2021 meta-analysis found that bariatric surgery was associated with 59% and 30% reductions in all-cause mortality among obese adults with or without type 2 diabetes respectively. It also found that median life expectancy was 9 years longer for obese adults with diabetes who received bariatric surgery as compared to routine (non-surgical) care, whereas the life expectancy gain was 5 years longer for obese adults without diabetes. The overall cancer risk in bariatric surgery patients was decreased by 44%, especially in colorectal, endometrial, breast, and ovarian cancer. Improvements in cardiovascular health are the most well-described changes after bariatric surgery, with notable reductions in the incidence of stroke (except in patients with T2DM), heart attack, atrial fibrillation, all-cause cardiovascular mortality, and ischemic heart disease.
Bariatric surgery in older patients is a safety concern; the relative benefits and risks in this population are not known.
=== Fertility and pregnancy ===
In 2017, the American Society for Metabolic and Bariatric Surgery stated that it was not clear whether medical weight-loss treatments or bariatric surgery affected subsequent treatments for infertility in both men and women.
Bariatric surgery reduces the risk of gestational diabetes and hypertensive disorders of pregnancy in women who later become pregnant, but increases the risks of preterm birth and maternal anemia. A 2021 systematic review found that post-bariatric surgery normalized hormonal levels and menstrual cycles, and improved fertility, with no increased short-term risk of miscarriages or congenital malformations.
For women with polycystic ovary syndrome, post-operatively there tends to be a reduction in menstrual irregularity, hirsutism, infertility, and the overall prevalence of polycystic ovary syndrome is reduced by bariatric surgery at 12 and 23 months.
=== Mental health ===
Among people seeking bariatric surgery, pre-operative mental health disorders are commonly reported. Some studies indicate that psychological health can improve after bariatric surgery, due in part to improved body image, self-esteem, and change in self-concept; these findings were found in children (see Considerations in adolescent patients below). Bariatric surgery has consistently been associated with postoperative decreases in depression symptoms and reduced severity.
== Risks and complications ==
Weight loss surgery in adults is associated with an elevated risk of complications compared to nonsurgical treatments for obesity. Complications can be separated into 2 stages, early complication (within 30 days after surgeries) and late complications (after 30 days).
The overall risk of mortality is low in bariatric surgery at 0 to .01%. Severe complications, such as gastric perforation or necrosis, have been significantly reduced by improved surgical experience and training. Bariatric surgery morbidity is also low at 5%. In fact, several studies have reported a reduced overall long-term all-cause mortality compared to controls. However, obese populations maintain an elevated risk of disease and mortality compared to the general population even after surgery, therefore elevated mortality after surgery may be related to the ongoing complications of existing obesity-related disease.
The percentage of procedures requiring reoperations due to complications was 8% for adjustable gastric banding, 6% after Roux-en-Y gastric bypass, 1% for sleeve gastrectomy, and 5% after biliopancreatic diversion. Over a 10-year study while using a common data model to allow for comparisons, 9% of patients who received a sleeve gastrectomy required some form of reoperation within 5 years compared to 12% of patients who received a Roux-en-Y gastric bypass. Both of the effects were fewer than those reported with adjustable gastric banding.
=== Postoperative ===
Laparoscopic bariatric surgery requires an average hospital stay of 2–5 days, barring potential complications. Minimally invasive procedures (i.e. adjustable gastric band) tend to have less complications than open procedures (i.e. Roux-en-Y). Similar to other surgical procedures, there is a risk of atelectasis (collapse of small airways) and pleural effusion (fluid buildup in lungs), and pneumonia which tends to be less associated with minimally invasive procedures.
Complications specific to the laparoscopic gastric band procedure include esophageal perforation from the advancement of the calibration probe, gastric perforation from the creation of a retrograde gastric tunnel, esophageal dilation, and acute dilation of the gastric pouch due to malpositioning of the gastric band. Gastric band malpositioning can be devastating, leading to gastric prolapse, overdistention, and resultingly, gastric ischemia and necrosis. Erosion and migration of the band may also occur post-operatively, in which case, if over 50% of the circumference of the band migrates, then surgical repositioning is necessary.
Risks of Roux-en-Y gastric bypass include anastomotic stenosis (narrowing of the intestine where the two segments are rejoined), bleeding, leaks, fistula formation, ulcers (ulcers near the rejoined segment), internal hernia, small bowel obstruction, kidney stones, and gallstones. Bowel obstruction tends to be more difficult to diagnose in post-bariatric surgery patients due to their reduced ability to vomit; symptoms mainly involve abdominal pain and are intermittent due to twisting and untwisting of the intestinal mesentery.
Sleeve gastrectomy also carries a small risk of stenosis, staple line leak, stricture formation, leaks, fistula formation, bleeding, and gastro-esophageal reflux disease (also known as GERD or heartburn).
Deficiencies of micronutrients like iron (15%), vitamin D, vitamin B12, fat-soluble vitamins, thiamine, and folate are common after bariatric procedures. Such deficiencies are potentiated by alterations in absorption and lack of appetite and often require supplementation. Notably, chronic vitamin D deficiency may contribute to osteoporosis; insufficiency fractures, especially of the upper extremity, are of higher incidence in bariatric surgery patients. Sleeve gastrectomy leads to fewer long-term vitamin deficiencies compared to gastric banding.
==== Sleeve Gastrectomy (SG) ====
Early complication: Bleeding is present in approximately 5% of cases of sleeve gastrectomy. Symptoms can vary widely, ranging from gastrointestinal bleeding to internal bleeding. Venous thromboembolism (VTE) may occur, causing a decrease in flow through the splenic system, potentially leading to system collapse or death.
Late complications: They include gastric stenosis, nutrient deficiencies, and Gastroesophageal reflux disease. For gastric stenosis, the symptoms are food intolerance and vomiting. For the gastroesophageal reflux disease, which due to post-surgery changes of reduced lower esophageal sphincter tension and increased intragastric pressure. Patients may suffer from heartburn after eating or upper abdominal pain.
===== Roux-En-Y Gastric Bypass (RYGB) =====
An early complication of Roux-En-Y Gastric Bypass: Small bowel obstruction, which can be caused by the internal hernias due to the laparoscopic RYGB surgery techniques that were used. And it is life-threatening to patients since it is hard to diagnose through clinical or radiographic imaging. The symptoms included vomiting, abdominal pain and peritonitis. Common complications such as internal gastrointestinal hemorrhage (bleeding) and staple line leakage occur in both surgeries.
Late complication: For the anastomotic stricture, there is a 2.9%-23% chance for patients to experience gastrojejunal anastomosis. This complication more often occurs in the laparoscopic era than open RYGB surgery. Symptoms such as difficulty swallowing and vomiting.
=== Gastrointestinal ===
The most common complication, especially after sleeve gastrectomy, is GERD, which may occur in up to 25% of cases. Dumping syndrome (rapid emptying of undigested stomach contents) is another common complication of bariatric surgery, especially after Roux-en-Y, which is further classified into early and late dumping syndrome. Dumping syndrome in some cases may be associated with more efficient weight loss, however, it can be uncomfortable. Symptoms of dumping syndrome include nausea, diarrhea, painful abdominal cramps, bloating, and autonomic symptoms such as tachycardia, palpitations, flushing, and sweating. Early dumping syndrome (emptying within 1 hour of eating) is also associated with a rapid drop in blood pressure, which may cause fainting. Late dumping syndrome is characterized by low blood sugar 1–3 hours after a meal, presenting with palpitations, tremors, sweating, a feeling of faintness, and irritability. Dumping syndrome is best mitigated by consuming small meals and avoiding high carb or high-fat foods.
=== Gallstones ===
Rapid weight loss after obesity surgery can contribute to the development of gallstones, especially at 6 and 18 months. Estimates for prevalence of symptomatic gallstones after Roux-En-Y gastric bypass range from 3–13%. The risk of gallstones following bariatric surgery has shown to be higher among those of the female sex.
=== Kidney stones ===
Kidney stones are common after Roux-En-Y gastric bypass, with estimates of prevalence ranging from 7-11%. All surgical modalities are associated with a significant increase in the risk of kidney stones compared to nonsurgical weight loss treatment, with biliopancreatic diversion being the most associated at a ten-fold increase in one study.
=== Micronutrient malnutrition ===
Bariatric surgery as a treatment for obesity can lead to vitamin deficiencies. Long-term follow-up reported deficiencies for vitamins D, E, A, K and B12. There are guidelines for multivitamin supplementation, but adherence rates are reported to be less than 20%.
=== Pregnancy ===
Pregnancy in patients post-bariatric surgery must be carefully monitored. Infant mortality, preterm birth, small fetal size, congenital anomalies, and NICU admission are all elevated in bariatric surgery patients. This elevation in adverse outcomes is thought to be because of malnutrition. Most notably, a reduction in serum folate and iron are well-established correlates to neural tube defects and preterm birth, respectively. People considering pregnancy should consult with their physician before conceiving to optimize their health and nutritional status before pregnancy.
== Technique ==
=== Mechanisms of action ===
Bariatric procedures function by a variety of mechanisms, such as alteration of gut hormones, reduction of the gut size (reducing the amount of food that may pass through), and reduction or blockage of nutrient absorption. The distinction in these mechanisms, and which are at work for a particular bariatric procedure is not always clearly defined, as multiple mechanisms may be used by a single procedure. For instance, while sleeve gastrectomy (discussed below) was initially thought to work simply by reducing the size of the stomach, research has begun to elucidate changes in gut hormone signaling as well. The two most frequently performed procedures are sleeve gastrectomy and Roux-en-Y gastric bypass (also called gastric bypass), with sleeve gastrectomy accounting for more than half of all procedures since 2014.
==== Hormone regulation ====
Studies have shown that bariatric procedures may have additional effects on the hormones that affect hunger and satiety (such as ghrelin and leptin), despite initial development to target reduction of food intake and/or nutrient absorption. This is especially important when considering the durability of weight loss compared to lifestyle changes. While diet and exercise are essential for maintaining a healthy weight and physical fitness, metabolism typically slows as the individual loses weight, a process known as metabolic adaptation. Thus, efforts for obese individuals to lose weight often stall, or result in weight re-gain. Bariatric surgery is thought to affect the weight "set point," leading to a more durable weight loss. This is not completely understood but may involve the cell-signaling pathways and hunger/satiety hormones.
==== Restricting food intake ====
Procedures may reduce food intake by reducing the size of the stomach that is available to hold a meal (see below: gastric sleeve or stomach folding). Filling the stomach faster enables an individual to feel more full after a smaller meal.
==== Nutrient absorption ====
Procedures may reduce the amount of intestine that food passes through to decrease the absorption of nutrients from food. For example, a Roux-en-Y gastric bypass connects the stomach to a more distal part of the intestine, which reduces the ability of the intestines to absorb nutrients from the food.
==== Disruption of the gut-brain axis by partial vagotomy ====
Roux-en-Y gastric bypass disrupts the gastric branches of the vagal nerve completely and sleeve gastrectomy does so partially. Before current bariatriac was introduced, isolated vagotomy was used for the treatment of obesity. Vagotomy leads to a reduction of gastric acid and consequently to a reduction in nutrient absorption and a delay in gastric emptying. In addition, the effect of the hunger hormone Ghrelin is reduced, because it acts through the vagal nerve. This leads to a reduction of the hunger feeling and weight loss.
=== Most common techniques ===
==== Sleeve gastrectomy ====
Sleeve gastrectomy, also known as a gastric sleeve, is a surgical weight-loss procedure where the stomach size is reduced by the surgical removal of a large portion of the stomach, following along the major curve of the stomach. The open edges are then attached (typically with surgical staples, sutures, or both) to leave the stomach shaped more like a tube, or a sleeve, with a banana shape.
The procedure is performed laparoscopically and is not reversible. It has been found to produce a weight loss comparable to that of Roux-en-Y gastric bypass. The risk of ulcers or narrowing of the gut due to intestinal strictures is less so with sleeve gastrectomy versus Roux-en-Y gastric bypass, but it is not as effective at treating GERD or type 2 diabetes.
This was the most commonly performed bariatric surgery as of 2021 in the United States, and is one of the two most commonly performed bariatric surgeries in the world. Though initially thought to work strictly by reducing the size of the stomach, recent research has shown that there are also changes in gut signaling hormones with this procedure leading to weight loss.
The sleeve gastrectomy mechanism works by creating a narrow gastric lumen which restricts food intake and prevents receptive relaxation, alongside ongoing research into hormonal changes, and gastrointestinal motility.
The physical mechanism that will make the SG stand out to other bariatric surgery is its reduction of the storage of the stomach significantly, allowing patients to control their calorie intakes.
The mechanism related to hormone regulation, SG can help to improve Insulin sensitivity, aiming for better glucose regulation and contributing to the remission of type 2 diabetes in many patients. The levels of gut hormones such as GLP-1 and PYY increase after operation of SG. GLP-1 enhances insulin secretion and has a satiety-inducing effect, while PYY helps reduce appetite. These hormonal changes are pivotal in the metabolic improvements observed after SG, including better control of blood sugar levels and reduced hunger.
SG will affect the metabolism and absorption of nutrients, hence causing an effect on nutrient dynamics. Postoperative observation shows patients' nutrient levels of Vitamin B1 and B12 have significantly declined, necessitating careful postoperative nutritional management to prevent deficiencies.
Research suggests SG surgery can alter the composition of the gut microbiota, which plays a role in obesity and metabolic health. Changes in the gut microbial community post-SG may influence energy harvest from the diet, impact inflammatory pathways, and affect the host's metabolic profile.
The key mechanism is gastrointestinal motility adjustment of SG surgery, which impacts the speed and efficiency of food processing. Studies have observed a modification in the pressure of the lower esophageal sphincter and an increase in intragastric pressure post-surgery, which collectively impact the gastrointestinal motility.
Techniques:
Hiatal Hernia Repair. During SG, identifying and repairing a hiatal hernia (HH) is a significant step that can influence the surgery's outcome, especially concerning gastroesophageal reflux disease (GERD) management postoperatively. The procedure involves dissecting the pars flaccida to open a plane between the right crus of the liver and the esophagus, performing an intrathoracic esophageal dissection, and identifying the left crus. A hiatal hernia repair is conducted, if necessary, with a posterior cruroplasty using a durable suture material. This step is vital as it ensures the proper positioning of the gastroesophageal junction (GEJ) and reduces the risk of postoperative GERD by securing the stomach below the diaphragm, preventing potential acid reflux.
Bougie Sizing and Stapling Alongside. The insertion of a bougie during LSG is a crucial technique for guiding the creation of the gastric sleeve. The bougie, which ranges from 38 to 40 French in size, is inserted down to the pylorus under direct visualisation, serving as a mold around which the stomach is stapled and resected. This technique ensures that the sleeve is of uniform size and reduces the risk of narrowing a passage or obstruction post-surgery. Stapling begins 3-6 cm from the pylorus and proceeds upwards towards the angle of His, closely aligned with the bougie to create a narrow gastric tube. The careful placement and size of the bougie are instrumental in achieving optimal sleeve shape and function, minimising complications such as leaks or strictures.
After 1-3 postoperative days, patients begin oral intake, contingent on a successful gastrografin leak test, and receive continuous metabolic monitoring. To reduce early respiratory risk, prophylactic measures such as oxygen support and ultrasound evaluations are employed.
Late postoperative care involves careful observation for anastomotic leaks, patient change to a clear liquid diet, and managing potential nausea and vomiting. After discharge, the focus shifts to dietary management, starting with a full liquid diet and gradually incorporating soft, solid foods. Monitoring includes regular check-ups for weight and blood pressure, along with comprehensive lab tests to ensure optimal recovery.
==== Roux-en-Y gastric bypass surgery ====
Roux-en-Y gastric bypass surgery involves the creation of a new connection in the gastrointestinal tract, from a smaller portion of the stomach to the middle of the small intestine.
The surgery is a permanent procedure that aims to decrease the absorption of nutrients due to the new, limited connection created. The surgery also works by affecting gut hormones, resetting hunger and satiety levels. The physically smaller stomach and increase in baseline satiety hormones help people to feel full with less food after the surgery.
This is the most commonly performed operation for weight loss in the United States, with approximately 140,000 gastric bypass procedures performed in 2005. A 2021 evidence update comparing the benefits and harms of bariatric procedures found that Roux-en-Y gastric bypass surgery and sleeve gastrectomy both effectively reduced weight and led to Type 2 diabetes remission. After five years, Roux-en-Y resulted in greater weight loss (26% compared to 19% for sleeve gastrectomy) and a 25% lower rate of diabetes relapse. However, Roux-en-Y patients had a higher likelihood of hospitalization and additional abdominal surgeries compared to sleeve gastrectomy. Though, since 2013, sleeve gastrectomy has overtaken RYGB as the most common bariatric procedure. RYGB remains one of the two most commonly performed bariatric surgeries in the world.
Gastric bypass is the most frequently employed technique for weight reduction, the abnormal absorption in the intestines and the physical restriction of the stomach. The types of surgeries can be categorized by the effects and the changes made. Reconstruction of the small intestine to reduce the mucosal area which is used to absorb nutrients is called the Malabsorption operation. The jejunoileal bypass (JIB) is the most traditional technique for gastric bypass. This procedure has no limitations in the flow and processing of food; it only allows the transport of nutrients from the small intestine to the surrounding areas of the intestine. The impact of weight loss is apparent and remarkable. Individuals who undergo Roux-en-Y gastric bypass (RYGB) consume fewer snacks and meals compared to those who undergo JIB. The RYGB procedure has been proved to be the most effective medical treatment for type 2 diabetes and weight loss. After performing gastric bypass surgery, the two hormones related to obesity, leptin and insulin, fall in levels and while lose weight.
Roux-en-Y (RYGB) offers two surgical approaches for processing: an open technique or the laparoscopic technique. The majority of cases are still performed with laparoscopy. The laparoscopic approach is a safe procedure that is associated with fewer problems resulting from wound inflammation.
There are three main areas of techniques for performing laparoscopic RYGB: (1) Anastomotic technique including Linear Circular stapler. 2) Alimentary limb configuration, such as Antecolic or Retrocolic and Antegastric or Retrogastric. 3) Limb-length of the bilio-pancreatic (BP) limb.
Linear stapling: this technique has two variations. 1) Perform the jejuno-jejunal (JJ) anastomosis, then act on the gastro-jejunal (GJ) anastomosis. 2) reverse the first process.
Jejuno-jejunal first: This technique is prevalent within gastric bypass surgery.
JJ Anastomosis
In order to facilitate identification of duodenum-jejunum (DJ) flexion and Treitz ligaments, it will act on the Cephalic greater omentum using the laparoscopic staplers and Surgical energy device separate the mesentery. It also includes measuring the Roux limb between the distal end of the binding and the chosen length. For example, if the weight index is 40, the length should be 100cm.
Gastric pouch formation
On the lesser curve of the stomach, a window will be opened between the second and third vessel at the perigastric border. The pouch will be formed using the laparoscopic stapling device. The orogastric tube which will be removed before the first launch of the stapler horizontally. The pouch is produced over the tube with next firings in another direction. These may need the mobilisation to help further divide the stomach.
Gastro-jejunal anastomosis
Gastrostomy is created at the specific angle (the part of the pouch with the least blood supply). The separated alimentary limbs are translocated to the pouch antecolically. Enterotomy will processed within the jejunum. At the same time, between the gastric pouch and alimentary limb, the laparoscopic stapling devices create the single firing. According to the JJ anastomosis, the anastomotic defect closes with 2 continuously absorbed sutures. Finally, 50 ml of Dilute methylene blue dye is needed to assess leakage and ensure anastomotic integrity.
Other techniques include the Omega Loop Technique and Trans-abdominal technique employ different operating approaches along with different process orders. All of them will show positive weight loss results.
The duration of the recuperation phase typically ranges from 2 to 4 weeks. The length of the period is dependent upon the self-perception of the patients and their future state of mental and physical ability. For patients to resume their normal activities, a minimum of 3-5 weeks recovery period is required. Doctors should determine the length of the recovery period based on a range of body mass index.
==== Biliopancreatic diversion with duodenal switch ====
The biliopancreatic diversion with duodenal switch (BPD/DS) is a slightly less common bariatric procedure, but is increasing in use with proven efficacy for sustainable weight loss.
This procedure has multiple steps. First, a sleeve gastrectomy (see above section) is performed. This part of the procedure causes food intake restriction due to the physical reduction of the stomach size, and is permanent. Next, the stomach is then disconnected from the upper part of the small intestine and connected to a farther part of the small intestine (ileum), creating the alimentary limb. The leftover section of the far part of the small intestine is then used to make a connection that brings digestive fluids from the gallbladder and pancreas to the alimentary limb.
Weight loss following the surgery is largely due to the alteration of gut hormones that control hunger and satiety, as well as the physical restriction of the stomach and decrease in nutrient absorption. Compared to the sleeve gastrectomy and Roux-en-Y gastric bypass, BPD/DS produces better results with lasting weight loss and resolution of type 2 diabetes.
=== Other related bariatric procedures ===
==== Vertical banded gastroplasty ====
Vertical banded gastroplasty was more commonly used in the 1980s, and is not typically performed in the 21st century.
In the vertical banded gastroplasty, a part of the stomach is permanently stapled to create a smaller, new stomach. This new stomach is physically restricted, allowing people to feel full with smaller meals. Short-term weight loss is similar to other bariatric procedures, but long-term complications may be higher.
==== Gastric plication ====
This procedure is similar to the sleeve gastrectomy surgery, but a sleeve is created by suturing, rather than physically removing stomach tissue. This allows for the natural ability of the stomach to absorb nutrients to remain intact. This procedure is reversible, is a less invasive procedure, and does not use hardware or staples.
Gastric plication significantly reduces the volume of the patient's stomach, so smaller amounts of food provide a feeling of satiety. In a 2020 review and meta-analysis, long-term weight loss was not as durable as other, more common bariatric techniques. Gastric plication has not performed as well as the sleeve gastrectomy, with the sleeve gastrectomy associated with greater weight loss and fewer complications.
=== Implants and devices ===
==== Adjustable gastric band ====
The restriction of the stomach also can be created using a silicone band, which can be adjusted by the addition or removal of saline through a port placed just under the skin, a procedure called adjustable gastric band surgery. This operation can be performed laparoscopically, and is commonly referred to as a "lap band". Weight loss is predominantly due to the restriction of nutrient intake that is created by the small gastric pouch and the narrow outlet. It is considered somewhat of a safe surgical procedure, with a mortality rate of 0.05%.
==== Intragastric balloon ====
Intragastric balloon involves placing a deflated balloon into the stomach, and then filling it to decrease the amount of gastric space, resulting in the feeling of fullness after a smaller meal. The balloon can be left in the stomach for a maximum of 6 months and results in weight loss of 3 BMI or 3–8 kg within several study ranges. Weight loss with the gastric balloon tends to be more modest than other interventions. The intragastric balloon may be used before another bariatric surgery to assist the patient in reaching a weight that is suitable for surgery but can be used repeatedly and unrelated to other procedures.
==== Implantable gastric stimulation ====
This procedure where a device similar to a heart pacemaker that is implanted by a surgeon, with the electrical leads stimulating the external surface of the stomach, was under preliminary research in 2015. Electrical stimulation is thought to modify the activity of the enteric nervous system of the stomach, which is interpreted by the brain to give a sense of satiety, or fullness. Early evidence suggests that it is less effective than other forms of bariatric surgery.
== Recovery ==
People are followed closely both before and after bariatric procedures by a healthcare team. The care team may include people in a variety of disciplines, such as social workers, dietitians, and medical weight management specialists. Follow-up after surgery is typically focused on helping avoid complications and tracking the progress toward body weight goals. Having a structure of social support in the post-operative time may be beneficial as people work through the changes that present physically and emotionally following surgery.
=== Dietary recommendations ===
Dietary restrictions after recovery from surgery depend in part on the type of surgery. In general, immediately after bariatric surgery, the person is restricted to a clear liquid diet, which includes foods such as broth, diluted fruit juices, or sugar-free drinks. This diet is continued until the gastrointestinal tract begins to recover approximately 2–3 weeks after surgery. The next stage provides a puréed liquid or soft-solid diet that is slightly increased in viscosity. This may consist of high protein, liquid, or soft foods such as protein shakes, soft meats, and dairy products. People in recovery are encouraged to compose their diet mainly of plant-based foods and soft proteins (1.0–1.5g/kg/day). During recovery, people must adapt to eating more slowly and avoid eating past fullness; overeating may lead to nausea and vomiting. Alcohol is avoided completely in the first 6 months to 1 year after surgery. Some people may take a daily multivitamin to compensate for reduced absorption of essential nutrients.
=== Fertility and family planning ===
In general, women are advised to avoid pregnancy for 12–24 months after bariatric surgery to reduce the possibility of intrauterine growth restriction or nutrient deficiency, since a person having bariatric surgery will likely undergo significant weight loss and changes in metabolism. Over many years, the rates of potential adverse maternal and fetal outcomes have been reduced for mothers following bariatric surgery.
=== Post-operative bariatric plastic surgery ===
After a person successfully loses weight following bariatric surgery, excess skin may occur. Bariatric plastic surgery procedures, sometimes called body contouring, may be an option for people wishing to remove excess skin following the large change in weight. Targeted areas include the arms, buttocks and thighs, abdomen, and breasts, with changes occurring slowly over years.
== Society and culture ==
The rising prevalence of lawsuits related to gastric bypass surgery is a legal concern in different countries. The causes are complex, including the immature characteristics of this technology and an increasing number of patients. In the future, the number of emergent patients who have stomach reduction surgery, long-term complications, and the number of lawsuits due to non-eligible surgery will increase.
=== Economic implications ===
In the 21st century, obesity rates increased globally, and with this, a proportional rise in related diseases and complication. In the United States during 2017-20, an estimated 40% of adults were obese, up from 30% in 1999-2000. The costs of treating obesity and related conditions has a large economic impact globally. This economic impact results from direct treatment of obesity, treatment of obesity-related conditions, as well as other economic losses from decreased workforce productivity.
Bariatric surgery is cost-effective when compared to savings estimated from treatment or prevention of obesity-related conditions. Cost-effectiveness occurs at the individual level due to fewer healthcare expenses for medications, and nationally with a reduction in the overall lifetime healthcare costs.
== Special populations ==
=== Adolescents ===
During the early 21st century, obesity among children and adolescents increased globally, as did treatment options including lifestyle changes, drug treatments, and surgical procedures. The medical complications and health concerns associated with childhood obesity may have short or long-term effects, with a growing concern of a potential decline in overall life expectancy. Childhood obesity may affect mental health and impact eating practices.
Difficulties surrounding obesity treatment selection among children and adolescents include ethical considerations when obtaining consent from those who may be unable to do so without adult guidance or understanding the potential lasting effects of invasive procedures. Among high-quality randomized control trial data for surgical treatment of obesity, many studies are not specific to children and adolescents. Concerns for bullying about overweight or body image exist for those with childhood obesity; self-harm among children and adolescents bullied for their weight also occurs.
Bariatric surgical procedures available to adolescents include: Roux-en-Y gastric bypass, vertical sleeve gastrectomy, and adjustable gastric banding. Multiple organizations have created guidelines for bariatric surgery indications in children and adolescents. In 2022-23, such guidelines overlapped with recommendations for potential bariatric surgical management in children and adolescents with a BMI of 40 or higher, or a BMI of 35 or higher while also experiencing related experiences.
Reviews have shown similar weight loss in adolescents following bariatric surgery as in adults. Reduction of eating disorders for several years after bariatric surgery has also been shown in adolescents after bariatric surgery. Long-term reduction in or resolution of weight-related conditions, such as diabetes and high blood pressure, occurred in adolescents after bariatric surgery. Long-term effects of bariatric surgery in adolescents remains under research, as of 2023.
== History ==
Techniques for weight loss have been reported for decades, with a more formal transition to noting weight loss following surgical intervention in the 1950s when subsequent weight loss after surgical shortening of the small intestine in dogs and people was observed. Specifically, anastomosis between upper and lower portions of the small intestine to skip, or bypass, part of the small intestine led to what was called the jejuno-ileal bypass. A modified version of this procedure showed long-term improvement of lipid levels in people with known high levels of cholesterol following the procedure.
Further modification of the bypass procedure achieved weight loss in obesity, during which an anastomosis between the small intestine and upper lower intestine, known as a jejunocolic bypass, was performed. During the late 1960s, the initiation of bariatric surgery followed the development of a procedure to bypass portions of the stomach – the gastric bypass.
Sleeve gastrectomy (SG), is one of the most popular stomach reduction surgeries and was earliest performed in 1990 as a first-stage operation of duodenal switch (DS) surgery. Patients who go through SG typically experience substantial weight loss, preventing the need for the second phase of DS.
Laparoscopic techniques revolutionized bariatric surgery, making procedures less invasive and recovery quicker. The first laparoscopic gastric bypass performed by Alan Wittgrove in 1994 exemplifies this leap in surgical innovation.The SG laparoscopic version was first performed in 1999.
Historically, the RYGBP is the best bariatric surgery for obese patients, but now being rivalled by the SG. The complication of RYGBP leads people to find less intricate and safer surgeries, the complication including internal hernias and anastomotic complications. Nowadays, SG has a lower risk of complication, and the mortality rate has become the more favorable option for the patients.
== See also ==
Revision weight loss surgery
Endoscopic sleeve gastroplasty
== References ==
== External links ==
Media related to Bariatric surgery at Wikimedia Commons | Wikipedia/Bariatric_surgery |
Chelation therapy is a medical procedure that involves the administration of chelating agents to remove heavy metals from the body. Chelation therapy has a long history of use in clinical toxicology and remains in use for some very specific medical treatments, although it is administered under very careful medical supervision due to various inherent risks, including the mobilization of mercury and other metals through the brain and other parts of the body by the use of weak chelating agents that unbind with metals before elimination, exacerbating existing damage. To avoid mobilization, some practitioners of chelation use strong chelators, such as selenium, taken at low doses over a long period of time.
Chelation therapy must be administered with care as it has a number of possible side effects, including death. In response to increasing use of chelation therapy as alternative medicine and in circumstances in which the therapy should not be used in conventional medicine, various health organizations have confirmed that medical evidence does not support the effectiveness of chelation therapy for any purpose other than the treatment of heavy metal poisoning. Over-the-counter chelation products are not approved for sale in the United States.
== Medical uses ==
Chelation therapy is the preferred medical treatment for metal poisoning, including acute mercury, iron (including in cases of sickle-cell disease and thalassemia), arsenic, lead, uranium, plutonium and other forms of toxic metal poisoning. The chelating agent may be administered intravenously, intramuscularly, or orally, depending on the agent and the type of poisoning.
=== Chelating agents ===
There are a variety of common chelating agents with differing affinities for different metals, physical characteristics, and biological mechanism of action. For the most common forms of heavy metal intoxication – lead, arsenic, or mercury – a number of chelating agents are available. Dimercaptosuccinic acid (DMSA) has been recommended by poison control centers around the world for the treatment of lead poisoning in children. Other chelating agents, such as 2,3-dimercaptopropanesulfonic acid (DMPS) and alpha lipoic acid (ALA), are used in conventional and alternative medicine. Some common chelating agents are ethylenediaminetetraacetic acid (EDTA), 2,3-dimercaptopropanesulfonic acid (DMPS), and thiamine tetrahydrofurfuryl disulfide (TTFD). Calcium-disodium EDTA and DMSA are only approved for the removal of lead by the Food and Drug Administration while DMPS and TTFD are not approved by the FDA. These drugs bind to heavy metals in the body and prevent them from binding to other agents. They are then excreted from the body. The chelating process also removes vital nutrients such as vitamins C and E, therefore these must be supplemented.
The German Environmental Agency (Umweltbundesamt) listed DMSA and DMPS as the two most useful and safe chelating agents available.
== Side effects ==
Chelation therapy, used to remove toxic metals such as lead, arsenic, or mercury from the body, carries a range of potential side effects. When administered appropriately under medical supervision, side effects may include dehydration, hypocalcemia (low calcium levels), renal impairment, elevated liver enzymes, electrolytes imbalances, and allergic reactions. The loss of essential dietary elements such as zinc, magnesium, and iron is common, especially with prolonged therapy, potentially leading to fatigue, weakened immunity, or neurological disturbances.
In contrast, inappropriate or non-medical use for example, in unapproved treatments for autism or cardiovascular disease - has been associated with serious complications, including severe hypocalcemia, neurodevelopmental disorders, and even death. Notably, disodium EDTA had been linked to fatal outcome when used incorrectly, such as through rapid IV administration. For these reasons, regulating authorities like FDA, CDC strongly discourage off label or unsupervised use of chelation agents.
== History ==
Chelation therapy can be traced back to the early 1930s, when Ferdinand Münz, a German chemist working for I.G. Farben, first synthesized ethylenediaminetetraacetic acid (EDTA). Munz was looking for a replacement for citric acid as a water softener. Chelation therapy itself began during World War II when chemists at the University of Oxford searched for an antidote for lewisite, an arsenic-based chemical weapon. The chemists learned that EDTA was particularly effective in treating lead poisoning.
Following World War II, chelation therapy was used to treat workers who had painted United States naval vessels with lead-based paints. In the 1950s, Norman Clarke Sr. was treating workers at a battery factory for lead poisoning when he noticed that some of his patients had improved angina pectoris following chelation therapy. Clarke subsequently administered chelation therapy to patients with angina pectoris and other occlusive vascular disease and published his findings in The American Journal of the Medical Sciences in December 1956. He hypothesized that "EDTA could dissolve disease-causing plaques in the coronary systems of human beings." In a series of 283 patients treated by Clarke et al. From 1956 to 1960, 87% showed improvement in their symptomatology. Other early medical investigators made similar observations of EDTA's role in the treatment of cardiovascular disease (Bechtel, 1956; Bessman, 1957; Perry, 1961; Szekely, 1963; Wenig, 1958: and Wilder, 1962). However, later systemic reviews found that chelation was no better than placebo in treating heart disease.
In the 1960s, BAL was modified into DMSA, a related dithiol with far fewer side effects. DMSA quickly replaced both BAL and EDTA as the primary treatment for lead, arsenic and mercury poisoning in the United States. Esters of DMSA have been developed which are reportedly more effective; for example, the monoisoamyl ester (MiADMSA) is reportedly more effective than DMSA at clearing mercury and cadmium. Research in the former Soviet Union led to the introduction of DMPS, another dithiol, as a mercury-chelating agent. The Soviets also introduced ALA, which is transformed by the body into the dithiol dihydrolipoic acid, a mercury- and arsenic-chelating agent. DMPS has experimental status in the United States, while ALA is a common nutritional supplement.
Since the 1970s, iron chelation therapy has been used as an alternative to regular phlebotomy to treat excess iron stores in people with haemochromatosis. Other chelating agents have been discovered. They all function by making several chemical bonds with metal ions, thus rendering them much less chemically reactive. The resulting complex is water-soluble, allowing it to enter the bloodstream and be excreted harmlessly.
In 1973, a group of practicing physicians created the Academy of Medical Preventics, later renamed the American College for Advancement in Medicine (ACAM). The academy trains and certifies physicians in the safe administration of chelation therapy. Members of the academy continued to use EDTA therapy for the treatment of vascular disease and developed safer administration protocols. However, in 1998 the U.S. Federal Trade Commission (FTC) pursued the ACAM, an organization that promotes "complementary, alternative and integrative medicine" over the claims made regarding the treatment of atherosclerosis in advertisements for EDTA chelation therapy. The FTC concluded that there was a lack of scientific studies to support these claims and that the statements by the ACAM were false. In 1999, the ACAM agreed to stop presenting chelation therapy as effective in treating heart disease, avoiding legal proceedings. In 2010 the U.S. Food and Drug Administration (FDA) warned companies who sold over-the-counter (OTC) chelation products and stated that such "products are unapproved drugs and devices and that it is a violation of federal law to make unproven claims about these products. There are no FDA-approved OTC chelation products."
== Controversies ==
In 1998, the U.S. Federal Trade Commission (FTC) charged that the web site of the American College for Advancement in Medicine (ACAM) and a brochure they published had made false or unsubstantiated claims. In December 1998, the FTC announced that it had secured a consent agreement barring ACAM from making unsubstantiated advertising claims that chelation therapy is effective against atherosclerosis or any other disease of the circulatory system.
In August 2005, doctor error led to the death of a five-year-old boy with autism who was undergoing chelation therapy. Others, including a three-year-old non-autistic girl and a non-autistic adult, have died while undergoing chelation therapy. These deaths were due to cardiac arrest caused by hypocalcemia during chelation therapy. In two of the cases, hypocalcemia appears to have been caused by the administration of Na2EDTA (disodium EDTA) and in the third case the type of EDTA was unknown. Only the three-year-old girl had been found to have an elevated blood lead level and resulting low iron levels and anemia, which is the conventional medical cause for administration of chelation therapy.
According to protocol, EDTA should not be used in the treatment of children. More than 30 deaths have been recorded in association with IV-administered disodium EDTA since the 1970s.
=== Use in alternative medicine ===
In alternative medicine, some practitioners claim chelation therapy can treat a variety of ailments, including heart disease and autism. The use of chelation therapy by alternative medicine practitioners for behavioral and other disorders is considered pseudoscientific; there is no proof that it is effective. Chelation therapy prior to heavy metal testing can artificially raise urinary heavy metal concentrations ("provoked" urine testing) and lead to inappropriate and unnecessary treatment. The American College of Medical Toxicology and the American Academy of Clinical Toxicology warn the public that chelating drugs used in chelation therapy may have serious side effects, including liver and kidney damage, blood pressure changes, allergies and in some cases even death of the patient.
==== Cancer ====
The American Cancer Society says of chelation therapy: "Available scientific evidence does not support claims that it is effective for treating other conditions such as cancer. Chelation therapy can be toxic and has the potential to cause kidney damage, irregular heartbeat, and even death."
==== Cardiovascular disease ====
According to the findings of a 1997 systematic review, EDTA chelation therapy is not effective as a treatment for coronary artery disease and this use is not approved in the United States by the US Food and Drug Administration (FDA).
The American Heart Association stated in 1997 that there is "no scientific evidence to demonstrate any benefit from this form of therapy." The FDA, the National Institutes of Health (NIH) and the American College of Cardiology "all agree with the American Heart Association" that "there have been no adequate, controlled, published scientific studies using currently approved scientific methodology to support this therapy for cardiovascular disease." They speculate that any improvement among heart patients undergoing chelation therapy can be attributed to the placebo effect and generally recommended lifestyle changes such as "quitting smoking, losing weight, eating more fruits and vegetables, avoiding foods high in saturated fats and exercising regularly." They also are concerned that patients could put off proven treatments for heart disease like drugs or surgery.
A systematic review published in 2005 found that controlled scientific studies did not support chelation therapy for heart disease. It found that very small trials and uncontrolled descriptive studies have reported benefits while larger controlled studies have found results no better than placebo.
In 2009, the Montana Board of Medical Examiners issued a position paper concluding that "chelation therapy has no proven efficacy in the treatment of cardiovascular disease, and in some patients could be injurious."
The U.S. National Center for Complementary and Alternative Medicine (NCCAM) conducted a trial on the chelation therapy's safety and efficacy for patients with coronary artery disease. NCCAM Director Stephen E. Straus cited the "widespread use of chelation therapy in lieu of established therapies, the lack of adequate prior research to verify its safety and effectiveness, and the overall impact of coronary artery disease" as factors motivating the trial. The study has been criticized by some who said it was unethical, unnecessary and dangerous, and that multiple studies conducted prior to it demonstrated that the treatment provides no benefit.
The US National Center for Complementary and Alternative Medicine began the Trial to Assess Chelation Therapy (TACT) in 2003. Patient enrollment was to be completed around July 2009 with final completion around July 2010, but enrollment in the trial was voluntarily suspended by organizers in September 2008 after the Office for Human Research Protections began investigating complaints such as inadequate informed consent. Additionally, the trial was criticized for lacking prior Phase I and II studies, and critics summarized previous controlled trials as having "found no evidence that chelation is superior to placebo for treatment of CAD or PVD." The same critics argued that methodological flaws and lack of prior probability made the trial "unethical, dangerous, pointless, and wasteful." The American College of Cardiology supported the trial and research to explore whether chelation therapy was effective in treating heart disease. Evidence of insurance fraud and other felony convictions among (chelation proponent) investigators further undermined the credibility of the trial.
The final results of TACT were published in November 2012. The authors concluded that disodium EDTA chelation "modestly" reduced the risk of adverse cardiovascular outcomes among stable patients with a history of myocardial infarction. The study also showed a "marked" reduction in cardiovascular events in diabetic patients treated with EDTA chelation. An editorial published in the Journal of the American Medical Association said that "the study findings may provide novel hypotheses that merit further evaluation to help understand the pathophysiology of secondary prevention of vascular disease." Critics of the study characterized the study as showing no support for the use of chelation therapy in coronary heart disease, particularly the claims to reduce the need for coronary artery bypass grafting (CABG, pronounced "cabbage").
==== Autism ====
Quackwatch says that autism is one of the conditions for which chelation therapy has been falsely promoted as effective, and practitioners falsify diagnoses of metal poisoning to trick parents into having their children undergo the risky process. As of 2008, up to 7% of children with autism worldwide had been subjected to chelation therapy. The death of two children in 2005 was caused by the administration of chelation treatments, according to the American Center for Disease Control. One of them had autism. Parents either have a doctor use a treatment for lead poisoning, or buy unregulated supplements, in particular DMSA and lipoic acid. Aspies For Freedom, an autism rights organization, considers this use of chelation therapy unethical and potentially dangerous. There is little to no credible scientific research that supports the use of chelation therapy for the effective treatment of autism.
== See also ==
List of ineffective cancer treatments
Detoxification
== References ==
== External links ==
Chelation Therapy: Unproven Claims and Unsound Theories - Quackwatch | Wikipedia/Chelation_therapy |
Attentional control, commonly referred to as concentration, refers to an individual's capacity to choose what they pay attention to and what they ignore. It is also known as endogenous attention or executive attention. In lay terms, attentional control can be described as an individual's ability to concentrate. Primarily mediated by the frontal areas of the brain including the anterior cingulate cortex, attentional control and attentional shifting are thought to be closely related to other executive functions such as working memory.
== General overview of research ==
Sources of attention in the brain create a system of three networks: alertness (maintaining awareness), orientation (information from sensory input), and executive control (resolving conflict). These three networks have been studied using experimental designs involving adults, children, and monkeys, with and without abnormalities of attention. Research designs include the Stroop task
and flanker task, which study executive control with analysis techniques including event-related functional magnetic resonance image (fMRI). While some research designs focus specifically on one aspect of attention (such as executive control), others experiments view several areas, which examine interactions between the alerting, orienting, and executive control networks. More recently, the Attention Network Test (ANT), designed by Fan and Posner, has been used to obtain efficiency measures of the three networks, and allow their relationships to be examined. It was designed as a behavioural task simple enough to obtain data from children, patients, and animals. The task requires participants to quickly respond to cues given on a computer screen, while having their attention fixated on a center target.
== Development ==
=== Infancy ===
Early researchers studying the development of the frontal cortex thought that it was functionally silent during the first year of life. Similarly, early research suggested that infants aged one year or younger are completely passive in the allocation of their attention, and have no capacity to choose what they pay attention to and what they ignore. This is shown, for example, in the phenomenon of 'sticky fixation', whereby infants are incapable of disengaging their attention from a particularly salient target. Other research has suggested, however, that even very young infants do have some capacity to exercise control over their allocation of attention, albeit in a much more limited sense.
=== Childhood ===
As the frontal lobes mature, children's capacity to exercise attentional control increases, although attentional control abilities remain much poorer in children than they do in adults. Some children show impaired development of attentional control abilities, thought to arise from the relatively slower development of frontal areas of the brain, which sometimes results in a diagnosis of Attention Deficit Hyperactivity Disorder (ADHD).
=== Elderly ===
Some studies of aging and cognition focus on working memory processes and declines in attentional control. One study used fMRI measures during a Stroop task comparing neural activity of attentional control in younger (21–27 years) and older participants (60–75 years). Conditions included increased competition and increased conflict. Results showed evidence of decreases in responsiveness in brain areas associated with attentional control for the older group. This result suggests that older people may have decreases in their ability to utilize attentional control in their everyday lives.
A major contributor to age-related decreased attentional control includes the weight of the brain. Several studies conclude that the brain experiences rapid weight loss after the age of 60. This loss of brain weight results from a decrease in cerebral white matter and gray matter. White matter is the area in the brain responsible for exchanging information between gray matter areas. Gray matter tissue in the central nervous system enables individuals to interact with the world and carry out highly skilled functions. Studies reveal that individuals who engage in physical activity increase the cortical volume of gray matter later in life, preventing age-related atrophy and promoting attentional control. However, because most individuals' brains undergo pathological changes after the age of 80 or develop cardiac disease, neuron loss occurs and the brain volume decreases.
== Abnormal development ==
Disrupted attentional control has been noted not just in the early development of conditions for which the core deficit is related to attention such as ADHD, but also in conditions such as autism and anxiety. Disrupted attentional control has also been reported in infants born preterm, as well as in infants with genetic disorders such as Down syndrome and Williams syndrome. Several groups have also reported impaired attentional control early in development in children from lower socioeconomic status families.
The patterns of disrupted attentional control relate to findings of disrupted performance on executive functions tasks such as working memory across a wide number of different disorder groups. The question of why the executive functions appear to be disrupted across so many different disorder groups remains, however, poorly understood.
=== Relevance to mental illness ===
Studies have shown that there is a high probability that those with low attentional control also experience other mental conditions. Low attentional control is more common among those with attention deficit hyperactivity disorder (ADHD), "a disorder with persistent age-inappropriate symptoms of inattention, hyperactivity, and impulsivity that are sufficient to cause impairment in major life activities". Low attentional control is also common in individuals with schizophrenia and Alzheimer's disease, those with social anxiety, trait anxiety, and depression, and attention difficulties following a stroke. Individuals respond quicker and have stronger overall executive control when they have low levels of anxiety and depression. Weak attentional control is also thought to increase chances of developing a psychopathological condition, as these individuals have disrupted threat processing and magnified emotional responses to threat. More researchers are accounting for attentional control in studies that might not necessarily focus on attention by having participants fill out an Attentional Control Scale (ACS) or a Cognitive Attentional Syndrome-1 (CAS1), both of which are self-reporting questionnaires that measure attentional focus and shifting. Researchers suggest that people should use experimental and longitudinal designs to address the relationship between ACS, emotional functioning, CAS, and attention to threat. This is due to the increasing problematic occurrences experts are seeing in the field regarding attentional control in relation to other mental illnesses.
Attention problems are also characteristic of anxiety disorders like PTSD (Post-Traumatic Stress Disorder). A recent review revealed that 61.2% of current studies found that participants who experienced PTSD suffered from significant attentional control problems. These problems caused by PTSD can lead to the development of an attentional bias, which causes a person to process emotionally negative information preferentially over emotionally positive information. Patients who suffer from PTSD commonly struggle to concentrate on certain tasks for longer periods of time, allowing intrusive thoughts to override their current focus. This interference can be caused by many different factors, but it is most commonly triggered by emotional cues, particularly the emotion of fear. Attention is considered a gateway function to advanced cognitive processes such as memory and learning, and attentional interference can cause such cognitive processes to decrease. In recent years, attentional control therapies have been used to improve attentional control in patients who suffer from PTSD. More recently, yoga and meditation were found to positivity affect attentional control in patients who have experienced PTSD.
== Applications ==
=== Performance ===
Attentional control theory focuses on anxiety and cognitive performance. The assumption of this theory is that the effects of anxiety on attentional control are key to understanding the relationship between anxiety and performance. In general, anxiety inhibits attentional control on a specific task by impairing processing efficiency. There are three functions associated with this theory. The inhibition function prevents stimuli unrelated to a task and responses from disrupting performance. The shifting function is used to allocate attention to the stimuli that are most relevant to the task. The updating function is used to update and monitor information in working memory. There are three main hypotheses associated with attentional control theory. First, the efficiency of the central executive is impaired by anxiety. Second, anxiety impairs the inhibition function, and third, anxiety impairs the shifting function.
Studies related to attentional control and performance take two differing approaches. Specifically, research on attentional capture has two modes: voluntary and reflexive. The voluntary mode is a top down approach where attention is shifted according to high-level cognitive processes. The reflexive mode is a bottom up approach where attention shifts involuntarily based on a stimulus's attention attracting properties. These modes are important to understanding how attentional control works.
=== Mindfulness ===
Even four days of mindfulness meditation training can significantly improve visuo-spatial processing, working memory and executive functioning. However, research has shown mixed results surrounding whether mindfulness effects attentional control directly. Participants did tasks of sustained attention, inhibition, switching, and object detection. These tasks were done before and after an 8-week mindfulness based stress reduction course (MBSR), and were compared to a control group. There were no significant differences between the groups, meaning that the MBSR course did not affect attentional control. However, an active randomized controlled trial showed that a mobile-based mindfulness app with extensive self-assessment features may have long-term benefits for attentional control in healthy participants. Mindfulness influences non-directed attention and other things like emotional well-being.
=== Learning ===
Modular approaches view cognitive development as a mosaic-like process, according to which cognitive faculties develop separately according to genetically predetermined maturational timetables. Prominent authors who take a modular approach to cognitive development include Jerry Fodor, Elizabeth Spelke and Steven Pinker. In contrast, other authors such as Annette Karmiloff-Smith, Mark Johnson and Linda Smith have instead advocated taking a more interactive or dynamical systems approaches to cognitive development. According to these approaches, which are known as neuroconstructivist approaches, cognitive systems interact over developmental time as certain cognitive faculties are required for the subsequent acquisition of other faculties in other areas.
Amongst authors who take neuroconstructivist approaches to development, particular importance has been attached to attentional control, since it is thought to be a domain-general process that may influence the subsequent acquisition of other skills in other areas. The ability to regulate and direct attention releases the child from the constraints of only responding to environmental events, and means they are able to actively guide their attention towards the information-rich areas key for learning. For example, a number of authors have looked at the relationship between an infant's capacity to exercise attentional control and their subsequent performance during language acquisition.
Working memory capacity has been studied to understand how memory functions. The ability to predict the effectiveness of someone's working memory capacity comes from attentional control mechanisms. These mechanisms help with the regulation of goals, behavior, and outside distractions, which are all important for effective learning.
== Visual attentional control ==
Our brains have distinct attention systems that have been shaped throughout time by evolution. Visual attention operates mainly on three different representations: location
, feature, and object-based. The spatial separation between two objects has an effect on attention. People can selectively pay attention to one of two objects in the same general location. Research has also been done on attention to non-object based things like motion. When directing attention to a feature like motion, neuronal activity increases in areas specific for the feature. When visually searching for a non-spatial feature or a perceptual feature, selectively enhancing the sensitivity to that specific feature plays a role in directing attention. When people are told to look for motion, then motion will capture their attention, but attention is not captured by motion if they are told to look for color.
=== Spatial focus of attention ===
According to fMRI studies of the brain and behavioral observations, visual attention can be moved independently of moving eye position. Studies have had participants fixate their eyes on a central point and measured brain activity as stimuli were presented outside the visual fixation point. fMRI findings show changes in brain activity correlated with the shift in spatial attention to the various stimuli. Behavioral studies have also shown that when a person knows where a stimulus is likely to appear, their attention can shift to it more rapidly and process it better.
Other studies have demonstrated that perceptual and cognitive load affect spatial focusing of attention. These two mechanisms interact oppositely so that when cognitive load is decreased, perceptual load must be high to increase spatial attention focusing.
== Auditory alertness ==
The cocktail party effect is the phenomenon that a person hears his or her name even when not attending to the conversation. To study this, a screening measure for attentional control was given that tested a person's ability to keep track of words while also doing math problems. Participants were separated into two groups---low and high span attentional control ability groups. They listened to two word lists read simultaneously by a male and a female voice and were told to ignore the male voice. Their name was read by the "ignored" male voice. Low span people were more likely to hear their name compared to high span people. This result suggests that people with lower attentional control ability have more trouble inhibiting information from the surrounding environment.
== See also ==
== References ==
== Further reading ==
Mangun, George R. (2012). The Neuroscience of Attention. New York, New York: Oxford University Press, Inc.
Bear, Mark; Connors, Barry; Paradiso, Michael (2007). Neuroscience Exploring the Brain. Baltimore, MD: Lippincott Williams & Wilkins. ISBN 9780781760034.
Linnell, Karina J.; Serge Caparos (18 July 2011). "Perceptual and Cognitive Load interact to Control the Spatial Focus of Attention". Journal of Experimental Psychology. 5. 37 (5): 1643–1648. doi:10.1037/a0024669. PMID 21767051.
== External links == | Wikipedia/Attentional_control |
Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the gastrointestinal tract may include anemia, skin rashes, arthritis, inflammation of the eye, and fatigue. The skin rashes may be due to infections, as well as pyoderma gangrenosum or erythema nodosum. Bowel obstruction may occur as a complication of chronic inflammation, and those with the disease are at greater risk of colon cancer and small bowel cancer.
Although the precise causes of Crohn's disease (CD) are unknown, it is believed to be caused by a combination of environmental, immune, and bacterial factors in genetically susceptible individuals. It results in a chronic inflammatory disorder, in which the body's immune system defends the gastrointestinal tract, possibly targeting microbial antigens. Although Crohn's is an immune-related disease, it does not seem to be an autoimmune disease (the immune system is not triggered by the body itself). The exact underlying immune problem is not clear; however, it may be an immunodeficiency state.
About half of the overall risk is related to genetics, with more than 70 genes involved. Tobacco smokers are three times as likely to develop Crohn's disease as non-smokers. Crohn's disease is often triggered after a gastroenteritis episode. Other conditions with similar symptoms include irritable bowel syndrome and Behçet's disease.
There is no known cure for Crohn's disease. Treatment options are intended to help with symptoms, maintain remission, and prevent relapse. In those newly diagnosed, a corticosteroid may be used for a brief period of time to improve symptoms rapidly, alongside another medication such as either methotrexate or a thiopurine to prevent recurrence. Cessation of smoking is recommended for people with Crohn's disease. One in five people with the disease is admitted to the hospital each year, and half of those with the disease will require surgery at some time during a ten-year period. Surgery is kept to a minimum whenever possible, but it is sometimes essential for treating abscesses, certain bowel obstructions, and cancers. Checking for bowel cancer via colonoscopy is recommended every 1-3 years, starting eight years after the disease has begun.
Crohn's disease affects about 3.2 per 1,000 people in Europe and North America; it is less common in Asia and Africa. It has historically been more common in the developed world. Rates have, however, been increasing, particularly in the developing world, since the 1970s. Inflammatory bowel disease resulted in 47,400 deaths in 2015, and those with Crohn's disease have a slightly reduced life expectancy. Onset of Crohn's disease tends to start in adolescence and young adulthood, though it can occur at any age. Males and females are affected roughly equally.
== Name controversy ==
The disease was named after gastroenterologist Burrill Bernard Crohn, who in 1932, together with Leon Ginzburg (1898–1988) and Gordon D. Oppenheimer (1900–1974) at Mount Sinai Hospital in New York, described a series of people with inflammation of the terminal ileum of the small intestine, the area most commonly affected by the illness. The decision to name the disease after Crohn remains controversial. While Crohn, in his memoir, describes his original investigation of the disease, Ginzburg provided strong evidence of how he and Oppenheimer were the first to study the disease.
== Signs and symptoms ==
=== Gastrointestinal ===
Many people with Crohn's disease have symptoms for years before the diagnosis. The usual onset is in the teens and twenties, but can occur at any age. People with Crohn's disease experience chronic recurring periods of flare-ups and remission.
=== Perianal ===
Perianal discomfort may also be prominent in Crohn's disease. Itchiness or pain around the anus may be suggestive of inflammation of the anus, or perianal complications such as anal fissures, fistulae, or abscesses around the anal area. Perianal skin tags are also common in Crohn's disease, and may appear with or without the presence of colorectal polyps.
=== Intestines ===
The intestines, especially the colon and terminal ileum, are the areas of the body affected most commonly. Abdominal pain is a common initial symptom of Crohn's disease, especially in the lower right abdomen. Flatulence, bloating, and abdominal distension are additional symptoms and may also add to the intestinal discomfort. Pain is often accompanied by non-bloody diarrhea, however in some cases the diarrhea can be bloody. Inflammation in different areas of the intestinal tract can affect the quality of the feces. Ileitis typically results in large-volume, watery feces, while colitis may result in a smaller volume of feces of greater frequency. Fecal consistency may range from solid to watery. In severe cases, an individual may have more than 20 bowel movements per day, and may need to awaken at night to defecate. Visible bleeding in the feces is less common in Crohn's disease than in ulcerative colitis, but is not unusual. Bloody bowel movements are usually intermittent, and may be bright red, dark maroon, or even black in color. The color of bloody stool depends on the location of the bleed. In severe Crohn's colitis, bleeding may be copious.
=== Stomach and esophagus ===
The stomach is rarely the sole or predominant site of Crohn's disease. To date, there are only a few documented case reports of adults with isolated gastric Crohn's disease and no reports in the pediatric population. Isolated stomach involvement is very unusual presentation accounting for less than 0.07% of all gastrointestinal Crohn's disease. However, the esophagus and stomach are increasingly understood to be affected in people with intestinal Crohn's disease. Recent studies suggest upper GI involvement occurs in 13-16% of cases, typically presenting after distal symptoms. Upper gastrointestinal symptoms may include difficulty swallowing (dysphagia), painful swallowing (odynophagia), upper abdominal pain, and vomiting.
=== Oropharynx (mouth) ===
The mouth may be affected by recurrent canker sores (aphthous ulcers). Recurrent aphthous ulcers are common; however, it is not clear whether this is due to Crohn's disease or simply that they are common in the general population. Other findings may include diffuse or nodular swelling of the mouth, a cobblestone appearance inside the mouth, granulomatous ulcers, or pyostomatitis vegetans. Medications that are commonly prescribed to treat Crohn's disease, such as anti-inflammatory and sulfa-containing drugs, may cause lichenoid drug reactions in the mouth. Fungal infection such as candidiasis is also common due to the immunosuppression required in the treatment of the disease. Signs of anemia such as pallor and angular cheilitis or glossitis are also common due to nutritional malabsorption.
People with Crohn's disease are also susceptible to angular stomatitis, an inflammation of the corners of the mouth, and pyostomatitis vegetans.
=== Systemic ===
Like many other chronic, inflammatory diseases, Crohn's disease can cause a variety of systemic symptoms. Among children, growth failure is common. Many children are first diagnosed with Crohn's disease based on inability to maintain growth. As it may manifest at the time of the growth spurt in puberty, as many as 30% of children with Crohn's disease may have retardation of growth. Fever may also be present, though fevers greater than 38.5 °C (101.3 °F) are uncommon unless there is a complication such as an abscess. Among older individuals, Crohn's disease may manifest as weight loss, usually related to decreased food intake, since individuals with intestinal symptoms from Crohn's disease often feel better when they do not eat and might lose their appetite. People with extensive small intestine disease may also have malabsorption of carbohydrates or lipids, which can further exacerbate weight loss.
=== Extraintestinal ===
Crohn's disease can affect many organ systems beyond the gastrointestinal tract.
==== Visual ====
Inflammation of the interior portion of the eye, known as uveitis, can cause blurred vision and eye pain, especially when exposed to light (photophobia). Uveitis can lead to loss of vision if untreated.
Inflammation may also involve the white part of the eye (sclera) or the overlying connective tissue (episclera), which causes conditions called scleritis and episcleritis, respectively.
Other very rare ophthalmological manifestations include: conjunctivitis, glaucoma, and retinal vascular disease.
The pathophysiology of ocular inflammation in people with Crohn's disease is complex and remains uncertain. The association between inflammatory conditions of the eye and Crohn's disease is due to many people with Crohn's disease having genetic markers such as HLA-B07, HLA-B27 and HLA-DRB1*0103. Additionally, cytokines IL-6, IL-10, and IL-17 which are produced in the bowel enter the circulatory system and travel to the eyes to trigger inflammation.
==== Gallbladder and liver ====
Crohn's disease that affects the ileum may result in an increased risk of gallstones. This is due to a decrease in bile acid resorption in the ileum, resulting in bile excretion in the stool. As a result, the cholesterol/bile ratio increases in the gallbladder, resulting in an increased risk for gallstones. Although the association is greater in the context of ulcerative colitis, Crohn's disease may also be associated with primary sclerosing cholangitis, a type of inflammation of the bile ducts. Specifically, 0.96% of people with Crohn's disease also have primary sclerosing cholangitis.
Liver involvement of Crohn's disease can include cirrhosis and steatosis. Nonalcoholic fatty liver disease (nonalcoholic steatohepatitis, NAFLD) are relatively common and can slowly progress to end-stage liver disease. NAFLD sensitizes the liver to injury and increases the risk of developing acute or chronic liver failure following another liver injury.
Other rare hepatobiliary manifestations of Crohn's disease include: cholangiocarcinoma, granulomatous hepatitis, cholelithiasis, autoimmune hepatitis, hepatic abscess, and pericholangitis.
==== Renal and urological ====
Nephrolithiasis, obstructive uropathy, and fistulization of the urinary tract directly result from the underlying disease process. Nephrolithiasis is due to calcium oxalate or uric acid stones. Calcium oxalate stones due to hyperoxaluria are typically associated with either distal ileal Crohn's disease or ileal resection. Oxalate absorption increases in the presence of unabsorbed fatty acids in the colon. The fatty acids compete with oxalate to bind calcium, displacing the oxalate, which can then be absorbed as unbound sodium oxalate across colonocytes and excreted into the urine. Because sodium oxalate is only absorbed in the colon, calcium oxalate stones form only in people with an intact colon. People with an ileostomy are prone to formation of uric acid stones because of frequent dehydration. The sudden onset of severe abdominal, back, or flank pain in patients with IBD, particularly if different from the usual discomfort, should lead to inclusion of a renal stone in the differential diagnosis.
Urological manifestations in people with IBD may include ureteral calculi, enterovesical fistula, perivesical infection, perinephric abscess, and obstructive uropathy with hydronephrosis. Ureteral compression is associated with retroperitoneal extension of the phlegmonous inflammatory process involving the terminal ileum and cecum, and may result in hydronephrosis severe enough to cause hypertension.
Immune complex glomerulonephritis presenting with proteinuria and hematuria has been described in children and adults with Crohn's disease or ulcerative colitis. Diagnosis is by renal biopsy, and treatment parallels the underlying IBD.
Amyloidosis (see endocrinological involvement) secondary to Crohn's disease has been described and is known to affect the kidneys.
==== Pancreatic ====
Pancreatitis may be associated with both ulcerative colitis and Crohn's disease. The most common cause is iatrogenic and involves sensitivity to medications used to treat IBD, including sulfasalazine, mesalamine, 6-mercaptopurine, and azathioprine. Pancreatitis may present as symptomatic or more commonly asymptomatic disease in adults with IBD.
==== Cardiovascular and circulatory ====
Children and adults with IBD have been rarely (<1%) reported developing pleuropericarditis either at initial presentation or during active or quiescent disease. The pathogenesis of pleuropericarditis is unknown, although certain medications (e.g., sulfasalazine and mesalamine derivatives) have been implicated in some cases. The clinical presentation may include chest pain, dyspnea, or in severe cases pericardial tamponade requiring rapid drainage. Nonsteroidal anti-inflammatory drugs have been used as therapy, although this should be weighed against the hypothetical risk of exacerbating the underlying IBD.
In rare cases, cardiomyopathy, endocarditis, and myocarditis have been described.
Crohn's disease also increases the risk of blood clots; painful swelling of the lower legs can be a sign of deep venous thrombosis, while difficulty breathing may be a result of pulmonary embolism.
==== Respiratory ====
Laryngeal involvement in inflammatory bowel disease is extremely rare. Only 12 cases of laryngeal involvement in Crohn's disease have been reported as of 2019. Moreover, only one case of laryngeal manifestations in ulcerative colitis has been reported as of the same date. Nine people complained of difficulty in breathing due to edema and ulceration from the larynx to the hypopharynx. Hoarseness, sore throat, and odynophagia are other symptoms of laryngeal involvement of Crohn's disease.
Considering extraintestinal manifestations of Crohn's disease, those involving the lung are relatively rare. However, there is a wide array of lung manifestations, ranging from subclinical alterations, airway diseases and lung parenchymal diseases to pleural diseases and drug-related diseases. The most frequent manifestation is bronchial inflammation and suppuration with or without bronchiectasis. There are a number of mechanisms by which the lungs may become involved in Crohn's disease. These include the same embryological origin of the lung and gastrointestinal tract by ancestral intestine, similar immune systems in the pulmonary and intestinal mucosa, the presence of circulating immune complexes and auto-antibodies, and the adverse pulmonary effects of some drugs. A complete list of known pulmonary manifestations include: fibrosing alveolitis, pulmonary vasculitis, apical fibrosis, bronchiectasis, bronchitis, bronchiolitis, tracheal stenosis, granulomatous lung disease, and abnormal pulmonary function.
==== Musculoskeletal ====
Crohn's disease is associated with a type of rheumatologic disease known as seronegative spondyloarthropathy. This group of diseases is characterized by inflammation of one or more joints (arthritis) or muscle insertions (enthesitis). The arthritis in Crohn's disease can be divided into two types. The first type affects larger weight-bearing joints such as the knee (most common), hips, shoulders, wrists, or elbows. The second type symmetrically involves five or more of the small joints of the hands and feet. The arthritis may also involve the spine, leading to ankylosing spondylitis if the entire spine is involved, or simply sacroiliitis if only the sacroiliac joint is involved.
Crohn's disease increases the risk of osteoporosis or thinning of the bones. Individuals with osteoporosis are at increased risk of bone fractures.
==== Dermatological ====
Crohn's disease may also involve the skin, blood, and endocrine system. Erythema nodosum is the most common type of skin problem, occurring in around 8% of people with Crohn's disease, producing raised, tender red nodules usually appearing on the shins. Erythema nodosum is due to inflammation of the underlying subcutaneous tissue, and is characterized by septal panniculitis.
Pyoderma gangrenosum is a less common skin problem, occurring in under 2%, and is typically a painful ulcerating nodule.
Clubbing, a deformity of the ends of the fingers, may also be a result of Crohn's disease.
Other very rare dermatological manifestations include: pyostomatitis vegetans, erythema multiforme, epidermolysis bullosa acquista (described in a case report), and metastatic Crohn's disease (the spread of Crohn's inflammation to the skin). It is unknown if Sweet's syndrome is connected to Crohn's disease.
==== Neurological ====
Crohn's disease can also cause neurological complications (reportedly in up to 15% of cases). The most common of these are seizures, stroke, myopathy, peripheral neuropathy, headache, and depression.
Central and peripheral neurological disorders are described in people with IBD and include peripheral neuropathies, myopathies, focal central nervous system defects, convulsions, confusional episodes, meningitis, syncope, optic neuritis, and sensorineural loss. Autoimmune mechanisms are proposed for involvement with IBD. Nutritional deficiencies associated with neurological manifestations, such as vitamin B12 deficiency, should be investigated. Spinal abscess has been reported in both a child and an adult with initial complaints of severe back pain due to extension of a psoas abscess from the epidural space to the subarachnoid space.
==== Psychiatric and psychological ====
Crohn's disease is linked to many psychological disorders, including depression and anxiety, denial of one's disease, the need for dependence or dependent behaviors, feeling overwhelmed, and having a poor self-image.
Many studies have found that people with IBD report a higher frequency of depressive and anxiety disorders than the general population; most studies confirm that women with IBD are more likely than men to develop affective disorders and show that up to 65% of them may have depression and anxiety disorder.
==== Endocrinological or hematological ====
Leukocytosis and thrombocytopenia are usually due to immunosuppressant treatments or sulfasalazine. Plasma erythropoietin levels often are lower in patients with IBD than expected, in conjunction with severe anemia.
Thrombocytosis and thromboembolic events resulting from a hypercoagulable state in people with IBD can lead to pulmonary embolism or thrombosis elsewhere in the body. Thrombosis has been reported in 1.8% of people with ulcerative colitis and 3.1% of people with Crohn's disease. Thromboembolism and thrombosis are less frequently reported among children, with three people with ulcerative colitis and one with Crohn's disease described in case reports.
In rare cases, hypercoagulation disorders and portal vein thrombosis have been described.
==== Malnutrition symptoms ====
People with Crohn's disease may develop anemia due to vitamin B12, folate, iron deficiency, or due to anemia of chronic disease. The most common is iron deficiency anemia from chronic blood loss, reduced dietary intake, and persistent inflammation leading to increased hepcidin levels, restricting iron absorption in the duodenum. As Crohn's disease most commonly affects the terminal ileum where the vitamin B12/intrinsic factor complex is absorbed, B12 deficiency may be seen. This is particularly common after one has had a surgical procedure to remove the ileum. Involvement of the duodenum and jejunum can impair the absorption of many other nutrients including folate. People with Crohn's often also have issues with small bowel bacterial overgrowth syndrome, which can produce micronutrient deficiencies.
=== Complications ===
==== Intestinal damage ====
Crohn's disease can lead to several mechanical complications within the intestines, including obstruction, fistulae, and abscesses. Obstruction typically occurs from strictures or adhesions that narrow the lumen, blocking the passage of the intestinal contents. A fistula can develop between two loops of bowel, between the bowel and bladder, between the bowel and vagina, and between the bowel and skin. Abscesses are walled-off concentrations of infection, which can occur in the abdomen or in the perianal area. Crohn's is responsible for 10% of vesicoenteric fistulae, and is the most common cause of ileovesical fistulae.
Symptoms caused by intestinal stenosis, or the tightening and narrowing of the bowel, are also common in Crohn's disease. Abdominal pain is often most severe in areas of the bowel with stenosis. Persistent vomiting and nausea may indicate stenosis from small bowel obstruction or disease involving the stomach, pylorus, or duodenum.
Intestinal granulomas are a walled-off portions of the intestine by macrophages in order to isolate infections. Granuloma formation is more often seen in younger people, and mainly in the severe, active penetrating disease. Granuloma is considered the hallmark of microscopic diagnosis in Crohn's disease, but granulomas can be detected in only 21–60% of people with Crohn's disease.
==== Cancer ====
Crohn's disease also increases the risk of cancer in the area of inflammation. For example, individuals with Crohn's disease involving the small bowel are at higher risk for small intestinal cancer. Similarly, people with Crohn's colitis have a relative risk of 5.6 for developing colon cancer. Screening for colon cancer with colonoscopy is recommended for anyone who has had Crohn's colitis for at least eight years.
Some studies suggest there is a role for chemoprotection in the prevention of colorectal cancer in Crohn's involving the colon; two agents have been suggested, folate and mesalamine preparations. Also, immunomodulators and biologic agents used to treat this disease may promote the development of extra-intestinal cancers.
Some cancers, such as acute myelocytic leukaemia have been described in cases of Crohn's disease. Hepatosplenic T-cell lymphoma (HSTCL) is a rare, lethal disease generally seen in young males with inflammatory bowel disease. TNF-α Inhibitor treatments (infliximab, adalimumab, certolizumab, natalizumab, and etanercept) are thought to be the cause of this rare disease.
==== Major complications ====
Major complications of Crohn's disease include bowel obstruction, abscesses, free perforation, and hemorrhage, which in rare cases may be fatal.
==== Other complications ====
Individuals with Crohn's disease are at risk of malnutrition for many reasons, including decreased food intake and malabsorption. The risk increases following resection of the small bowel. Such individuals may require oral supplements to increase their caloric intake, or in severe cases, total parenteral nutrition (TPN). Most people with moderate or severe Crohn's disease are referred to a dietitian for assistance with nutrition.
Small intestinal bacterial overgrowth (SIBO) is characterized by excessive proliferation of colonic bacterial species in the small bowel. Potential causes of SIBO include fistulae, strictures, or motility disturbances. Hence, people with Crohn's disease are especially predisposed to develop SIBO. As a result, people with Crohn's disease may experience malabsorption and report symptoms such as weight loss, watery diarrhea, meteorism, flatulence, and abdominal pain, mimicking acute flare.
==== Pregnancy ====
Crohn's disease can be problematic during pregnancy, and some medications can cause adverse outcomes for the fetus or mother. Consultation with an obstetrician and gastroenterologist about Crohn's disease and all medications facilitates preventive measures. In some cases, remission occurs during pregnancy. Certain medications can also lower sperm count or otherwise adversely affect a man's fertility.
==== Ostomy-related complications ====
Common complications of an ostomy (a common surgery in Crohn's disease) are: mucosal edema, peristomal dermatitis, retraction, ostomy prolapse, mucosal/skin detachment, hematoma, necrosis, parastomal hernia, and stenosis.
== Etiology ==
The etiology, or cause, of Crohn's disease is unknown. Many theories have been disputed, with four main theories hypothesized to be the primary mechanism of Crohn's disease. In autoimmune diseases, antibodies and T lymphocytes are the primary mode of inflammation. These cells and bodies are part of the adaptive immune system, or the part of the immune system that learns to fight foreign bodies when first identified. Autoinflammatory diseases are diseases where the innate immune system, or the immune system we are genetically coded with, is designed to attack our own cells. Crohn's disease likely has involvement of both the adaptive and innate immune systems.
=== Autoinflammatory theory ===
Crohn's disease can be described as a multifactorial autoinflammatory disease. The etiopathogenesis of Crohn's disease is still unknown. In any event, a loss of the regulatory capacity of the immune apparatus would be implicated in the onset of the disease. In this respect interestingly enough, as for Blau's disease (a monogenic autoinflammatory disease), the NOD2 gene mutations have been linked to Crohn's disease. However, in Crohn's disease, NOD2 mutations act as a risk factor, being more common among people with Crohn's disease than the background population, while in Blau's disease NOD2 mutations are linked directly to this syndrome, as it is an autosomal-dominant disease. All this new knowledge in the pathogenesis of Crohn's disease allows us to put this multifactorial disease in the group of autoinflammatory syndromes.
Some examples of how the innate immune system affects bowel inflammation have been described. A meta-analysis of Crohn's disease genome-wide association studies revealed 71 distinct Crohn's disease-susceptibility loci. Interestingly, three very important Crohn's disease-susceptibility genes (the intracellular pathogen-recognition receptor, NOD2; the autophagy-related 16-like 1, ATG16L1 and the immunity-related GTPase M, IRGM) are involved in innate immune responses against gut microbiota, while one (the X-box binding protein 1) is involved in regulation of the [adaptive] immune pathway via MHC class II, resulting in autoinflammatory inflammation. Studies have also found that increased ILC3 can overexpress major histocompatibility complex (MHC) II. MHC class II can induce CD4+ T cell apoptosis, thus avoiding the T cell response to normal bowel micro bacteria. Further studies of people with IBD compared with people without IBD found that the expression of MHC II by ILC3 was significantly reduced in people with IBD, thus causing an immune reaction against intestinal cells or normal bowel bacteria and damaging the intestines. This can also make the intestines more susceptible to environmental factors, such as food or bacteria.
The thinking is that because Crohn's disease has strong innate immune system involvement and has NOD2 mutations as a predisposition, Crohn's disease is more likely an autoinflammatory disease than an autoimmune disease.
=== Immunodeficiency theory ===
A substantial body of data has emerged in recent years to suggest that the primary defect in Crohn's disease is actually one of relative immunodeficiency. This view has been bolstered recently by novel immunological and clinical studies that have confirmed gross aberrations in this early response, consistent with subsequent genetic studies that have highlighted molecules important for innate immune function. The suggestion therefore is that Crohn's pathogenesis actually results from partial immunodeficiency, a theory that coincides with the frequent recognition of a virtually identical, non-infectious inflammatory bowel disease arising in people with congenital monogenic disorders impairing phagocyte function.
== Risk factors ==
While the exact cause or causes are unknown, Crohn's disease seems to be due to a combination of environmental factors and genetic predisposition. Crohn's is the first genetically complex disease in which the relationship between genetic risk factors and the immune system is understood in considerable detail. Each individual risk mutation makes a small contribution to the overall risk of Crohn's (approximately 1:200). The genetic data, and direct assessment of immunity, indicates a malfunction in the innate immune system. In this view, the chronic inflammation of Crohn's is caused when the adaptive immune system tries to compensate for a deficient innate immune system.
=== Genetics ===
Crohn's has a genetic component. Because of this, siblings of known people with Crohn's are 30 times more likely to develop Crohn's than the general population.
The first mutation found to be associated with Crohn's was a frameshift in the NOD2 gene (also known as the CARD15 gene), followed by the discovery of point mutations. Over 30 genes have been associated with Crohn's; a biological function is known for most of them. For example, one association is with mutations in the XBP1 gene, which is involved in the unfolded protein response pathway of the endoplasmic reticulum. The gene variants of NOD2/CARD15 seem to be related with small-bowel involvement. Other well documented genes which increase the risk of developing Crohn's disease are ATG16L1, IL23R, IRGM, and SLC11A1.
There is considerable overlap between susceptibility loci for IBD and mycobacterial infections. Genome-wide association studies have shown that Crohn's disease is genetically linked to coeliac disease.
Crohn's has been linked to the gene LRRK2 with one variant potentially increasing the risk of developing the disease by 70%, while another lowers it by 25%. The gene is responsible for making a protein, which collects and eliminates waste product in cells, and is also associated with Parkinson's disease.
=== Immune system ===
There was a prevailing view that Crohn's disease is a primary T cell autoimmune disorder; however, a newer theory hypothesizes that Crohn's results from an impaired innate immunity. The later hypothesis describes impaired cytokine secretion by macrophages, which contributes to impaired innate immunity and leads to a sustained microbial-induced inflammatory response in the colon, where the bacterial load is high. Another theory is that the inflammation of Crohn's was caused by an overactive Th1 and Th17 cytokine response.
In 2007, the ATG16L1 gene was implicated in Crohn's disease, which may induce autophagy and hinder the body's ability to attack invasive bacteria. Another study theorized that the human immune system traditionally evolved with the presence of parasites inside the body and that the lack thereof due to modern hygiene standards has weakened the immune system. Test subjects were reintroduced to harmless parasites, with positive responses.
=== Microbes ===
It is hypothesized that maintenance of commensal microorganism growth in the GI tract is dysregulated, either as a result or cause of immune dysregulation.
There is an apparent connection between Crohn's disease, Mycobacterium, other pathogenic bacteria, and genetic markers. A number of studies have suggested a causal role for Mycobacterium avium subspecies paratuberculosis (MAP), which causes a similar disease, Johne's disease, in cattle. In many individuals, genetic factors predispose individuals to Mycobacterium avium subsp. paratuberculosis infection. This bacterium may produce certain compounds containing mannose, which may protect both itself and various other bacteria from phagocytosis, thereby possibly causing a variety of secondary infections.
NOD2 is a gene involved in Crohn's genetic susceptibility. It is associated with macrophages' diminished ability to phagocytize MAP. This same gene may reduce innate and adaptive immunity in gastrointestinal tissue and impair the ability to resist infection by the MAP bacterium. Macrophages that ingest the MAP bacterium are associated with high production of TNF-α.
Other studies have linked specific strains of enteroadherent E. coli to the disease. Adherent-invasive Escherichia coli (AIEC), more common in people with Crohn's disease, have the ability to make strong biofilms compared to non-AIEC strains correlating with high adhesion and invasion indices of neutrophils and the ability to block autophagy at the autolysosomal step, which allows for intracellular survival of the bacteria and induction of inflammation. Inflammation drives the proliferation of AIEC and dysbiosis in the ileum, irrespective of genotype. AIEC strains replicate extensively inside macrophages inducing the secretion of very large amounts of TNF-α.
Mouse studies have suggested some symptoms of Crohn's disease, ulcerative colitis, and irritable bowel syndrome have the same underlying cause. Biopsy samples taken from the colons of all three patient groups were found to produce elevated levels of a serine protease. Experimental introduction of the serine protease into mice has been found to produce widespread pain associated with irritable bowel syndrome, as well as colitis, which is associated with all three diseases. Regional and temporal variations in those illnesses follow those associated with infection with the protozoan Blastocystis.
The "cold-chain" hypothesis is that psychrotrophic bacteria such as Yersinia and Listeria species contribute to the disease. A statistical correlation was found between the advent of the use of refrigeration in the United States and various parts of Europe and the rise of the disease.
There is also a tentative association between Candida colonization and Crohn's disease.
Still, these relationships between specific pathogens and Crohn's disease remain unclear.
=== Environmental factors ===
The increased incidence of Crohn's disease in the industrialized world indicates an environmental component. Crohn's is associated with an increased intake of animal protein, milk protein, and an increased ratio of omega-6 to omega-3 polyunsaturated fatty acids.
Those who consume vegetable proteins appear to have a lower incidence of Crohn's disease. Consumption of fish protein has no association.
Smoking increases the risk of the return of active disease (flares). The introduction of hormonal contraception in the United States in the 1960s is associated with a dramatic increase in incidence, and one hypothesis is that these drugs work on the digestive system in ways similar to smoking. Isotretinoin is associated with Crohn's.
Although stress is sometimes claimed to exacerbate Crohn's disease, there is no concrete evidence to support such claim. Still, it is well known that immune function is related to stress. Dietary microparticles, such as those found in toothpaste, have been studied as they produce effects on immunity, but they were not consumed in greater amounts in people with Crohn's. The use of doxycycline has also been associated with increased risk of developing inflammatory bowel diseases. In one large retrospective study, participants who were prescribed doxycycline for their acne had a 2.25-fold greater risk of developing Crohn's disease.
== Pathophysiology ==
During a colonoscopy, biopsies of the colon are often taken to confirm the diagnosis. Certain characteristic features of the pathology seen point toward Crohn's disease. Common features include a transmural pattern of inflammation, meaning the inflammation may span the entire depth of the intestinal wall. Granulomas, aggregates of macrophage derivatives known as giant cells, are found in 50% of cases and are most specific for Crohn's disease. The granulomas of Crohn's disease do not show "caseation", a cheese-like appearance on microscopic examination characteristic of granulomas associated with infections, such as tuberculosis. Biopsies may also show chronic mucosal damage, as evidenced by blunting of the intestinal villi, atypical branching of the crypts, and a change in the tissue type (metaplasia). One example of such metaplasia, Paneth cell metaplasia, involves the development of Paneth cells (typically found in the small intestine and a key regulator of intestinal microbiota) in other parts of the gastrointestinal system.
== Diagnosis ==
The diagnosis of Crohn's disease can sometimes be challenging, and many tests are often required to assist the physician in making the diagnosis. Even with a full battery of tests, it may not be possible to diagnose Crohn's with complete certainty; a colonoscopy is approximately 70% effective in diagnosing the disease, with further tests being less effective. Disease in the small bowel is particularly difficult to diagnose, as a traditional colonoscopy allows access to only the colon and lower portions of the small intestines; introduction of the capsule endoscopy aids in endoscopic diagnosis. Intestinal ultrasound should be considered an early step in the diagnosis and follow-up of people with Crohn's disease even in people with a proximal small bowel localization of the disease. Giant (multinucleate) cells, a common finding in the lesions of Crohn's disease, are less common in the lesions of lichen nitidus.
=== Classification ===
Crohn's disease is one type of inflammatory bowel disease (IBD). It typically manifests in the gastrointestinal tract and can be categorized by the specific tract region affected.
Gastroduodenal Crohn's disease causes inflammation in the stomach and the first part of the small intestine called the duodenum. Jejunoileitis causes spotty patches of inflammation in the top half of the small intestine, called the jejunum. The disease can attack any part of the digestive tract, from the mouth to the anus. However, individuals affected by the disease rarely fall outside these three classifications, with presentations in other areas.
Crohn's disease may also be categorized by the behavior of the disease as it progresses. These categorizations formalized in the Vienna classification of the disease. There are three categories of disease presentation in Crohn's disease: stricturing, penetrating, and inflammatory. Stricturing disease causes narrowing of the bowel that may lead to bowel obstruction or changes in the caliber of the feces. Penetrating disease creates abnormal passageways (fistulae) between the bowel and other structures, such as the skin. Inflammatory disease (or nonstricturing, nonpenetrating disease) causes inflammation without causing strictures or fistulae.
=== Endoscopy ===
A colonoscopy is the best test for making the diagnosis of Crohn's disease, as it allows direct visualization of the colon and the terminal ileum, identifying the pattern of disease involvement. On occasion, the colonoscope can travel past the terminal ileum, but it varies from person to person. During the procedure, the gastroenterologist can also perform a biopsy, taking small samples of tissue for laboratory analysis, which may help confirm a diagnosis. As 30% of Crohn's disease involves only the ileum, cannulation of the terminal ileum is required in making the diagnosis. Finding a patchy distribution of disease, with involvement of the colon or ileum, but not the rectum, is suggestive of Crohn's disease, as are other endoscopic stigmata.
The utility of capsule endoscopy for this, however, is still uncertain.
=== Radiologic tests ===
A small bowel follow-through may suggest the diagnosis of Crohn's disease and is useful when the disease involves only the small intestine. Because colonoscopy and gastroscopy allow direct visualization of only the terminal ileum and beginning of the duodenum, they cannot be used to evaluate the remainder of the small intestine. As a result, a barium follow-through X-ray, wherein barium sulfate suspension is ingested and fluoroscopic images of the bowel are taken over time, is useful for looking for inflammation and narrowing of the small bowel. Barium enemas, in which barium is inserted into the rectum and fluoroscopy is used to image the bowel, are rarely used in the work-up of Crohn's disease due to the advent of colonoscopy. They remain useful for identifying anatomical abnormalities when strictures of the colon are too small for a colonoscope to pass through, or in the detection of colonic fistulae (in this case contrast should be performed with iodate substances).
CT and MRI scans are useful for evaluating the small bowel with enteroclysis protocols. They are also useful for looking for intra-abdominal complications of Crohn's disease, such as abscesses, small bowel obstructions, or fistulae. Magnetic resonance imaging (MRI) is another option for imaging the small bowel as well as looking for complications, though it is more expensive and less readily available. MRI techniques such as diffusion-weighted imaging and high-resolution imaging are more sensitive in detecting ulceration and inflammation compared to CT.
=== Pediatrics considerations ===
Imaging in pediatric Crohn's disease requires careful consideration to minimize radiation exposure while ensuring accurate diagnosis and monitoring. Magnetic Resonance Enterography (MRE) is favored over Computed Tomography Enterography (CTE) due to its lack of ionizing radiation and superior soft tissue contrast. MRE effectively assesses bowel wall thickening, inflammation, and complications such as strictures or fistulas. However, it demands longer scan times and patient cooperation, which can be challenging for younger children.
Ultrasound (US), particularly contrast-enhanced ultrasound, serves as a valuable, radiation-free alternative for evaluating bowel wall thickness, vascularity, and inflammatory changes. It is especially useful for initial assessments and ongoing disease monitoring, though its effectiveness can be operator-dependent.
In urgent situations where rapid imaging is necessary to evaluate severe disease complications, such as bowel perforation or abscess formation, CTE may be utilized despite its associated radiation exposure.
Regular imaging follow-ups should be guided by clinical symptoms and biomarkers to minimize unnecessary scans. Emerging imaging techniques continue to improve the safety and efficacy of pediatric Crohn's disease evaluation.
=== Blood tests ===
A complete blood count may reveal anemia, which commonly is caused by blood loss leading to iron deficiency or by vitamin B12 deficiency, usually caused by ileal disease impairing vitamin B12 absorption. Rarely autoimmune hemolysis may occur. Ferritin levels help assess if iron deficiency is contributing to the anemia. Erythrocyte sedimentation rate (ESR) and C-reactive protein help assess the degree of inflammation, which is important as ferritin can also be raised in inflammation.
Other causes of anemia include medication used in the treatment of inflammatory bowel disease, like azathioprine, which can lead to cytopenia, and sulfasalazine, which can also result in folate deficiency. Testing for Saccharomyces cerevisiae antibodies (ASCA) and antineutrophil cytoplasmic antibodies (ANCA) has been evaluated to identify inflammatory diseases of the intestine and to differentiate Crohn's disease from ulcerative colitis. Furthermore, increasing amounts and levels of serological antibodies such as ASCA, antilaminaribioside [Glc(β1,3)Glb(β); ALCA], antichitobioside [GlcNAc(β1,4)GlcNAc(β); ACCA], antimannobioside [Man(α1,3)Man(α)AMCA], antiLaminarin [(Glc(β1,3))3n(Glc(β1,6))n; anti-L] and antichitin [GlcNAc(β1,4)n; anti-C] associate with disease behavior and surgery, and may aid in the prognosis of Crohn's disease.
Low serum levels of vitamin D are associated with Crohn's disease. Further studies are required to determine the significance of this association.
=== Comparison with ulcerative colitis ===
The most common disease that mimics the symptoms of Crohn's disease is ulcerative colitis, as both are inflammatory bowel diseases that can affect the colon with similar symptoms. It is important to differentiate these diseases, since the course of the diseases and treatments may be different. In some cases, however, it may not be possible to tell the difference, in which case the disease is classified as indeterminate colitis.
=== Differential diagnosis ===
Other conditions with similar symptoms as Crohn's disease includes intestinal tuberculosis, Behçet's disease, ulcerative colitis, nonsteroidal anti-inflammatory drug enteropathy, irritable bowel syndrome and celiac disease. Irritable bowel syndrome is excluded when there are inflammatory changes. Celiac disease cannot be excluded if specific antibodies (anti-transglutaminase antibodies) are negative, nor in the absence of intestinal villi atrophy.
== Management ==
There is no cure for Crohn's disease and remission may not be possible or prolonged if achieved. In cases where remission is possible, relapse can be prevented and symptoms controlled with medication, lifestyle and dietary changes, changes to eating habits (eating smaller amounts more often), reduction of stress, moderate activity, and exercise. Surgery is generally contraindicated and has not been shown to prevent relapse. Adequately controlled, Crohn's disease may not significantly restrict daily living. Treatment for Crohn's disease involves first treating the acute problem and its symptoms, then maintaining remission of the disease.
=== Lifestyle changes ===
Certain lifestyle changes can reduce symptoms, including dietary adjustments, elemental diet, proper hydration, and smoking cessation. Some reviews underlined the importance to adopt diets that are best supported by evidence, even if little is known about the impact of diets on these people.
Diets that include higher levels of fiber and fruit are associated with reduced risk, while diets rich in total fats, polyunsaturated fatty acids, meat, and omega-6 fatty acids may increase the risk of Crohn's. Maintaining a balanced diet with proper portion control can help manage symptoms of the disease. Eating small meals frequently instead of big meals may also help with a low appetite. A food diary may help with identifying foods that trigger symptoms. Despite the recognized importance of dietary fiber for intestinal health, some people should follow a low residue diet to control acute symptoms especially if foods high in insoluble fiber cause symptoms, e.g., due to obstruction or irritation of the bowel. Some find relief in eliminating casein (a protein found in cow's milk) and gluten (a protein found in wheat, rye and barley) from their diets. They may have specific dietary intolerances (not allergies), for example, lactose. Fatigue can be helped with regular exercise, a healthy diet, and enough sleep, and for those with malabsorption of vitamin B12 due to disease or surgical resection of the terminal ileum, cobalamin injections. Smoking may worsen symptoms and the course of the disease, and stopping is recommended. Alcohol consumption can also worsen symptoms, and moderation or cessation is advised.
=== Medication ===
Acute treatment uses medications to treat any infection (normally antibiotics) and to reduce inflammation (normally corticosteroids). When symptoms are in remission, treatment enters maintenance, intending to avoid the recurrence of symptoms. Prolonged use of corticosteroids has significant side-effects; as a result, they are, in general, not used for long-term treatment. Alternatives include aminosalicylates alone, though only a minority can maintain the treatment, and many require immunosuppressive drugs. It has also been suggested that antibiotics change the enteric flora, and their continuous use may pose the risk of overgrowth with pathogens such as Clostridioides difficile.
Medications used to treat the symptoms of Crohn's disease include 5-aminosalicylic acid (5-ASA) formulations, prednisone, immunomodulators such as azathioprine (given as the prodrug for 6-mercaptopurine), methotrexate, and anti-TNF therapies and monoclonal antibodies, such as infliximab, adalimumab, certolizumab, vedolizumab, ustekinumab, natalizumab,risankizumab-rzaa, and upadacitinib Hydrocortisone should be used in severe attacks of Crohn's disease. Biological therapies are medications used to avoid long-term steroid use, decrease inflammation, and treat people who have fistulas with abscesses. The monoclonal antibody ustekinumab appears to be a safe treatment option, and may help people with moderate to severe active Crohn's disease. The long term safety and effectiveness of monoclonal antibody treatment is not known. The monoclonal antibody briakinumab is not effective for people with active Crohn's disease and it is no longer being manufactured.
The gradual loss of blood from the gastrointestinal tract, as well as chronic inflammation, often leads to anemia, and professional guidelines suggest routine monitoring for this.
=== Immunosuppressant therapies, infection risks and vaccinations ===
Many people affected by Crohn's disease need immunosuppressant therapies, which are known to be associated with a higher risk of contracting opportunistic infectious diseases and of pre-neoplastic or neoplastic lesions such as cervical high-grade dysplasia and cancer.
Many of these potentially harmful diseases, such as Hepatitis B, Influenza, herpes zoster virus, pneumococcal pneumonia, or human papilloma virus, can be prevented by vaccines.
Compared to the rest of the population, people affected by IBD are known to be at higher risk of contracting some vaccine-preventable diseases such as the flu and pneumonia.
Nevertheless, despite the increased risk of infections, vaccination rates in people with IBD are known to be suboptimal and may also be lower than vaccination rates in the general population.
=== Surgery ===
Crohn's cannot be cured by surgery, as the disease eventually recurs, though it is used in the case of partial or full blockage of the intestine. Surgery may also be required for complications such as obstructions, fistulas, or abscesses, or if the disease does not respond to drugs. After the first surgery, Crohn's usually comes back at the site where the diseased intestine was removed and the healthy ends were rejoined; it can also come back in other locations. After a resection, scar tissue builds up, which can cause strictures, which form when the intestines become too small to allow excrement to pass through easily, which can lead to a blockage. After the first resection, another resection may be necessary within five years. For people with an obstruction due to a stricture, two options for treatment are strictureplasty and resection of that portion of the bowel. There is no statistical significance between strictureplasty alone versus strictureplasty and resection in cases of duodenal involvement. In these cases, re-operation rates were 31% and 27%, respectively, indicating that strictureplasty is a safe and effective treatment for selected people with duodenal involvement.
Postsurgical recurrence of Crohn's disease is relatively common. Crohn's lesions are nearly always found at the site of the resected bowel. The join (or anastomosis) after surgery may be inspected, usually during a colonoscopy, and disease activity graded. The "Rutgeerts score" is an endoscopic scoring system for postoperative disease recurrence in Crohn's disease. Postsurgical remission per the Rutgeerts score is graded as i0; while mild postsurgical recurrences are graded i1 and i2, and moderate to severe recurrences are graded i3 and i4. Fewer lesions result in a lower grade. Based on the score, treatment plans can be designed to give the patient the best chance of managing the recurrence of the disease.
Short bowel syndrome (SBS, also short gut syndrome or simply short gut) is caused by the surgical removal of part of the small intestine. It usually develops in those people who have had half or more of their small intestines removed. Diarrhea is the main symptom, but others may include weight loss, cramping, bloating, and heartburn. Short bowel syndrome is treated with changes in diet, intravenous feeding, vitamin and mineral supplements, and treatment with medications. In some cases of SBS, intestinal transplant surgery may be considered; though the number of transplant centres offering this procedure is quite small and it comes with a high risk due to the chance of infection and rejection of the transplanted intestine.
Bile acid diarrhea is another complication following surgery for Crohn's disease in which the terminal ileum has been removed. This leads to the development of excessive watery diarrhea. It is usually thought to be due to an inability of the ileum to reabsorb bile acids after resection of the terminal ileum and was the first type of bile acid malabsorption recognized.
=== Microbiome modification ===
The use of oral probiotic supplements to modify the composition and behaviour of the gastrointestinal microbiome has been researched to understand whether it may help to improve remission rates in people with Crohn's disease. However, only two controlled trials were available in 2020, with no clear overall evidence of higher remission nor lower adverse effects, in people with Crohn's disease receiving probiotic supplementation.
=== Mental health ===
Crohn's may result in anxiety or mood disorders, especially in young people who may have stunted growth or embarrassment from fecal incontinence. Counselling as well as antidepressant or anxiolytic medication may help some people manage.
As of 2017 there is a small amount of research looking at mindfulness-based therapies, hypnotherapy, and cognitive behavioural therapy. A meta analysis of interventions to improve mood (including talking therapy, antidepressants, and exercise) in people with inflammatory bowel disease found that they reduced inflammatory markers such as C-reactive protein and faecal calprotectin. Psychological therapies reduced inflammation more than antidepressants or exercise.
=== Alternative medicine ===
It is common for people with Crohn's disease to try complementary or alternative therapy. These include diets, probiotics, fish oil, and other herbal and nutritional supplements. A 2006 survey in Germany found that about half of people with IBD used some form of alternative medicine, with the most common being homeopathy, and a study in France found that about 30% used alternative medicine.
There is insufficient evidence to recommend the use of acupuncture.
Homeopathic preparations are of no benefit with this or any other condition.
There is no good evidence that cannabis or cannabis oil are an effective or safe treatment.
== Prognosis ==
Crohn's disease is a chronic condition for which there is no known cure. It is characterised by periods of improvement followed by episodes when symptoms flare up. With treatment, most people achieve a healthy weight, and the mortality rate for the disease is relatively low. It can vary from being benign to very severe, and people with CD could experience just one episode or have continuous symptoms. It usually reoccurs, although some people can remain disease-free for years or decades. Up to 80% of people with Crohn's disease are hospitalized at some point during the course of their disease, with the highest rate occurring in the first year after diagnosis. Most people diagnosed with Crohn's require surgery for complications or symptoms of the disease within their lifetime, although the rate associated with this is decreasing with better access to modern treatments. Most people with Crohn's live a normal lifespan. However, Crohn's disease is associated with a small increase in risk of small bowel and colorectal carcinoma (bowel cancer).
== Epidemiology ==
The percentage of people with Crohn's disease has been determined in Norway and the United States and is similar at 6 to 7.1:100,000. The Crohn's & Colitis Foundation of America cites this number as approx 149:100,000; NIH cites 28 to 199 per 100,000. Crohn's disease is more common in northern countries, and with higher rates still in the northern areas of these countries. The incidence of Crohn's disease is thought to be similar in Europe but lower in Asia and Africa. It also has a higher incidence in Ashkenazi Jews and smokers.
Crohn's disease begins most commonly in people in their teens and 20s, and people in their 50s through to their 70s. It is rarely diagnosed in early childhood. It usually affects female children more severely than males. However, only slightly more women than men have Crohn's disease. Parents, siblings or children of people with Crohn's disease are 3 to 20 times more likely to develop the disease. Twin studies find that if one has the disease there is a 55% chance the other will too.
The incidence of Crohn's disease is increasing in Europe and in newly industrialised countries. For example, in Brazil, there has been an annual increase of 11% in the incidence of Crohn's disease since 1990.
== History ==
Inflammatory bowel diseases were described by Giovanni Battista Morgagni (1682–1771) and by Scottish physician Thomas Kennedy Dalziel in 1913.
Ileitis terminalis was first described by Polish surgeon Antoni Leśniowski in 1904, although it was not conclusively distinguished from intestinal tuberculosis. In Poland, it is still called Leśniowski-Crohn's disease (Polish: choroba Leśniowskiego-Crohna). Burrill Bernard Crohn, an American gastroenterologist at New York City's Mount Sinai Hospital, described fourteen cases in 1932, and submitted them to the American Medical Association under the rubric of "Terminal ileitis: A new clinical entity". Later that year, he, along with colleagues Leon Ginzburg and Gordon Oppenheimer, published the case series "Regional ileitis: a pathologic and clinical entity". However, due to the precedence of Crohn's name in the alphabet, it later became known in the worldwide literature as Crohn's disease.
== References ==
== Further reading ==
Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE (April 2018). "ACG Clinical Guideline: Management of Crohn's Disease in Adults". The American Journal of Gastroenterology. 113 (4): 481–517. doi:10.1038/ajg.2018.27. PMID 29610508.
== External links ==
"Crohn's disease". MedlinePlus. U.S. National Library of Medicine.
Media related to Crohn's disease at Wikimedia Commons | Wikipedia/Crohn's_disease |
Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can be diagnosed by blood tests. Nephrosis is non-inflammatory kidney disease. Nephritis and nephrosis can give rise to nephritic syndrome and nephrotic syndrome respectively. Kidney disease usually causes a loss of kidney function to some degree and can result in kidney failure, the complete loss of kidney function. Kidney failure is known as the end-stage of kidney disease, where dialysis or a kidney transplant is the only treatment option.
Chronic kidney disease is defined as prolonged kidney abnormalities (functional and/or structural in nature) that last for more than three months. Acute kidney disease is now termed acute kidney injury and is marked by the sudden reduction in kidney function over seven days.
Rates for both chronic kidney disease and mortality have increased, associated with the rising prevalence of diabetes and the ageing global population. The World Health Organization has reported that "kidney diseases have risen from the world’s nineteenth leading cause of death to the ninth, with the number of deaths increasing by 95% between 2000 and 2021." In the United States, prevalence has risen from about one in eight in 2007, to one in seven in 2021.
== Causes ==
Causes of kidney disease include deposition of the Immunoglobulin A antibodies in the glomerulus, administration of analgesics, xanthine oxidase deficiency, toxicity of chemotherapy agents, and a long-term exposure to lead or its salts. Chronic conditions that can produce nephropathy include systemic lupus erythematosus, diabetes mellitus and high blood pressure (hypertension), which lead to diabetic nephropathy and hypertensive nephropathy, respectively.
=== Analgesics ===
One cause of nephropathy is the long term usage of pain medications known as analgesics. The pain medicines which can cause kidney problems include aspirin, acetaminophen, and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen. This form of nephropathy is "chronic analgesic nephritis", a chronic inflammatory change characterized by loss and atrophy of tubules and interstitial fibrosis and inflammation (BRS Pathology, 2nd ed.).
Specifically, long-term use of the analgesic phenacetin has been linked to renal papillary necrosis (necrotizing papillitis).
=== Diabetes ===
Diabetic nephropathy is a progressive kidney disease caused by angiopathy of the capillaries in the glomeruli. It is characterized by nephrotic syndrome and diffuse scarring of the glomeruli. It is particularly associated with poorly managed diabetes mellitus and is a primary reason for dialysis in many developed countries. It is classified as a small blood vessel complication of diabetes.
=== Autosomal dominant polycystic kidney disease ===
Gabow 1990 talks about autosomal dominant polycystic kidney disease and how this disease is genetic. They go on to say "Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease, affecting a half million Americans. The clinical phenotype can result from at least two different gene defects. One gene that can cause ADPKD has been located on the short arm of chromosome 16." The same article also goes on to say that millions of Americans are affected by this disease and it is very common.
=== COVID-19 ===
COVID-19 is associated with kidney disease. In patients hospitalized with COVID-19, the prevalence of acute kidney injury is estimated to be 28%, and the prevalence of renal replacement therapy is estimated to be 9%.
=== Diet ===
Higher dietary intake of animal protein, animal fat, and cholesterol may increase risk for microalbuminuria, a sign of kidney function decline, and generally, diets higher in fruits, vegetables, and whole grains but lower in meat and sweets may be protective against kidney function decline. This may be because sources of animal protein, animal fat, and cholesterol, and sweets are more acid-producing, while fruits, vegetables, legumes, and whole grains are more base-producing.
=== IgA nephropathy ===
IgA nephropathy is the most common glomerulonephritis throughout the world Primary IgA nephropathy is characterized by deposition of the IgA antibody in the glomerulus. The classic presentation (in 40–50% of the cases) is episodic frank hematuria which usually starts within a day or two of a non-specific upper respiratory tract infection (hence synpharyngitic) as opposed to post-streptococcal glomerulonephritis which occurs some time (weeks) after initial infection. Less commonly gastrointestinal or urinary infection can be the inciting agent. All of these infections have in common the activation of mucosal defenses and hence IgA antibody production.
=== Iodinated contrast media ===
Kidney disease induced by iodinated contrast media (ICM) is called contrast induced nephropathy (CIN) or contrast-induced acute kidney injury (AKI). Currently, the underlying mechanisms are unclear. But there is a body of evidence that several factors including apoptosis-induction seem to play a role.
=== Lithium ===
Lithium, a medication commonly used to treat bipolar disorder and schizoaffective disorders, can cause nephrogenic diabetes insipidus; its long-term use can lead to nephropathy.
=== Lupus ===
Despite expensive treatments, lupus nephritis remains a major cause of morbidity and mortality in people with relapsing or refractory lupus nephritis.
=== Xanthine oxidase deficiency ===
Another possible cause of Kidney disease is due to decreased function of xanthine oxidase in the purine degradation pathway. Xanthine oxidase will degrade hypoxanthine to xanthine and then to uric acid. Xanthine is not very soluble in water; therefore, an increase in xanthine forms crystals (which can lead to kidney stones) and result in damage to the kidney. Xanthine oxidase inhibitors, like allopurinol, can cause nephropathy.
=== Polycystic disease of the kidneys ===
Additional possible cause of nephropathy is due to the formation of cysts or pockets containing fluid within the kidneys. These cysts become enlarged with the progression of aging causing renal failure. Cysts may also form in other organs including the liver, brain, and ovaries. Polycystic kidney disease is a genetic disease caused by mutations in the PKD1, PKD2, and PKHD1 genes. This disease affects about half a million people in the US. Polycystic kidneys are susceptible to infections and cancer.
=== Toxicity of chemotherapy agents ===
Nephropathy can be associated with some therapies used to treat cancer. The most common form of kidney disease in cancer patients is acute kidney injury (AKI) which can usually be due to volume depletion from vomiting and diarrhea that occur following chemotherapy or occasionally due to kidney toxicities of chemotherapeutic agents. Kidney failure from break down of cancer cells, usually after chemotherapy, is unique to onconephrology. Several chemotherapeutic agents, for example cisplatin, are associated with acute and chronic kidney injuries. Newer agents such as anti-vascular endothelial growth factor (anti-VEGF) are also associated with similar injuries, as well as proteinuria, hypertension, and thrombotic microangiopathy.
== Diagnosis ==
The standard diagnostic workup of suspected kidney disease includes a medical history, physical examination, a urine test, and an ultrasound of the kidneys (renal ultrasonography). An ultrasound is essential in the diagnosis and management of kidney disease.
== Treatment ==
Treatment approaches for kidney disease focus on managing the symptoms, controlling the progression, and also treating co-morbidities that a person may have.
=== Dialysis ===
=== Transplantation ===
Millions of people across the world have kidney disease. Of those millions, several thousand will need dialysis or a kidney transplant at its end-stage. In the United States, as of 2008, 16,500 people needed a kidney transplant. Of those, 5,000 died while waiting for a transplant. Currently, there is a shortage of donors, and in 2007 there were only 64,606 kidney transplants in the world. This shortage of donors is causing countries to place monetary value on kidneys. Countries such as Iran and Singapore are eliminating their lists by paying their citizens to donate. Also, the black market accounts for 5–10 percent of transplants that occur worldwide. The act of buying an organ through the black market is illegal in the United States. To be put on the waiting list for a kidney transplant, patients must first be referred by a physician, then they must choose and contact a donor hospital. Once they choose a donor hospital, patients must then receive an evaluation to make sure they are sustainable to receive a transplant. In order to be a match for a kidney transplant, patients must match blood type and human leukocyte antigen factors with their donors. They must also have no reactions to the antibodies from the donor's kidneys.
== Prognosis ==
Kidney disease can have serious consequences if it cannot be controlled effectively. Generally, the progression of kidney disease is from mild to serious. Some kidney diseases can cause kidney failure.
== See also ==
Hematologic Diseases Information Service
Mesoamerican nephropathy, an enigmatic chronic kidney disease of Central America
Protein toxicity
== References ==
== External links == | Wikipedia/Renal_disease |
An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated that there are more than 80 recognized autoimmune diseases, with recent scientific evidence suggesting the existence of potentially more than 100 distinct conditions. Nearly any body part can be involved.
Autoimmune diseases are a separate class from autoinflammatory diseases. Both are characterized by an immune system malfunction which may cause similar symptoms, such as rash, swelling, or fatigue, but the cardinal cause or mechanism of the diseases is different. A key difference is a malfunction of the innate immune system in autoinflammatory diseases, whereas in autoimmune diseases there is a malfunction of the adaptive immune system.
Symptoms of autoimmune diseases can significantly vary, primarily based on the specific type of the disease and the body part that it affects. Symptoms are often diverse and can be fleeting, fluctuating from mild to severe, and typically comprise low-grade fever, fatigue, and general malaise. However, some autoimmune diseases may present with more specific symptoms such as joint pain, skin rashes (e.g., urticaria), or neurological symptoms.
The exact causes of autoimmune diseases remain unclear and are likely multifactorial, involving both genetic and environmental influences. While some diseases like lupus exhibit familial aggregation, suggesting a genetic predisposition, other cases have been associated with infectious triggers or exposure to environmental factors, implying a complex interplay between genes and environment in their etiology.
Some of the most common diseases that are generally categorized as autoimmune include coeliac disease, type 1 diabetes, Graves' disease, inflammatory bowel diseases (such as Crohn's disease and ulcerative colitis), multiple sclerosis, alopecia areata, Addison's disease, pernicious anemia, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus. Diagnosing autoimmune diseases can be challenging due to their diverse presentations and the transient nature of many symptoms.
Treatment modalities for autoimmune diseases vary based on the type of disease and its severity. Therapeutic approaches primarily aim to manage symptoms, reduce immune system activity, and maintain the body's ability to fight diseases. Nonsteroidal anti-inflammatory drugs (NSAIDs) and immunosuppressants are commonly used to reduce inflammation and control the overactive immune response. In certain cases, intravenous immunoglobulin may be administered to regulate the immune system. Despite these treatments often leading to symptom improvement, they usually do not offer a cure and long-term management is often required.
In terms of prevalence, a UK study found that 10% of the population were affected by an autoimmune disease. Women are more commonly affected than men. Autoimmune diseases predominantly begin in adulthood, although they can start at any age. The initial recognition of autoimmune diseases dates back to the early 1900s, and since then, advancements in understanding and management of these conditions have been substantial, though much more is needed to fully unravel their complex etiology and pathophysiology.
== Signs and symptoms ==
Autoimmune diseases represent a vast and diverse category of disorders that, despite their differences, share some common symptomatic threads. These shared symptoms occur as a result of the body's immune system mistakenly attacking its own cells and tissues, causing inflammation and damage. However, due to the broad range of autoimmune diseases, the specific presentation of symptoms can significantly vary based on the type of disease, the organ systems affected, and individual factors such as age, sex, hormonal status, and environmental influences.
An individual may simultaneously have more than one autoimmune disease (known as polyautoimmunity), further complicating the symptomatology.
=== Common symptoms ===
Symptoms that are commonly associated with autoimmune diseases include:
fatigue. This is the most common complaint of people with autoimmune disease. A 2015 US survey found that 98% of people with autoimmune diseases experienced fatigue, 89% said it was a "major issue", 68% said "fatigue is anything but normal. It is profound and prevents [them] from doing the simplest everyday tasks." and 59% said it was "probably the most debilitating symptom of having an [autoimmune disease]."
low-grade fever
malaise (a general feeling of discomfort or unease)
muscle aches
joint pain
skin rashes
Autoimmune diseases can present a diverse array of symptoms. For instance, some people may experience dry mouth or dry eyes, tingling or numbness in various body parts, unexpected changes in weight, and diarrhea.
=== Patterns of symptom occurrence ===
These symptoms often reflect the body's systemic inflammatory response. However, their occurrence and intensity can fluctuate over time, leading to periods of heightened disease activity, referred to as flare-ups, and periods of relative inactivity, known as remissions.
The specific presentation of symptoms largely depends on the location and type of autoimmune response. For instance, in rheumatoid arthritis, an autoimmune disease primarily affecting the joints, symptoms typically include joint pain, swelling, and stiffness. On the other hand, type 1 diabetes, which results from an autoimmune attack on the insulin-producing cells of the pancreas, primarily presents with symptoms related to high blood sugar, such as increased thirst, frequent urination, and unexplained weight loss.
=== Commonly affected body areas ===
Commonly affected areas in autoimmune diseases include blood vessels, connective tissues, joints, muscles, red blood cells, skin, and endocrine glands such as the thyroid gland (in diseases like Hashimoto's thyroiditis and Graves' disease) and the pancreas (in type 1 diabetes). The impacts of these diseases can range from localized damage to certain tissues, alteration in organ growth and function, to more systemic effects when multiple tissues throughout the body are affected.
=== Value of tracking symptom occurrence ===
The appearance of these signs and symptoms can not only provide clues for the diagnosis of an autoimmune condition, often in conjunction with tests for specific biological markers, but also help monitor disease progression and response to treatment. Ultimately, due to the diverse nature of autoimmune diseases, a multidimensional approach is often needed for the management of these conditions, taking into consideration the variety of symptoms and their impacts on individuals' lives.
== Types ==
While it is estimated that over 80 recognized types of autoimmune diseases exist, this section provides an overview of some of the most common and well-studied forms.
=== Coeliac disease ===
Coeliac disease is an immune reaction to eating gluten, a protein found in wheat, barley, and rye. For those with the disease, eating gluten triggers an immune response in the small intestine, leading to damage on the villi, small fingerlike projections that line the small intestine and promote nutrient absorption. This explains the increased risk of gastrointestinal cancers, as the gastrointestinal tract includes the esophagus, stomach, small intestine, large intestine, rectum, and anus, all areas that the ingested gluten would traverse in digestion. The incidence of gastrointestinal cancer can be partially reduced or eliminated if a patient removes gluten from their diet. Additionally, coeliac disease is correlated with lymphoproliferative disorders.
=== Graves' disease ===
Graves' disease is a condition characterized by development of autoantibodies to thyroid-stimulating hormone receptors. The binding of the autoantibodies to the receptors results in unregulated production and release of thyroid hormone, which can lead to stimulatory effects such as rapid heart rate, weight loss, nervousness, and irritability. Other symptoms more specific to Graves' disease include bulging eyes and swelling of the lower legs.
=== Inflammatory bowel disease ===
Inflammatory bowel disease encompasses conditions characterized by chronic inflammation of the digestive tract, including Crohn's disease and ulcerative colitis. In both cases, individuals lose immune tolerance for normal bacteria present in the gut microbiome. Symptoms include severe diarrhea, abdominal pain, fatigue, and weight loss. Inflammatory bowel disease is associated with cancers of the gastrointestinal tract and some lymphoproliferative cancers.
=== Multiple sclerosis ===
Multiple sclerosis (MS) is a neurodegenerative disease in which the immune system attacks myelin, a protective covering of nerve fibers in the central nervous system, causing communication problems between the brain and the rest of the body. Symptoms can include fatigue, difficulty walking, numbness or tingling, muscle weakness, and problems with coordination and balance. MS is associated with an increased risk of central nervous system cancer, primarily in the brain.
=== Rheumatoid arthritis ===
Rheumatoid arthritis (RA) primarily targets the joints, causing persistent inflammation that results in joint damage and pain. It is often symmetrical, meaning that if one hand or knee has it, the other one does too. RA can also affect the heart, lungs, and eyes. Additionally, the chronic inflammation and over-activation of the immune system creates an environment that favors further malignant transformation of other cells, perhaps explaining the associations with cancer of the lungs and skin as well as the increased risk of other hematologic cancers, none of which are directly affected by the inflammation of joints.
=== Psoriasis and psoriatic arthritis ===
Psoriasis is a skin condition characterized by the rapid buildup of skin cells, leading to scaling on the skin's surface. Inflammation and redness around the scales is common. Some individuals with psoriasis also develop psoriatic arthritis, which causes joint pain, stiffness, and swelling.
=== Sjögren's syndrome ===
Sjögren syndrome is a long-term autoimmune disease that affects the body's moisture-producing glands (lacrimal and salivary), and often seriously affects other organ systems, such as the lungs, kidneys, and nervous system.
=== Systemic lupus erythematosus ===
Systemic lupus erythematosus, referred to simply as lupus, is a systemic autoimmune disease that affects multiple organs, including the skin, joints, kidneys, and the nervous system. It is characterized by a widespread loss of immune tolerance. The disease is characterized by periods of flares and remissions, and symptoms range from mild to severe. Women, especially those of childbearing age, are disproportionately affected.
=== Type 1 diabetes ===
Type 1 diabetes is a condition resulting from the immune system attacking insulin-producing beta cells in the pancreas, leading to high blood sugar levels. Symptoms include increased thirst, frequent urination, and unexplained weight loss. It is most commonly diagnosed in children and young adults.
=== Undifferentiated connective tissue disease ===
Undifferentiated connective tissue disease occurs when people have features of connective tissue disease, such as blood test results and external characteristics, but do not fulfill the diagnostic criteria established for any one connective tissue disease. Some 30–40% transition to a specific connective tissue disease over time.
== Causes ==
The exact causes of autoimmune diseases remain largely unknown; however, research has suggested that a combination of genetic, environmental, and hormonal factors, as well as certain infections, may contribute to the development of these disorders.
The human immune system is equipped with several mechanisms to maintain a delicate balance between defending against foreign invaders and protecting its own cells. To achieve this, it generates both T cells and B cells, which are capable of reacting with self-proteins. However, in a healthy immune response, self-reactive cells are generally either eliminated before they become active, rendered inert via a process called anergy, or their activities are suppressed by regulatory cells.
=== Genetics ===
A familial tendency to develop autoimmune diseases suggests a genetic component. Some conditions, like lupus and multiple sclerosis, often occur in several members of the same family, indicating a potential hereditary link. Additionally, certain genes have been identified that increase the risk of developing specific autoimmune diseases.
==== Genetic predisposition ====
Evidence suggests a strong genetic component in the development of autoimmune diseases. For instance, conditions such as lupus and multiple sclerosis frequently appear in multiple members of the same family, signifying a potential hereditary link. Furthermore, certain genes have been identified that augment the risk of developing specific autoimmune diseases.
Experimental methods like genome-wide association studies have proven instrumental in pinpointing genetic risk variants potentially responsible for autoimmune diseases. For example, these studies have been used to identify risk variants for diseases such as type 1 diabetes and rheumatoid arthritis.
In twin studies, autoimmune diseases consistently demonstrate a higher concordance rate among identical twins compared with fraternal twins. For instance, the rate in multiple sclerosis is 35% in identical twins compared to 6% in fraternal twins.
==== Balancing infection and autoimmunity ====
There is increasing evidence that certain genes selected during evolution offer a balance between susceptibility to infection and the capacity to avoid autoimmune diseases. For example, variants in the ERAP2 gene provide some resistance to infection even though they increase the risk of autoimmunity (positive selection). In contrast, variants in the TYK2 gene protect against autoimmune diseases but increase the risk of infection (negative selection). This suggests the benefits of infection resistance may outweigh the risks of autoimmune diseases, particularly given the historically high risk of infection.
Several experimental methods such as the genome-wide association studies have been used to identify genetic risk variants that may be responsible for diseases such as type 1 diabetes and rheumatoid arthritis.
=== Environmental factors ===
A significant number of environmental factors have been implicated in the development and progression of various autoimmune diseases, either directly or as catalysts. Current research suggests that up to seventy percent of autoimmune diseases could be attributed to environmental influences, which encompass an array of elements such as chemicals, infectious agents, dietary habits, and gut dysbiosis. However, a unifying theory that definitively explains the onset of autoimmune diseases remains elusive, emphasizing the complexity and multifaceted nature of these conditions.
Various environmental triggers are identified, some of which include:
Impaired oral tolerance
Gut dysbiosis
Increased gut permeability
Heightened immune reactivity
Chemicals, which are either a part of the immediate environment or found in drugs, are key players in this context. Examples of such chemicals include hydrazines, hair dyes, trichloroethylene, tartrazines, hazardous wastes, and industrial emissions.
Ultraviolet radiation has been implicated as a potential causative factor in the development of autoimmune diseases, such as dermatomyositis. Furthermore, exposure to pesticides has been linked with an increased risk of developing rheumatoid arthritis. Vitamin D, on the other hand, appears to play a protective role, particularly in older populations, by preventing immune dysfunctions.
Infectious agents are also being increasingly recognized for their role as T cell activators — a crucial step in triggering autoimmune diseases. The exact mechanisms by which they contribute to disease onset remain to be fully understood. For instance, certain autoimmune conditions like Guillain-Barre syndrome and rheumatic fever are thought to be triggered by infections. Furthermore, analysis of large-scale data has revealed a significant link between SARS-CoV-2 infection (the causative agent of COVID-19) and an increased risk of developing a wide range of new-onset autoimmune diseases.
=== Gender ===
Women typically make up some 80% of autoimmune disease patients. Whilst many proposals have been made for the cause of this high weighting, no clear explanation is available. A possible role for hormonal factors has been suggested. For example, some autoimmune diseases tend to flare during pregnancy (possibly as an evolutionary mechanism to increase health protection for the child), when hormone levels are high, and improve after menopause, when hormone levels decrease. Women may also naturally have autoimmune disease trigger events in puberty and pregnancy. Under-reporting by men may also be a factor, as men may interact less with the health system than women.
=== Infections ===
Certain viral and bacterial infections have been linked to autoimmune diseases. For instance, research suggests that the bacterium that causes strep throat, Streptococcus pyogenes, might trigger rheumatic fever, an autoimmune response affecting the heart. Similarly, some studies propose a link between the Epstein–Barr virus, responsible for mononucleosis, and the subsequent development of multiple sclerosis or lupus.
=== Dysregulated immune response ===
Another area of interest is the immune system's ability to distinguish between self and non-self, a function that is compromised in autoimmune diseases. In healthy individuals, immune tolerance prevents the immune system from attacking the body's own cells. When this process fails, the immune system may produce antibodies against its own tissues, leading to an autoimmune response.
=== Negative selection and the role of the thymus ===
The elimination of self-reactive T cells occurs primarily through a mechanism known as "negative selection" within the thymus, an organ responsible for the maturation of T cells. This process serves as a key line of defense against autoimmunity. If these protective mechanisms fail, a pool of self-reactive cells can become functional within the immune system, contributing to the development of autoimmune diseases.
=== Molecular mimicry ===
Some infectious agents, like Campylobacter jejuni, bear antigens that resemble, but are not identical to, the body's self-molecules. This phenomenon, known as molecular mimicry, can lead to cross-reactivity, where the immune response to such infections inadvertently results in the production of antibodies that also react with self-antigens. An example of this is Guillain–Barré syndrome, in which antibodies generated in response to a C. jejuni infection also react with the gangliosides in the myelin sheath of peripheral nerve axons.
== Diagnosis ==
Diagnosing autoimmune disorders can be complex due to the wide range of diseases within this category and their often overlapping symptoms. Accurate diagnosis is crucial for determining appropriate treatment strategies. Generally, the diagnostic process involves a combination of medical history evaluation, physical examination, laboratory tests, and, in some cases, imaging or biopsies.
=== Medical history and examination ===
The first step in diagnosing autoimmune disorders typically involves a thorough evaluation of the patient's medical history and a comprehensive physical examination. Clinicians often pay close attention to the patient's symptoms, family history of autoimmune diseases, and any exposure to environmental factors that might trigger an autoimmune response. The physical examination can reveal signs of inflammation or organ damage, which are common features of autoimmune disorders.
=== Laboratory tests ===
Laboratory testing plays a pivotal role in the diagnosis of autoimmune diseases. These tests can identify the presence of certain autoantibodies or other immune markers that indicate a self-directed immune response.
Autoantibody testing: Many autoimmune diseases are characterized by the presence of autoantibodies. Blood tests can identify these antibodies, which are directed against the body's own tissues. For example, antinuclear antibody (ANA) testing is commonly used in the diagnosis of systemic lupus erythematosus and other autoimmune diseases.
Complete Blood Count: Blood counts can provide valuable information about the number and characteristics of different blood cells, which can be affected in some autoimmune diseases.
C-Reactive Protein and Erythrocyte Sedimentation Rate: These tests measure the levels of inflammation in the body, which is often elevated in autoimmune disorders.
Organ-specific tests: Certain autoimmune diseases target specific organs, so tests to evaluate the function of these organs can aid in diagnosis. For example, thyroid function tests are used in diagnosing autoimmune thyroid disorders, while a biopsy can diagnose coeliac disease by identifying damage to the small intestine.
=== Imaging studies ===
In some cases, imaging studies may be used to assess the extent of organ involvement and damage. For example, chest x-rays or CT scans can identify lung involvement in diseases like rheumatoid arthritis or systemic lupus erythematosus, while an MRI can reveal inflammation or damage in the brain and spinal cord in multiple sclerosis.
=== Differential diagnosis ===
Given the variety and nonspecific nature of symptoms that can be associated with autoimmune diseases, differential diagnosis—determining which of several diseases with similar symptoms is causing a patient's illness—is an important part of the diagnostic process. This often involves ruling out other potential causes of symptoms, such as infections, malignancies, or genetic disorders.
=== Multidisciplinary approach ===
Given the systemic nature of many autoimmune disorders, a multidisciplinary approach may be necessary for their diagnosis and management. This can involve rheumatologists, endocrinologists, gastroenterologists, neurologists, dermatologists, and other specialists, depending on the organs or systems affected by the disease.
In summary, the diagnosis of autoimmune disorders is a complex process that requires a thorough evaluation of clinical, laboratory, and imaging data. Due to the diverse nature of these diseases, an individualized approach, often involving multiple specialists, is crucial for an accurate diagnosis.
== Treatment ==
Treatment depends on the type and severity of the condition. The majority of the autoimmune diseases are chronic and there is no definitive cure, but symptoms can be alleviated and controlled with treatment.
Standard treatment methods include:
Vitamin or hormone supplements for what the body is lacking due to the disease (insulin, vitamin B12, thyroid hormone, etc.)
Blood transfusions if the disease is blood related
Physical therapy if the disease impacts bones, joints, or muscles
Pharmaceutical treatment options include immunosuppressant drugs to reduce the immune response against the body's own tissues, such as:
Non-steroidal anti-inflammatory drugs (NSAIDs) to reduce inflammation
Glucocorticoids to reduce inflammation
Disease-modifying anti-rheumatic drugs (DMARDs) to decrease the damaging tissue and organ effects of the inflammatory autoimmune response
Because immunosuppressants weaken the overall immune response, relief of symptoms must be balanced with preserving the patient's ability to combat infections, which could potentially be life-threatening.
Non-traditional treatments are being researched, developed, and used, especially when traditional treatments fail. These methods aim to either block the activation of pathogenic cells in the body, or alter the pathway that suppresses these cells naturally. These treatments aim to be less toxic to the patient and have more specific targets. Such options include:
Monoclonal antibodies that can be used to block pro-inflammatory cytokines
Antigen-specific immunotherapy which allows immune cells to specifically target the abnormal cells that cause autoimmune disease
Co-stimulatory blockade that works to block the pathway that leads to the autoimmune response
Regulatory T cell therapy that utilizes this special type of T cell to suppress the autoimmune response
Thymoquinone, a compound found in the flower Nigella sativa, has been studied for potential in treating several autoimmune diseases due to its effects on inflammation.
== Epidemiology ==
The first estimate of US prevalence for autoimmune diseases as a group was published in 1997 by Jacobson, et al. They reported US prevalence to be around 9 million, applying prevalence estimates for 24 diseases to a US population of 279 million. Jacobson's work was updated by Hayter & Cook in 2012. This study used Witebsky's postulates, as revised by Rose & Bona, to extend the list to 81 diseases and estimated overall cumulative US prevalence for the 81 autoimmune diseases at 5.0%, with 3.0% for males and 7.1% for females.
The estimated community prevalence, which takes into account the observation that many people have more than one autoimmune disease, was 4.5% overall, with 2.7% for males and 6.4% for females.
A 2024 estimate was that 1 in 15 people in the U.S. had at least one autoimmune disease.
== Research ==
In both autoimmune and inflammatory diseases, the condition arises through aberrant reactions of the human adaptive or innate immune systems. In autoimmunity, the patient's immune system is activated against the body's own proteins. In chronic inflammatory diseases, neutrophils and other leukocytes are constitutively recruited by cytokines and chemokines, resulting in tissue damage.
Mitigation of inflammation by activation of anti-inflammatory genes and the suppression of inflammatory genes in immune cells is a promising therapeutic approach. There is a body of evidence that once the production of autoantibodies has been initialized, autoantibodies have the capacity to maintain their own production.
=== Stem-cell therapy ===
Stem cell transplantation is being studied and has shown promising results in certain cases.
Medical trials to replace the pancreatic β cells that are destroyed in type 1 diabetes are in progress.
=== Altered glycan theory ===
According to this theory, the effector function of the immune response is mediated by the glycans (polysaccharides) displayed by the cells and humoral components of the immune system. Individuals with autoimmunity have alterations in their glycosylation profile such that a proinflammatory immune response is favored. It is further hypothesized that individual autoimmune diseases will have unique glycan signatures.
=== Hygiene hypothesis ===
According to the hygiene hypothesis, high levels of cleanliness expose children to fewer antigens than in the past, causing their immune systems to become overactive and more likely to misidentify own tissues as foreign, resulting in autoimmune or allergic conditions such as asthma.
=== Vitamin D influence on immune response ===
Vitamin D is known as an immune regulator that assists in the adaptive and innate immune response. A deficiency in vitamin D, from hereditary or environmental influence, can lead to a more inefficient and weaker immune response and seen as a contributing factor to the development of autoimmune diseases. With vitamin D present, vitamin D response elements are encoded and expressed via pattern recognition receptors responses and the genes associated with those responses. The specific DNA target sequence expressed is known as 1,25-(OH)2D3. The expression of 1,25-(OH)2D3 can be induced by macrophages, dendritic cells, T-cells, and B-cells. In the presence of 1,25-(OH)2D3, the immune system's production of inflammatory cytokines are suppressed and more tolerogenic regulatory T-cells are expressed. This is due to vitamin D's influence on cell maturation, specifically T-cells, and their phenotype expression. Lack of 1,25-(OH)2D3 expression can lead to less tolerant regulatory T-cells, larger presentation of antigens to less tolerant T-cells, and increased inflammatory response.
== See also ==
Epigenetics of autoimmune disorders
List of autoimmune diseases
Immune dysregulation
== References ==
== Further reading ==
== External links ==
Media related to Autoimmune diseases and disorders at Wikimedia Commons | Wikipedia/Autoimmune_disease |
Menkes disease (MNK), also known as Menkes syndrome, is an X-linked recessive disorder caused by mutations in genes coding for the copper-transport protein ATP7A, leading to copper deficiency. Characteristic findings include kinky hair, growth failure, and nervous system deterioration. Like all X-linked recessive conditions, Menkes disease is more common in males than in females. The disorder was first described by John Hans Menkes in 1962.
Onset occurs during infancy, with incidence of about 1 in 100,000 to 250,000 newborns; affected infants often do not live past the age of three years, though there are rare cases in which less severe symptoms emerge later in childhood.
== Signs and symptoms ==
Affected infants may be born prematurely. Signs of the disease appear during infancy, typically after a two- to three-month period of normal or slightly slowed development that is followed by a loss of early developmental skills and subsequent developmental delay. Patients exhibit hypotonia (weak muscle tone), failure to thrive, hypothermia (subnormal body temperature), sagging facial features, seizures, and metaphyseal widening. Hair appears strikingly peculiar: kinky, colorless or silvery, and brittle. There can be extensive neurodegeneration in the gray matter of the brain. Arteries in the brain can also be twisted with frayed and split inner walls. This can lead to rupture or blockage of the arteries. Weakened bones (osteoporosis) may result in fractures.
Occipital horn syndrome (sometimes called X-linked cutis laxa and previously called Ehlers-Danlos type 9) is a mild form of Menkes syndrome that begins in early to middle childhood. It is characterized by calcium deposits in a bone at the base of the skull (occipital bone), coarse hair, and loose skin and joints.
== Cause ==
Mutations in the ATP7A gene, located on chromosome Xq21.1, lead to Menkes syndrome. This condition is inherited in an X-linked recessive pattern. About 30% of MNK cases are due to new mutations and 70% are inherited, almost always from the mother. Even though the disease is more common in males, females can still be a carrier of the disease. As the result of a mutation in the ATP7A gene, copper is poorly distributed to cells in the body. Copper accumulates in some tissues, such as the small intestine and kidneys, while the brain and other tissues have unusually low levels. The decreased supply of copper can reduce the activity of numerous copper-containing enzymes that are necessary for the structure and function of bone, skin, hair, blood vessels and the nervous system such as lysyl oxidase. As with other X-linked disorders, female children of a carrier mother have an even chance of carrying the disorder, but are normally well; male children have an even chance of having the disorder or of being free from it. A genetic counselor may have useful advice.
== Mechanism ==
The ATP7A gene encodes a transmembrane protein that transport copper across the cell membranes. It is found throughout the body, except for the liver. In the small intestines, the ATP7A protein helps control the absorption of copper from food. In other cells, the protein travels between the Golgi apparatus and the cell membrane to maintain copper concentrations in the cell. The protein is normally found in the Golgi apparatus, which is important for modifying proteins, including enzymes. In the Golgi apparatus, ATP7A protein provides copper to certain enzymes that are critical for the structure and function of bone, skin, hair, blood vessels, and the nervous system. One of the enzymes, lysyl oxidase, requires copper for proper function. This enzyme cross-links tropocollagen into strong collagen fibrils. The defective collagen contributes to many of the aforementioned connective tissue manifestations of this disease.
If copper levels become excessive, the protein will travel to the cell membrane and eliminate excess copper from the cell. Mutations in the ATP7A gene such as deletions and insertions lead to parts of the gene being deleted, resulting in a shortened ATP7A protein. This prevents the production of a functional ATP7A protein, leading to the impaired absorption of copper from food and copper will not be supplied to certain enzymes.
== Diagnosis ==
Menkes syndrome can be diagnosed by blood tests of the copper and ceruloplasmin levels, skin biopsy, and optical microscopic examination of the hair to view characteristic Menkes abnormalities. X-rays of the skull and skeleton are conducted to look for abnormalities in bone formation. Urine homovanillic acid/vanillylmandelic acid ratio has been proposed as a screening tool to support earlier detection. Since 70% of MNK cases are inherited, genetic testing of the mother can be performed to search for a mutation in the ATP7A gene.
== Treatment ==
There is no cure for Menkes disease. Early treatment with injections of copper supplements (acetate or glycinate) may be of some slight benefit. 11 of 12 newborns who were diagnosed with MNK were alive at age 4.6. Other treatment is symptomatic and supportive. Treatments to help relieve some of the symptoms includes pain medication, anti-seizure medication, feeding tube when necessary, and physical and occupational therapy. The earlier treatment is given, the better the prognosis.
== Epidemiology ==
One European study reported a rate of 1 in 254,000; a Japanese study reported a rate of 1 in 357,143. No correlation with other inherited characteristics, or with ethnic origin, is known.
== See also ==
Copper in health
Folliculitis decalvans
Hereditary copper metabolic diseases
List of cutaneous conditions
List of radiographic findings associated with cutaneous conditions
Wilson's disease
== References ==
== External links ==
GeneReviews/NCBI/NIH/UW entry on ATP7A-Related Copper Transport Disorders | Wikipedia/Menkes_disease |
Wilson's disease (also called hepatolenticular degeneration) is a genetic disorder characterized by the excess build-up of copper in the body. Symptoms are typically related to the brain and liver. Liver-related symptoms include vomiting, weakness, fluid build-up in the abdomen, swelling of the legs, yellowish skin, and itchiness. Brain-related symptoms include tremors, muscle stiffness, trouble in speaking, personality changes, anxiety, and psychosis.
Wilson's disease is caused by a mutation in the Wilson disease protein (ATP7B) gene. This protein transports excess copper into bile, where it is excreted in waste products. The condition is autosomal recessive; for people to be affected, they must inherit a mutated copy of the gene from both parents. Diagnosis may be difficult and often involves a combination of blood tests, urine tests, and a liver biopsy. Genetic testing may be used to screen family members of those affected.
Wilson's disease is typically treated with dietary changes and medication. Dietary changes involve eating a low-copper diet and not using copper cookware. Medications used include chelating agents, such as trientine and D-penicillamine, and zinc supplements. Complications of Wilson's disease can include liver failure and kidney problems. A liver transplant may be helpful to those for whom other treatments are not effective or if liver failure occurs.
Wilson's disease occurs in about one in 30,000 people. Symptoms usually begin between the ages of 5 and 35 years. It was first described in 1854 by German pathologist Friedrich Theodor von Frerichs and is named after British neurologist Samuel Wilson.
== Signs and symptoms ==
The main sites of copper accumulation are the liver and brain. Consequently, liver disease and neuropsychiatric symptoms are the main features that lead to diagnosis. People with liver problems tend to come for medical attention earlier (generally as children or teenagers) than those with neurological and psychiatric symptoms, who tend to be in their 20s or older. Some are identified only because relatives have been diagnosed with Wilson's disease; many of these, when tested, turn out to have been experiencing symptoms of the condition but have not received a diagnosis.
=== Liver disease ===
Liver disease may present itself as tiredness, jaundice, increased bleeding tendency or confusion (due to hepatic encephalopathy), and portal hypertension. The last, a condition in which the pressure in the portal vein is markedly increased, leads to esophageal varices (distended veins in the esophagus that may bleed in a life-threatening fashion) as well as enlargement of the spleen (splenomegaly) and accumulation of fluid in the abdominal cavity (ascites). On examination, signs of chronic liver disease such as spider angiomata (small distended blood vessels, usually on the chest) may be observed. Chronic active hepatitis has already caused cirrhosis of the liver in most patients by the time they develop symptoms. While most people with cirrhosis have an increased risk of hepatocellular carcinoma (liver cancer), this risk is relatively low in Wilson's disease.
About 5% of all people are diagnosed only when they develop fulminant acute liver failure, often in the context of hemolytic anemia (anemia due to the destruction of red blood cells). This leads to abnormalities in protein production (identified by deranged coagulation) and metabolism by the liver. The deranged protein metabolism leads to the accumulation of waste products, such as ammonia, in the bloodstream. When these irritate the brain, patients develop hepatic encephalopathy – a serious condition that causes confusion, coma, seizures and, finally, life-threatening swelling of the brain).
=== Neuropsychiatric symptoms ===
About half of the people with Wilson's disease have neurological or psychiatric symptoms. Most initially have mild cognitive deterioration and clumsiness, as well as changes in behavior. Specific neurological symptoms usually then follow, often in the form of parkinsonism (lead-pipe or cogwheel rigidity, bradykinesia, and postural instability) with or without a typical hand tremor, masked facial expressions, slurred speech, ataxia (lack of coordination), or dystonia (twisting and repetitive movements of part of the body). Seizures and migraine appear to be more common in Wilson's disease. A characteristic tremor described as "wing-beating tremor" is encountered in many people with Wilson's; this is absent at rest but can be provoked by abducting the arms and flexing the elbows toward the midline.
Cognition can also be affected in Wilson's disease, in two non-mutually exclusive categories: frontal lobe disorder (may present as impulsivity, impaired judgement, promiscuity, apathy, and executive dysfunction with poor planning and decision-making) and subcortical dementia (may present as slow thinking, memory loss, and executive dysfunction, without signs of aphasia, apraxia, or agnosia). These cognitive involvements are thought to be related and closely linked to psychiatric manifestations of the disease.
Psychiatric problems due to Wilson's disease may include behavioral changes, depression, anxiety disorders, and psychosis. Psychiatric symptoms are commonly seen in conjunction with neurological symptoms and are rarely manifested on their own. These symptoms are often poorly defined and can sometimes be attributed to other causes. Because of this, diagnosis of Wilson's disease is rarely made when only psychiatric symptoms are present.
=== Other organ systems ===
Medical conditions have been linked with copper accumulation in Wilson's disease:
Eyes: Kayser–Fleischer rings (KF rings) may be visible in the cornea of the eyes, either directly or on slit lamp examination, as deposits of copper form a ring around the cornea. This is due to copper deposition in Descemet's membrane. These rings can be either dark brown, golden, or reddish-green, are 1 to 3mm wide, and appear at the corneal limbus. They do not occur in all people with Wilson's disease, and may be seen in people with chronic cholestasis. Wilson's disease is also associated with sunflower cataracts exhibited by brown or green pigmentation of the anterior and posterior lens capsule. Neither causes significant visual loss. KF rings occur in approximately 66% of diagnosed cases (more often in those with neurological symptoms rather than with liver problems).
Kidneys: renal tubular acidosis (Type 2), a disorder of bicarbonate handling by the proximal tubules leads to nephrocalcinosis (calcium accumulation in the kidneys), a weakening of bones (due to calcium and phosphate loss), and occasionally aminoaciduria (loss of essential amino acids needed for protein synthesis).
Heart: cardiomyopathy (weakness of the heart muscle) is a rare but recognized problem in Wilson's disease; it may lead to heart failure (fluid accumulation due to decreased pump function) and cardiac arrhythmias (episodes of irregular and/or abnormally fast or slow heart beat).
Hormones: hypoparathyroidism (failure of the parathyroid glands leading to low calcium levels), panhypopituitarism (leading to decreased production of hormones from the pituitary gland), infertility, and recurrent miscarriage.
Musculoskeletal: Arthritis and thinning of the bones (osteopenia or osteoporosis).
Fingers: Blue nails, or more formally Azure Lunula, is seen as a blue colouring fading proximally.
== Genetics ==
The Wilson's disease gene (ATP7B) is on chromosome 13 (13q14.3) and is expressed primarily in the liver, kidney, and placenta. The gene codes for a P-type (cation transport enzyme) ATPase that transports copper into bile and incorporates it into ceruloplasmin. Most people who have Wilson's disease – 60% – are homozygous for ATP7B mutations (two abnormal copies), and 30% of them have only one abnormal copy. In up to 7% of cases, people with Wilson's disease have no detectable mutations.
Although more than 500 mutations of ATP7B have been described, a very small number of those cause most cases of Wilson's disease; which mutation an individual will have tends to be specific to the population they are part of. For instance, in Western populations, the H1069Q mutation (replacement of a histidine by a glutamine at position 1069 in the protein) is present in 37%–63% of cases, while in China this mutation is very uncommon; R778L (arginine to leucine at 778) is found more often there. Relatively little is known about the relative impact of the various mutations, although the H1069Q mutation seems to predict later onset and predominantly neurological problems, according to some studies. A comprehensive clinically annotated resource, WilsonGen, provides a clinical classification for the variants as per the recent ACMG & AMP guidelines.
A normal variation in the PRNP gene can modify the course of the disease by delaying the age of onset and affecting the type of symptoms that develop. This gene produces prion protein, which is active in the brain and other tissues and also appears to be involved in transporting copper. A role for the ApoE gene was initially suspected, but could not be confirmed.
The condition is inherited in an autosomal recessive pattern. To inherit it, both of the parents of an individual must carry an affected gene. Most people with Wilson's disease have no family history of the condition. People with only one abnormal gene are called carriers (heterozygotes) and may have mild, but medically insignificant, abnormalities of copper metabolism.
There are several hereditary diseases that cause copper overload in the liver; Wilson's disease is the most common of them. All can cause cirrhosis at a young age. The other copper overload diseases are Indian childhood cirrhosis (ICC), endemic Tyrolean infantile cirrhosis, and idiopathic copper toxicosis. These three, unlike Wilson's disease, are not related to ATP7B mutations; for example, ICC has been linked to mutations in the KRT8 and the KRT18 genes.
== Pathophysiology ==
Copper is needed by the body for a number of functions, predominantly as a cofactor for a number of enzymes such as ceruloplasmin, cytochrome c oxidase, dopamine β-hydroxylase, superoxide dismutase, and tyrosinase.
Copper enters the body through the digestive tract. A transporter protein on the cells of the small bowel, copper membrane transporter 1 (Ctr1; SLC31A1), carries copper inside the cells, where some is bound to metallothionein and part is carried by ATOX1 to an organelle known as the trans-Golgi network. Here, in response to rising concentrations of copper, an enzyme called ATP7A (Menkes' protein) releases copper into the portal vein to the liver. Liver cells also carry the CMT1 protein, and metallothionein and ATOX1 bind it inside the cell, but here, ATP7B links copper to ceruloplasmin and releases it into the bloodstream, as well as removing excess copper by secreting it into bile. Both functions of ATP7B are impaired in Wilson's disease. Copper accumulates in the liver tissue; ceruloplasmin is still secreted, but in a form that lacks copper (termed apo-ceruloplasmin) and is rapidly degraded in the bloodstream.
When the amount of copper in the liver overwhelms the proteins that normally bind it, it causes oxidative damage to the liver through a process known as Fenton chemistry; this damage eventually leads to chronic active hepatitis, fibrosis (deposition of connective tissue), and cirrhosis. The liver also releases copper into the bloodstream that is not bound to ceruloplasmin. This free copper precipitates throughout the body, but particularly in the kidneys, eyes, and brain. In the brain, most copper is deposited in the basal ganglia, particularly in the putamen and globus pallidus (together called the lenticular nucleus); these areas normally participate in the coordination of movement and play a significant role in neurocognitive processes such as the processing of stimuli and mood regulation. Damage to these areas, again by Fenton chemistry, produces the neuropsychiatric symptoms seen in Wilson's disease.
Why Wilson's disease causes hemolysis is unclear, but various lines of evidence suggest that a high level of free (nonceruloplasmin-bound) copper may be directly affecting the oxidation of hemoglobin, or inhibiting the energy-supplying enzymes in red blood cells, or causing direct damage to cell membranes.
== Diagnosis ==
Wilson's disease may be suspected on the basis of any of the symptoms mentioned above, or when a close relative has been found to have Wilson's. Most have slightly abnormal liver function tests such as raised aspartate transaminase, alanine transaminase, and bilirubin levels. If the liver damage is significant, albumin may be decreased due to an inability of damaged liver cells to produce this protein; likewise, the prothrombin time (a test of coagulation) may be prolonged as the liver is unable to produce proteins known as clotting factors. Alkaline phosphatase levels are relatively low in those with Wilson's-related acute liver failure. If neurological symptoms are seen, magnetic resonance imaging of the brain is usually performed; this shows hyperintensities in the part of the brain called the basal ganglia in the T2 setting. MRI may also demonstrate the characteristic "face of the giant panda" pattern.
No totally reliable test for Wilson's disease is known, but levels of ceruloplasmin and copper in the blood, as well of the amount of copper excreted in urine during a 24-hour period, are together used to form an impression of the amount of copper in the body. The most accurate test is a liver biopsy.
=== Ceruloplasmin ===
Levels of ceruloplasmin are abnormally low (<0.2 g/L) in 80–95% of cases. It can be present at normal levels, though, in people with ongoing inflammation, as it is an acute phase protein. Low ceruloplasmin is also found in Menkes disease and aceruloplasminemia, which are related to, but much rarer than Wilson's disease. The combination of neurological symptoms, eye signs, and a low ceruloplasmin level is considered sufficient for the diagnosis of Wilson's disease. In many cases, however, further tests are needed.
=== Serum and urine copper ===
Serum copper is low, which may seem paradoxical given that Wilson's disease is a disease of copper excess. However, 95% of plasma copper is carried by ceruloplasmin, which is often low in Wilson's disease. Urine copper is elevated in Wilson's disease and is collected for 24 hours in a bottle with a copper-free liner. Levels above 100 μg/24h (1.6 μmol/24h) confirm Wilson's disease, and levels above 40 μg/24h (0.6 μmol/24h) are strongly indicative. High urine copper levels are not unique to Wilson's disease; they are sometimes observed in autoimmune hepatitis and in cholestasis (any disease obstructing the flow of bile from the liver to the small bowel).
In children, the following penicillamine test may be used: a 500 mg oral dose of penicillamine is administered, and all urine collected for 24 hours. If the entire day's urine contains more than 1600 μg (25 μmol) of copper, it is a reliable indicator of Wilson's disease. This test has not been validated in adults.
=== Slit-lamp examination ===
The eyes of the patient are examined using a slit lamp to look for Kayser–Fleischer rings, which are strongly associated with Wilson's disease and are caused by copper deposition on the inner cornea in Descemet's membrane.
=== Liver biopsy ===
Once other investigations have indicated Wilson's disease, the ideal test is the removal of a small amount of liver tissue through a liver biopsy. This is assessed microscopically for the degree of steatosis and cirrhosis, and histochemistry and quantification of copper are used to measure the severity of the copper accumulation. A level of 250 μg of copper per gram of dried liver tissue confirms Wilson's disease. Occasionally, lower levels of copper are found; in that case, the combination of the biopsy findings with all other tests could still lead to a formal diagnosis of Wilson's.
In the earlier stages of the disease, the biopsy typically shows steatosis (deposition of fatty material), increased glycogen in the nucleus, and areas of necrosis (cell death). In more advanced disease, the changes observed are quite similar to those seen in autoimmune hepatitis, such as infiltration by inflammatory cells, piecemeal necrosis, and fibrosis (scar tissue). In advanced disease, finally, cirrhosis is the main finding. In acute liver failure, degeneration of the liver cells and collapse of the liver tissue architecture is seen, typically on a background of cirrhotic changes. Histochemical methods for detecting copper are inconsistent and unreliable, and taken alone are regarded as insufficient to establish a diagnosis.
=== Genetic testing ===
Mutation analysis of the ATP7B gene, as well as other genes linked to copper accumulation in the liver, may be performed. Once a mutation is confirmed, family members can be screened for the disease as part of clinical genetics family counseling. Regional distributions of genes associated with Wilson's disease are important to follow, as this can help clinicians design appropriate screening strategies. Since mutations of the ATP7B gene vary between populations, research and genetic testing done in countries such as the USA or United Kingdom can pose problems, as they tend to have more mixed populations.
== Treatment ==
=== Diet ===
In general, a diet low in copper-containing foods is recommended. High-copper foods avoided in Wilson's disease include mushrooms, nuts, chocolate, dried fruit, liver, sesame seeds, sesame oil, and shellfish.
=== Medication ===
Medical treatments are available for Wilson's disease. Some increase the removal of copper from the body, while others prevent the absorption of copper from the diet.
Generally, penicillamine is the first treatment used. This binds to copper (by chelation) and leads to excretion of copper in the urine. Hence, monitoring of the amount of copper in the urine can be done to ensure a sufficiently high dose is taken. Penicillamine is not without problems; about 20% experience a side effect or complication of penicillamine treatment, such as drug-induced lupus (causing joint pains and a skin rash) or myasthenia (a nerve condition leading to muscle weakness). In those who presented with neurological symptoms, almost half experience a paradoxical worsening in their symptoms. While this phenomenon is observed in other treatments for Wilson's, it is usually taken as an indication for discontinuing penicillamine and commencing second-line treatment. Those intolerant to penicillamine may instead be commenced on trientine hydrochloride, which also has chelating properties. Some recommend trientine as first-line treatment, but experience with penicillamine is more extensive. A further agent with known activity in Wilson's disease, under clinical investigation by Wilson Therapeutics, is tetrathiomolybdate. It is regarded as experimental, though some studies have shown a beneficial effect.
Once all results have returned to normal, zinc (usually in the form of a zinc acetate prescription called Galzin) may be used instead of chelators to maintain stable copper levels in the body. Zinc stimulates metallothionein, a protein in gut cells that binds copper and prevents its absorption and transport to the liver. Zinc therapy is continued unless symptoms recur or if the urinary excretion of copper increases.
In rare cases where none of the oral treatments is effective, especially with severe neurological disease, dimercaprol (British anti-Lewisite) is occasionally necessary. This treatment is injected intramuscularly (into a muscle) every few weeks and has unpleasant side effects such as pain.
People who are asymptomatic (for instance, those diagnosed through family screening or only as a result of abnormal test results) are generally treated, as the copper accumulation may cause long-term damage in the future. Whether these people are best treated with penicillamine or zinc acetate is unclear.
=== Physical and occupational therapies ===
Physiotherapy and occupational therapy are beneficial for patients with the neurological form of the disease. The copper-chelating treatment may take up to six months to start working, and these therapies can assist in coping with ataxia, dystonia, and tremors, as well as preventing the development of contractures that can result from dystonia.
=== Transplantation ===
Liver transplantation is an effective cure for Wilson's disease, but is used only in particular scenarios because of the risks and complications associated with the procedure. It is used mainly in people with fulminant liver failure who fail to respond to medical treatment or in those with advanced chronic liver disease. Liver transplantation is avoided in severe neuropsychiatric illnesses, in which its benefit has not been demonstrated.
== Prognosis ==
Left untreated, Wilson's disease tends to become progressively worse and is eventually fatal. Serious complications include liver cirrhosis, acute kidney failure, and psychosis. Liver cancer and cholangiocarcinoma may occur, but at a lower incidence than other chronic liver diseases, and the risk is greatly reduced with treatment. With early detection and treatment, most of those affected can live relatively normal lives and have a life expectancy close to that of the general population. Liver and neurological damage that occurs prior to treatment may improve, but it is often permanent. Fertility is usually normal and pregnancy complications are not increased in those with Wilson's disease that is treated.
== History ==
The disease bears the name of British physician Samuel Alexander Kinnier Wilson (1878–1937), a neurologist who described the condition, including the pathological changes in the brain and liver, in 1912. Wilson's work had been predated by, and drew on, reports from German neurologist Karl Westphal (in 1883), who termed it "pseudo-sclerosis"; by the British neurologist William Gowers (in 1888); by the Finnish neuropathologist Ernst Alexander Homén (in 1889–1892), who noted the hereditary nature of the disease; and by Adolph Strümpell (in 1898), who noted hepatic cirrhosis. Neuropathologist John Nathaniel Cumings made the link with copper accumulation in both the liver and the brain in 1948. The occurrence of hemolysis was noted in 1967.
In 1951, Cumings (in England), and New Zealand neurologist Derek Denny-Brown (working in the United States), simultaneously reported the first effective treatment, using the metal chelator British anti-Lewisite. This treatment had to be injected, but was one of the first therapies available in the field of neurology, a field that classically was able to observe and diagnose, but had few treatments to offer. The first oral chelation agent effective in Wilson's disease, penicillamine, was discovered in 1956 by British neurologist John Walshe. In 1982, Walshe also introduced trientine, and was the first to develop tetra-thiomolybdate for clinical use. Zinc acetate therapy initially made its appearance in the Netherlands, where physicians Schouwink and Hoogenraad used it in 1961 and in the 1970s, respectively, and was further developed later by Brewer and colleagues at the University of Michigan.
The genetic basis of Wilson's disease, and its link to ATP7B mutations, was elucidated by several research groups in the 1980s and 1990s.
== In other animals ==
Hereditary copper accumulation has been described in Bedlington Terriers, where it generally only affects the liver. In Bedlington Terriers it is due to mutations in the COMMD1 (or MURR1) gene. The discovery of these mutations in the dogs led researchers to examine the corresponding human genes, but COMMD1 mutations could not be detected in humans with non-Wilsonian copper accumulation states (such as Indian childhood cirrhosis).
== See also ==
Copper in health
== References ==
== External links ==
Wilson disease at NLM Genetics Home Reference | Wikipedia/Wilson's_disease |
Amyloid beta (Aβ, Abeta or beta-amyloid) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid-beta precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ in a cholesterol-dependent process and substrate presentation. Both neurons and oligodendrocytes produce and release Aβ in the brain, contributing to formation of amyloid plaques. Aβ molecules can aggregate to form flexible soluble oligomers which may exist in several forms. It is now believed that certain misfolded oligomers (known as "seeds") can induce other Aβ molecules to also take the misfolded oligomeric form, leading to a chain reaction akin to a prion infection. The oligomers are toxic to nerve cells. The other protein implicated in Alzheimer's disease, tau protein, also forms such prion-like misfolded oligomers, and there is some evidence that misfolded Aβ can induce tau to misfold.
A study has suggested that APP and its amyloid potential is of ancient origins, dating as far back as early deuterostomes.
== Normal function ==
The normal function of Aβ is not yet known. Though some animal studies have shown that the absence of Aβ does not lead to any obvious loss of physiological function, several potential activities have been discovered for Aβ, including activation of kinase enzymes, protection against oxidative stress, regulation of cholesterol transport, functioning as a transcription factor, and anti-microbial activity (potentially associated with Aβ's pro-inflammatory activity).
The glymphatic system clears metabolic waste from the mammalian brain, and in particular amyloid beta. A number of proteases have been implicated by both genetic and biochemical studies as being responsible for the recognition and degradation of amyloid beta; these include insulin degrading enzyme and presequence protease. The rate of removal is significantly increased during sleep. However, the significance of the glymphatic system in Aβ clearance in Alzheimer's disease is unknown.
== Intervention strategies ==
Aβ is the main component of amyloid plaques, extracellular deposits found in the brains of people with Alzheimer's disease. Aβ can also form the deposits that line cerebral blood vessels in cerebral amyloid angiopathy. The plaques are composed of a tangle of Aβ oligomers and regularly ordered aggregates called amyloid fibrils, a protein fold shared by other peptides such as the prions associated with protein misfolding disease, also known as proteinopathy.
=== Alzheimer's disease ===
Research suggests that soluble oligomeric forms of the amyloid beta may be causative agents in the development of Alzheimer's disease. It is generally believed that Aβ oligomers are the most toxic. Several genetic, cell biology, biochemical and animal studies using experimental models support the concept that Aβ plays a central role in the development of Alzheimer's disease pathology.
Brain Aβ is elevated in people with sporadic Alzheimer's disease. Aβ is the main constituent of brain parenchymal and vascular amyloid; it contributes to cerebrovascular lesions and is neurotoxic. It is unresolved how Aβ accumulates in the central nervous system and subsequently initiates the disease of cells. Significant efforts have been focused on the mechanisms responsible for Aβ production, including the proteolytic enzymes gamma- and β-secretases which generate Aβ from its precursor protein, APP (amyloid precursor protein). Aβ circulates in plasma, cerebrospinal fluid (CSF) and brain interstitial fluid (ISF) mainly as soluble Aβ40. Amyloid plaques contain both Aβ40 and Aβ42, while vascular amyloid is predominantly the shorter Aβ40. Several sequences of Aβ were found in both lesions.
Increases in either total Aβ levels or the relative concentration of both Aβ40 and Aβ42 (where the former is more concentrated in cerebrovascular plaques and the latter in neuritic plaques) have been implicated in the pathogenesis of both familial and sporadic Alzheimer's disease. Due to its more hydrophobic nature, the Aβ42 is the most amyloidogenic form of the peptide. However the central sequence KLVFFAE is known to form amyloid on its own, and probably forms the core of the fibril. One study further correlated Aβ42 levels in the brain not only with onset of Alzheimer's disease, but also reduced cerebrospinal fluid pressure, suggesting that a build-up or inability to clear Aβ42 fragments may play a role into the pathology.
The "amyloid hypothesis" — that the plaques are responsible for the pathology of Alzheimer's disease — is accepted by the majority of researchers, but is not conclusively established. An alternative hypothesis is that amyloid oligomers rather than plaques are responsible for the disease. This more recent variation of the amyloid hypothesis identifies the cytotoxic species as an intermediate misfolded form of amyloid beta, neither a soluble monomer nor a mature aggregated polymer but an oligomeric species. This ion channel hypothesis postulates that oligomers of soluble, non-fibrillar Aβ form membrane ion channels allowing unregulated calcium influx into neurons.
This cytotoxic-fibril hypothesis presents a clear target for drug development: inhibit the fibrillization process. Much early development work on lead compounds has focused on this inhibition; most are also reported to reduce neurotoxicity, but the toxic-oligomer theory suggests that prevention of oligomeric assembly is more important
For example, apomorphine was seen to significantly improve memory function through the increased successful completion of the Morris Water Maze.
=== Cancer ===
While Aβ has been implicated in cancer development, prompting studies on a variety of cancers to elucidate the nature of its possible effects, results are largely inconclusive. Aβ levels have been assessed in relation to a number of cancers, including esophageal, colorectal, lung, and hepatic, in response to observed reductions in risk for developing Alzheimer's disease in survivors of these cancers. All cancers were shown to be associated positively with increased Aβ levels, particularly hepatic cancers. This direction of association however has not yet been established. Studies focusing on human breast cancer cell lines have further demonstrated that these cancerous cells display an increased level of expression of amyloid precursor protein.
=== Down syndrome ===
Adults with Down syndrome had accumulation of amyloid in association with evidence of Alzheimer's disease, including declines in cognitive functioning, memory, fine motor movements, executive functioning, and visuospatial skills.
== Formation ==
Aβ is formed after sequential cleavage of the amyloid precursor protein (APP), a transmembrane glycoprotein of undetermined function. APP can be cleaved by the proteolytic enzymes α-, β- and γ-secretase; Aβ protein is generated by successive action of the β and γ secretases. The γ secretase, which produces the C-terminal end of the Aβ peptide, cleaves within the transmembrane region of APP and can generate a number of isoforms of 30–51 amino acid residues in length. The most common isoforms are Aβ40 and Aβ42; the longer form is typically produced by cleavage that occurs in the endoplasmic reticulum, while the shorter form is produced by cleavage in the trans-Golgi network.
== Genetics ==
Autosomal-dominant mutations in APP cause hereditary early-onset Alzheimer's disease (familial AD, fAD). This form of AD accounts for no more than 10% of all cases, and the vast majority of AD is not accompanied by such mutations. However, familial Alzheimer's disease is likely to result from altered proteolytic processing. This is evidenced by the fact that many mutations that lead to fAD occur near γ-secretase cleavage sites on APP. One of the most common mutations causing fAD, London Mutation, occurs at codon 717 of the APP gene, and results in a valine to isoleucine amino acid substitution. Histochemical analysis of the APP V717I mutation has revealed extensive Aβ pathology throughout neuroaxis as well as widespread cerebral amyloid angiopathy (CAA).
The gene for the amyloid precursor protein is located on chromosome 21, and accordingly people with Down syndrome have a very high incidence of Alzheimer's disease.
== Structure and toxicity ==
Amyloid beta is commonly thought to be intrinsically unstructured, meaning that in solution it does not acquire a unique tertiary fold but rather populates a set of structures. As such, it cannot be crystallized and most structural knowledge on amyloid beta comes from NMR and molecular dynamics. Early NMR-derived models of a 26-aminoacid polypeptide from amyloid beta (Aβ 10–35) show a collapsed coil structure devoid of significant secondary structure content. However, the most recent (2012) NMR structure of (Aβ 1-40) has significant secondary and tertiary structure. Replica exchange molecular dynamics studies suggested that amyloid beta can indeed populate multiple discrete structural states; more recent studies identified a multiplicity of discrete conformational clusters by statistical analysis. By NMR-guided simulations, amyloid beta 1-40 and amyloid beta 1-42 also seem to feature highly different conformational states, with the C-terminus of amyloid beta 1-42 being more structured than that of the 1-40 fragment.
Low-temperature and low-salt conditions allowed to isolate pentameric disc-shaped oligomers devoid of beta structure. In contrast, soluble oligomers prepared in the presence of detergents seem to feature substantial beta sheet content with mixed parallel and antiparallel character, different from fibrils; computational studies suggest an antiparallel beta-turn-beta motif instead for membrane-embedded oligomers.
== Immunotherapy research ==
Immunotherapy may stimulate the host immune system to recognize and attack Aβ, or provide antibodies that either prevent plaque deposition or enhance clearance of plaques or Aβ oligomers. Oligomerization is a chemical process that converts individual molecules into a chain consisting of a finite number of molecules. Prevention of oligomerization of Aβ has been exemplified by active or passive Aβ immunization. In this process antibodies to Aβ are used to decrease cerebral plaque levels. This is accomplished by promoting microglial clearance and/or redistributing the peptide from the brain to systemic circulation. Antibodies that target Aβ and were tested in clinical trials included aducanumab, bapineuzumab, crenezumab, gantenerumab, lecanemab, and solanezumab.
== Measuring amyloid beta ==
Imaging compounds, notably Pittsburgh compound B, (6-OH-BTA-1, a thioflavin), can selectively bind to amyloid beta in vitro and in vivo. This technique, combined with PET imaging, is used to image areas of plaque deposits in those with Alzheimer's.
=== Post mortem or in tissue biopsies ===
Amyloid beta can be measured semiquantitatively with immunostaining, which also allows one to determine location. Amyloid beta may be primarily vascular, as in cerebral amyloid angiopathy, or in amyloid plaques in white matter.
One sensitive method is ELISA which is an immunosorbent assay which utilizes a pair of antibodies that recognize amyloid beta.
Atomic force microscopy, which can visualize nanoscale molecular surfaces, can be used to determine the aggregation state of amyloid beta in vitro.
Vibrational microspectroscopy is a label-free method that measures the vibration of molecules in tissue samples. Amyloid proteins like Aβ can be detected with this technique because of their high content of β-sheet structures. Recently, the formation of Aβ fibrils was resolved in different plaque-types in Alzheimer's disease, indicating that plaques transit different stages in their development.
Dual polarisation interferometry is an optical technique which can measure early stages of aggregation by measuring the molecular size and densities as the fibrils elongate. These aggregate processes can also be studied on lipid bilayer constructs.
== See also ==
TPM21
Sylvain Lesné – Aβ*56
== References ==
== External links ==
Online Mendelian Inheritance in Man (OMIM): 104300 | Wikipedia/Amyloid_beta_protein |
The year 2000 in science and technology involved some significant events.
== Astronomy and space exploration ==
May 4 – A rare astronomical conjunction occurs on the new moon including all seven of the traditional celestial bodies known from ancient times until the discovery of Uranus in 1781; this conjunction consists of the Sun and Moon, Mercury, Venus, Mars, Jupiter and Saturn.
July 14 – Bastille Day solar storm: A powerful solar flare causes a geomagnetic storm on Earth.
August 10 – Publication of the M–sigma relation in The Astrophysical Journal.
November 2 – Expedition 1 to the International Space Station begins.
== Biology ==
January 6 – The last naturally conceived Pyrenean ibex is found dead, apparently killed by a falling tree.
June 26 – 'Rough draft' of the human genome is announced jointly by President of the United States Bill Clinton and British Prime Minister Tony Blair.
December 14 – The full genome sequence of the flowering plant Arabidopsis thaliana is published in Nature.
A population of the Siamese crocodile, previously believed extinct in the wild since 1992, is located in the Cardamom Mountains of Cambodia.
10-year Census of Marine Life launched.
== Computer science ==
January 1 – Year 2000 problem proves to be of little global significance.
March 4 – Sony Computer Entertainment releases the PlayStation 2 sixth generation home video game console in Japan.
March 14 – Stephen King's horror story Riding the Bullet is published in e-book format only, the world's first mass-market electronic book.
May 5 – After originating in the Philippines, the ILOVEYOU computer virus spreads quickly throughout the world.
September – First system enabling the selection, automatic downloading and storage of serial episodic audio content on PCs and portable devices, origin of the podcast, is launched by early MP3 player manufacturer i2Go.
== Earth sciences ==
March – Iceberg B-15, with a surface area of 11,000 km2 (4,200 sq mi), calves from the Ross Ice Shelf of Antarctica.
April – Cave of the Crystals discovered at the Naica Mine in Mexico.
== History of science and technology ==
August 8 – The Confederate States of America submarine H. L. Hunley is raised to the surface after 136 years on the ocean floor.
== Mathematics ==
Omer Reingold, Salil Vadhan and Avi Wigderson introduce the zig-zag product.
== Medicine ==
January – Douglas Hanahan and Robert Weinberg publish "The Hallmarks of Cancer".
January 31 – English doctor Harold Shipman is found guilty of killing fifteen of his elderly patients by lethal injections of diamorphine, the only British physician ever convicted of murdering his patients; he is actually considered to have killed at least 215.
== Paleontology ==
First fossil of Orrorin, an early species of Homininae, discovered in the Tugen Hills of Kenya.
== Philosophy ==
== Physics ==
May 1 – A new class of composite material is fabricated, which has a combination of physical properties never before seen in a natural or human-made material.
== Institutions ==
November 13 – Museu de les Ciències Príncipe Felipe in Valencia, Spain, opens to the public.
== Awards ==
Nobel Prizes
Physics – Zhores Alferov, Herbert Kroemer - Jack Kilby
Chemistry – Alan J Heeger, Alan G MacDiarmid, Hideki Shirakawa
Medicine – Arvid Carlsson, Paul Greengard, Eric R. Kandel
Turing Award: Andrew Yao
Wollaston Medal for Geology: William Sefton Fyfe
== Deaths ==
January 12 – Margaret Hutchinson Rousseau (b. 1910), American chemical engineer
January 19 – G. Ledyard Stebbins (b. 1906), American botanist and geneticist
March 7 – W. D. Hamilton (b. 1936), English evolutionary biologist, widely recognised as one of the greatest evolutionary theorists of the 20th century
March 10 – Nim Chimpsky (b. 1973), chimpanzee
May 6 – John Clive Ward (b. 1924), English-born physicist
May 19 – Yevgeny Khrunov (b. 1933), cosmonaut
June 14 – Elsie Widdowson (b. 1908), English nutritionist
July 8 – W. David Kingery (b. 1926), American materials scientist specializing in ceramic materials
July 14 – Sir Mark Oliphant (b. 1901), Australian nuclear physicist
July 29 – René Favaloro (b. 1923), Argentine cardiac surgeon
September 20 – Gherman Titov (b. 1935), cosmonaut
October 4 – Michael Smith (b. 1932), English-born Canadian chemist, 1993 Nobel Prize winner
November 20 – Nikolay Dollezhal (b. 1899), a key figure in Soviet atomic bomb project and chief designer of nuclear reactors
== References == | Wikipedia/2000_in_science |
A low-energy house is characterized by an energy-efficient design and technical features which enable it to provide high living standards and comfort with low energy consumption and carbon emissions. Traditional heating and active cooling systems are absent, or their use is secondary. Low-energy buildings may be viewed as examples of sustainable architecture. Low-energy houses often have active and passive solar building design and components, which reduce the house's energy consumption and minimally impact the resident's lifestyle. Throughout the world, companies and non-profit organizations provide guidelines and issue certifications to guarantee the energy performance of buildings and their processes and materials. Certifications include passive house, BBC—Bâtiment Basse Consommation—Effinergie (France), zero-carbon house (UK), and Minergie (Switzerland).
Buildings alone were responsible for 38% of all human Greenhouse gas emissions (GHG) as of 2008, with 20% attributed to residential buildings and 18% to commercial buildings. According to the Intergovernmental Panel on Climate Change (IPCC), buildings is the sector which presents the most cost effective opportunities for GHG reductions.
== Background ==
During the 1970s, research on low-energy buildings was done in Denmark, Sweden, Germany, Canada, and the United States. The implementation of standardized low-energy building concepts has developed differently in each country.
=== Canada ===
In the late 1970s, the province of Saskatchewan contracted the Saskatchewan Research Council to design and build a passive solar house suitable for the extreme climate of the Canadian prairies, where winter temperatures can drop to negative 40 degrees Celsius (-40°F). The project resulted in the construction of the Saskatchewan Conservation House in Regina in 1977 by a team led by engineer Harold Orr. The project developed a heat recovery air exchanger (HRV), hot water recovery, and a blower-door apparatus to measure building air-tightness, techniques that became common in low-energy building in other parts of the world. Orr would go on to apply many of those techniques to retro-fitting existing buildings to improve energy efficiency.
=== Germany ===
Triggered in the 1970s by the first energy crisis and growing environmental awareness, energy conservation became increasingly important in Germany. In 1977, the country's first energy-related building standard was enacted. The German Passivhaus Institute introduced the first certified passive house in 1990. The annual heating requirement was introduced as an important parameter by the third German Thermal Insulation Ordinance (1995). In 2013, however, there was no clear legal requirement for a low-energy building standard in Germany. According to Maria Panagiotidou and Robert J. Fuller, definitions, policies and construction activity of zero-energy buildings must be clear. The European Union's Energy Performance Directive requires that beginning in 2021, only low-energy buildings may be built.
=== United Kingdom ===
Changes to national policies have occurred since May 2015 in the UK. One of the most significant has been the withdrawal of the Code for Sustainable Homes (CfSH) as a system for assessing and encouraging improvements in the environmental design of dwellings. This has abandoned the code's schematic which provided a framework of achievement levels and to which low-energy designers could aspire to meet or surpass. Although energy-conservation legislation still exists in the building regulations, there is a lack of suitable standards exceeding basic regulations. As a result, the Passive House Standard may expand its influence and impact on energy-efficient houses.
=== United States ===
Interest in low-energy buildings has increased in the United States, primarily due to rising energy prices, decreasing costs for onsite renewable-energy systems, and increasing concern about climate change. California requires all new residential construction to be zero net energy by 2020.
== Types ==
Low-energy houses are broadly defined, but are generally known as houses with a lower energy demand than common buildings regulated by the national building code. The term "low-energy house" is used in some countries for a specific type of building.
A low-energy house is a guideline rarely specified in actual values (heat load or space-heating minimum). A passive house is a standard, with specific recommendations to save heating energy.
At one end of the spectrum are buildings with an ultra-low space-heating requirement which require low levels of imported energy (even in winter), approaching an autonomous building. At the opposite end are buildings where few attempts are made to reduce their space-heating requirement and which use high levels of imported energy in winter. Although this may be balanced by high levels of renewable-energy generation throughout the year, it imposes greater demands on the national energy infrastructure during winter.
== National standards ==
The term "low-energy houses" may refer to national building standards. These standards sometimes seek to limit the energy used for space heating, which is the largest energy consumer in many climate zones. Other energy uses may also be regulated. The history of passive solar building design provides an international view of one form of low-energy-building development and standards.
=== Europe ===
Standards for low-energy buildings in Europe have proceeded differently in each country, and there is no common certification or legislation for low-energy buildings valid in all EU member states. As a movement towards reducing energy use and emissions, a common legislation concerning buildings’ energy performance, the Energy Performance of Buildings Directive (EPBD) was published in 2002 and became effective in January 2003.
==== Norway ====
In NS 3700, the draft official standard, low-energy buildings are defined. About the buildings' energy performance, two alternatives for rating their primary energy use are under discussion:
A limit on a building's annual CO2 emissions, calculated by multiplying the annual supplied energy by a CO2 factor
A percentage of its heating demand must be met with renewable energy.
==== Denmark ====
Low-energy houses are defined in the National Building Regulation Building Regulations 08, and are divided into two classes. They are regulated in the regulations' chapter 7.2.4: Low-energy.
==== Germany ====
Low-energy houses certified by RAL-GZ 965 have 30 percent less heat losses than regulated in the EnEV, a national building code. Other criteria affect insulation, air tightness and ventilation. Low-energy buildings may be certified by RAL-GZ 965 for planning or construction.
==== Switzerland ====
Low-energy buildings may receive the Minergie certification, a "quality label for new and refurbished buildings". The Minergie standard requires that buildings do not exceed 75 percent of average building energy consumption and fossil-fuel consumption must not exceed 50 percent of the average.
=== North America ===
The European Union directive has clarified low-energy houses in Europe, and a large portion of the discussions on zero-energy building in North America derives from the U.S. National Renewable Energy Laboratory (NREL).
The Energy Star program is the largest certifier of low-energy homes and consumer products in the U.S. Although certified Energy Star homes use at least 15 percent less energy than standard new homes built in accordance with the International Residential Code, they typically achieve a 20- to 30-percent savings. The United States Department of Energy introduced a program in 2008 to distribute zero-energy housing across the country.
Canadian builders may use a range of standards, labels, and certification programs to demonstrate a high level of energy performance in a given project. These include:
Net Zero Home and Net Zero Ready Home certifications, administered by the Canadian Home Builders' Association
Built Green labels, administered by Built Green Canada
Energy Star for Homes, administered by Natural Resources Canada
The Canadian Passive House standard, administered by the Canadian Passive House Institute
In British Columbia the above programs align with the BC Energy Step Code, a provincial regulation to incentivize (or require) a level of energy efficiency in new construction beyond the base building code. The code was designed as a technical road map to help the province reach its target of all new net-zero-energy-ready buildings by 2032.
== Obstacles and issues ==
Energy efficient housing affects indoor air quality. Airtight houses will trap pollutants inside them, whether produced indoors or outdoors, and lead to an increase in human exposure and potential health issues.
Energy-efficient design often relies on new technologies and techniques. These may create technical obstacles in addition to social, cultural, and economic non-technical obstacles.
Buildings designed for good energy efficiency do not always live up to the design goals; various reasons lead to this performance gap.
== Technology ==
Low-energy building design is considered important to encourage resource efficiency and reduce global climate change associated with the burning of fossil fuels. Design involves two general strategies: minimizing the need for energy use in buildings (especially for heating and cooling) through energy-efficient measures (EEMs) and adopting renewable energy and other technologies (RETs) to meet remaining energy needs. EEMs include building envelopes, internal conditions, and building-services systems; RETs include photovoltaic or building-integrated photovoltaic, wind turbines, solar thermal (solar water heaters), heat pumps, and district heating and cooling. Impacts include life-cycle costs, environmental impacts, and climate-change and social-policy issues. The best low-energy designs offer occupants a better environment and more stable, controlled thermal comfort in addition to reduced energy costs.
GHG emissions associated with buildings construction are mainly coming from:
Materials manufacturing (e.g., concrete)
Materials transport
Demolition wastes transport
Demolition wastes treatment
The construction, renovation, and deconstruction of a typical building is on average responsible for the emissions of 1,000–1,500 kg CO2e/m2 (around 500 kg CO2e/m2 for construction only).
Strategies adopted by low-carbon buildings to reduce GHG emissions during construction include:
Reduce quantity of materials used
Select materials with low emissions factors associated (e.g., recycled materials)
Select materials suppliers as close as possible to the construction.
Divert demolition wastes to recycling instead of landfills or incineration
=== Energy efficiency ===
Reduction of energy consumption is more environmentally and financially advantageous than increasing onsite production to reach a low-energy goal. The less a home consumes, the smaller renewable-energy system it requires to reach net zero. Energy efficiency should always be the primary design strategy of a low-energy house.
=== Improvements ===
=== Passive solar design and landscaping ===
Passive solar building design and energy-efficient landscaping support the low-energy house in conservation and can integrate it into a neighborhood and environment. Following passive solar building techniques, where buildings are compact in shape to reduce surface area and principal windows oriented towards the equator (south in the Northern Hemisphere and north in the Southern Hemisphere) maximizes passive solar gain. However, solar gain (especially in temperate climates) is secondary to minimizing the overall house-energy requirements. In hot temperatures, excess heat can create uncomfortable indoor conditions. Passive alternatives to air-conditioning systems, such as temperature-dependent venting, have been shown to be effective in regions with cooling needs. Other techniques to reduce excess solar heat include brise-soleils, trees, attached pergolas with vines, vertical gardens, and green roofs.
Although low-energy houses can be constructed from dense or lightweight materials, internal thermal mass is normally incorporated to reduce summer peak temperatures, maintain stable winter temperatures, and prevent possible overheating in spring or autumn before the higher sun angle "shades" midday wall exposure and window penetration. Exterior wall color (when the surface allows choice) reflection or absorption depends on the predominant year-round outdoor temperature. The use of deciduous trees and wall trellised (or self-attaching) vines can assist in temperate climates.
=== Lighting and electrical appliances ===
To minimize total primary energy consumption, passive and active daylighting are the first daytime solutions to employ. For low-light days, non-daylight spaces and nighttime, sustainable lighting design with low-energy sources (such as standard-voltage compact fluorescent lamps and solid-state lighting with LED lamps, OLEDs and polymer light-emitting diodes and low-voltage incandescent light bulbs, compact metal halide, xenon and halogen lamps) can be used.
Solar-powered exterior security and landscape lighting, with solar cells on each fixture or connecting to a central solar panel, are available for gardens and outdoor needs. Low-voltage systems can be used for more controlled (or independent) illumination, using less electricity than conventional fixtures and lamps. Timers, motion detection and daylighting operation sensors further reduce energy consumption and light pollution.
Home appliances meeting independent energy-efficiency testing and receiving Ecolabel certification marks for reduced electrical and natural-gas consumption and product-manufacturing carbon emission labels are preferred for low-energy houses. Energy Star and EKOenergy are other certification marks.
== See also ==
== References ==
== Further reading ==
Voss, Karsten and Musall, Eike. Net zero energy buildings - International projects of carbon neutrality in buildings. 2nd edition, November 2012, Institut für internationale Architektur-Dokumentation GmbH & Co. KG, München, ISBN 978-3-920034-80-5.
Raad Z. Homod, Intelligent HVAC Control for High Energy Efficiency in Buildings. Lambert Academic Publishing (2014), ISBN 978-3-8473-0625-2.
Per Krusche, Dirk Althaus, Ingo Gabriel, Maria Weig-Krusche: Ökologisches Bauen, Bauverlag Wiesbaden and Berlin, (1982), ISBN 3-7625-1412-7
Peter Steiger, Conrad U. Brunner, et al.: PLENAR - Planung, Energie, Architektur, Niggli-Verlag, Teufen (1975), ISBN 9978-3-7212-0078-2
== External links ==
bigEE - Your guide to energy efficiency in buildings
IEA research program "Net Zero Energy Solar Buildings"
IEA Energy Conservation in Buildings and Community Systems Programme.
Common Fire Foundation overview of green building and information on the net-zero-energy Greenest Building in the Eastern US
Article on Low-Energy Housing
=== Examples ===
World Map of international known Net Zero Energy Buildings
Building of low energy houses with Insulating Concrete Forms | Wikipedia/Low-energy_house |
The energy efficiency implementation industry pertains to the firms which retrofit or replace inefficient equipment with the goal of reducing energy consumption and GHG emissions. Retrofitting can enhance existing equipment by increasing operational energy efficiency at a lower cost. As a comparison, complete replacement of equipment may be more costly, but can reduce the implementation complexity. The overarching goal of energy efficiency implementation is to save kilowatt hours (kWh is a measurement of energy actually consumed).
== Public policy ==
Energy sector regulators can have wide discretion in the implementation and/or monitoring energy efficiency (EE) initiatives. The most likely roles involve giving technical advice to the agency developing EE initiatives, since changes in demand patterns will have implications for the operations and investment plans of utilities. Particularly when the EE outlays are by the utility, the energy sector regulator needs to monitor outcomes to ensure that the resources are being used in ways that are consistent with overarching public policies. Furthermore, interactions of utility initiatives with other EE policies need to be taken into account when evaluating whether the scale and scope of existing utility-based demand-side management programs. Utilities are in a position to analyze bills and conduct on-premises energy audits to identify areas of saving. Regulators could require utilities to undertake costly audit programs. A high tech approach to improving operations and the customer interface involves smart meters and information systems that enable the utility to track system performance in real time.
The costs of implementing such systems need to be balanced against the benefits, including the possibility that outlays on other projects might be more cost-effective. Thus, the role of regulators primarily involves providing technical input into the development of EE policies initiated by other agencies or via legislated tax programs. In addition, the regulator must determine, unless specified in law, which benefit-cost test is appropriate for evaluating utility-based EE programs. The regulatory tests include the participant cost test (will participants benefit over the measure's life?), the program administrator cost test (will utility bills increase?), the ratepayer impact measure (will utility prices increase?), the total resource cost test (will the total costs of energy decrease?) and the societal cost test (is the utility, state, or nation better off, including environmental impacts?).
== Effects ==
Energy efficiency implementation can also play a role in increased revenue when environmentalist consumers choose a "greener" product over another that is not. Energy efficiency implementation may need to be tailored to one's environmental needs. For instance, Christiann Abeelen's research on the energy efficiency projects in the Netherlands showed "Our findings show that large differences exist in the realized savings between individual companies. There is however no significant difference in savings observed between companies that participate in the Emission Trading System (ETS) and companies that do not. Although it is impossible to disentangle the drivers behind the implementation of these projects, the amount of savings suggest that at least part of them was implemented because of different energy policy instruments."
== See also ==
Jevons's paradox
Efficient energy use
== References == | Wikipedia/Energy_efficiency_implementation |
The United States Department of Energy (DOE) is an executive department of the U.S. federal government that oversees U.S. national energy policy and energy production, the research and development of nuclear power, the military's nuclear weapons program, nuclear reactor production for the United States Navy, energy-related research, and energy conservation.
The DOE was created in 1977 in the aftermath of the 1973 oil crisis. It sponsors more physical science research than any other U.S. federal agency, the majority of which is conducted through its system of National Laboratories. The DOE also directs research in genomics, with the Human Genome Project originating from a DOE initiative.
The department is headed by the secretary of energy, who reports directly to the president of the United States and is a member of the Cabinet. The current secretary of energy is Chris Wright, who has served in the position since February 2025. The department's headquarters are in southwestern Washington, D.C., in the James V. Forrestal Building, with additional offices in Germantown, Maryland.
== History ==
=== Formation and consolidation ===
In 1942, during World War II, the United States started the Manhattan Project to develop the atomic bomb under the U.S. Army Corps of Engineers. After the war, in 1946, the Atomic Energy Commission (AEC) was created to control the future of the project. The Atomic Energy Act of 1946 also created the framework for the first National Laboratories. Among other nuclear projects, the AEC produced fabricated uranium fuel cores at locations such as Fernald Feed Materials Production Center in Cincinnati, Ohio. The Energy Reorganization Act of 1974 split the responsibilities of the AEC into the new Nuclear Regulatory Commission, which was charged with regulating the nuclear power industry, and the Energy Research and Development Administration, which was assigned to manage the nuclear weapon, naval reactor, and energy development programs.
The 1973 oil crisis called attention to the need to consolidate energy policy. In 1977, President Jimmy Carter signed into law the Department of Energy Organization Act, which established the Department of Energy. The new agency, which began operations on October 1, 1977, consolidated the Federal Energy Administration, the Energy Research and Development Administration, the Federal Power Commission, and programs of various other agencies. Former Secretary of Defense James Schlesinger, who served under Presidents Nixon and Ford during the Vietnam War, was appointed as the first secretary.
President Carter proposed the Department of Energy with the goal of promoting energy conservation and energy independence, and developing alternative sources of energy to reduce the use of fossil fuels. With international energy's future uncertain for America, Carter acted quickly to have the department come into action the first year of his presidency. This was an extremely important issue of the time as the oil crisis was causing shortages and inflation. With the Three Mile Island accident, Carter was able to intervene with the help of the department. Through the DOE, Carter was able to make changes within the Nuclear Regulatory Commission, including improving management and procedures, since nuclear energy and weapons are responsibilities of the department.
=== Weapon plans stolen ===
In December 1999, the FBI was investigating how China obtained plans for a specific nuclear device. Wen Ho Lee was accused of stealing nuclear secrets from Los Alamos National Laboratory for the People's Republic of China. Federal officials, including then-Energy Secretary Bill Richardson, publicly named Lee as a suspect before he was charged with a crime. The U.S. Congress held hearings to investigate the Department of Energy's handling of his case. Republican senators thought that an independent agency should be in charge of nuclear weapons and security issues, rather than the DOE. All but one of the 59 charges against Lee were eventually dropped because the investigation proved the plans the Chinese obtained could not have come from Lee. Lee filed suit and won a $1.6 million settlement against the federal government and news agencies. The episode eventually led to the creation of the National Nuclear Security Administration, a semi-autonomous agency within the department.
=== Loan guarantee program of 2005 ===
In 2001, American Solar Challenge was sponsored by the DOE and the National Renewable Energy Laboratory. After the 2005 race, the DOE discontinued its sponsorship.
Title XVII of Energy Policy Act of 2005 authorizes the DOE to issue loan guarantees to eligible projects that "avoid, reduce, or sequester air pollutants or anthropogenic emissions of greenhouse gases" and "employ new or significantly improved technologies as compared to technologies in service in the United States at the time the guarantee is issued". In loan guarantees, a conditional commitment requires to meet an equity commitment, as well as other conditions, before the loan guarantee is completed.
In September 2008, the DOE, the Nuclear Threat Initiative (NTI), the Institute of Nuclear Materials Management (INMM), and the International Atomic Energy Agency (IAEA) partnered to develop and launch the World Institute for Nuclear Security (WINS), an international non-governmental organization designed to provide a forum to share best practices in strengthening the security and safety of nuclear and radioactive materials and facilities.
In December 2024, the Loan Programs Office announced it would extend the largest loan ever sanctioned – a $15 billion (US) low-interest loan to support the modernization of Pacific Gas & Electric’s hydroelectric power structure, enhance transmission lines critical for renewable energy integration, data center operations, and the growing fleet of electric vehicles. Initially requested as a $30 billion (US) loan, the amount was reduced due to concerns over the company’s repayment capacity.
== Organization ==
The department announced a reorganization with new names of under secretaries in 2022.
The department is under the control and supervision of a United States Secretary of Energy, a political appointee of the President of the United States. The Energy Secretary is assisted in managing the department by a United States Deputy Secretary of Energy, also appointed by the president, who assumes the duties of the secretary in the secretary's absence. The department also has three under secretaries, each appointed by the president, who oversee the major areas of the department's work. The president also appoints seven officials with the rank of Assistant Secretary of Energy who have line management responsibility for major organizational elements of the department. The Energy Secretary assigns their functions and duties.
=== Symbolism in the seal ===
Excerpt from the Code of Federal Regulations, in Title 10: Energy:
The official seal of the Department of Energy "includes a green shield bisected by a gold-colored lightning bolt, on which is emblazoned a gold-colored symbolic sun, atom, oil derrick, windmill, and dynamo. It is crested by the white head of an eagle, atop a white rope. Both appear on a blue field surrounded by concentric circles in which the name of the agency, in gold, appears on a green background."
"The eagle represents the care in planning and the purposefulness of efforts required to respond to the Nation's increasing demands for energy. The sun, atom, oil derrick, windmill, and dynamo serve as representative technologies whose enhanced development can help meet these demands. The rope represents the cohesiveness in the development of the technologies and their link to our future capabilities. The lightning bolt represents the power of the natural forces from which energy is derived and the Nation's challenge in harnessing the forces."
"The color scheme is derived from nature, symbolizing both the source of energy and the support of man's existence. The blue field represents air and water, green represents mineral resources and the earth itself, and gold represents the creation of energy in the release of natural forces. By invoking this symbolism, the color scheme represents the Nation's commitment to meet its energy needs in a manner consistent with the preservation of the natural environment."
=== Facilities ===
The Department of Energy operates a system of national laboratories and technical facilities for research and development, as follows:
Other major DOE facilities include:
Airstrip:
Pahute Mesa Airstrip – Nye County, Nevada, part of Nevada National Security Site
=== Nuclear weapons sites ===
The DOE/NNSA has federal responsibility for the design, testing and production of all nuclear weapons. NNSA in turn uses contractors to carry out its responsibilities at the following government owned sites:
Research, development, and manufacturing guidance: Los Alamos National Laboratory and Lawrence Livermore National Laboratory
Engineering of the non-nuclear components and system integration: Sandia National Laboratories
Manufacturing of key components: The Kansas City Plant, Savannah River Site and Y-12 National Security Complex.
Testing: Nevada Test Site
Final weapon and warhead assembling and dismantling: Pantex
== Related legislation ==
1920 – Federal Power Act
1935 – Public Utility Holding Company Act of 1935
1946 – Atomic Energy Act PL 79-585 (created the Atomic Energy Commission) [Superseded by the Atomic Energy Act of 1954]
1954 – Atomic Energy Act of 1954, as Amended PL 83-703
1956 – Colorado River Storage Project PL 84-485
1957 – Atomic Energy Commission Acquisition of Property PL 85-162
1957 – Price-Anderson Nuclear Industries Indemnity Act PL 85-256
1968 – Natural Gas Pipeline Safety Act PL 90-481
1973 – Mineral Leasing Act Amendments (Trans-Alaska Oil Pipeline Authorization) PL 93-153
1974 – Energy Reorganization Act PL 93-438 (Split the AEC into the Energy Research and Development Administration and the Nuclear Regulatory Commission)
1975 – Energy Policy and Conservation Act PL 94-163
1977 – Department of Energy Organization Act PL 95-91 (Dismantled ERDA and replaced it with the Department of Energy)
1978 – National Energy Act PL 95-617, 618, 619, 620, 621
1980 – Energy Security Act PL 96-294
1989 – Natural Gas Wellhead Decontrol Act PL 101-60
1992 – Energy Policy Act of 1992 PL 102-486
2000 – National Nuclear Security Administration Act PL 106-65
2005 – Energy Policy Act of 2005 PL 109-58
2007 – Energy Independence and Security Act of 2007 PL 110-140
2008 – Food, Conservation, and Energy Act of 2008 PL 110-234
== Budget ==
On May 7, 2009 President Barack Obama unveiled a $26.4 billion budget request for DOE for fiscal year (FY) 2010, including $2.3 billion for the DOE Office of Energy Efficiency and Renewable Energy (EERE). That budget aimed to substantially expand the use of renewable energy sources while improving energy transmission infrastructure. It also proposed significant investments in hybrids and plug-in hybrids, smart grid technologies, and scientific research and innovation.
As part of the $789 billion economic stimulus package in the American Recovery and Reinvestment Act of 2009, Congress provided Energy with an additional $38.3 billion for fiscal years 2009 and 2010, adding about 75 percent to Energy's annual budgets. Most of the stimulus spending was in the form of grants and contracts. For fiscal year 2013, each of the operating units of the Department of Energy operated with the following budgets:
In March 2018, Energy Secretary Rick Perry testified to a Senate panel about the Trump administration's DOE budget request for fiscal year 2019. The budget request prioritized nuclear security while making large cuts to energy efficiency and renewable energy programs. The proposal was a $500 million increase in funds over fiscal year 2017. It "promotes innovations like a new Office of Cybersecurity, Energy Security, and Emergency Response (CESER) and gains for the Office of Fossil Energy. Investments would be made to strengthen the National Nuclear Security Administration and modernize the nuclear force, as well as in weapons activities and advanced computing." However, the budget for the Office of Energy Efficiency and Renewable Energy would be lowered to $696 million under the plan, down from $1.3 billion in fiscal year 2017. Overall, the department's energy and related programs would be cut by $1.9 billion.
== Programs and contracts ==
=== Energy Savings Performance Contract ===
Energy Savings Performance Contracts (ESPCs) are contracts under which a contractor designs, constructs, and obtains the necessary financing for an energy savings project, and the federal agency makes payments over time to the contractor from the savings in the agency's utility bills. The contractor guarantees the energy improvements will generate savings, and after the contract ends, all continuing cost savings accrue to the federal agency.
=== Energy Innovation Hubs ===
Energy Innovation Hubs are multi-disciplinary, meant to advance highly promising areas of energy science and technology from their early stages of research to the point that the risk level will be low enough for industry to commercialize the technologies. The Consortium for Advanced Simulation of Light Water Reactors (CASL) was the first DOE Energy Innovation Hub established in July 2010, for the purpose of providing advanced modeling and simulation (M&S) solutions for commercial nuclear reactors.
The 2009 DOE budget includes $280 million to fund eight Energy Innovation Hubs, each of which is focused on a particular energy challenge. Two of the eight hubs are included in the EERE budget and will focus on integrating smart materials, designs, and systems into buildings to better conserve energy and on designing and discovering new concepts and materials needed to convert solar energy into electricity. Another two hubs, included in the DOE Office of Science budget, were created to tackle the challenges of devising advanced methods of energy storage and creating fuels directly from sunlight without the use of plants or microbes. Yet another hub was made to develop "smart" materials to allow the electrical grid to adapt and respond to changing conditions.
In 2012, the DOE awarded $120 million to the Ames Laboratory to start a new EIH, the Critical Materials Institute, which will focus on improving the supply of rare earth elements.
=== Advanced Research Projects Agency-Energy ===
ARPA-E was officially created by the America COMPETES Act , authored by Congressman Bart Gordon, within the United States Department of Energy (DOE) in 2007, though without a budget. The initial budget of about $400 million was a part of the economic stimulus bill of February 2009.
=== Other ===
DOE Isotope Program - coordinates isotope production
Federal Energy Management Program
Foundation for Energy Security and Innovation - a 501(c)(3) organization dedicated to supporting DOE research
Fusion Energy Sciences - a program to research nuclear fusion, with a yearly budget in 2020 of $670 million, with $250 million of that going to ITER
GovEnergy - an annual event partly sponsored by the DOE
Grid Deployment Office - a division dedicated to spreading adoption of grid-enhancing technologies and improving transmission permitting
National Science Bowl - a high school and middle school science knowledge competition
Solar Decathlon - an international collegiate competition to design and build solar-powered houses
State Energy Program
Weatherization Assistance Program
== List of secretaries of energy ==
== See also ==
Federal Energy Regulatory Commission
National Council on Electricity Policy
United States federal executive departments
== References ==
== Further reading ==
Cumming, Alfred (February 9, 2009). "Polygraph Use by the Department of Energy: Issues for Congress" (PDF). Congressional Research Service. Archived from the original (PDF) on March 28, 2014 – via Federation of American Scientists.
== External links ==
Official website
Department of Energy in the Federal Register
Department of Energy on USAspending.gov
Works by the United States Department of Energy at Project Gutenberg
Works by United States Department of Energy at LibriVox (public domain audiobooks)
Advanced Energy Initiative
Twenty In Ten | Wikipedia/US_Department_of_Energy |
The Energy Modeling Forum (EMF) is a structured forum for discussing important issues related to energy and the environment. The EMF was established in 1976 at Stanford University. The EMF works through a series of ad hoc working groups, each focusing on specific corporate or policy decisions. The EMF provides a non-partisan platform that ensures objective consideration of opposing views. Participation is by invitation only.
Since the late 1990s, the EMF has made contributions to the economics of climate change, as reflected in the reports of the Intergovernmental Panel on Climate Change (IPCC) and in the field of integrated assessment modeling more generally.
John Weyant is the current director of the EMF. Other members of the EMF include Hillard Huntington, James Sweeney, and Frank Wolak.
== Ethos ==
The EMF was convened in 1976 over concerns that the insights that large-scale energy models could provide policymakers were being overshadowed by the "plethora of detailed quantitative results" being disseminated and discussed.: 449 As a result, the EMF sought to bring energy modelers together to provide a proper context for their work. Indeed, the EMF was "formed to foster better communication between the builders and users of energy models in energy planning and policy analysis".: 449
The EMF periodically establishes ad hoc working groups to conduct studies on selected energy topics. A working group then identifies relevant existing models and sets a series of tests to illuminate the basic structure and behavior of each model. Results are then compared, and the strengths and weaknesses of each model are documented in a report, which, as of 1982 is freely available.
== List of EMF projects ==
Reports for most completed projects are available on the EMF website. However, reports since 2006 occasionally been published exclusively in special editions of paywalled academic journals instead.
== See also ==
Open Energy Modelling Initiative – an open source energy modeling initiative centered on Europe
== References ==
== External links ==
EMF home page | Wikipedia/Energy_Modeling_Forum |
Energy efficiency may refer to:
Energy efficiency (physics), the ratio between the useful output and input of an energy conversion process
Electrical efficiency, useful power output per electrical power consumed
Mechanical efficiency, a ratio of the measured performance to the performance of an ideal machine
Thermal efficiency, the extent to which the energy added by heat is converted to net work output or vice versa
Luminous efficiency, a measure of how well a light source produces visible light
Fuel efficiency, the efficiency of converting potential energy in a fuel into kinetic energy
Energy efficiency in transportation, the fuel economy of various modes of transportation
Energy-efficient landscaping, a type of landscaping designed for the purpose of conserving energy
Efficient energy use, minimizing the amount of energy used for a given, constant energy service
Energy conservation, reducing energy consumption by using less of an energy service
== See also ==
Energy (disambiguation)
Efficiency (disambiguation)
Energy rating (disambiguation)
All pages with titles containing Energy efficiency
All pages with titles containing Energy efficient | Wikipedia/Energy_efficiency_(disambiguation) |
The Consortium for Energy Efficiency (CEE) is a nonprofit 501(c)(3) organization that promotes the adoption of energy efficient products and services. CEE specifications are referenced by the United States Department of Energy and by the efficiency programs of many natural gas and electric utilities in the United States and Canada. The organization's Annual Industry Report documents the efficiency industry's US$8 billion in annual expenditures.
== Activities and funding ==
CEE influences the market for efficient products and services through 17 initiatives covering the residential, commercial and industrial sectors; Product examples include space heating, refrigeration lighting, and industrial water treatment. These initiatives are voluntarily adopted by CEE members—such as utility efficiency programs—to establish common levels for high efficiency equipment. Member organizations implement initiatives through rebates, technical assistance, or other efforts in their service territories, states, or provinces. CEE also publishes Qualified Product Lists of equipment meeting high levels of efficiency performance. Some equipment criteria are specifically cited by US law for energy-related federal tax credits.
Since 2000, CEE has conducted the Household ENERGY STAR Survey, identifying the ENERGY STAR program as one of the most recognized brands among US consumers.
According to the organization's 2013 IRS Form 990, membership dues represented US$2,533,118 (64%) of annual revenue. CEE received significant additional funding through its partnerships with the US Environmental Protection Agency, the US Department of Energy, and Natural Resources Canada. Founded in 1991, CEE members consist of more than 100 natural gas and electric utilities, 10 efficiency organizations and state agencies, and 4 DOE national laboratories.
== Annual Industry Report ==
The CEE Annual Industry Report provides funding information and program activities for natural gas and electric demand side management. The 2014 study identified US$7.6 billion in investment in the US and Canada, and detailed expenditures by customer class and state. The report indicated an increase in program budgets from US$4.4 billion in 2008 to US$7.3 billion in 2013.
== References == | Wikipedia/Consortium_for_Energy_Efficiency |
Energy development is the field of activities focused on obtaining sources of energy from natural resources. These activities include the production of renewable, nuclear, and fossil fuel derived sources of energy, and for the recovery and reuse of energy that would otherwise be wasted. Energy conservation and efficiency measures reduce the demand for energy development, and can have benefits to society with improvements to environmental issues.
Societies use energy for transportation, manufacturing, illumination, heating and air conditioning, and communication, for industrial, commercial, agricultural and domestic purposes. Energy resources may be classified as primary resources, where the resource can be used in substantially its original form, or as secondary resources, where the energy source must be converted into a more conveniently usable form. Non-renewable resources are significantly depleted by human use, whereas renewable resources are produced by ongoing processes that can sustain indefinite human exploitation.
Thousands of people are employed in the energy industry. The conventional industry comprises the petroleum industry, the natural gas industry, the electrical power industry, and the nuclear industry. New energy industries include the renewable energy industry, comprising alternative and sustainable manufacture, distribution, and sale of alternative fuels.
== Classification of resources ==
Energy resources may be classified as primary resources, suitable for end use without conversion to another form, or secondary resources, where the usable form of energy required substantial conversion from a primary source. Examples of primary energy resources are wind power, solar power, wood fuel, fossil fuels such as coal, oil and natural gas, and uranium. Secondary resources are those such as electricity, hydrogen, or other synthetic fuels.
Another important classification is based on the time required to regenerate an energy resource. "Renewable resources" are those that recover their capacity in a time significant by human needs. Examples are hydroelectric power or wind power, when the natural phenomena that are the primary source of energy are ongoing and not depleted by human demands. Non-renewable resources are those that are significantly depleted by human usage and that will not recover their potential significantly during human lifetimes. An example of a non-renewable energy source is coal, which does not form naturally at a rate that would support human use.
== Fossil fuels ==
Fossil fuel (primary non-renewable fossil) sources burn coal or hydrocarbon fuels, which are the remains of the decomposition of plants and animals. There are three main types of fossil fuels: coal, petroleum, and natural gas. Another fossil fuel, liquefied petroleum gas (LPG), is principally derived from the production of natural gas. Heat from burning fossil fuel is used either directly for space heating and process heating, or converted to mechanical energy for vehicles, industrial processes, or electrical power generation. These fossil fuels are part of the carbon cycle and allow solar energy stored in the fuel to be released.
The use of fossil fuels in the 18th and 19th century set the stage for the Industrial Revolution.
Fossil fuels make up the bulk of the world's current primary energy sources. In 2005, 81% of the world's energy needs was met from fossil sources. The technology and infrastructure for the use of fossil fuels already exist. Liquid fuels derived from petroleum deliver much usable energy per unit of weight or volume, which is advantageous when compared with lower energy density sources such as batteries. Fossil fuels are currently economical for decentralized energy use.
Energy dependence on imported fossil fuels creates energy security risks for dependent countries. Oil dependence in particular has led to war, funding of radicals, monopolization, and socio-political instability.
Fossil fuels are non-renewable resources, which will eventually decline in production and become exhausted. While the processes that created fossil fuels are ongoing, fuels are consumed far more quickly than the natural rate of replenishment. Extracting fuels becomes increasingly costly as society consumes the most accessible fuel deposits. Extraction of fossil fuels results in environmental degradation, such as the strip mining and mountaintop removal for coal.
Fuel efficiency is a form of thermal efficiency, meaning the efficiency of a process that converts chemical potential energy contained in a carrier fuel into kinetic energy or work. The fuel economy is the energy efficiency of a particular vehicle, is given as a ratio of distance travelled per unit of fuel consumed. Weight-specific efficiency (efficiency per unit weight) may be stated for freight, and passenger-specific efficiency (vehicle efficiency) per passenger. The inefficient atmospheric combustion (burning) of fossil fuels in vehicles, buildings, and power plants contributes to urban heat islands.
Conventional production of oil peaked, conservatively, between 2007 and 2010. In 2010, it was estimated that an investment of $8 trillion in non-renewable resources would be required to maintain current levels of production for 25 years. In 2010, governments subsidized fossil fuels by an estimated $500 billion a year. Fossil fuels are also a source of greenhouse gas emissions, leading to concerns about global warming if consumption is not reduced.
The combustion of fossil fuels leads to the release of pollution into the atmosphere. The fossil fuels are mainly carbon compounds. During combustion, carbon dioxide is released, and also nitrogen oxides, soot and other fine particulates. The carbon dioxide is the main contributor to recent climate change.
Other emissions from fossil fuel power station include sulphur dioxide, carbon monoxide (CO), hydrocarbons, volatile organic compounds (VOC), mercury, arsenic, lead, cadmium, and other heavy metals including traces of uranium.
A typical coal plant generates billions of kilowatt hours of electrical power per year.
== Nuclear ==
=== Fission ===
Nuclear power is the use of nuclear fission to generate useful heat and electricity. Fission of uranium produces nearly all economically significant nuclear power. Radioisotope thermoelectric generators form a very small component of energy generation, mostly in specialized applications such as deep space vehicles.
Nuclear power plants, excluding naval reactors, provided about 5.7% of the world's energy and 13% of the world's electricity in 2012.
In 2013, the IAEA report that there are 437 operational nuclear power reactors, in 31 countries, although not every reactor is producing electricity. In addition, there are approximately 140 naval vessels using nuclear propulsion in operation, powered by some 180 reactors. As of 2013, attaining a net energy gain from sustained nuclear fusion reactions, excluding natural fusion power sources such as the Sun, remains an ongoing area of international physics and engineering research. More than 60 years after the first attempts, commercial fusion power production remains unlikely before 2050.
There is an ongoing debate about nuclear power. Proponents, such as the World Nuclear Association, the IAEA and Environmentalists for Nuclear Energy contend that nuclear power is a safe, sustainable energy source that reduces carbon emissions. Opponents contend that nuclear power poses many threats to people and the environment.
Nuclear power plant accidents include the Chernobyl disaster (1986), Fukushima Daiichi nuclear disaster (2011), and the Three Mile Island accident (1979). There have also been some nuclear submarine accidents. In terms of lives lost per unit of energy generated, analysis has determined that nuclear power has caused less fatalities per unit of energy generated than the other major sources of energy generation. Energy production from coal, petroleum, natural gas and hydropower has caused a greater number of fatalities per unit of energy generated due to air pollution and energy accident effects. However, the economic costs of nuclear power accidents is high, and meltdowns can take decades to clean up. The human costs of evacuations of affected populations and lost livelihoods is also significant.
Comparing Nuclear's latent cancer deaths, such as cancer with other energy sources immediate deaths per unit of energy generated(GWeyr). This study does not include fossil fuel related cancer and other indirect deaths created by the use of fossil fuel consumption in its "severe accident" classification, which would be an accident with more than 5 fatalities.
As of 2012, according to the IAEA, worldwide there were 68 civil nuclear power reactors under construction in 15 countries, approximately 28 of which in the People's Republic of China (PRC), with the most recent nuclear power reactor, as of May 2013, to be connected to the electrical grid, occurring on February 17, 2013, in Hongyanhe Nuclear Power Plant in the PRC. In the United States, two new Generation III reactors are under construction at Vogtle. U.S. nuclear industry officials expect five new reactors to enter service by 2020, all at existing plants. In 2013, four aging, uncompetitive, reactors were permanently closed.
Recent experiments in extraction of uranium use polymer ropes that are coated with a substance that selectively absorbs uranium from seawater. This process could make the considerable volume of uranium dissolved in seawater exploitable for energy production. Since ongoing geologic processes carry uranium to the sea in amounts comparable to the amount that would be extracted by this process, in a sense the sea-borne uranium becomes a sustainable resource.
Nuclear power is a low carbon power generation method of producing electricity, with an analysis of the literature on its total life cycle emission intensity finding that it is similar to renewable sources in a comparison of greenhouse gas (GHG) emissions per unit of energy generated. Since the 1970s, nuclear fuel has displaced about 64 gigatonnes of carbon dioxide equivalent (GtCO2-eq) greenhouse gases, that would have otherwise resulted from the burning of oil, coal or natural gas in fossil-fuel power stations.
==== Nuclear power phase-out and pull-backs ====
Japan's 2011 Fukushima Daiichi nuclear accident, which occurred in a reactor design from the 1960s, prompted a rethink of nuclear safety and nuclear energy policy in many countries. Germany decided to close all its reactors by 2022, and Italy has banned nuclear power. Following Fukushima, in 2011 the International Energy Agency halved its estimate of additional nuclear generating capacity to be built by 2035.
===== Fukushima =====
Following the 2011 Fukushima Daiichi nuclear disaster – the second worst nuclear incident, that displaced 50,000 households after radioactive material leaked into the air, soil and sea, and with subsequent radiation checks leading to bans on some shipments of vegetables and fish – a global public support survey by Ipsos (2011) for energy sources was published and nuclear fission was found to be the least popular
==== Fission economics ====
The economics of new nuclear power plants is a controversial subject, since there are diverging views on this topic, and multibillion-dollar investments ride on the choice of an energy source. Nuclear power plants typically have high capital costs for building the plant, but low direct fuel costs. In recent years there has been a slowdown of electricity demand growth and financing has become more difficult, which affects large projects such as nuclear reactors, with very large upfront costs and long project cycles which carry a large variety of risks. In Eastern Europe, a number of long-established projects are struggling to find finance, notably Belene in Bulgaria and the additional reactors at Cernavoda in Romania, and some potential backers have pulled out. Where cheap gas is available and its future supply relatively secure, this also poses a major problem for nuclear projects.
Analysis of the economics of nuclear power must take into account who bears the risks of future uncertainties. To date all operating nuclear power plants were developed by state-owned or regulated utility monopolies where many of the risks associated with construction costs, operating performance, fuel price, and other factors were borne by consumers rather than suppliers. Many countries have now liberalized the electricity market where these risks, and the risk of cheaper competitors emerging before capital costs are recovered, are borne by plant suppliers and operators rather than consumers, which leads to a significantly different evaluation of the economics of new nuclear power plants.
==== Costs ====
Costs are likely to go up for currently operating and new nuclear power plants, due to increased requirements for on-site spent fuel management and elevated design basis threats. While first of their kind designs, such as the EPRs under construction are behind schedule and over-budget, of the seven South Korean APR-1400s presently under construction worldwide, two are in S.Korea at the Hanul Nuclear Power Plant and four are at the largest nuclear station construction project in the world as of 2016, in the United Arab Emirates at the planned Barakah nuclear power plant. The first reactor, Barakah-1 is 85% completed and on schedule for grid-connection during 2017.
Two of the four EPRs under construction (in Finland and France) are significantly behind schedule and substantially over cost.
== Renewable sources ==
Renewable energy is generally defined as energy that comes from resources which are naturally replenished on a human timescale such as sunlight, wind, rain, tides, waves and geothermal heat. Renewable energy replaces conventional fuels in four distinct areas: electricity generation, hot water/space heating, motor fuels, and rural (off-grid) energy services.
Including traditional biomass usage, about 19% of global energy consumption is accounted for by renewable resources. Wind powered energy production is being turned to as a prominent renewable energy source, increasing global wind power capacity by 12% in 2021. While not the case for all countries, 58% of sample countries linked renewable energy consumption to have a positive impact on economic growth. At the national level, at least 30 nations around the world already have renewable energy contributing more than 20% of energy supply. National renewable energy markets are projected to continue to grow strongly in the coming decade and beyond.[76]
Unlike other energy sources, renewable energy sources are not as restricted by geography. Additionally deployment of renewable energy is resulting in economic benefits as well as combating climate change. Rural electrification has been researched on multiple sites and positive effects on commercial spending, appliance use, and general activities requiring electricity as energy. Renewable energy growth in at least 38 countries has been driven by the high electricity usage rates. International support for promoting renewable sources like solar and wind have continued grow.
While many renewable energy projects are large-scale, renewable technologies are also suited to rural and remote areas and developing countries, where energy is often crucial in human development. To ensure human development continues sustainably, governments around the world are beginning to research potential ways to implement renewable sources into their countries and economies. For example, the UK Government’s Department for Energy and Climate Change 2050 Pathways created a mapping technique to educate the public on land competition between energy supply technologies. This tool provides users the ability to understand what the limitations and potential their surrounding land and country has in terms of energy production.
=== Hydroelectricity ===
Hydroelectricity is electric power generated by hydropower; the force of falling or flowing water. In 2015 hydropower generated 16.6% of the world's total electricity and 70% of all renewable electricity and was expected to increase about 3.1% each year for the following 25 years.
Hydropower is produced in 150 countries, with the Asia-Pacific region generating 32 percent of global hydropower in 2010. China is the largest hydroelectricity producer, with 721 terawatt-hours of production in 2010, representing around 17 percent of domestic electricity use. There are now three hydroelectricity plants larger than 10 GW: the Three Gorges Dam in China, Itaipu Dam across the Brazil/Paraguay border, and Guri Dam in Venezuela.
The cost of hydroelectricity is relatively low, making it a competitive source of renewable electricity. The average cost of electricity from a hydro plant larger than 10 megawatts is 3 to 5 U.S. cents per kilowatt-hour. Hydro is also a flexible source of electricity since plants can be ramped up and down very quickly to adapt to changing energy demands. However, damming interrupts the flow of rivers and can harm local ecosystems, and building large dams and reservoirs often involves displacing people and wildlife. Once a hydroelectric complex is constructed, the project produces no direct waste, and has a considerably lower output level of the greenhouse gas carbon dioxide than fossil fuel powered energy plants.
=== Wind ===
Wind power harnesses the power of the wind to propel the blades of wind turbines. These turbines cause the rotation of magnets, which creates electricity. Wind towers are usually built together on wind farms. There are offshore and onshore wind farms. Global wind power capacity has expanded rapidly to 336 GW in June 2014, and wind energy production was around 4% of total worldwide electricity usage, and growing rapidly.
Wind power is widely used in Europe, Asia, and the United States. Several countries have achieved relatively high levels of wind power penetration, such as 21% of stationary electricity production in Denmark, 18% in Portugal, 16% in Spain, 14% in Ireland, and 9% in Germany in 2010.: 11 By 2011, at times over 50% of electricity in Germany and Spain came from wind and solar power. As of 2011, 83 countries around the world are using wind power on a commercial basis.: 11
Many of the world's largest onshore wind farms are located in the United States, China, and India. Most of the world's largest offshore wind farms are located in Denmark, Germany and the United Kingdom. The two largest offshore wind farm are currently the 630 MW London Array and Gwynt y Môr.
=== Solar ===
=== Biofuels ===
A biofuel is a fuel that contains energy from geologically recent carbon fixation. These fuels are produced from living organisms. Examples of this carbon fixation occur in plants and microalgae. These fuels are made by a biomass conversion (biomass refers to recently living organisms, most often referring to plants or plant-derived materials). This biomass can be converted to convenient energy containing substances in three different ways: thermal conversion, chemical conversion, and biochemical conversion. This biomass conversion can result in fuel in solid, liquid, or gas form. This new biomass can be used for biofuels. Biofuels have increased in popularity because of rising oil prices and the need for energy security.
Bioethanol is an alcohol made by fermentation, mostly from carbohydrates produced in sugar or starch crops such as corn or sugarcane. Cellulosic biomass, derived from non-food sources, such as trees and grasses, is also being developed as a feedstock for ethanol production. Ethanol can be used as a fuel for vehicles in its pure form, but it is usually used as a gasoline additive to increase octane and improve vehicle emissions. Bioethanol is widely used in the USA and in Brazil. Current plant design does not provide for converting the lignin portion of plant raw materials to fuel components by fermentation.
Biodiesel is made from vegetable oils and animal fats. Biodiesel can be used as a fuel for vehicles in its pure form, but it is usually used as a diesel additive to reduce levels of particulates, carbon monoxide, and hydrocarbons from diesel-powered vehicles. Biodiesel is produced from oils or fats using transesterification and is the most common biofuel in Europe. However, research is underway on producing renewable fuels from decarboxylation
In 2010, worldwide biofuel production reached 105 billion liters (28 billion gallons US), up 17% from 2009, and biofuels provided 2.7% of the world's fuels for road transport, a contribution largely made up of ethanol and biodiesel. Global ethanol fuel production reached 86 billion liters (23 billion gallons US) in 2010, with the United States and Brazil as the world's top producers, accounting together for 90% of global production. The world's largest biodiesel producer is the European Union, accounting for 53% of all biodiesel production in 2010. As of 2011, mandates for blending biofuels exist in 31 countries at the national level and in 29 states or provinces.: 13–14 The International Energy Agency has a goal for biofuels to meet more than a quarter of world demand for transportation fuels by 2050 to reduce dependence on petroleum and coal.
=== Geothermal ===
Geothermal energy is thermal energy generated and stored in the Earth. Thermal energy is the energy that determines the temperature of matter. The geothermal energy of the Earth's crust originates from the original formation of the planet (20%) and from radioactive decay of minerals (80%). The geothermal gradient, which is the difference in temperature between the core of the planet and its surface, drives a continuous conduction of thermal energy in the form of heat from the core to the surface. The adjective geothermal originates from the Greek roots γη (ge), meaning earth, and θερμος (thermos), meaning hot.
Earth's internal heat is thermal energy generated from radioactive decay and continual heat loss from Earth's formation. Temperatures at the core-mantle boundary may reach over 4000 °C (7,200 °F). The high temperature and pressure in Earth's interior cause some rock to melt and solid mantle to behave plastically, resulting in portions of mantle convecting upward since it is lighter than the surrounding rock. Rock and water is heated in the crust, sometimes up to 370 °C (700 °F).
From hot springs, geothermal energy has been used for bathing since Paleolithic times and for space heating since ancient Roman times, but it is now better known for electricity generation. Worldwide, 11,400 megawatts (MW) of geothermal power is online in 24 countries in 2012. An additional 28 gigawatts of direct geothermal heating capacity is installed for district heating, space heating, spas, industrial processes, desalination and agricultural applications in 2010.
Geothermal power is cost effective, reliable, sustainable, and environmentally friendly, but has historically been limited to areas near tectonic plate boundaries. Recent technological advances have dramatically expanded the range and size of viable resources, especially for applications such as home heating, opening a potential for widespread exploitation. Geothermal wells release greenhouse gases trapped deep within the earth, but these emissions are much lower per energy unit than those of fossil fuels. As a result, geothermal power has the potential to help mitigate global warming if widely deployed in place of fossil fuels.
The Earth's geothermal resources are theoretically more than adequate to supply humanity's energy needs, but only a very small fraction may be profitably exploited. Drilling and exploration for deep resources is very expensive. Forecasts for the future of geothermal power depend on assumptions about technology, energy prices, subsidies, and interest rates. Pilot programs like EWEB's customer opt in Green Power Program show that customers would be willing to pay a little more for a renewable energy source like geothermal. But as a result of government assisted research and industry experience, the cost of generating geothermal power has decreased by 25% over the past two decades. In 2001, geothermal energy cost between two and ten US cents per kWh.
=== Oceanic ===
Marine Renewable Energy (MRE) or marine power (also sometimes referred to as ocean energy, ocean power, or marine and hydrokinetic energy) refers to the energy carried by the mechanical energy of ocean waves, currents, and tides, shifts in salinity gradients, and ocean temperature differences. MRE has the potential to become a reliable and renewable energy source because of the cyclical nature of the oceans. The movement of water in the world's oceans creates a vast store of kinetic energy or energy in motion. This energy can be harnessed to generate electricity to power homes, transport, and industries.
The term marine energy encompasses both wave power, i.e. power from surface waves, and tidal power, i.e. obtained from the kinetic energy of large bodies of moving water. Offshore wind power is not a form of marine energy, as wind power is derived from the wind, even if the wind turbines are placed over water. The oceans have a tremendous amount of energy and are close to many if not most concentrated populations. Ocean energy has the potential to provide a substantial amount of new renewable energy around the world.
Marine energy technology is in its first stage of development. To be developed, MRE needs efficient methods of storing, transporting, and capturing ocean power, so it can be used where needed. Over the past year, countries around the world have started implementing market strategies for MRE to commercialize. Canada and China introduced incentives, such as feed-in tariffs (FiTs), which are above-market prices for MRE that allow investors and project developers a stable income. Other financial strategies consist of subsidies, grants, and funding from public-private partnerships (PPPs). China alone approved 100 ocean projects in 2019. Portugal and Spain recognize the potential of MRE in accelerating decarbonization, which is fundamental to meeting the goals of the Paris Agreement. Both countries are focusing on solar and offshore wind auctions to attract private investment, ensure cost-effectiveness, and accelerate MRE growth. Ireland sees MRE as a key component to reduce its carbon footprint. The Offshore Renewable Energy Development Plan (OREDP) supports the exploration and development of the country's significant offshore energy potential. Additionally, Ireland has implemented the Renewable Electricity Support Scheme (RESS) which includes auctions designed to provide financial support for communities, increase technology diversity, and guarantee energy security.
However, while research is increasing, there have been concerns associated with threats to marine mammals, habitats, and potential changes to ocean currents. MRE can be a renewable energy source for coastal communities helping their transition from fossil fuel, but researchers are calling for a better understanding of its environmental impacts. Because ocean-energy areas are often isolated from both fishing and sea traffic, these zones may provide shelter from humans and predators for some marine species. MRE devices can be an ideal home for many fish, crayfish, mollusks, and barnacles; and may also indirectly affect seabirds, and marine mammals because they feed on those species. Similarly, such areas may create an "artificial reef effect" by boosting biodiversity nearby. Noise pollution generated from the technology is limited, also causing fish and mammals living in the area of the installation to return. In the most recent State of Science Report about MRE, the authors claim that there is no evidence for fish, mammals, or seabirds to be injured by either collision, noise pollution, or the electromagnetic field. The uncertainty of its environmental impact comes from the low quantity of MRE devices in the ocean today where data is collected.
=== 100% renewable energy ===
The incentive to use 100% renewable energy, for electricity, transport, or even total primary energy supply globally, has been motivated by global warming and other ecological as well as economic concerns. Renewable energy use has grown much faster than anyone anticipated. The Intergovernmental Panel on Climate Change has said that there are few fundamental technological limits to integrating a portfolio of renewable energy technologies to meet most of total global energy demand. At the national level, at least 30 nations around the world already have renewable energy contributing more than 20% of energy supply. Also, Stephen W. Pacala and Robert H. Socolow have developed a series of "stabilization wedges" that can allow us to maintain our quality of life while avoiding catastrophic climate change, and "renewable energy sources," in aggregate, constitute the largest number of their "wedges."
Mark Z. Jacobson says producing all new energy with wind power, solar power, and hydropower by 2030 is feasible and existing energy supply arrangements could be replaced by 2050. Barriers to implementing the renewable energy plan are seen to be "primarily social and political, not technological or economic". Jacobson says that energy costs with a wind, solar, water system should be similar to today's energy costs.
Similarly, in the United States, the independent National Research Council has noted that "sufficient domestic renewable resources exist to allow renewable electricity to play a significant role in future electricity generation and thus help confront issues related to climate change, energy security, and the escalation of energy costs ... Renewable energy is an attractive option because renewable resources available in the United States, taken collectively, can supply significantly larger amounts of electricity than the total current or projected domestic demand." .
Critics of the "100% renewable energy" approach include Vaclav Smil and James E. Hansen. Smil and Hansen are concerned about the variable output of solar and wind power, but Amory Lovins argues that the electricity grid can cope, just as it routinely backs up nonworking coal-fired and nuclear plants with working ones.
Google spent $30 million on their "Renewable Energy Cheaper than Coal" project to develop renewable energy and stave off catastrophic climate change. The project was cancelled after concluding that a best-case scenario for rapid advances in renewable energy could only result in emissions 55 percent below the fossil fuel projections for 2050.
== Increased energy efficiency ==
Although increasing the efficiency of energy use is not energy development per se, it may be considered under the topic of energy development since it makes existing energy sources available to do work.: 22
Efficient energy use reduces the amount of energy required to provide products and services. For example, insulating a home allows a building to use less heating and cooling energy to maintain a comfortable temperature. Installing fluorescent lamps or natural skylights reduces the amount of energy required for illumination compared to incandescent light bulbs. Compact fluorescent lights use two-thirds less energy and may last 6 to 10 times longer than incandescent lights. Improvements in energy efficiency are most often achieved by adopting an efficient technology or production process.
Reducing energy use may save consumers money, if the energy savings offsets the cost of an energy efficient technology. Reducing energy use reduces emissions. According to the International Energy Agency, improved energy efficiency in buildings, industrial processes and transportation could reduce the global energy demand in 2050 to around 8% smaller than today, but serving an economy more than twice as big and a population of about 2 billion more people.
Energy efficiency and renewable energy are said to be the twin pillars of sustainable energy policy. In many countries energy efficiency is also seen to have a national security benefit because it can be used to reduce the level of energy imports from foreign countries and may slow down the rate at which domestic energy resources are depleted.
It's been discovered "that for OECD countries, wind, geothermal, hydro and nuclear have the lowest hazard rates among energy sources in production".
== Transmission ==
While new sources of energy are only rarely discovered or made possible by new technology, distribution technology continually evolves. The use of fuel cells in cars, for example, is an anticipated delivery technology. This section presents the various delivery technologies that have been important to historic energy development. They all rely in way on the energy sources listed in the previous section.
=== Shipping and pipelines ===
Coal, petroleum and their derivatives are delivered by boat, rail, or road. Petroleum and natural gas may also be delivered by pipeline, and coal via a Slurry pipeline. Fuels such as gasoline and LPG may also be delivered via aircraft. Natural gas pipelines must maintain a certain minimum pressure to function correctly. The higher costs of ethanol transportation and storage are often prohibitive.
=== Wired energy transfer ===
Electricity grids are the networks used to transmit and distribute power from production source to end user, when the two may be hundreds of kilometres away. Sources include electrical generation plants such as a nuclear reactor, coal burning power plant, etc. A combination of sub-stations and transmission lines are used to maintain a constant flow of electricity. Grids may suffer from transient blackouts and brownouts, often due to weather damage. During certain extreme space weather events solar wind can interfere with transmissions. Grids also have a predefined carrying capacity or load that cannot safely be exceeded. When power requirements exceed what's available, failures are inevitable. To prevent problems, power is then rationed.
Industrialised countries such as Canada, the US, and Australia are among the highest per capita consumers of electricity in the world, which is possible thanks to a widespread electrical distribution network. The US grid is one of the most advanced, although infrastructure maintenance is becoming a problem. CurrentEnergy provides a realtime overview of the electricity supply and demand for California, Texas, and the Northeast of the US. African countries with small scale electrical grids have a correspondingly low annual per capita usage of electricity. One of the most powerful power grids in the world supplies power to the state of Queensland, Australia.
=== Wireless energy transfer ===
Wireless power transfer is a process whereby electrical energy is transmitted from a power source to an electrical load that does not have a built-in power source, without the use of interconnecting wires. Currently available technology is limited to short distances and relatively low power level.
Orbiting solar power collectors would require wireless transmission of power to Earth. The proposed method involves creating a large beam of microwave-frequency radio waves, which would be aimed at a collector antenna site on the Earth. Formidable technical challenges exist to ensure the safety and profitability of such a scheme.
== Storage ==
Energy storage is accomplished by devices or physical media that store energy to perform useful operation at a later time. A device that stores energy is sometimes called an accumulator.
All forms of energy are either potential energy (e.g. Chemical, gravitational, electrical energy, temperature differential, latent heat, etc.) or kinetic energy (e.g. momentum). Some technologies provide only short-term energy storage, and others can be very long-term such as power to gas using hydrogen or methane and the storage of heat or cold between opposing seasons in deep aquifers or bedrock. A wind-up clock stores potential energy (in this case mechanical, in the spring tension), a battery stores readily convertible chemical energy to operate a mobile phone, and a hydroelectric dam stores energy in a reservoir as gravitational potential energy. Ice storage tanks store ice (thermal energy in the form of latent heat) at night to meet peak demand for cooling. Fossil fuels such as coal and gasoline store ancient energy derived from sunlight by organisms that later died, became buried and over time were then converted into these fuels. Even food (which is made by the same process as fossil fuels) is a form of energy stored in chemical form.
== History ==
Since prehistory, when humanity discovered fire to warm up and roast food, through the Middle Ages in which populations built windmills to grind the wheat, until the modern era in which nations can get electricity splitting the atom. Man has sought endlessly for energy sources.
Except nuclear, geothermal and tidal, all other energy sources are from current solar isolation or from fossil remains of plant and animal life that relied upon sunlight. Ultimately, solar energy itself is the result of the Sun's nuclear fusion. Geothermal power from hot, hardened rock above the magma of the Earth's core is the result of the decay of radioactive materials present beneath the Earth's crust, and nuclear fission relies on man-made fission of heavy radioactive elements in the Earth's crust; in both cases these elements were produced in supernova explosions before the formation of the Solar System.
Since the beginning of the Industrial Revolution, the question of the future of energy supplies has been of interest. In 1865, William Stanley Jevons published The Coal Question in which he saw that the reserves of coal were being depleted and that oil was an ineffective replacement. In 1914, U.S. Bureau of Mines stated that the total production was 5.7 billion barrels (910,000,000 m3). In 1956, Geophysicist M. King Hubbert deduces that U.S. oil production would peak between 1965 and 1970 and that oil production will peak "within half a century" on the basis of 1956 data. In 1989, predicted peak by Colin Campbell In 2004, OPEC estimated, with substantial investments, it would nearly double oil output by 2025
=== Sustainability ===
The environmental movement has emphasized sustainability of energy use and development. Renewable energy is sustainable in its production; the available supply will not be diminished for the foreseeable future - millions or billions of years. "Sustainability" also refers to the ability of the environment to cope with waste products, especially air pollution. Sources which have no direct waste products (such as wind, solar, and hydropower) are brought up on this point. With global demand for energy growing, the need to adopt various energy sources is growing. Energy conservation is an alternative or complementary process to energy development. It reduces the demand for energy by using it efficiently.
=== Resilience ===
Some observers contend that idea of "energy independence" is an unrealistic and opaque concept. The alternative offer of "energy resilience" is a goal aligned with economic, security, and energy realities. The notion of resilience in energy was detailed in the 1982 book Brittle Power: Energy Strategy for National Security. The authors argued that simply switching to domestic energy would not be secure inherently because the true weakness is the often interdependent and vulnerable energy infrastructure of a country. Key aspects such as gas lines and the electrical power grid are often centralized and easily susceptible to disruption. They conclude that a "resilient energy supply" is necessary for both national security and the environment. They recommend a focus on energy efficiency and renewable energy that is decentralized.
In 2008, former Intel Corporation Chairman and CEO Andrew Grove looked to energy resilience, arguing that complete independence is unfeasible given the global market for energy. He describes energy resilience as the ability to adjust to interruptions in the supply of energy. To that end, he suggests the U.S. make greater use of electricity. Electricity can be produced from a variety of sources. A diverse energy supply will be less affected by the disruption in supply of any one source. He reasons that another feature of electrification is that electricity is "sticky" – meaning the electricity produced in the U.S. is to stay there because it cannot be transported overseas. According to Grove, a key aspect of advancing electrification and energy resilience will be converting the U.S. automotive fleet from gasoline-powered to electric-powered. This, in turn, will require the modernization and expansion of the electrical power grid. As organizations such as The Reform Institute have pointed out, advancements associated with the developing smart grid would facilitate the ability of the grid to absorb vehicles en masse connecting to it to charge their batteries.
=== Present and future ===
Extrapolations from current knowledge to the future offer a choice of energy futures. Predictions parallel the Malthusian catastrophe hypothesis. Numerous are complex models based scenarios as pioneered by Limits to Growth. Modeling approaches offer ways to analyze diverse strategies, and hopefully find a road to rapid and sustainable development of humanity. Short term energy crises are also a concern of energy development. Extrapolations lack plausibility, particularly when they predict a continual increase in oil consumption.
Energy production usually requires an energy investment. Drilling for oil or building a wind power plant requires energy. The fossil fuel resources that are left are often increasingly difficult to extract and convert. They may thus require increasingly higher energy investments. If investment is greater than the value of the energy produced by the resource, it is no longer an effective energy source. These resources are no longer an energy source but may be exploited for value as raw materials. New technology may lower the energy investment required to extract and convert the resources, although ultimately basic physics sets limits that cannot be exceeded.
Between 1950 and 1984, as the Green Revolution transformed agriculture around the globe, world grain production increased by 250%. The energy for the Green Revolution was provided by fossil fuels in the form of fertilizers (natural gas), pesticides (oil), and hydrocarbon fueled irrigation. The peaking of world hydrocarbon production (peak oil) may lead to significant changes, and require sustainable methods of production. One vision of a sustainable energy future involves all human structures on the earth's surface (i.e., buildings, vehicles and roads) doing artificial photosynthesis (using sunlight to split water as a source of hydrogen and absorbing carbon dioxide to make fertilizer) efficiently than plants.
With contemporary space industry's economic activity and the related private spaceflight, with the manufacturing industries, that go into Earth's orbit or beyond, delivering them to those regions will require further energy development. Researchers have contemplated space-based solar power for collecting solar power for use on Earth. Space-based solar power has been in research since the early 1970s. Space-based solar power would require construction of collector structures in space. The advantage over ground-based solar power is higher intensity of light, and no weather to interrupt power collection.
== Energy technology ==
Energy technology is an interdisciplinary engineering science having to do with the efficient, safe, environmentally friendly, and economical extraction, conversion, transportation, storage, and use of energy, targeted towards yielding high efficiency whilst skirting side effects on humans, nature, and the environment.
For people, energy is an overwhelming need, and as a scarce resource, it has been an underlying cause of political conflicts and wars. The gathering and use of energy resources can be harmful to local ecosystems and may have global outcomes.
Energy is also the capacity to do work. We can get energy from food. Energy can be of different forms such as kinetic, potential, mechanical, heat, light etc. Energy is required for individuals and the whole society for lighting, heating, cooking, running, industries, operating transportation and so forth. Basically there are two types of energy depending on the source s they are;
1.Renewable Energy Sources
2.Non-Renewable Energy Sources
=== Interdisciplinary fields ===
As an interdisciplinary science Energy technology is linked with many interdisciplinary fields in sundry, overlapping ways.
Physics, for thermodynamics and nuclear physics
Chemistry for fuel, combustion, air pollution, flue gas, battery technology and fuel cells.
Electrical engineering
Engineering, often for fluid energy machines such as combustion engines, turbines, pumps and compressors.
Geography, for geothermal energy and exploration for resources.
Mining, for petrochemical and fossil fuels.
Agriculture and forestry, for sources of renewable energy.
Meteorology for wind and solar energy.
Water and Waterways, for hydropower.
Waste management, for environmental impact.
Transportation, for energy-saving transportation systems.
Environmental studies, for studying the effect of energy use and production on the environment, nature and climate change.
(Lighting Technology), for Interior and Exterior Natural as well as Artificial Lighting Design, Installations, and Energy Savings
(Energy Cost/Benefit Analysis), for Simple Payback and Life Cycle Costing of Energy Efficiency/Conservation Measures Recommended
=== Electrical engineering ===
Electric power engineering deals with the production and use of electrical energy, which can entail the study of machines such as generators, electric motors and transformers. Infrastructure involves substations and transformer stations, power lines and electrical cable. Load management and power management over networks have meaningful sway on overall energy efficiency. Electric heating is also widely used and researched.
=== Thermodynamics ===
Thermodynamics deals with the fundamental laws of energy conversion and is drawn from theoretical Physics.
=== Thermal and chemical energy ===
Thermal and chemical energy are intertwined with chemistry and environmental studies. Combustion has to do with burners and chemical engines of all kinds, grates and incinerators along with their energy efficiency, pollution and operational safety.
Exhaust gas purification technology aims to lessen air pollution through sundry mechanical, thermal and chemical cleaning methods. Emission control technology is a field of process and chemical engineering. Boiler technology deals with the design, construction and operation of steam boilers and turbines (also used in nuclear power generation, see below), drawn from applied mechanics and materials engineering.
Energy conversion has to do with internal combustion engines, turbines, pumps, fans and so on, which are used for transportation, mechanical energy and power generation. High thermal and mechanical loads bring about operational safety worries which are dealt with through many branches of applied engineering science.
=== Nuclear energy ===
Nuclear technology deals with nuclear power production from nuclear reactors, along with the processing of nuclear fuel and disposal of radioactive waste, drawing from applied nuclear physics, nuclear chemistry and radiation science.
Nuclear power generation has been politically controversial in many countries for several decades but the electrical energy produced through nuclear fission is of worldwide importance. There are high hopes that fusion technologies will one day replace most fission reactors but this is still a research area of nuclear physics.
=== Renewable energy ===
Renewable energy has many branches.
==== Wind power ====
Wind turbines convert wind energy into electricity by connecting a spinning rotor to a generator. Wind turbines draw energy from atmospheric currents and are designed using aerodynamics along with knowledge taken from mechanical and electrical engineering. The wind passes across the aerodynamic rotor blades, creating an area of higher pressure and an area of lower pressure on either side of the blade. The forces of lift and drag are formed due to the difference in air pressure. The lift force is stronger than the drag force; therefore the rotor, which is connected to a generator, spins. The energy is then created due to the change from the aerodynamic force to the rotation of the generator.
Being recognized as one of the most efficient renewable energy sources, wind power is becoming more and more relevant and used in the world. Wind power does not use any water in the production of energy making it a good source of energy for areas without much water. Wind energy could also be produced even if the climate changes in line with current predictions, as it relies solely on wind.
==== Geothermal ====
Deep within the Earth, is an extreme heat producing layer of molten rock called magma. The very high temperatures from the magma heats nearby groundwater. There are various technologies that have been developed in order to benefit from such heat, such as using different types of power plants (dry, flash or binary), heat pumps, or wells. These processes of harnessing the heat incorporate an infrastructure which has in one form or another a turbine which is spun by either the hot water or the steam produced by it. The spinning turbine, being connected to a generator, produces energy. A more recent innovation involves the use of shallow closed-loop systems that pump heat to and from structures by taking advantage of the constant temperature of soil around 10 feet deep.
==== Hydropower ====
Hydropower draws mechanical energy from rivers, ocean waves and tides. Civil engineering is used to study and build dams, tunnels, waterways and manage coastal resources through hydrology and geology. A low speed water turbine spun by flowing water can power an electrical generator to produce electricity.
==== Bioenergy ====
Bioenergy deals with the gathering, processing and use of biomasses grown in biological manufacturing, agriculture and forestry from which power plants can draw burning fuel. Ethanol, methanol (both controversial) or hydrogen for fuel cells can be had from these technologies and used to generate electricity.
==== Enabling technologies ====
Heat pumps and Thermal energy storage are classes of technologies that can enable the utilization of renewable energy sources that would otherwise be inaccessible due to a temperature that is too low for utilization or a time lag between when the energy is available and when it is needed. While enhancing the temperature of available renewable thermal energy, heat pumps have the additional property of leveraging electrical power (or in some cases mechanical or thermal power) by using it to extract additional energy from a low quality source (such as seawater, lake water, the ground, the air, or waste heat from a process).
Thermal storage technologies allow heat or cold to be stored for periods of time ranging from hours or overnight to interseasonal, and can involve storage of sensible energy (i.e. by changing the temperature of a medium) or latent energy (i.e. through phase changes of a medium, such between water and slush or ice). Short-term thermal storages can be used for peak-shaving in district heating or electrical distribution systems. Kinds of renewable or alternative energy sources that can be enabled include natural energy (e.g. collected via solar-thermal collectors, or dry cooling towers used to collect winter's cold), waste energy (e.g. from HVAC equipment, industrial processes or power plants), or surplus energy (e.g. as seasonally from hydropower projects or intermittently from wind farms). The Drake Landing Solar Community (Alberta, Canada) is illustrative. borehole thermal energy storage allows the community to get 97% of its year-round heat from solar collectors on the garage roofs, which most of the heat collected in summer. Types of storages for sensible energy include insulated tanks, borehole clusters in substrates ranging from gravel to bedrock, deep aquifers, or shallow lined pits that are insulated on top. Some types of storage are capable of storing heat or cold between opposing seasons (particularly if very large), and some storage applications require inclusion of a heat pump. Latent heat is typically stored in ice tanks or what are called phase-change materials (PCMs).
== See also ==
World energy supply and consumption
Technology
Water-energy nexus
Policy
Energy policy, Energy policy of the United States, Energy policy of China, Energy policy of India, Energy policy of the European Union, Energy policy of the United Kingdom, Energy policy of Russia, Energy policy of Brazil, Energy policy of Canada, Energy policy of the Soviet Union, Energy Industry Liberalization and Privatization (Thailand)
General
Seasonal thermal energy storage (Interseasonal thermal energy storage), Geomagnetically induced current, Energy harvesting, Timeline of sustainable energy research 2020–present
Feedstock
Raw material, Biomaterial, Energy consumption, Materials science, Recycling, Upcycling, Downcycling
Others
Thorium-based nuclear power, List of oil pipelines, List of natural gas pipelines, Ocean thermal energy conversion, Growth of photovoltaics
== References ==
== Sources ==
Armstrong, Robert C., Catherine Wolfram, Robert Gross, Nathan S. Lewis, and M.V. Ramana et al. The Frontiers of Energy, Nature Energy, Vol 1, 11 January 2016.
Serra, J. "Alternative Fuel Resource Development", Clean and Green Fuels Fund, (2006).
Bilgen, S. and K. Kaygusuz, Renewable Energy for a Clean and Sustainable Future, Energy Sources 26, 1119 (2004).
Energy analysis of Power Systems, UIC Nuclear Issues Briefing Paper 57 (2004).
Silvestre B. S., Dalcol P. R. T. (2009). "Geographical proximity and innovation: Evidences from the Campos Basin oil & gas industrial agglomeration — Brazil". Technovation. 29 (8): 546–561. doi:10.1016/j.technovation.2009.01.003.
== Journals ==
Energy Sources, Part A: Recovery, Utilization and Environmental Effects
Energy Sources, Part B: Economics, Planning and Policy
International Journal of Green Energy
== External links ==
Bureau of Land Management 2012 Renewable Energy Priority Projects
Energypedia - a wiki about renewable energies in the context of development cooperation
Hidden Health and Environmental Costs Of Energy Production and Consumption In U.S.
IEA-ECES - International Energy Agency - Energy Conservation through Energy Conservation programme.
IEA HPT TCP - International Energy Agency - Technology Collaboration Programme on Heatpumping Technologies.
IEA-SHC - International Energy Agency - Solar Heating and Cooling programme.
SDH - Solar District Heating Platform. (European Union) | Wikipedia/Energy_resilience |
The Tesla Model S is a battery-electric, four-door full-size car produced by the American automaker Tesla since 2012. The automaker's second vehicle and longest-produced model, the Model S has both received mixed reviews from critics and also been described as one of the most influential electric cars in the industry. Its various accolades include the Motor Trend Car of the Year Award in 2013.
Tesla started developing the Model S around 2007 under the codename WhiteStar. Initially, Henrik Fisker was appointed as the lead designer for the WhiteStar project; after a dispute with Elon Musk, Tesla's CEO, Fisker was replaced by Franz von Holzhausen. By 2008, von Holzhausen had designed what would become the production Model S's exterior. Tesla unveiled a prototype of the vehicle in March 2009 in Hawthorne, California. In 2010, Tesla acquired a facility in Fremont, California, to produce the Model S, which was previously owned by General Motors and Toyota. Series manufacture of the car officially began at the Tesla Fremont Factory in June 2012. Tesla carried out the final assembly for European markets at its facilities in Tilburg, Netherlands, between 2013 and 2021.
The Model S typically uses either one or initially two alternating current induction motors; since 2019, dual-motor versions have used a permanent magnet motor in the rear, though the high-performance Model S Plaid's three motors are permanent magnet units by default. Constructed mostly of aluminum, the Model S shares 30 percent of its components with the Model X—a crossover SUV that was introduced in 2015. The Model S has undergone several updates during its production, the most prominent ones occurring in 2016 and 2021. These updates have usually included modifications to the motor, such as changes to power or torque, revised exterior elements, and refreshed interior features. One such change included the 2015 introduction of Tesla Autopilot—a partial vehicle automation advanced driver-assistance system.
In 2015, the Model S was the world's best-selling plug-in electric vehicle. In 2012, it was included on Time's list of the Best Inventions of the Year, and the magazine later included it on its list of the 10 Best Gadgets of the 2010s in 2019. In 2014, The Daily Telegraph described the Model S as a "car that changed the world". Road & Track argued that, with the introduction of the Plaid and features such as the yoke steering wheel, Tesla managed to turn the Model S into "perhaps one of the worst [cars in the world]".
== Development ==
In January 2007, the American automaker Tesla Motors opened a facility in Rochester Hills, Michigan, employing sixty people to work on new projects, including a four-door sedan. Beginning development under the codename WhiteStar, Tesla planned for the car to have two powertrain options. The first would be a battery-electric version with an all-electric range of 200 miles (320 km). The second was to be a hybrid electric vehicle with a range extender, capable of traveling between 40 and 50 miles (64 and 80 km) on electric power before a small gasoline engine would recharge its batteries and power the vehicle, giving it a total range of 400 miles (640 km). However, at the GoingGreen conference in September 2008, Elon Musk—the chief executive officer of Tesla—announced that the company would exclusively produce battery-electric vehicles.
In 2007, Musk appointed Henrik Fisker, known for his work with Aston Martin, as the lead designer of the WhiteStar project. Fisker signed a US$875,000 contract to design the car. The company requested that he design a "sleek, four-door sedan" priced from $50,000–$70,000 (equivalent to $75,823–$106,152 in 2023), and that it be ready between late 2009 and early 2010. Fisker owned a design studio in Orange County, California, which Tesla employees visited to view his designs. Their reactions were generally negative; Ron Lloyd, the vice president of the WhiteStar project, described the designs as "terrible [...] some of the early styles were like a giant egg". When Musk rejected his designs, Fisker attributed the decision to the project's physical constraints, saying, "they wouldn't let me make the car sexy". Shortly after the meetings, Fisker started his own company and debuted the Fisker Karma in 2008 at the North American International Auto Show. Musk filed a lawsuit against Fisker, accusing him of stealing Tesla's design ideas and using the $875,000 to launch his own company. Fisker won the lawsuit in November 2008, and an arbitrator declared Tesla's claims to be without merit and ordered Tesla to reimburse Fisker's legal fees.
A small team of Tesla engineers went to a Mercedes-Benz car dealership where they test-drove a CLS and an E-Class. Both cars shared a chassis, and the engineers assessed different aspects of the two vehicles, evaluating their positives and negatives. They ultimately preferred the CLS's styling and used it as the baseline for the Model S. After purchasing a CLS, they disassembled it, modified the battery pack of a Tesla Roadster, cut out the CLS's floor, and integrated it with the battery pack. They subsequently put all of its electronics and systems in the CLS's trunk and replaced the interior. After three months of development, the engineers completed a battery-electric version of the CLS. They frequently tested the car on public roads. It had 120 miles (190 km) of all-electric range per charge and weighed more than the Roadster.
In August 2008, Musk hired Franz von Holzhausen—who formerly designed for Mazda—as project WhiteStar's lead designer. Von Holzhausen reviewed Fisker's sketches and clay models but was unimpressed with what he saw, stating that "it was clear [...] that the people [who] had been working on this were novices". To save money, Tesla established its design center within a factory for SpaceX—a company also owned by Musk. As von Holzhausen began designing the exterior of the Model S, Tesla engineers initiated a project to construct another electric version of a CLS. They stripped it to its core, removed the body structure, and extended the wheelbase by four inches (10 cm) to align with early Model S specifications. Within three months, von Holzhausen had designed what would become the production Model S's exterior, and the engineers had begun building a prototype around the design. Given the battery pack's substantial weight, Musk and the team began efforts to minimize the weight of other components. To address this issue, Musk opted to use aluminum instead of steel, stating that the non-battery-pack portion of the vehicle must be lighter than equivalent gasoline vehicles. He noted that the primary challenge was that if aluminum were not used in its construction, the car's performance would be compromised. To accelerate the development of the Model S, one group of engineers worked during the day, while another arrived late evening and worked through the night, both operating within a 3,000 square feet (280 m2) tent in the SpaceX factory.
Tesla debuted a prototype version of the Model S in Hawthorne, California, on March 26, 2009. Tesla initially intended to manufacture the Model S in Albuquerque, New Mexico, and later in San Jose, California, but later withdrew from both plans mainly due to financial problems. During the Great Recession, American automaker General Motors decided to abandon the NUMMI facility in 2009, with Toyota soon following. A month after the last car was produced at the manufacturing line in April 2010, Toyota and Tesla announced a partnership and the transfer of the factory. Tesla agreed to purchase a significant portion of the facility for $42 million (equivalent $57 million in 2024), while Toyota invested $50 million (equivalent to $68 million in 2024) in Tesla for a 2.5 percent stake in the company.
During the early 2010s, Musk expanded the engineering teams for the Model S, while von Holzhausen grew the design teams in Los Angeles. The engineers operated in a lab with forty-five personnel. The pre-production version of the Model S, featuring newly stamped body parts from the Fremont factory, a revamped battery pack, and improved power electronics, was completed in the basement of an office in Palo Alto, California. Twelve of the cars were produced; some were sent to suppliers such as Bosch, while others were preserved for testing and design alterations. On June 22, 2012, Tesla invited its employees, select customers, and the press to see the first production Model S in Fremont.
== Design ==
The body and the chassis of the Model S are made mostly of aluminum. The car shares its platform and thirty percent of its parts with the Model X, a mid-size luxury crossover SUV that was introduced in 2015. The Model S is a full-size sedan with four doors and five seats; until 2018, it had an optional folding third row with rear-facing seats for two children with a five-point harness. The company claimed a drag coefficient of Cd=0.24, the lowest of any production car at release. This claim was independently verified by the magazine Car and Driver in the middle of 2014. The vehicle's drag coefficient was improved by a solid front fascia instead of a grille, retractable door handles, and a flat underbody with no exhaust pipes to disrupt the airflow.
The Model S's battery pack is its heaviest component and is located inside of the car's floor. The battery pack consists of thousands of identical cylindrical 18650 battery cells, each measuring 18 millimeters (0.71 in) in diameter and 65 millimeters (2.6 in) in height. These cells feature a graphite/silicon anode, and a nickel-cobalt-aluminum cathode. The Model S has a center of gravity height of 18 inches (460 mm), reducing the risk of rollovers. Since the heavier components of the drivetrain are positioned behind the rear axle's centerline, the Model S has a weight distribution of 46 percent at the front and 54 percent at the rear. The Model S has a single-speed reduction gear transmission. Rear-wheel drive models use a single alternating current induction motor; all-wheel drive models before 2019 featured two. However, from 2019, the dual-motor models featured a rear induction motor and front permanent magnet synchronous reluctance motor. The Plaid model, introduced in 2021, uses three permanent magnet synchronous reluctance motors.
A cast aluminum cross-member attached to the vehicle's body structure supports the front suspension and electrically assisted rack-and-pinion steering system. At the rear, a cast subframe is connected to the body using four rubber-isolated mounts to reduce vibrations. The front suspension features a double control arm design, while the rear suspension uses a multi-link arrangement, each with an air spring for improved ride comfort. This chassis also features disc brake components produced by Brembo. Since the Model S lacks a front engine, Tesla implemented a "frunk", which has 5.3 cubic feet (150 L) of storage. The car's rear trunk possesses 26.6 cubic feet (750 L) of storage with the rear seats upright and 58.1 cubic feet (1,650 L) when the seats are folded down. Initially, the seats and steering wheel of the Model S were offered in both synthetic and non-synthetic leather options. In 2017, following a request from People for the Ethical Treatment of Animals to become the first cruelty-free automaker, Tesla switched exclusively to synthetic leather.
== Models and updates ==
=== 2012–2016: Initial years ===
Tesla allocated its initial 1,000 Model S units to the "Signature" limited edition configurations. The AC induction motor of the base Signature model generates a power output of 270 kW (362 hp) and a torque output of 439 newton-meters (324 lb⋅ft). The Signature Performance's motor produces 310 kW (416 hp) and 601 newton-meters (443 lb⋅ft). Both models incorporate an 85 kilowatt-hour (kWh) lithium-ion battery, and have an all-electric range of 265 miles (426 km).
Beginning in 2012, three battery pack configurations of the Model S were offered as 2013 model year vehicles. Initially, a 40 kWh lithium-ion model was planned as the entry-level version, but Tesla announced in 2013 that this version would not be produced. The motor of this version was to produce a power output of 175 kilowatts (235 hp) and a torque of 420 newton-meters (310 lb⋅ft). Instead, a more powerful model with a 60 kWh model—with its output limited to 40 kWh via software—was introduced to substitute the 40 kWh model. Its motor generates 225 kilowatts (302 hp) and 430 newton-meters (317 lb⋅ft), providing it with a range of 208 miles (335 km). Two versions of the 85 kWh model were created: one with specifications similar to the aforementioned Signature model, and a performance version, the "P85", with specifications akin to the Signature Performance.
In 2014, Tesla discontinued the P85, replacing it with the P85D ("D" stands for "dual"). Tesla introduced a front motor in the P85D, in addition to the existing rear motor used in previous models. This configuration powers both the front and rear wheels, resulting in an all-wheel drive powertrain. The two motors produce a combined output of 515 kilowatts (691 hp) and 931 newton-meters (687 lb⋅ft), giving it a range of 275 miles (443 km). Replacing the 60 kWh model, the 70D was introduced as a 2015 model year vehicle. It features dual motors that produce a combined output of 383 kilowatts (514 hp) and 387 newton-meters (285 lb⋅ft), allowing it to have a range of 240 miles (390 km). A single-motor version of the 70 kWh model was also produced, with an output of 235 kilowatts (315 hp) and 325 newton-meters (240 lb⋅ft), giving it a range of 210 miles (340 km).
In 2015, Tesla launched the standard 90D and the performance P90D to succeed the 85 kWh model and the P85D, respectively. The 90D's motor produces 311 kilowatts (417 hp) and 658 newton-meters (485 lb⋅ft), and a range of 288 miles (463 km). The P90D's dual motors generate a combined output of 568 kilowatts (762 hp) and 967 newton-meters (713 lb⋅ft), and the car has a range of 268 miles (431 km).
=== 2016–2019: First major update ===
In April 2016, Tesla implemented a facelift for the Model S, releasing these cars for the 2017 model year. Its most prominent update lies in its front fascia, where the previous black grille has been replaced by a continuation of the body, leaving only a thin gap between the leading edge of the hood and the bumper, which houses the Tesla logo. The updated model also includes restyled, full-LED adaptive headlights that turn with the car to enhance visibility at night.
That same year, Tesla reintroduced the 60 kWh model and introduced an all-wheel-drive version, the 60D. The former produces 235 kilowatts (315 hp) of power and 325 newton-meters (240 lb⋅ft) of torque, giving it a range of 210 miles (340 km). The latter has dual motors that produce 242 kilowatts (324 hp) and 430 newton-meters (317 lb⋅ft), with a range of 253 miles (407 km). Customers also had the option to upgrade the battery capacity to 75 kWh through an over-the-air update, extending the range by 40 miles (64 km). In March 2017, Tesla discontinued the 60 kWh model to distinguish its premium cars from the cheaper options, making the 75 kWh model the new entry-level offering.
In late 2016, Tesla introduced the P100D as a replacement for the P90D. The P100D's motors generate a combined output 510 kilowatts (680 hp) and 1,072 newton-meters (791 lb⋅ft), allowing it to have a range of 315 miles (507 km). In early 2017, Tesla introduced the 100D. Its dual motors deliver 360 kilowatts (483 hp) and 660 newton-meters (487 lb⋅ft), and it has a range of 335 miles (539 km). Midway through 2017, Tesla discontinued the 90D. Tesla subsequently ended production of the rear-wheel-drive 75 kWh model in late 2017. In 2019, Tesla replaced the 75D, 100D, and P100D variants as part of the company's shift towards a revamped model range.
=== 2019–present: Second major update and simplified naming scheme ===
In favor of a more streamlined lineup, in the middle of 2019, the previous 75D, 100D, and P100D models were replaced with the Standard Range, Long Range, and Performance models, respectively; the foremost model was discontinued later that year. The Performance and Long Range variants feature a permanent magnet synchronous reluctance motor—initially used in the Model 3—as the front motor, while the rear motor remains an AC induction unit.
The Model S Long Range, equipped with a 100 kWh battery, has dual motors that generate a total output of 350 kilowatts (469 hp) and 730 newton-meters (540 lb⋅ft), giving the Long Range a range of 375 miles (604 km). The Performance model's two motors produce a combined output of 562 kilowatts (754 hp) and 931 newton-meters (687 lb⋅ft); it also has a 100 kWh battery and a range of 365 miles (587 km). For 2020, the Long Range model was replaced with the Long Range Plus. Its dual motors deliver a combined output of 311 kilowatts (417 hp) and 658 newton-meters (485 lb⋅ft). It has a range of 400 miles (640 km).
In 2021, Tesla launched a significant update to the Model S, known internally as the "Palladium" project, which involved an overhaul of most of its components and spawned the high-performance Plaid. The revised Model S was revealed in January 2021. At its debut, the updated Model S had the lowest drag coefficient of any automobile, with a value of Cd=0.208. The updated Long Range delivers 500 kilowatts (670 hp) and achieves a range of 405 miles (652 km). The Plaid, which features a 95 kWh battery, has—in contrast to all other models—three permanent magnet synchronous motors, as well as an all-wheel drive layout. The trio produce a total output of 760 kilowatts (1,020 hp) and 1,050 newton-meters (770 lb⋅ft), providing the car with a 0 to 60 mph (97 km/h) acceleration of 1.98 seconds and a maximum speed of 200 mph (320 km/h), with a range of 390 miles (630 km). In 2023, Tesla reintroduced the Standard Range model, which has a range of 370 miles (600 km).
== Technology ==
=== Features ===
The instrument panel is positioned directly before the driver and features a 12.3-inch (310 mm) liquid crystal display electronic instrument cluster. Initially, the infotainment control touchscreen featured a 17-inch (430 mm) multi-touch display divided into four sections. The top section shows status icons and offers quick access to features like charging, HomeLink, Driver Profiles, vehicle information, and Bluetooth. Below that, the second section provides access to various apps, such as Media, Navigation, Energy, Web, Camera, and Phone. The central viewing area displays two active apps, split into upper and lower areas, with most apps expandable to fill the entire screen. The bottom section contains controls and settings for the vehicle, including doors, locks, lights, temperature settings, and a secondary volume control.
Originally, the Model S's touchscreen was powered by a Nvidia Tegra 3 3D Visual Computing Module (VCM), with a separate Nvidia Tegra 2 VCM handling the instrument cluster. Around 2018, Tesla upgraded these two Tegra System-on-a-Chip (SoC) units to a single Intel Atom–based SoC, which powered both the main touchscreen display and the instrument cluster. With the Palladium refresh, Tesla further updated the system, switching to a horizontal touchscreen orientation and an AMD Ryzen-based SoC. The touchscreen includes features like driver-side climate control, My App, the app launcher, recent apps, passenger-side climate control, and volume control. Features, such as lock and unlock, trunk, glove box, and mirrors, could be controlled from the touchscreen. Also for the 2021 refresh, Tesla implemented a "yoke" steering wheel.
==== Autopilot ====
In 2014, Tesla introduced Autopilot, an advanced driver-assistance system developed by the automaker that amounts to partial vehicle automation. Every Model S produced from September 2014 onward included the Autopilot hardware, and it was officially released in October 2015 as a software update. Autopilot uses cameras, radar and ultrasound to detect road signs, lane markings, obstacles, pedestrians, cyclists, motorcyclists, traffic lights, and other vehicles. It also includes adaptive cruise control, lane centering, auto lane changing, auto parking and other semi-autonomous driving and parking capabilities. The Model S's operating systems are partly built using open-source software (OSS), which is publicly available. Tesla uses OSS like Linux, the GNU toolchain, Buildroot, and community projects like Ubuntu. From 2021, Tesla began using a system known as "Tesla Vision", which relies solely on cameras, replacing the previous radar-based sensors. In 2023, Tesla discontinued the ultrasonic system as part of its shift towards Tesla Vision.
The Autopilot system has been the subject of criticism. Following a crash in Florida, the National Transportation Safety Board found that the driver's usage of the system "indicated an over-reliance on the automation and a lack of understanding of the system limitations". Tesla has faced accusations of misleading advertising, with critics alleging that the company led consumers to believe the vehicles were fully autonomous. Tesla has defended itself by arguing that the state's prolonged lack of objection to the Autopilot branding implied approval of its advertising practices. In a 2019 survey by Bloomberg News, hundreds of Tesla owners reported experiencing dangerous behaviors with Autopilot, including phantom braking, lane departures, and failure to stop for road hazards. Users also noted issues like sudden software crashes, unexpected shutdowns, collisions with off-ramp barriers, radar failures, abrupt swerving, tailgating, and inconsistent speed changes.
=== Charging ===
Tesla has devised numerous ways to charge the Model S: a 240-volt home wall connector, which provides up to 44 miles (71 km) of range per hour of charging; and a mobile connector, intended for use away from home, which offers up to 30 miles (48 km) of range per hour. Models prior to 2016 could be configured with two onboard chargers, which provide up to 62 miles (100 km) of range per hour. Tesla partnered with businesses to install Tesla Wall Connectors to provide a public charging network called Tesla Destination. The units are provided to the businesses by Tesla for free or at a cheap price. The business is responsible for the cost of electricity. Some businesses limit them to customers, employees, or residents only. In late 2012, Tesla began operating a network of 480-volt charging stations, dubbed Superchargers.
Tesla initially planned for the Model S to allow fast battery swapping. In 2013, the company demonstrated a battery-swap operation that took about ninety seconds—roughly half the time needed to refill a gas tank. While Tesla initially planned to make battery swapping widely available, they reportedly abandoned the idea due to a perceived lack of customer interest. Jeremy Michalek, a mechanical engineering professor, suggested that the high cost, bulkiness, and resource demands of batteries made the creation of extensive networks of swappable packs—requiring storage, charging, and maintenance—economically and environmentally impractical. Critics have accused Tesla of exploiting California's zero-emission vehicle credit system by introducing the battery-swap program without ever making it accessible to the public. In 2020, Tesla announced plans to integrate the batteries into the vehicle's body to enhance strength and reduce weight and cost.
== Environmental impact ==
A 2015 study by the Union of Concerned Scientists (UCS) concluded that in U.S. regions where the Model S is popular, its 68 percent higher manufacturing emissions are offset within a few years of average driving. However, the UCS report assumes that electric materials are recycled at rates similar to other cars and excludes the issue of battery disposal due to limited data on recycling practices and future intentions at the time. Over their lifecycle, electric vehicles—like the Model S—emit about half as much CO2 as comparable fossil fuel cars. The lithium-ion batteries within the Model S contain nickel and small amounts of cobalt, which have a high environmental impact due to resource depletion, ecological toxicity, and extraction processes.
In 2021, Tesla wrote in its impact report that it recycles all returned battery packs. It stated that Gigafactory Nevada can recycle up to 92 percent of the elements from old batteries, creating a "closed loop" system where old batteries are turned into new ones. In 2020, the company recycled significant amounts of metals: 1,300 tons of nickel, 400 tons of copper, and 80 tons of cobalt. Tesla's report states that most of its batteries are recycled in some form; according to Vice, it does not specify that 92 percent of each individual battery is fully recycled. The company has articulated an ultimate goal of achieving "high recovery rates, low costs, and low environmental impact" through its recycling program, though it does not provide details on its progress toward this. A 2021 scientific study showed that recycling the Tesla Model S battery pack is profitable due to its low disassembly costs and high revenues from cobalt recovery. The materials scientist Dana Thompson from the University of Leicester cautions that the recycling of batteries may pose significant hazards. According to Thompson, if a Tesla cell is punctured too deeply or at an inappropriate location, it risks short-circuiting, potentially leading to combustion and the release of toxic fumes.
== Production and initial deliveries ==
The Model S is the company's second vehicle and, as of 2025, its longest-produced model. It has been produced at the 5,400,000 square feet (500,000 m2) Fremont, California, facility since June 2012. Tesla initially projected it would produce 1,000 units per month, aiming for a total of 5,000 units by the end of 2012. For 2013, Tesla aimed to quadruple that. Tesla built its 1,000th Model S by October 31, 2012, and delivered 2,650 units by the end of the year. In the first half of the subsequent year, 10,050 units were delivered to customers.
From August 2013, for European countries, final assembly was carried out at Tesla's facilities in Tilburg, Netherlands. The aim of the Tilburg factory was to shorten delivery times for customers in Britain and the EU, improve product quality, and establish the automaker's presence in Europe by producing the Model S and the Model X. The assembly of both the Model S and Model X at the Tilburg facility ceased in early 2021. According to the Dutch newspaper NU.nl, the 2021 refresh introduced changes to the production process that made it impossible to complete final assembly at the Tilburg location.
The Model S was the first vehicle by Tesla produced at the Fremont facility. It was followed by the Model X in 2015, the Model 3 in 2017 and the Model Y in 2020. These cars form the "S3XY" acronym. In 2015, the Model S was the world's best-selling plug-in electric vehicle, with Tesla selling 50,366 in that year. It was the second-best-selling car in 2016 after the Nissan Leaf. Since its inception, the Model S has been equipped with batteries supplied primarily by the electronics company Panasonic in Japan. Since January 2017, the car's batteries have also been produced at Gigafactory Nevada. European retail deliveries began between August and September 2013, with Norway, Switzerland, the Netherlands, Belgium, France, and Germany. The first Australian delivery took place in Sydney on December 9, 2014. Deliveries to the mainland Chinese market began on April 22, 2014, followed by Hong Kong in July 2014. Deliveries to the United Kingdom began in June 2014.
== Safety ==
=== Testing ===
In a European New Car Assessment Programme testing conducted in 2022, the Model S received a five-star rating:
In a National Highway Traffic Safety Administration (NHTSA) testing conducted in 2015, the Model S received a five-star rating. Tesla subsequently claimed that—based on the details of the test—it actually achieved 5.4 stars, prompting the NHTSA to release a statement reaffirming that it does not award more than five stars, and that Tesla was "misleading the public" by claiming in their marketing that the NHTSA had awarded them a higher rating.
=== Recalls ===
On June 14, 2013, Tesla recalled Model S vehicles manufactured between May 10 and June 8, 2013, due to improper methods for aligning the left hand seat back striker to the bracket, which could weaken the weld between the bracket and frame. Musk stated that the weld had not detached on any car, there had been no complaints, and no injuries had occurred. In early January 2014, Tesla issued a recall for Model S vehicles from 2013 due to the risk of overheating with the adapter, cord, or wall outlet during charging. Following the recall, Jérôme Guillen, Tesla's vice president of sales, announced that nearly all Model S adapters had already been updated via over-the-air software to address the charging problem. Tesla noted that the recall impacted nearly all Model S vehicles and adapters produced in 2013. Tesla announced a voluntary recall on November 20, 2015, of all of its 90,000 Model S vehicles, to check for a possible defect in the cars' front seat belt assemblies. The problem was raised by one customer in Europe. Tesla's resulting investigation was unable to identify a root cause for the failure, and the company decided to examine every car. Tesla reported that no accidents or injuries were related to the problem.
On January 20, 2017, Tesla recalled every Model S manufactured from 2012 because of defective Takata airbags. This recall not only impacted the Model S but also affected about 652,000 other vehicles from other automakers across the United States, which, at the time, was the largest automotive recall in the country's history. On April 20, 2017, Tesla issued a worldwide recall of 53,000 of the 76,000 Model S and Model X vehicles sold in 2016 due to faulty parking brakes. Tesla assured that this issue was unlikely to cause safety problems and had not resulted in any accidents or injuries. Despite this, the company asked customers to have their cars inspected, a process that took about forty-five minutes. About five percent of the vehicles were affected, and Brembo, the supplier of the defective part, would cover the repair costs. All 123,000 Model S cars manufactured before April 2016 were recalled on March 30, 2018, due to excessive corrosion of the bolts which secure the power steering, particularly those cars used in cold countries where roads are salted. Tesla's stock dropped nearly four percent in after-hours trading on Thursday following the announcement of the Model S recall.
In December 2021, 119,009 Model S vehicles produced between 2017 and 2020 were recalled because of the possibility of latch failure allowing front hoods to open unexpectedly. The recall, according to the company, affected around 14 percent of all Model S vehicles. In February 2024, Tesla recalled over two million Tesla vehicles in the United States due to the compact size of the warning lights on the instrument panel. Documents indicated that the recall was issued to enhance warnings and alerts for drivers. The NHTSA reported that the font size of the brake, park, and antilock brake warning lights was smaller than mandated by federal safety standards. This size made information difficult to read, thereby increasing the risk of a collision. The Model S was part of a major recall in July 2024 affecting approximately 1.8 million vehicles. The recall addressed a software issue that could prevent the detection of an unlatched hood, posing a risk of it unexpectedly opening while the vehicle was in motion. According to NHTSA documentation, this malfunction could obstruct the driver's vision, increasing the likelihood of a crash.
=== Fires ===
==== First fire ====
A fire involving a Model S occurred on October 1, 2013, after the vehicle struck metal debris on Washington State Route 167 in Kent, Washington. The driver was alerted by the onboard system and was able to safely exit the highway, stop the car, and leave the vehicle without injury. Tesla later explained that the fire was triggered by a "direct impact of a large metallic object" to one of the car's 16 battery modules. The vehicle's design, which included firewalls separating the modules, limited the fire to a small section at the front of the car. The debris that caused the fire was identified as a "curved section" that had fallen off a truck and was recovered nearby. According to Tesla, the debris pierced a 3-inch (80 mm) hole through the vehicle's 0.25 in (6 mm) armor plate, with an estimated force of 25 short tons (23 t). Vents directed the flames away from the passenger compartment, preventing them from entering the cabin.
On October 24, 2013, the NHTSA announced that it had not found evidence suggesting the fire resulted from a vehicle safety defect or noncompliance with federal safety standards. However, in the following month, the NHTSA initiated a preliminary evaluation to assess the potential risks associated with undercarriage strikes on 2013 Tesla Model S vehicles. On March 28, 2014, the investigation was closed, with the NHTSA stating that "Tesla's revision of vehicle ride height and addition of increased underbody protection should reduce both the frequency of underbody strikes and the resultant fire risk".
==== Subsequent fires ====
On November 6, 2013, another fire occurred when a Tesla Model S struck a tow hitch on the road, causing damage to the underside of the vehicle. In response to these incidents, Tesla extended its vehicle warranty to cover fire damage and issued a software update to increase the car's ground clearance at highway speeds. In early February 2014, another fire incident was reported in Toronto, Canada. The Model S was parked in a garage and was not charging at the time. The cause of the fire remains undetermined. Tesla stated, "in this particular case, we don't yet know the precise cause, but have definitively determined that it did not originate in the battery, the charging system, the adapter or the electrical receptacle, as these components were untouched by the fire".
On January 1, 2016, a 2014 Model S caught fire in Norway while supercharging unsupervised. The vehicle was destroyed but nobody was injured. An investigation by the Norwegian Accident Investigation Board concluded that the fire started within the car, but the exact cause could not be determined. In March 2016, Tesla announced that their own investigation found that the fire was caused by a short circuit in the vehicle's distribution box, but the extent of the damage made it impossible to determine the exact cause. A three-month-old Model S caught fire three times in December 2018, requiring firefighters to spend nearly ten hours preventing reignition. In July 2021, a Model S Plaid caught fire, and its electronic door system failed, forcing the driver to "use force to push it open". The vehicle then moved approximately 35 to 40 feet (11 to 12 m) before erupting into a "fireball".
== Reception and legacy ==
The Model S has been referred to by several critics as one of the most influential and important electric cars. In a 2014 review for the newspaper The Sunday Times, Nick Rufford remarked, "the Model S represents the last throw of the electric dice [...] if this vehicle can't persuade people to ditch petrol and switch to battery power, no car can". In 2014, The Daily Telegraph included the Model S on its list of "cars that changed the world" and called it the most important car of the last 20 years. The BBC-owned magazine Top Gear described it as "one of the most appealing electric vehicles in the world [...] and one that almost single-handedly forced mainstream manufacturers to embrace electricity". Keith Barry of Consumer Reports mentioned that the introduction of specific features, such as a yoke-style steering wheel, has "distracted from the flagship sedan's underlying brilliance, as has Musk's public image". Consumer Reports additionally pointed out that the success of the Model S prompted other automakers to rethink how they design and market their vehicles. The magazine Car and Driver noted that the Model S was the "first long-range, widely desired electric vehicle" when it was released, adding that "mainstream automakers [...] [struggled] to catch up".
The Model S has received mixed reviews from automotive critics. Samuel Gibbs from the newspaper The Guardian referred to it as a "swish saloon car", writing that, unlike many other electric vehicles, it did not resemble "a bug or bubble-car". Gibbs was also impressed by its acceleration, remarking that it has "it has enough power to beat even the Aston Martin Rapide, all without petrol and with no emissions". Reviewing for The Independent, Lee Williams called the Model S "a beautiful car that symbolizes humanity's march towards automation", but criticized its large size, describing the car as "too damn big". Road & Track's Chris Perkins argued that Tesla managed to turn the "most important car of the century into a bad joke", describing the Model S Plaid as "perhaps one of the worst [cars in the world]". He called its yoke steering wheel "incredibly stupid", described its damping as "irritating", and stated that "it doesn't have the chassis, steering, or brakes to deal with the horsepower". The U.S. News & World Report thought that its "basic interior feels out of step with its price, and newer rivals offer more room, style and, in some cases, range". Lee Hutchinson, the senior technology writer for Ars Technica, opined that its "almond-shaped headlights and prominent nosecone conjure images of Maserati, while the rear half has a distinct Aston Martin DBS flavor, [and] the taillights and rear evoke the Jaguar XF". While being in two completely different classes, critics frequently compare the Model S to the first generation of the Nissan Leaf, a hatchback.
Hutchinson, in another review, thought of its acceleration as "instant, ludicrous, [and] neck-snapping", believing that it was "more appropriate for a roller-coaster than a car". He described its styling as "graceful, with a precisely engineered exterior". Mat Watson, prominent for his Carwow reviews, praised the Model S Plaid as "astonishingly quick" and "extremely quiet", but he criticized its high price and noted that competing models offer greater comfort. Watson ultimately rated it eight out of ten. Writing for Car, Keith Adams described the Model S as "the king of the hill". He called the thrust "stomach-churning from rest", believing that the driver would "crave to relive the experience—again and again". Jalopnik's Lawrence Hodge criticized the yoke steering wheel, describing it as "stupid" and suggesting that its introduction was more of a downgrade than an upgrade. In 2012, Time magazine named the Model S one of the best inventions of the year. It was later featured in the magazine's list of the 10 best gadgets of the 2010s. Car and Driver included the Model S 60 on its list of the 10 best cars of the year in 2015, while entering the 70 and 70D models on its 2016 list.
Some companies have developed modified cars based on the Model S with different body styles. In February 2019, a one-off version of the Model S with a shooting brake body style, named the Model SB, was announced by Niels van Roij Design. While an initial production run of twenty was considered, only a single unit was built. The single unit was finished in British racing green, mirrored by the glove compartment lining, a color choice inspired by the green found in the logo of Elipo, the company that assisted in the car's design, as well as foliage in Elipo owner Floris de Raadt's garden. It made its public debut at the Geneva Motor Show in March 2019. In 2020 and 2023, coachbuilders Coleman Milne and Binz debuted their hearse conversions of the Model S, named the Wisper and Binz.E, respectively. Both versions have 220 miles (350 km) of electric range.
== Awards ==
The Model S is the recipient of numerous awards, as listed in the table below:
== Notes ==
== References ==
== Bibliography ==
== External links ==
Official website | Wikipedia/Tesla_Model_S |
The Energy Efficiency Directive 2012/27/EU (abbreviated EED) is a European Union directive which mandates energy efficiency improvements within the European Union. It was approved on 25 October 2012 and entered into force on 4 December 2012.: 2 The directive introduces legally binding measures to encourage efforts to use energy more efficiently in all stages and sectors of the supply chain. It establishes a common framework for the promotion of energy efficiency within the EU in order to meet its energy efficiency headline target of 20% by 2020. It also paves the way for further improvements thereafter.
The directive provides for the establishment of indicative national energy efficiency targets for 2020. Member states were to have submitted their National Energy Efficiency Action Plans (NEEAP) by 30 April 2014, outlining the measures they have implemented to improve energy efficiency and their expected and/or achieved energy savings. In addition, member states are required to report annually on progress toward their national targets. The policy requirements in the directive are minimum obligations and member states may introduce more stringent measures.
The Energy Efficiency Directive 2012/27/EU was preceded by the Energy Services Directive 2006/32/EC. This earlier directive contained a target of a 9% reduction in energy usage within 9 years of the directive coming into force. The earlier directive also required EU members to submit National Energy Efficiency Action Plans, with the first plan to be lodged by 30 June 2007.
On 23 July 2014, the European Commission announced a new target of a 30% improvement in energy efficiency by 2030.
== Development ==
Documents leaked in mid-2012 show that the United Kingdom repeatedly fought to water down key measures during the development of the directive and forced some measures to become voluntary rather than mandatory. As a result, a new version of the directive allows member states to set their own energy efficiency targets, instead of the original requirement of a mandatory EU-wide target of 20% improvement.
== Measures ==
The directive promotes rules to remove barriers in energy markets and to overcome market failures that may impede the uptake of energy efficiency. Under the directive, the public sector is to play an exemplary role and consumers will have a right to know how much energy they consume.
The following categories are covered by the directive:
energy efficiency targets
building renovation
an exemplary role for public buildings
energy efficiency obligation schemes
energy audits and energy management systems
metering and billing information systems and the right to access this data
consumer information and empowerment
promotion of efficiency in heating and cooling
energy transformation, transmission, and distribution
availability of qualification, accreditation, and certification schemes
information and training
energy services
an energy efficiency national fund, financing, and technical support
other measures to promote energy efficiency
== National Energy Efficiency Action Plans and Annual Reports ==
Individual National Energy Efficiency Action Plans (NEEAP) for 2014 and Annual Reports for 2016 are available for download. Some national action plans have Wikipedia articles as well:
German National Action Plan on Energy Efficiency
== Reception and effectiveness ==
A 2014 study finds that, despite the directive being technically complex and lacking binding targets, it is an improvement over earlier European Union policy on energy efficiency. Notwithstanding, the document is weakened by the number of exemptions and the number of passages it contains requiring interpretation. The process of implementation was also subject to problems.: 3–4
In June 2014 the UK government directed through a Procurement Policy Note issued to all government departments that they were to comply after 5 June 2014 with the energy efficiency standards of Article 6 and Annex III to the Directive when purchasing goods and services and when renting or purchasing buildings, as long as this is "consistent with achieving value for money, economic
feasibility, wider sustainability, technical suitability and ensuring sufficient competition". Further information issued in January 2015 made clear that "the obligation under Article 6 is a qualified one" and that public bodies "need only buy to the standards set out in Annex III of the Directive where this is cost effective". Public bodies in the wider public sector outside of central government were "encouraged" to follow the central government example.
A 2016 study examined the treatment of article 7 of the directive: 15 by each of the 28 member states. Titled Energy efficiency obligation schemes, this key article requires that countries "implement energy efficiency obligations and/or alternative policy instruments in order to reach a reduction in final energy use of 1.5% per year".: 1 To fulfill this requirement, the member states have proposed very different policy measures and adopted very different calculation methods and monitoring and verification schemes. The study analyses each national action plan and estimates whether the projected savings are likely to materialise and whether these will be sufficient to meet the article 7 target.
== Future developments ==
Directive 2018/2002/EC was adopted on 21 December 2018. It amends this one.
== See also ==
Energy conservation
Energy efficiency in Europe (study) – a study as part of the Odyssee Mure project
Energy efficiency in Europe § National Energy Efficiency Action Plans
Energy policy of the European Union
Energy Taxation Directive
EU Renewable Energy Directive 2009/28/EC – a similar directive covering renewable energy
European Union directive
German National Action Plan on Energy Efficiency (abbreviated NAPE)
List of European Union directives
White certificates – which certify a reduction in energy consumption
== Further reading ==
Directive 2012/27/EU of the European Parliament and of the Council of 25 October 2012 on energy efficiency, amending Directives 2009/125/EC and 2010/30/EU and repealing Directives 2004/8/EC and 2006/32/EC. Brussels, Belgium: European Council. 14 November 2012. Retrieved 20 September 2016.
== References ==
== External links ==
Complete list of National Energy Efficiency Plans and Annual Reports.
European Commission Energy Efficiency Directive website
Odyssee Mure energy efficiency monitoring project for Europe | Wikipedia/EU_Energy_Efficiency_Directive_2012/27/EU |
Energy conservation is the effort to reduce wasteful energy consumption by using fewer energy services. This can be done by using energy more effectively (using less and better sources of energy for continuous service) or changing one's behavior to use less and better source of service (for example, by driving vehicles which consume renewable energy or energy with more efficiency). Energy conservation can be achieved through efficient energy use, which has some advantages, including a reduction in greenhouse gas emissions and a smaller carbon footprint, as well as cost, water, and energy savings.
Green engineering practices improve the life cycle of the components of machines which convert energy from one form into another.
Energy can be conserved by reducing waste and losses, improving efficiency through technological upgrades, improving operations and maintenance, changing users' behaviors through user profiling or user activities, monitoring appliances, shifting load to off-peak hours, and providing energy-saving recommendations. Observing appliance usage, establishing an energy usage profile, and revealing energy consumption patterns in circumstances where energy is used poorly, can pinpoint user habits and behaviors in energy consumption. Appliance energy profiling helps identify inefficient appliances with high energy consumption and energy load. Seasonal variations also greatly influence energy load, as more air-conditioning is used in warmer seasons and heating in colder seasons. Achieving a balance between energy load and user comfort is complex yet essential for energy preservation. On a large scale, a few factors affect energy consumption trends, including political issues, technological developments, economic growth, and environmental concerns.
== User-oriented energy conservation ==
User behavior has a significant effect on energy conservation. It involves user activity detection, profiling, and appliance interaction behaviors. User profiling consists of the identification of energy usage patterns of the user and replacing required system settings with automated settings that can be initiated on request. Within user profiling, personal characteristics are instrumental in affecting energy conservation behavior. These characteristics include household income, education, gender, age, and social norms.
User behavior also relies on the impact of personality traits, social norms, and attitudes on energy conservation behavior. Beliefs and attitudes toward a convenient lifestyle, environmentally friendly transport, energy security, and residential location choices affect energy conservation behavior. As a result, energy conservation can be made possible by adopting pro-environmental behavior and energy-efficient systems. Education on approaches to energy conservation can result in wise energy use. The choices made by the users yield energy usage patterns. Rigorous analysis of these usage patterns identifies waste energy patterns, and improving those patterns may reduce significant energy load. Therefore, human behavior is critical to determining the implications of energy conservation measures and solving environmental problems. Substantial energy conservation may be achieved if users' habit loops are modified.
== User habits ==
User habits significantly impact energy demand; thus, providing recommendations for improving user habits contributes to energy conservation. Micro-moments are essential in realizing energy consumption patterns and are identified using a variety of sensing units positioned in prominent areas across the home. The micro-moment is an event that changes the state of the appliance from inactive to active and helps in building users' energy consumption profiles according to their activities. Energy conservation can be achieved through user habits by following energy-saving recommendations at micro-moments. Unnecessary energy usage can be decreased by selecting a suitable schedule for appliance operation. Creating an effective scheduling system requires an understanding of user habits regarding appliances.
== Off-peak scheduling ==
Many techniques for energy conservation comprise off-peak scheduling, which means operating an appliance in a low-price energy hour. This schedule can be achieved after user habits regarding appliance use are understood. Most energy providers divide the energy tariff into high and low-price hours; therefore, scheduling an appliance to work an off-peak hour will significantly reduce electricity bills.
== User activity detection ==
User activity detection leads to the precise detection of appliances required for an activity. If an appliance is active but not required for a user's current activity, it wastes energy and can be turned off to conserve energy. The precise identification of user activities is necessary to achieve this method of energy conservation.
== Energy conservation opportunities by sector ==
=== Buildings ===
==== Existing buildings ====
Energy conservation measures have primarily focused on technological innovations to improve efficiencies and financial incentives with theoretical explanations obtained from the mentioned analytical traditions. Existing buildings can improve energy efficiency by changing structural maintenance materials, adjusting the composition of air conditioning systems, selecting energy-saving equipment, and formulating subsidy policies. These measures can improve users' thermal comfort and reduce buildings' environmental impact. The selection of combinatorial optimization schemes that contain measures to guide and restrict users' behavior in addition to carrying out demand-side management can dynamically adjust energy consumption. At the same time, economic means should enable users to change their behavior and achieve a low-carbon life. Combination optimization and pricing incentives reduce building energy consumption and carbon emissions and reduce users' costs.
Energy monitoring through energy audits can achieve energy efficiency in existing buildings. An energy audit is an inspection and analysis of energy use and flows for energy conservation in a structure, process, or system intending to reduce energy input without negatively affecting output. Energy audits can determine specific opportunities for energy conservation and efficiency measures as well as determine cost-effective strategies. Training professionals typically accomplish this and can be part of some national programs discussed above. The recent development of smartphone apps enables homeowners to complete relatively sophisticated energy audits themselves. For instance, smart thermostats can connect to standard HVAC systems to maintain energy-efficient indoor temperatures. In addition, data loggers can also be installed to monitor the interior temperature and humidity levels to provide a more precise understanding of the conditions. If the data gathered is compared with the users' perceptions of comfort, more fine-tuning of the interiors can be implemented (e.g., increasing the temperature where A.C. is used to prevent over-cooling). Building technologies and smart meters can allow commercial and residential energy users to visualize the impact their energy use can have in their workplaces or homes. Advanced real-time energy metering can help people save energy through their actions.
Another approach towards energy conservation is the implementation of ECMs in commercial buildings, which often employ Energy Service Companies (ESCOs) experienced in energy performance contracting. This industry has been around since the 1970s and is more prevalent than ever today. The US-based organization EVO (Efficiency Valuation Organization) has created a set of guidelines for ESCOs to adhere to in evaluating the savings achieved by ECMs. These guidelines are called the International Performance Measurement and Verification Protocol (IPMVP).
Energy efficiency can also be achieved by upgrading certain aspects of existing buildings. Making thermal improvements by adding insulation to crawl spaces and ensuring no leaks achieves an efficient building envelope, reducing the need for mechanical systems to heat and cool the space. High-performance insulation is also supported by adding double/triple-glazed windows to minimize thermal heat transmission. Minor upgrades in existing buildings include changing mixers to low flow greatly aids in water conservation, changing light bulbs to LED lights results in 70-90% less energy consumption than a standard incandescent or C.F.L. bulb, changing inefficient appliances with Energy Star-rated appliances will consume less energy, and finally adding vegetation in the landscape surrounding the building to function as a shading element. A window windcatcher can reduce the total energy use of a building by 23.3%.
Energy conservation through users' behaviors requires understanding household occupants' lifestyle, social, and behavioral factors in analyzing energy consumption. This involves one-time investments in energy efficiency, such as purchasing new energy-efficient appliances or upgrading the building insulation without curtailing economic utility or the level of energy services, and energy curtailment behaviors which are theorized to be driven more by social-psychological factors and environmental concerns in comparison to the energy efficiency behaviors. Replacing existing appliances with newer and more efficient ones leads to energy efficiency as less energy is wasted throughout. Overall, energy efficiency behaviors are identified more with one-time, cost-incurring investments in efficient appliances and retrofits, while energy curtailment behaviors include repetitive, low-cost energy-saving efforts.
To identify and optimize residential energy use, conventional and behavioral economics, technology adoption theory and attitude-based decision-making, social and environmental psychology, and sociology must be analyzed. The techno-economic and psychological literature analysis focuses on the individual attitude, behavior, and choice/context/external conditions. In contrast, the sociological literature relies more on the energy consumption practices shaped by the social, cultural, and economic factors in a dynamic setting.
==== New buildings ====
Many steps can be taken toward energy conservation and efficiency when designing new buildings. Firstly, the building can be designed to optimize building performance by having an efficient building envelope with high-performing insulation and window glazing systems, window facades strategically oriented to optimize daylighting, shading elements to mitigate unwanted glare, and passive energy systems for appliances. In passive solar building designs, windows, walls, and floors are made to collect, store, and distribute solar energy in the form of heat in the winter and reject solar heat in the summer.
The key to designing a passive solar building is to best take advantage of the local climate. Elements to be considered include window placement and glazing type, thermal insulation, thermal mass, and shading. Optimizing daylighting can decrease energy waste from incandescent bulbs, windows, and balconies, allow natural ventilation, reduce the need for heating and cooling, low flow mixers aid in water conservation, and upgrade to Energy star rated appliances consume less energy. Designing a building according to LEED guidelines while incorporating smart home technology can help save a lot of energy and money in the long run. Passive solar design techniques can be applied most easily to new buildings, but existing buildings can be retrofitted.
Mainly, energy conservation is achieved by modifying user habits or providing an energy-saving recommendation of curtailing an appliance or scheduling it to low-price energy tariff hours. Besides changing user habits and appliance control, identifying irrelevant appliances concerning user activities in smart homes saves energy. Smart home technology can advise users on energy-saving strategies according to their behavior, encouraging behavioral change that leads to energy conservation. This guidance includes reminders to turn off lights, leakage sensors to prevent plumbing issues, running appliances on off-peak hours, and smart sensors that save energy. Such technology learns user-appliance activity patterns, gives a complete overview of various energy-consuming appliances, and can provide guidance to improve these patterns to contribute to energy conservation. As a result, they can strategically schedule appliances by monitoring the energy consumption profiles of the appliances, schedule devices to the energy-efficient mode, or plan to work during off-peak hours.
Appliance-oriented approaches emphasize appliance profiling, curtailing, and scheduling to off-peak hours, as supervision of appliances is key to energy preservation. It usually leads to appliance curtailment in which an appliance is either scheduled to work another time or is turned off. Appliance curtailment involves appliance recognition, activity-appliances model, unattended appliance detection, and energy conservation service. The appliance recognition module detects active appliances to identify the activities of smart home users. After identifying users' activities, the association between the functional appliances and user activities is established. The unattended appliance detection module looks for active appliances but is unrelated to user activity. These functional appliances waste energy and can be turned off by providing recommendations to the user.
Based on the smart home recommendations, users can give weight to certain appliances that increase user comfort and satisfaction while conserving energy. Energy consumption models of energy consumption of appliances and the level of comfort they create can balance priorities among smart home comfort levels and energy consumption. According to Kashimoto, Ogura, Yamamoto, Yasumoto, and Ito, the energy supply reduces based on the historical state of the appliance and increases according to the comfort level requirement of the user, leading to a targeted energy-saving ratio. Scenarios-based energy consumption can be employed as a strategy for energy conservation, with each scenario encompassing a specific set of rules for energy consumption.
=== Transportation ===
Transporting people, goods, and services represented 29% of U.S. energy consumption in 2007. The transportation sector also accounted for about 33% of U.S. carbon dioxide emissions in 2006, with highway vehicles accounting for about 84% of that, making transportation an essential target for addressing global climate change (E.I.A., 2008). Suburban infrastructure evolved during an age of relatively easy access to fossil fuels, leading to transportation-dependent living systems.[citation needed] The amount of energy used to transport people to and from a facility, whether they are commuters, customers, vendors, or homeowners, is known as the transportation energy intensity of the building. Land is developing at a faster rate than population growth, leading to urban sprawl and, therefore, high transportation energy intensity as more people need to commute longer distances to jobs. As a result, the location of a building is essential in decreasing embodied emissions.
In transportation, state and local efforts in energy conservation and efficiency measures tend to be more targeted and smaller in scale. However, with more robust fuel economy standards, new targets for the use of alternative transportation fuels, and new efforts in electric and hybrid electric vehicles, EPAct05 and EISA provide a new set of national policy signals and financial incentives to the private sector and state and local governments for the transportation sector. Zoning reforms that allow greater urban density and designs for walking and bicycling can greatly reduce energy consumed for transportation. Many Americans work in jobs that allow for remote work instead of commuting daily, which is a significant opportunity to conserve energy.[citation needed] Intelligent transportation systems (ITS) provide a solution to traffic congestion and C.E.s caused by increased vehicles. ITS combines improvements in information technology and systems, communications, sensors, controllers, and advanced mathematical methods with the traditional world of transportation infrastructure. It improves traffic safety and mobility, reduces environmental impact, promotes sustainable transportation, and increases productivity. The ITS strengthens the connection and cooperation between people, vehicles, roads, and the environment while improving road capacity, reducing traffic accidents, and improving transportation efficiency and safety by alleviating traffic congestion and reducing pollution. It makes full use of traffic information as an application service, which can enhance the operational efficiency of existing traffic facilities.
The most significant energy-saving potential is that there are the most problems in urban transportation in various countries, such as management systems, policies and regulations, planning, technology, operation, and management mechanism. Improvements in one or several aspects will improve road transportation. Efficiency has a positive impact, which leads to the improvement of the urban traffic environment and efficiency.
In addition to ITS, transit-oriented development (T.O.D.) significantly improves transportation in urban areas by emphasizing density, proximity to transit, diversity of uses, and streetscape design. Density is important for optimizing location and is a way to cut down on driving. Planners can regulate development rights by exchanging them from ecologically sensitive areas to growth-friendly zones according to density transfer procedures. Distance is defined as the accessibility of rail and bus transits, which serve as deterrents for driving. For transit-oriented development to be feasible, transportation stops must be close to where people live. Diversity refers to mixed-use areas that offer essential services close to homes and offices and include residential spaces for different socioeconomic categories, commercial and retail. This creates a pedestrian shed where one area can meet people's everyday needs on foot. Lastly, the streetscapes design involves minimal parking and walkable areas that calm traffic. Generous parking incentivizes people to use cars, whereas minimal and expensive parking deters commuters. At the same time, streetscapes can be designed to incorporate bicycling lanes and designated bicycle paths and trails. People may commute by bicycle to work without being concerned about their bicycles becoming wet because of covered bicycle storage. This encourages commuters to use bicycles rather than other modes of transportation and contributes to energy saving. People will be happy to walk a few blocks from a train stop if there are attractive, pedestrian-friendly outdoor spaces nearby with good lighting, park benches, outdoor tables at cafés, shade tree plantings, pedestrian courts that are blocked off to cars, and public internet connection. Additionally, this strategy calms traffic, improving the intended pedestrian environment.
New urban planning schemes can be designed to improve connectivity in cities through networks of interconnected streets that spread out traffic flow, slow down vehicles, and make walking more pleasant. By dividing the number of road links by the number of road nodes, the connectivity index is calculated. The higher the connectivity index, the greater the route choices and the better the pedestrian access. Realizing the transportation impacts associated with buildings allows commuters to take steps toward energy conservation. Connectivity encourages energy-conserving behaviors as commuters use fewer cars, walk and bike more, and use public transportation. For commuters who do not have the option of public transportation, smaller vehicles that are hybrid or have better mileage can be used.
=== Consumer products ===
Homeowners implementing ECMs in their residential buildings often start with an energy audit. This is a way homeowners look at what areas of their homes are using, and possibly losing energy. Residential energy auditors are accredited by the Building Performance Institute (BPI) or the Residential Energy Services Network (RESNET). Homeowners can hire a professional or do it themselves or use a smartphone to help do an audit.
Energy conservation measures are often combined into larger guaranteed Energy Savings Performance Contracts to maximize energy savings while minimizing disruption to building occupants by coordinating renovations. Some ECMs cost less to implement yet return higher energy savings. Traditionally, lighting projects were a good example of "low hanging fruit" that could be used to drive implementation of more substantial upgrades to HVAC systems in large facilities. Smaller buildings might combine window replacement with modern insulation using advanced building foams to improve energy for performance. Energy dashboard projects are a new kind of ECM that relies on the behavioral change of building occupants to save energy. When implemented as part of a program, case studies, such as that for the DC Schools, report energy savings up 30%. Under the right circumstances, open energy dashboards can even be implemented for free to improve upon these savings even more.
Consumers are often poorly informed of the savings of energy-efficient products. A prominent example of this is the energy savings that can be made by replacing an incandescent light bulb with a more modern alternative. When purchasing light bulbs, many consumers opt for cheap incandescent bulbs, failing to take into account their higher energy costs and lower lifespans when compared to modern compact fluorescent and LED bulbs. Although these energy-efficient alternatives have a higher upfront cost, their long lifespan and low energy use can save consumers a considerable amount of money. The price of LED bulbs has also been steadily decreasing in the past five years due to improvements in semiconductor technology. Many LED bulbs on the market qualify for utility rebates that further reduce the price of the purchase to the consumer. Estimates by the U.S. Department of Energy state that widespread adoption of LED lighting over the next 20 years could result in about $265 billion worth of savings in United States energy costs.
The research one must put into conserving energy is often too time-consuming and costly for the average consumer when there are cheaper products and technology available using today's fossil fuels. Some governments and NGOs are attempting to reduce this complexity with Eco-labels that make differences in energy efficiency easy to research while shopping.
To provide the kind of information and support people need to invest money, time and effort in energy conservation, it is important to understand and link to people's topical concerns. For instance, some retailers argue that bright lighting stimulates purchasing. However, health studies have demonstrated that headache, stress, blood pressure, fatigue and worker error all generally increase with the common over-illumination present in many workplace and retail settings. It has been shown that natural daylighting increases productivity levels of workers, while reducing energy consumption.
In warm climates where air conditioning is used, any household device that gives off heat will result in a larger load on the cooling system. Items such as stoves, dishwashers, clothes dryers, hot water, and incandescent lighting all add heat to the home. Low-power or insulated versions of these devices give off less heat for the air conditioning to remove. The air conditioning system can also improve efficiency by using a heat sink that is cooler than the standard air heat exchanger, such as geothermal or water.
In cold climates, heating air and water is a major demand for household energy use. Significant energy reductions are possible by using different technologies. Heat pumps are a more efficient alternative to electrical resistance heaters for warming air or water. A variety of efficient clothes dryers are available, and the clothes lines requires no energy- only time. Natural-gas (or bio-gas) condensing boilers and hot-air furnaces increase efficiency over standard hot-flue models. Standard electric boilers can be made to run only at hours of the day when they are needed by means of a time switch. This decreases energy use vastly. In showers, a semi-closed-loop system could be used. New construction implementing heat exchangers can capture heat from wastewater or exhaust air in bathrooms, laundry, and kitchens.
In both warm and cold climate extremes, airtight thermal insulated construction is the largest factor determining the efficiency of a home. Insulation is added to minimize the flow of heat to or from the home, but can be labor-intensive to retrofit to an existing home.
== Energy conservation by countries ==
=== Asia ===
Although energy efficiency is expected to play a vital role in cost-effectively cutting energy demand, only a small part of its economic potential is exploited in Asia. Governments have implemented a range of subsidies such as cash grants, cheap credit, tax exemptions, and co-financing with public-sector funds to encourage energy-efficiency initiatives across several sectors. Governments in the Asia-Pacific region have implemented a range of information provision and labeling programs for buildings, appliances, and the transportation and induel-economy labels, or actively seek to encourage behavioral changes, such as Japan's Cool Biz campaign that encourages setting air conditioners at 28-degrees Celsius and allowing employees to dress casually in the summer.
China's government has launched a series of policies since 2005 to effectively promote the goal of reducing energy-saving emissions; however, road transportation, the fastest-growing energy-consuming sector in the transportation industry, lacks specific, operational, and systematic energy-saving plans. Road transportation is the highest priority to achieve energy conservation effectively and reduce emissions, particularly since social and economic development has entered the "new norm" period. Generally speaking, the government should make comprehensive plans for conservation and emissions reduction in the road transportation industry within the three dimensions of demand, structure, and technology. For example, encouraging trips using public transportation and new transportation modes such as car-sharing and increasing investment in new energy vehicles in structure reform, etc.
=== European Union ===
At the end of 2006, the European Union (EU) pledged to cut its annual consumption of primary energy by 20% by 2020. The EU Energy Efficiency Directive 2012 mandates energy efficiency improvements within the EU.
As part of the EU's SAVE program, aimed at promoting energy efficiency and encouraging energy-saving behavior, the Boiler Efficiency Directive specifies minimum levels of efficiency for boilers using liquid or gaseous fuels.
There is steady progress on energy regulation implementation in Europe, North America, and Asia, with the highest number of building energy standards being adopted and implemented. Moreover, the performance of Europe is highly encouraging concerning energy standard activities. They recorded the highest percentage of mandatory energy standards compared to the other five regions.
In 2050, energy savings in Europe can reach 67% of the 2019 baseline scenario, amounting to a demand of 361 Mtoe in an "energy efficiency first" societal trend scenario. A condition is that there be no rebound effect, for otherwise the savings are 32% only or energy use may even increase by 42% if techno-economic potentials are not realized.
Germany has reduced its primary energy consumption by 11% from 1990 to 2015 and set itself goals of reducing it by 30% by the year 2030 and by 50% by the year 2050 in comparison to the level of 2008.
=== India ===
The Petroleum Conservation Research Association (PCRA) is an Indian governmental body created in 1978 that engages in promoting energy efficiency and conservation in every walk of life. In the recent past, PCRA has organised mass media campaigns in television, radio, and print media. This is an impact-assessment survey by a third party that revealed that due to these larger campaigns by PCRA, the public's overall awareness level has gone up leading to the saving of fossil fuels worth crores of rupees, besides reducing pollution.
The Bureau of Energy Efficiency is an Indian government organization created in 2001 that is responsible for promoting energy efficiency and conservation.
Protection and Conservation of Natural Resources are done by Community Natural Resources Management (CNRM).
=== Iran ===
Supreme leader of Iran Ali Khamenei had regularly criticized energy administration and high fuel consumption.
=== Japan ===
Since the 1973 oil crisis, energy conservation has been an issue in Japan. All oil-based fuel is imported, so domestic sustainable energy is being developed.
The Energy Conservation Center promotes energy efficiency in every aspect of Japan. Public entities are implementing the efficient use of energy for industries and research. It includes projects such as the Top Runner Program. In this project, new appliances are regularly tested on efficiency, and the most efficient ones are made the standard.
=== Middle East ===
The Middle East holds 40% of the world's crude oil reserves and 23% of its natural gas reserves. Conservation of domestic fossil fuels is, therefore, a legitimate priority for the Gulf countries, given domestic needs as well as the global market for these products. Energy subsidies are the chief barrier to conservation in the Gulf. Residential electricity prices can be a tenth of U.S. rates. As a result, increased tariff revenues from gas, electricity, and water sales would encourage investment in natural gas exploration and production and generation capacity, helping to alleviate future shortages.
Households in the MENA region are responsible for 53% of energy use in Saudi Arabia and 57% of the UAE's ecological footprint. This is partially due to poorly designed and constructed buildings, mainly under a cheap energy model that has left them without contemporary control technology or even proper insulation and efficient appliances. Building energy consumption can be cut by 20% under a combination of insulation, efficient windows and appliances, shading, reflective roofing, and a host of automated controls that adjust energy use.
Governments could also set minimum energy efficiency and water use standards on importing appliances sold inside their countries, effectively banning the sale of inefficient air conditioners, dishwashers, and washing machines. Administration of the laws would essentially be a function of national customs services. Governments could go further, offering incentives – or mandates – that air conditioners of a certain age be replaced.
==== Lebanon ====
In Lebanon and since 2002 The Lebanese Center for Energy Conservation (LCEC) has been promoting the development of efficient and rational uses of energy and the use of renewable energy at the consumer level. It was created as a project financed by the International Environment Facility (GEF) and the Ministry of Energy Water (MEW) under the management of the United Nations Development Programme (UNDP) and gradually established itself as an independent technical national center although it continues to be supported by the United Nations Development Programme (UNDP) as indicated in the Memorandum of Understanding (MoU) signed between MEW and UNDP on 18 June 2007.
=== Nepal ===
Until recently, Nepal has been focusing on the exploitation of its huge water resources to produce hydropower. Demand-side management and energy conservation were not in the focus of government action. In 2009, bilateral Development Cooperation between Nepal and the Federal Republic of Germany has agreed upon the joint implementation of the "Nepal Energy Efficiency Programme". The lead executing agencies for the implementation are the Water and Energy Commission Secretariat (WECS). The aim of the program is the promotion of energy efficiency in policymaking, in rural and urban households as well as in the industry.
Due to the lack of a government organization that promotes energy efficiency in the country, the Federation of Nepalese Chambers of Commerce and Industry (FNCCI) has established the Energy Efficiency Centre under his roof to promote energy conservation in the private sector. The Energy Efficiency Centre is a non-profit initiative that is offering energy auditing services to the industries. The centre is also supported by Nepal Energy Efficiency Programme of Deutsche Gesellschaft für Internationale Zusammenarbeit.
A study conducted in 2012 found out that Nepalese industries could save 160,000-megawatt hours of electricity and 8,000 terajoules of thermal energy (like diesel, furnace oil, and coal) every year. These savings are equivalent to annual energy cost cut of up to 6.4 Billion Nepalese Rupees.
As a result of Nepal Economic Forum 2014, an economic reform agenda in the priority sectors was declared focusing on energy conservation among others. In the energy reform agenda, the government of Nepal gave the commitment to introduce incentive packages in the budget of the fiscal year 2015/16 for industries that practices energy efficiency or use efficient technologies (incl. cogeneration).
=== New Zealand ===
In New Zealand the Energy Efficiency and Conservation Authority is the Government Agency responsible for promoting energy efficiency and conservation. The Energy Management Association of New Zealand is a membership-based organization representing the New Zealand energy services sector, providing training and accreditation services with the aim of ensuring energy management services are credible and dependable.
=== Nigeria ===
In Nigeria, the Lagos State Government is encouraging Lagosians to imbibe an energy conservation culture. In 2013, the Lagos State Electricity Board (LSEB) ran an initiative tagged "Conserve Energy, Save Money" under the Ministry of Energy and Mineral Resources. The initiative is designed to sensitize Lagosians around the theme of energy conservation by influencing their behavior through do-it-yourself tips. In September 2013, Governor Babatunde Raji Fashola of Lagos State and the campaign ambassador, rapper Jude "MI" Abaga participated in the Governor's conference video call on the topic of energy conservation.
In addition to this, during the month of October (the official energy conservation month in the state), LSEB hosted experience centers in malls around Lagos State where members of the public were encouraged to calculate their household energy consumption and discover ways to save money using a consumer-focused energy app. To get Lagosians started on energy conservation, solar lamps and energy-saving bulbs were also handed out.
In Kaduna State, the Kaduna Power Supply Company (KAPSCO) ran a program to replace all light bulbs in Public Offices; fitting energy-saving bulbs in place of incandescent bulbs. KAPSCO is also embarking on an initiative to retrofit all conventional streetlights in the Kaduna Metropolis to LEDs which consume much less energy.
=== Sri Lanka ===
Sri Lanka currently consumes fossil fuels, hydro power, wind power, solar power and dendro power for their day to day power generation. The Sri Lanka Sustainable Energy Authority is playing a major role regarding energy management and energy conservation. Today, most industries are requested to reduce their energy consumption by using renewable energy sources and optimizing their energy usage.
=== Turkey ===
Turkey aims to decrease by at least 20% the amount of energy consumed per GDP of Turkey by 2023 (energy intensity).
=== United Kingdom ===
The Department for Business, Energy and Industrial Strategy is responsible for promoting energy efficiency in the United Kingdom.
=== United States ===
The United States is currently the second-largest single consumer of energy, following China. The U.S. Department of Energy categorizes national energy use in four broad sectors: transportation, residential, commercial, and industrial.
About half of U.S. energy consumption in the transportation and residential sectors is primarily controlled by individual consumers. In the typical American home, space heating is the most significant energy use, followed by electrical technology (appliances, lighting, and electronics) and water heating. Commercial and industrial energy expenditures are determined by businesses entities and other facility managers. National energy policy has a significant effect on energy usage across all four sectors.
Since the oil embargoes and price spikes of the 1970s, energy efficiency and conservation have been fundamental tenets of U.S. energy policy. The scope of energy conservation and efficiency measures has been broadened throughout time by U.S. energy policies and programs, including federal and state legislation and regulatory actions, to include all economic sectors and all geographical areas of the nation. Measurable energy conservation and efficiency gains in the 1980s led to the 1987 Energy Security Report to the President (DOE, 1987) that "the United States uses about 29 quads less energy in a year today than it would have if our economic growth since 1972 had been accompanied by the less- efficient trends in energy use we were following at that time" The DOE Strategy and the legislation included new strategies for strengthening conservation and efficiency in buildings, industry, and electric power, such as integrated resource planning for electric and natural gas utilities and efficiency and labeling standards for 13 residential appliances and equipment categories. Lack of a national consensus on how to proceed interfered with developing a consistent and comprehensive approach. Nevertheless, the Energy Policy Act of 2005 (EPAct05; 109th U.S. Congress, 2005) contained many new energy conservation and efficiency provisions in the transportation, buildings, and electric power sectors.
The most recent federal law to increase and broaden U.S. energy conservation and efficiency laws, programs, and practices is the Energy Independence and Security Act of 2007 (EISA). Over the next few decades, it is anticipated that EISA will significantly reduce energy use because it has more standards and targets than previous legislation. Both acts reinforce the importance of lighting and appliance efficiency programs, targeting an additional 70% lighting efficiency by 2020, introducing 45 new standards for appliances, and setting up new standards for vehicle fuel economy. The Federal Government is also promoting a new 30% model code for efficient building practices in the construction industry. Additionally, according to the American Council for an Energy-Efficient Economy (ACEEE), the EISA's energy efficiency and conservation initiatives will cut carbon dioxide emissions by 9% in 2030. These requirements cover appliance and lighting efficiency, energy savings in homes, businesses, and public buildings, the effectiveness of industrial manufacturing facilities, and the efficiency of electricity supply and end use. Expectations are high for increased energy savings due to these initiatives, which have already started contributing to new federal, state, and local laws, programs, and practices across the U.S.
The development and use of alternative transportation fuels (whose supply is expected to expand by 15% by 2022), renewable energy sources, and other clean energy technologies have also received more attention and financial incentives. Recent policies also emphasize growing the use of coal with carbon capture and sequestration, solar, wind, nuclear, and other clean energy sources.
In February 2023 the United States Department of Energy proposed a set of new energy efficiency standards that, if implemented, will save to users of different electric machines in the United States around $3,500,000,000 per year and will reduce by the year 2050 carbon emissions by the same amount as emitted by 29,000,000 houses.
== Mechanisms to promote conservation ==
=== Governmental mechanisms ===
Governments at the national, regional, and local levels may implement policies to promote energy efficiency. Building energy rules can cover the energy consumption of an entire structure or specific building components, like heating and cooling systems. They represent some of the most frequently used instruments for energy efficiency improvements in buildings and can play an essential role in improving energy conservation in buildings. There are multiple reasons for the growth of these policies and programs since the 2000s, including cost savings as energy prices increased, growing concern about the environmental impacts of energy use, and public health concerns. The policies and programs related to energy conservation are critical to establishing safety and performance levels, assisting in consumer decision-making, and explicitly identifying energy-conserving and energy-efficient products. Recent policies include new programs and regulatory incentives that call for electric and natural gas utilities to increase their involvement in delivering energy-efficiency products and services to their customers. For example, the National Action Plan for Energy Efficiency (NAPEE) is a public-private partnership created in response to EPAct05 that brings together senior executives from electric and natural gas utilities, state public utility commissions, other state agencies, and environmental and consumer groups representing every region of the country. The success of building energy regulation in effectively controlling energy consumption in the building sector will be, to a great extent, associated with the adopted energy performance indicator and the promoted energy assessment tools. It can help overcome significant market barriers and ensure cost-effective energy efficiency opportunities are incorporated into new buildings. This is crucial in emerging nations where new constructions are rapidly developing, and market and energy prices sometimes discourage efficient technologies. The building energy standards development and adoption showed that 42% of emerging developing countries surveyed have no energy standard in place, 20% have mandatory, 22% have mixed, and 16% proposed.
The major impediments to implementing building energy regulations for energy conservation and efficiency in the building sector are institutional barriers and market failures rather than technical problems, as pointed out by Nature Publishing Group (2008). Among these, Santamouris (2005) includes a lack of owners' awareness of energy conservation benefits, building energy regulations benefits, insufficient awareness and training of property managers, builders, and engineers, and a lack of specialized professionals to ensure compliance. Based on the above information, the development and adoption of building energy regulations, such as energy standards in developing countries, are still far behind compared to building energy regulation adoption and implementation in developed countries.
Building energy standards are starting to appear in Africa, Latin America, and Middle East regions, even though this is a new development going to the result obtained in this study. The level of progress on energy regulation activities in Africa, Latin America, and the Middle East is increasing, given the higher number of energy standard proposals recorded in these regions. According to the Royal Institute of Chartered Surveyors, several codes are being developed in developing countries with UNDP and GEF support. These typically include elemental and integrated routes to compliance, such as a fundamental method defining the performance requirements of specific building elements. However, they are still far behind in building energy regulation development, implementation, and compliance compared to developed nations. Also, decision-making regarding energy regulations is still from the government only, with little or no input from non-governmental entities. As a result, lower energy regulation development is recorded in these regions compared to regions with integrated and consensus approaches.
Additionally, there is growing government involvement in the development and implementation of energy standards; 62% of Middle Eastern respondents, 45% of African respondents, and 43% of Latin American respondents indicated that existing government agencies, such as building agencies and energy agencies, are involved in implementing building energy standards in their respective nations, as opposed to 20% of European respondents, 38% of Asian respondents, and 0% of North American respondents, who indicated the involvement of existing agencies. Several North African nations, like Tunisia and Egypt, have programs relating to building energy standards, while Algeria and Morocco are now seeking to establish building energy standards, according to the Royal Institute of Chartered Surveyors. Similarly, Egypt's residential energy standard became law in 2005, and their commercial standard was anticipated to follow. The standards provide minimal performance requirements for applications involving air conditioners and other appliances and elemental and integrated pathways. However, it was claimed that enforcement legislation was still required in 2005. Additionally, Morocco launched a program in 2005 to create thermal energy requirements for construction, concentrating on the hospitality, healthcare, and communal housing industries.
==== Mandatory energy standards ====
Energy standards are the primary way governments foster energy efficiency as a public good. A recognized standard-setting organization prepares a standard. Standards developed by recognized organizations are often used as the basis for the development and updating of building codes. They allow innovative approaches and techniques to achieve effective energy use and optimum building performance. Besides, it encourages cost-effective energy use of building components, including building envelope, lighting, HVAC, electrical installations, lift and escalator, and other equipment. Energy-efficiency standards have been expanded and strengthened for appliances, building equipment, and lighting. For example, appliances and equipment standards are being developed for a new range of devices, including reduction goals for "standby" power that keeps consumer electronic products in a ready-to-use mode. Some devices require certain levels of energy performance from a car, building, appliance, or other technical equipment. If the vehicle, building, appliance, or equipment does not meet these standards, there may be restrictions on its sale or rent. In the U.K., these are called "minimum energy efficiency standards" or MEES and were applied to privately rented accommodation in 2019.
Energy codes and standards are vital in setting minimum energy-efficient design and construction requirements. Buildings should be developed following energy standards to save energy efficiently. They specify uniform requirements for new buildings, additions, and modifications. National organizations like the American Society of Heating, Refrigerating, and Air-Conditioning Engineers publish the standards (ASHRAE). State and municipal governments frequently use energy standards as the technical foundation for creating their energy regulations. Some energy standards are written in a mandatory and enforceable language, making it simple for governments to add the standards' provisions directly to their laws or regulations.
The American Society of Heating, Refrigeration, and Air-Conditioning Engineers (ASHRAE) is a well-known example of a standard-making organization. This organization dates to the nineteenth century and is international in its membership (About ASHRAE 2018). Examples of ASHRAE standards that relate to energy conservation in the built environment are:
Standard 62.1-2016 Ventilation for Acceptable Indoor Air Quality
Standard 90.2-2007 Energy Efficient Design of Low-Rise Residential Buildings
Standard 100-2018 Energy Efficiency in Existing Buildings
Standard 189.1-2014 Standard for the Design of High-Performance Green Buildings
The Residential Energy Services Network is a crucial benchmark for energy reduction (RESNET). The Home Energy Rating System (HERS) of RESNET, which is based on the International Code Council's (ICC) energy code, is used to rate home energy consumption with a standard numerical scale that examines factors in home energy use (About HERS 2018). The American National Standards Institute (ANSI) has acknowledged the HERS assessment system as a national benchmark for evaluating energy efficiency. The International Energy Conservation Code (IECC) of the ICC requires an energy rating index, and the main index used in the residential building sector is HERS. The mortgage financing sector makes substantial use of the HERS index. A home's expected energy usage may impact the available mortgage funds based on the HERS score, with more energy-efficient, lower energy-using homes potentially qualifying for a better mortgage rate or amount.
==== Mandatory energy labels ====
Many governments require that a car, building, or piece of equipment be labeled with its energy performance. This allows consumers and customers to see the energy implications of their choices, but does not restrict their choices or regulate which products are available to choose from.
It also does not enable easily comparing options (such as being able to filter by energy-efficiency in online stores) or have the best energy-conserving options accessible (such as energy-conserving options being available in the frequented local store). (An analogy would be nutritional labeling on food.)
A trial of estimated financial energy cost of refrigerators alongside EU energy-efficiency class (EEEC) labels online found that the approach of labels involves a trade-off between financial considerations and higher cost requirements in effort or time for the product-selection from the many available options which are often unlabelled and don't have any EEEC-requirement for being bought, used or sold within the EU. Moreover, in this one trial the labeling was ineffective in shifting purchases towards more sustainable options.
==== Energy taxes ====
Some countries employ energy or carbon taxes to motivate energy users to reduce their consumption. Carbon taxes can motivate consumption to shift to energy sources with fewer emissions of carbon dioxide, such as solar power, wind power, hydroelectricity or nuclear power while avoiding cars with combustion engines, jet fuel, oil, fossil gas and coal. On the other hand, taxes on all energy consumption can reduce energy use across the board while reducing a broader array of environmental consequences arising from energy production. The state of California employs a tiered energy tax whereby every consumer receives a baseline energy allowance that carries a low tax. As for usage increases above that baseline, the tax increases drastically. Such programs aim to protect poorer households while creating a larger tax burden for high energy consumers.
Developing countries specifically are less likely to impose policy measures that slow carbon emissions as this would slow their economic development. These growing countries may be more likely to support their own economic growth and support their citizens rather than decreasing their carbon emissions.
The following pros and cons of a carbon tax help one to see some of the potential effects of a carbon tax policy.
Pros of Carbon Tax include:
Making polluters pay the external cost of carbon emissions.
Enables greater social efficiency as all citizens pay the full social cost.
Raises revenue which can, in turn, be spent on mitigating the effects of pollution.
Encourages firms and consumers to search for non-carbon producing alternatives (ex. solar power, wind power, hydroelectricity, or nuclear power).
Reduces environmental costs associated with excess carbon pollution.
Cons of Carbon Tax include:
Businesses claim higher taxes which can discourage investment and economic growth.
A carbon tax may encourage tax evasion as firms may pollute in secret to avoid a carbon tax.
It may be difficult to measure external costs and how much the carbon tax should truly be.
There are administration costs in measuring pollution and collecting the associated tax.
Firms may move production to countries in which there is no carbon tax.
=== Non-governmental mechanisms ===
==== Voluntary energy standards ====
Another aspect of promoting energy efficiency is using the Leadership in Energy and Environmental Design (LEED) voluntary building design standards. This program is supported by the US Green Building Council. The "Energy and Atmosphere" Prerequisite applies to energy issues, it focuses on energy performance, renewable energy, and other. See green building.
== See also ==
== References ==
== Further reading ==
GA Mansoori, N Enayati, LB Agyarko (2016), Energy: Sources, Utilization, Legislation, Sustainability, Illinois as Model State, World Sci. Pub. Co., ISBN 978-981-4704-00-7
Alexeew, Johannes; Carolin Anders and Hina Zia (2015): Energy-efficient buildings – a business case for India? An analysis of incremental costs for four building projects of the Energy-Efficient Homes Programme. Berlin/New Delhi: Adelphi/TERI
Gary Steffy, Architectural Lighting Design, John Wiley and Sons (2001) ISBN 0-471-38638-3
Lumina Technologies, Analysis of energy consumption in a San Francisco Bay Area research office complex, for the (confidential) owner, Santa Rosa, Ca. 17 May 1996
Robb, Drew (2 June 2007). "GSA paves way for IT-based buildings – Government Computer News". Gcn.com. Archived from the original on 25 December 2008. Retrieved 29 July 2010.
== External links ==
bigEE – Your guide to energy efficiency in buildings
Energy saving advice and grants for UK consumers
Energy efficiency and renewable energy at the U.S. Department of Energy
EnergyStar Archived 28 June 2013 at the Wayback Machine – for commercial buildings and plants
Ulrich Hottelet: Want to Save the Earth? Pick a Clothesline, Atlantic Times, November 2007
Energy Efficiency in Asia and the Pacific Asian Development Bank
Energy Saving Tips Save up to $100 on power bills per year by switching off any unused appliances. | Wikipedia/Energy_conservation_measure |
The Energy Hierarchy is a classification of energy options, prioritised to assist progress towards a more sustainable energy system. It is a similar approach to the waste hierarchy for minimising resource depletion, and adopts a parallel sequence.
The highest priorities cover the prevention of unnecessary energy usage both through eliminating waste and improving energy efficiency. The sustainable production of energy resources is the next priority. Depletive and waste-producing energy generation options are the lowest priority.
For an energy system to be sustainable: the resources applied to producing the energy must be capable of lasting indefinitely; energy conversion should produce no harmful by-products, including net emissions, nor wastes which cannot be fully recycled; and it must be capable of meeting reasonable energy demands.
== Energy saving ==
The top priority under the Energy Hierarchy is energy conservation or the prevention of unnecessary use of energy. This category includes eliminating waste by turning off unneeded lights and appliances and by avoiding unnecessary journeys. Heat loss from buildings is a major source of energy wastage, so improvements to building insulation and air-tightness can make a significant contribution to energy conservation.
Many countries have agencies to encourage energy saving.
== Energy efficiency ==
The second priority under the energy hierarchy is to ensure that energy that is used is produced and consumed efficiently. Energy efficiency has two main aspects.
=== Conversion efficiency of energy consumption ===
Energy efficiency is the ratio of the productive output of a device to the energy it consumes.
Energy efficiency was a lower priority when energy was cheap and awareness of its environmental impact was low. In 1975 the average fuel economy of a car in the US was under 15 miles per gallon Incandescent light bulbs, which were the most common type until the late 20th century, waste 90% of their energy as heat, with only 10% converted to useful light.
More recently, energy efficiency has become a priority. The last reported average fuel efficiency of US cars had almost doubled from the 1975 level; LED lighting is now being promoted which are between five and ten times more efficient than incandescents. Many household appliances are now required to display labels to show their energy efficiency.
=== Conversion efficiency of energy production ===
Losses are incurred when energy is harvested from the natural resource from which it is derived, such as fossil fuels, radioactive materials, solar radiation or other sources. Most electricity production is in thermal power stations, where much of the source energy is lost as heat. The average efficiency of world electricity production in 2009 was c.37%.
A priority in the Energy Hierarchy is to improve the efficiency of energy conversion, whether in traditional power stations or by improving the performance ratio of photovoltaic power stations and other energy sources.
Overall efficiency and sustainability can also be improved by capacity- or fuel-switching from less efficient, less sustainable resources to better ones; but this is mainly covered under the fourth level of the hierarchy.
== Sustainable energy production ==
Renewable energy describes naturally occurring, theoretically inexhaustible sources of energy. These sources are treated as being inexhaustible, or naturally replenished, and fall into two classes.
=== Elemental renewables ===
The first class of renewables derive from climatic or elemental sources, such as sunlight, wind, waves, tides or rainfall (hydropower). Geothermal energy from the heat of the Earth's core also falls in this category.
These are treated as being inexhaustible because most derive ultimately from energy emanating from the sun, which has an estimated life of 6.5 billion years.
=== Bio-energy ===
The other main class of renewables, bioenergy, derives from biomass, where the relatively short growing cycle means that usage is replenished by new growth. Bioenergy is usually converted by combustion, and therefore gives rise to carbon emissions. It is treated as carbon neutral overall, because an equivalent amount of carbon dioxide will have been extracted from the atmosphere during the growing cycle.
Bioenergy sources can be solid, such as wood and energy crops; liquid, such as biofuels; or gaseous, such as biomethane from anaerobic digestion.
== Low impact energy production ==
The next priority in the hierarchy covers energy sources that are not entirely sustainable, but have a low environmental impact. These include the use of fossil fuels with carbon capture and storage.
Nuclear energy is sometimes treated as a low impact source, because it has low carbon emissions.
== High impact energy production ==
The lowest priority under the energy hierarchy is energy production using unsustainables sources, such as unabated fossil fuels. Some also place nuclear energy in this category, rather than the one above, because of the required management/storage of highly hazardous radioactive waste over extremely long (hundreds of thousands of years or more) timeframes and depletion of uranium resources.
There is a consensus that the share of such energy sources must decline.
Within this tier, there are possibilities for limiting adverse impacts by switching from the most damaging fuel sources, such as coal, to less emissive sources, such as gas.
Many suggest that when such high impact energy usage has been minimised, the effects of any unavoidable residual usage should be counterbalanced by emissions offsetting.
== Origins of the energy hierarchy ==
The Energy Hierarchy was first proposed in 2005 by Philip Wolfe, when he was Director General of the Renewable Energy Association. This first version had three levels; energy efficiency, renewables and traditional energy production. It was endorsed and adopted in 2006 by a consortium of institutions, associations and other bodies in the Sustainable Energy Manifesto. Subsequently, the concept has been adopted and refined by others in the energy industry and in government.
== See also ==
Energy law
Energy policy
Green transport hierarchy
List of books about energy issues
Maslow's hierarchy of needs
Soft energy path
Waste hierarchy
== References == | Wikipedia/Energy_hierarchy |
In the 21st century, the Earth's climate and its energy policy interact and their relationship is studied and governed by a variety of national and international institutions.
The relationships between energy-resource depletion, climate change, health resources and the environment, and the effects that they have on each other, have been subject to numerous scientific studies and research efforts. As a result, a majority of governments see climate and energy as two of the most important policy goals of the twenty first century.
The correlation between climate and energy rests on known causal relationships between human population growth, rising energy consumption and land use and the resulting greenhouse gas emissions and climate change. Environmental harm was caused early on during the industrial revolution, with air pollution being caused by soot coming from factories, as well as the greenhouse gas carbon dioxide being emitted into the atmosphere due to the burning of coal.
The concern for climate change control and mitigation has consequently spurred policy makers and scientists to treat energy use and global climate as an inextricable nexus with effects also going in reverse direction and create various initiatives, institutions and think tanks for a high-level treatment of the relationships. The varying approaches that are highly flawed and hold us back as a society when trying to stabilize the global climate include efficiency improvements, superconducting global electric grids, geoengineering, hydrogen production, storage, and transport.
Major Economies Forum on Energy and Climate Change (global)
Ministry of Climate, Energy and Utilities (Denmark)
Business for Innovative Climate and Energy Policy (US)
United States House Select Committee on Energy Independence and Global Warming (US)
European Union climate and energy package (EU)
Department of Energy and Climate Change (UK)
White House Office of Energy and Climate Change Policy (US)
Department of Climate Change, Energy, the Environment and Water (Australia)
Minister for the Environment and Water (Australia)
Climate Change and Sustainable Energy Act 2006
Wuppertal Institute for Climate, Environment and Energy (Germany)
Center for Climate and Energy Solutions (UK)
Energy Security and Net Zero Select Committee (UK)
San Diego Journal of Climate and Energy Law (US)
Renewable Energy Sources and Climate Change Mitigation (United Nations)
== See also ==
Environmental impact of the energy industry
Sustainable energy
Renewable energy
Energy policy
Energy industry
Climate policy
Water-energy nexus
Water, energy and food security nexus
Urbanization
== References == | Wikipedia/Climate_and_energy |
Energy is defined via work, so the SI unit of energy is the same as the unit of work – the joule (J), named in honour of James Prescott Joule and his experiments on the mechanical equivalent of heat. In slightly more fundamental terms, 1 joule is equal to 1 newton metre and, in terms of SI base units
1
J
=
1
k
g
(
m
s
)
2
=
1
k
g
⋅
m
2
s
2
{\displaystyle 1\ \mathrm {J} =1\ \mathrm {kg} \left({\frac {\mathrm {m} }{\mathrm {s} }}\right)^{2}=1\ {\frac {\mathrm {kg} \cdot \mathrm {m} ^{2}}{\mathrm {s} ^{2}}}}
An energy unit that is used in atomic physics, particle physics, and high energy physics is the electronvolt (eV). One eV is equivalent to 1.602176634×10−19 J.
In spectroscopy, the unit cm−1 ≈ 0.0001239842 eV is used to represent energy since energy is inversely proportional to wavelength from the equation
E
=
h
ν
=
h
c
/
λ
{\displaystyle E=h\nu =hc/\lambda }
.
In discussions of energy production and consumption, the units barrel of oil equivalent and ton of oil equivalent are often used.
== British imperial / US customary units ==
The British imperial units and U.S. customary units for both energy and work include the foot-pound force (1.3558 J), the British thermal unit (BTU) which has various values in the region of 1055 J, the horsepower-hour (2.6845 MJ), and the gasoline gallon equivalent (about 120 MJ).
The table illustrates the wide range of magnitudes among conventional units of energy. For example, 1 BTU is equivalent to about 1,000 joules, and there are 25 orders-of-magnitude difference between a kilowatt-hour and an electron-volt.
== Electricity ==
A unit of electrical energy, particularly for utility bills, is the kilowatt-hour (kWh); one kilowatt-hour is equivalent to 3.6 megajoules. Electricity usage is often given in units of kilowatt-hours per year or other periods. This is a measurement of average power consumption, meaning the average rate at which energy is transferred. One kilowatt-hour per year is around 0.11 watts.
== Natural gas ==
Natural gas is often sold in units of energy content or by volume. Common units for selling by energy content are joules or therms. One therm is equal to about 1,055 megajoules. Common units for selling by volume are cubic metre or cubic feet. Natural gas in the US is sold in therms or 100 cubic feet (100 ft3). In Australia, natural gas is sold in cubic metres. One cubic metre contains about 38 megajoules. In most of the world, natural gas is sold in gigajoules.
== Food industry ==
The calorie is defined as the amount of thermal energy necessary to raise the temperature of one gram of water by 1 Celsius degree, from a temperature of 14.5 °C, at a pressure of 1 atm. For thermochemistry a calorie of 4.184 J is used, but other calories have also been defined, such as the International Steam Table calorie of 4.1868 J. In many regions, food energy is measured in large calories (a large calory is a kilocalory, equal to 1000 calories), sometimes written capitalized as Calories. In the European Union, food energy labeling in joules is mandatory, often with calories as supplementary information.
== Atom physics and chemistry ==
In physics and chemistry, it is common to measure energy on the atomic scale in the non-SI, but convenient, units electronvolts (eV). One electronvolt (1 eV) is equivalent to the kinetic energy acquired by an electron in passing through a potential difference of 1 volt in a vacuum. It is common to use the SI magnitude prefixes (e.g. milli-, mega- etc) with electronvolts. Because of the relativistic equivalence between mass and energy, the eV is also sometimes used as a unit of mass. The Hartree (the atomic unit of energy) is commonly used in the field of computational chemistry since such units arise directly from the calculation algorithms without any need for conversion. Historically Rydberg units have been used.
== Spectroscopy ==
In spectroscopy and related fields it is common to measure energy levels in units of reciprocal centimetres. These units (cm−1) are strictly speaking not energy units but units proportional to energies, with
h
c
∼
2
⋅
10
−
23
J
c
m
{\displaystyle \ hc\sim 2\cdot 10^{-23}\ \mathrm {J} \ \mathrm {cm} }
being the proportionality constant.
== Explosions ==
A gram of TNT releases 4,100 to 4,600 joules (980 to 1,100 calories) upon explosion. To define the tonne of TNT, this was standardized to 1 kilocalorie (4,184 joules) giving a value of 4.184 gigajoules (1 billion calories) for the tonne of TNT.
== See also ==
Energy consumption
Conversion of units of temperature
Conversion of units of energy, work, or amount of heat
Kilokaiser
List of unusual units of measurement
Maximum demand indicator
Orders of magnitude (energy)
erg
Foe (unit)
== References == | Wikipedia/Unit_of_energy |
Energy subsidies are measures that keep prices for customers below market levels, or for suppliers above market levels, or reduce costs for customers and suppliers. Energy subsidies may be direct cash transfers to suppliers, customers, or related bodies, as well as indirect support mechanisms, such as tax exemptions and rebates, price controls, trade restrictions, and limits on market access.
During FY 2016–22, most US federal subsidies were for renewable energy producers (primarily biofuels, wind, and solar), low-income households, and energy-efficiency improvements. During FY 2016–22, nearly half (46%) of federal energy subsidies were associated with renewable energy, and 35% were associated with energy end uses. Federal support for renewable energy of all types more than doubled, from $7.4 billion in FY 2016 to $15.6 billion in FY 2022.
The International Renewable Energy Agency tracked some $634 billion in energy-sector subsidies in 2020, and found that around 70% were fossil fuel subsidies. About 20% went to renewable power generation, 6% to biofuels and just over 3% to nuclear.
== Overview of all sources of energy ==
If governments choose to subsidize one particular source of energy more than another, that choice can impact the environment. That distinguishing factor informs the below discussion on all energy subsidies of all sources of energy in general.
Main arguments for energy subsidies are:
Security of supply – subsidies are used to ensure adequate domestic supply by supporting indigenous fuel production in order to reduce import dependency, or supporting overseas activities of national energy companies, or to secure the electricity grid.
Environmental and health improvement – subsidies are used to improve health by reducing air pollution, and to fulfill international climate pledges. For example the IEA says the purchase price of heat pumps should be subsidized.
Economic benefits – subsidies in the form of reduced prices are used to stimulate particular economic sectors or segments of the population, e.g. alleviating poverty and increasing access to energy in developing countries. With regards to fossil fuel prices in particular, Ian Parry, the lead author of a 2021 IMF report said, "Some countries are reluctant to raise energy prices because they think it will harm the poor. But holding down fossil fuel prices is a highly inefficient way to help the poor, because most of the benefits accrue to wealthier households. It would be better to target resources towards helping poor and vulnerable people directly."
Employment and social benefits – subsidies are used to maintain employment, especially in periods of economic transition. In 2021, with regards to fossil fuel prices in particular, Ipek Gençsü, at the Overseas Development Institute, said: "[Subsidy reform] requires support for vulnerable consumers who will be impacted by rising costs, as well for workers in industries which simply have to shut down. It also requires information campaigns, showing how the savings will be redistributed to society in the form of healthcare, education and other social services. Many people oppose subsidy reform because they see it solely as governments taking something away, and not giving back."
Main arguments against energy subsidies are:
Some energy subsidies, such as the fossil fuel subsidies (oil, coal, and gas subsidies), counter the goal of sustainable development, as they may lead to higher consumption and waste, exacerbating the harmful effects of energy use on the environment, create a heavy burden on government finances and weaken the potential for economies to grow, undermine private and public investment in the energy sector. Also, most benefits from fossil fuel subsidies in developing countries go to the richest 20% of households.
Impede the expansion of distribution networks and the development of more environmentally benign energy technologies, and do not always help the people that need them most.
The study conducted by the World Bank finds that subsidies to the large commercial businesses that dominate the energy sector are not justified. However, under some circumstances it is reasonable to use subsidies to promote access to energy for the poorest households in developing countries. Energy subsidies should encourage access to the modern energy sources, not to cover operating costs of companies. The study conducted by the World Resources Institute finds that energy subsidies often go to capital intensive projects at the expense of smaller or distributed alternatives.
Types of energy subsidies are below. ("Fossil-fuel subsidies generally take two forms. Production subsidies...[and]...consumption subsidies."):
Direct financial transfers – grants to suppliers; grants to customers; low-interest or preferential loans to suppliers.
Preferential tax treatments – rebates or exemption on royalties, duties, supplier levies and tariffs; tax credit; accelerated depreciation allowances on energy supply equipment.
Trade restrictions – quota, technical restrictions and trade embargoes.
Energy-related services provided by government at less than full cost – direct investment in energy infrastructure; public research and development.
Regulation of the energy sector – demand guarantees and mandated deployment rates; price controls; market-access restrictions; preferential planning consent and controls over access to resources.
Failure to impose external costs – environmental externality costs; energy security risks and price volatility costs.
Depletion Allowance – allows a deduction from gross income of up to ~27% for the depletion of exhaustible resources (oil, gas, minerals).
Overall, energy subsidies require coordination and integrated implementation, especially in light of globalization and increased interconnectedness of energy policies, thus their regulation at the World Trade Organization is often seen as necessary.
== Support for new technology ==
Early support of solar power by the United States and Germany greatly helped renewable energy commercialization to reduce greenhouse gas emissions worldwide, but may not have helped local manufacturing. Support for nuclear fusion continues, although it is not expected to be commercially viable in time to contribute to countries net zero targets. Energy storage research is also supported.
== Fossil fuel subsidies ==
== See also ==
Fossil fuel subsidies
Corporate welfare
Building-integrated photovoltaics
Government subsidies
Feed-in tariff
Gasoline subsidies
Renewable Energy Certificates
Renewable energy commercialization
Renewable energy payments
Stranded assets
Financial incentives for photovoltaics
== References ==
== Bibliography ==
Difiglio, Prof. Carmine; Güray, Bora Şekip; Merdan, Ersin (November 2020). Turkey Energy Outlook. iicec.sabanciuniv.edu (Report). Sabanci University Istanbul International Center for Energy and Climate (IICEC). ISBN 978-605-70031-9-5.
== External links ==
Fossil Fuel Subsidy Tracker- a collaboration between the Organisation for Economic Co-operation and Development (OECD) and the International Institute for Sustainable Development (IISD)
Global Subsidies Initiative - a project of the International Institute for Sustainable Development
OECD-IEA analysis of fossil fuels and other support - OECD
European countries spend billions a year on fossil fuel subsidies, survey shows (2017) | Wikipedia/Energy_subsidies |
The Alliance to Save Energy is a bipartisan, nonprofit coalition of business, government, environmental, and consumer groups based in Washington, D.C. The Alliance states that it advocates for "energy-efficiency policies that minimize costs to society and individual consumers, and that lessen greenhouse gas emissions and their impact on the global climate." The Alliance's chief activities include public relations, research, and lobbying to change U.S. energy policy.
The Alliance was established on March 18, 1977, with the support of then U.S. President Jimmy Carter. It was the initiative of Senators Charles Percy (R-Ill.) and Hubert Humphrey (D-Minn.).
== Member organizations ==
The Alliance includes more than 100 organizations committed to energy efficiency as a primary way to achieve the nation's environmental, economic, energy security, and affordable housing goals. Members include a wide variety of companies, nonprofits, industry groups, and government organizations.
== Federal policy ==
The Alliance's primary activity is developing, vetting, and advocating for federal, bipartisan energy efficiency policies. Areas of policy work include tax incentives for energy efficiency, appropriations for federal energy efficiency programs at the Department of Energy's Office of Energy Efficiency & Renewable Energy and the Environmental Protection Agency, clean transportation solutions, federal energy management, funding for research and development, and more.
Over its four decades of work, the Alliance has had a hand in shaping of number of significant pieces of energy legislation. In recent years, these have included the Energy Act of 2020, the American Recovery and Reinvestment Act of 2009, the Energy and Tax Extenders Act of 2008, the Energy Independence and Security Act of 2007, the Energy Policy Act of 2005, the Energy Policy Act of 1992, and the National Appliance Energy Conservation Act of 1987. The Alliance also applauded the enactment of the Paris Climate Agreement in 2015.
=== 117th Congress ===
The Alliance states that it supports a suite of energy efficiency policies designed to both reduce carbon emissions and fuel economic recovery in the wake of the COVID-19 pandemic. In August 2021, the Alliance supported the introduction of the Main Street Efficiency Act of 2021 in the House by Rep. Peter Welch (D-Vt.) and in the Senate by Sen. Catherine Cortez Masto (D-Nev.). The bill would, "require the Secretary of Energy to establish a grant program to incentivize small business participation in demand side management programs."
The Alliance additionally supported the introduction of the Open Back Better Act of 2021 by Rep. Lisa Blunt Rochester (D-Del.) and Sen. Tina Smith (D-Minn.), which would "provide grants to federal and state agencies and tribal organizations to implement building projects that increase resiliency, energy efficiency, renewable energy, and grid integration."
Additional legislation supported by the Alliance in the 117th Congress includes the HOPE for HOMES Act, NO EXHAUST Act, and the Blue Collar to Green Collar Jobs Development Act.
== Alliance to Save Energy initiatives ==
=== 50x50 ===
The Alliance convened the 50x50 Commission on U.S. Transportation Sector Efficiency from 2017 to 2019 with the stated goal to reduce energy use in the transportation sector 50% by 2050. The Commission released two reports, "50x50: Reinventing U.S. Mobility," and "Building the Foundation for 50x50: A Policy Proposal for Infrastructure and Surface Transportation Authorization." Following release of the latter, the 50x50 Transportation Action Network was formed to implement the recommendations from the reports. The recommendations include a number of federal policy actions intended to encourage electric vehicle adoption, invest in sustainable infrastructure, improve port and airport efficiency, strengthen public transit and rail systems, and accelerate research and development.
=== Active Efficiency ===
In September 2019, the Alliance launched the Active Efficiency Collaborative, a group of industry leaders, NGOs, and public sector institutions that works to accelerate the adoption of Active Efficiency. Active Efficiency optimizes the use of energy by integrating the benefits of traditional energy efficiency measures with the opportunities presented by digital technologies. The Collaborative aims to take advantage of new advances in the energy sector, including digitalization, distributed energy resources, beneficial electrification, and smart devices to achieve deeper decarbonization and reduced energy burdens. According to the initiative's website, its activities include "deepening collaboration among stakeholders, cultivating champions, and developing strategies and policies to scale up Active Efficiency." In 2021, the Collaborative was chaired by Sarah Orban Salati of the New York Power Authority and Bert Van Hoof of Microsoft.
=== CarbonCount ===
CarbonCount is a metric developed by the Alliance to Save Energy that quantifies the impact of investments in U.S.-based energy-efficiency and renewable-energy projects given the expected reduction in carbon dioxide (CO2) emissions resulting from each $1,000 of investment. In 2015, Bloomberg New Energy Finance honored CarbonCount with its Finance for Resilience (FiRE) award. FiRE is an open and action-oriented platform that collects, develops and helps implement powerful ideas to accelerate finance for clean energy, climate, sustainability and green growth. FiRe singles out ideas that have the potential for incremental finance of at least $1bn in clean energy in the first three years of implementation, that are achievable within 1–3 years. Hannon Armstrong's 2015 issuance of Sustainable Yield Bonds secured by a portion of its utility scale solar and wind real estate related assets was the first investment to be certified under the CarbonCount methodology, receiving a CarbonCount score of 0.39 metric tons of CO2 offset per $1000 of investment. In 2016, Deutsche Bank received a CarbonCount score of 0.18 metric tons of CO2 offset per $1000 of investment in a portfolio of rooftop solar PV systems.
=== EmPowered Schools ===
Since 1996, the Alliance has led energy efficiency education programs in schools. In 2021, the EmPowered Schools program was active in more than 200 schools across the country, teaching students the fundamentals of energy efficiency and about opportunities in green careers. According to the Alliance, schools that participate in the EmPowered program generally see 5-15% energy savings on their energy bills.
=== Energy Efficiency Forums and Summits ===
The Alliance hosts an annual forum for leaders in energy efficiency. The Energy Efficiency Global Forum website states that the event, "brings together the brightest minds in energy efficiency to discuss pressing issues, identify emerging trends, and connect with peers from dozens of countries around the globe." The forum is typically hosted in Washington, D.C., but in 2018 it was held in Copenhagen, and in 2020 and 2021 it took place virtually due to the COVID-19 pandemic. The Alliance recently hosted Policy Summits in 2020 and 2022 with a focus on federal energy policies and priorities.
=== Stars of Energy Efficiency Awards ===
Since 1993, the Alliance has awarded progress in energy efficiency with its annual Star of Energy Efficiency Awards. Typically awarded at an annual dinner gala in Washington, D.C., winners have included individuals, government organizations, corporations, nonprofits, and utilities who demonstrated a commitment to advancing energy efficiency.
== Board of directors ==
The Alliance to Save Energy board includes CEOs, presidents, and senior executives of companies, associations, consumer, and environmental organizations, as well as officials from state government, universities, and law firms.
The first board of directors and board of advisors were chaired by Senator Percy and Henry A. Kissinger, respectively. Honorary chairmen included Senators Daniel J. Evans, H. John Heinz III and Timothy E. Wirth.
The current board Honorary Board of Advisors is chaired by Sen. Jeanne Shaheen (D-N.H.). Sen. Rob Portman (R-Ohio) and Sen. Chris Coons (D-Del.) serve as honorary vice-chairs. Honorary Board members include Rep. Michael Burgess, M.D. (R-Texas), Sen. Susan M. Collins (R-Maine), Rep. Mike Kelly (R-Pa.), Rep. Adam Kinzinger (R-Ill.), Sen. Edward Markey (D-Mass.), Rep. David McKinley (R-W. Va.), Sen. Lisa Murkowski (R-Alaska), Rep. Bobby Rush (D-Ill.), Rep. Paul Tonko (D-N.Y.), Sen. Mark Warner (D-Va.), Rep. Peter Welch (D-Vt.), Sen. Ron Wyden (D-Ore.), and Kandeh Yumkella.
The Board of Directors is chaired by Georgia Power President, Chairman, and CEO Christopher Womack. Other officers include Puget Sound Energy President and CEO Mary Kipp, Johnson Controls Vice President of Global Consumer Relations Katie McGinty, EnerGreen Capital Management LLC Founder and Managing Partner Carolyn Green, and Alliance President Paula Glover.
The Chair Emeritus is Gil Quiniones, CEO of ComEd.
== See also ==
Energy conservation
Energy conversion efficiency
Sustainable energy
Energy poverty
== References ==
== External links ==
Official website | Wikipedia/Alliance_to_Save_Energy |
Community wind projects are locally owned by farmers, investors, businesses, schools, utilities, or other public or private entities who utilize wind energy to support and reduce energy costs to the local community. The key feature is that local community members have a significant, direct financial stake in the project beyond land lease payments and tax revenue. Projects may be used for on-site power or to generate wholesale power for sale, usually on a commercial-scale greater than 100 kW.
== Community wind farms ==
=== Australia ===
The Hepburn Wind Project is a wind farm at Leonards Hill near Daylesford, Victoria, north-west of Melbourne, Victoria. It comprises two 2MW wind turbines which produce enough power for 2,300 households.
This is the first Australian community-owned wind farm. The initiative has emerged because the community felt that the state and federal governments were not doing enough to address climate change.
Telecommunication towers will be repowered with small wind turbines under a new project led by a Newcastle startup. Ten small wind turbines will be installed at ten remote Australian communication sites as part of a new project to boost the uptake of the technology.
=== Canada ===
Community wind power is in its infancy in Canada but there are reasons for optimism. One such reason is the launch of a new Feed-in Tariff (FIT) program in the Province of Ontario . A number of community wind projects are in development in Ontario but the first project that is likely to obtain a FIT contract and connect to the grid is the Pukwis Community Wind Park. Pukwis will be unique in that it is a joint Aboriginal/Community wind project that will be majority-owned by the Chippewas of Georgina Island First Nation, with a local renewable energy co-operative (the Pukwis Energy Co-operative) owning the remainder of the project.
=== Denmark ===
In Denmark, families were offered a tax exemption for generating their own electricity within their own or an adjoining commune. By 2001 over 100,000 families belonged to wind turbine cooperatives, which had installed 86% of all the wind turbines in Denmark, a world leader in wind power. Wind power has gained very high social acceptance in Denmark, with the development of community wind farms playing a major role.
In 1997, Samsø won a government competition to become a model renewable energy community. An offshore wind farm comprising 10 turbines (making a total of 21 altogether including land-based windmills), was completed, funded by the islanders. Now 100% of its electricity comes from wind power and 75% of its heat comes from solar power and biomass energy. An Energy Academy has opened in Ballen, with a visitor education center.
=== Germany ===
In Germany, hundreds of thousands of people have invested in citizens' wind farms across the country and thousands of small and medium-sized enterprises are running successful businesses in a new sector that in 2008 employed 90,000 people and generated 8 percent of Germany's electricity. Wind power has gained very high social acceptance in Germany, with the development of community wind farms playing a major role.
In the German district of North Frisia there are more than 60 wind farms with a capacity of about 700 MW, and 90 percent are community-owned. North Frisia is seen to be a model location for community wind, leading the way for other regions, especially in southern Germany.
=== India ===
Starting in 2006, a village panchayat (local self-governing body) in Tamil Nadu state has become completely self-sufficient in energy by using renewable sources like wind, solar and biogas.
The Odanthurai village panchayat near Coimbatore city comprises 11 villages and has a population of about 8,000. By 2009, it had set up its own 350 kW windfarm to meet its energy needs. The windmill was set up at Malwadi near Udumalpet and generates about 8 lakh (800,000) units annually. The power requirement for Odanthurai stands at about 4.5 lakh (450,000) units, and the local panchayat body is now selling the surplus power to the state grid. This gives the panchayat an annual income of 19 lakh rupees.
The village cooperative is also using other sources of renewable energy. It has 65 solar streetlights in two hamlets and a nine-KW (kilowatt) biomass gasifier to pump drinking water from the river to the overhead tanks. Doing so, Odanthurai became the first local body in India to utilize the remunerative enterprises' scheme of the state government.
=== The Netherlands ===
Sixty-three farmers in "De Zuidlob", the southern part of the municipality of Zeewolde, have entered into a cooperative agreement that aims to develop a wind farm of at least 108 MW. The project will include the installation of three phases of 12 wind turbines with capacities of 3 to 4.5 MW each. The aim is to put the wind farm into service in 2012.
The Netherlands has an active community of wind cooperatives. They build and operate wind parks in all regions of the Netherlands. This started in the 1980s with the first Lagerweij turbines. Back then, these turbines could be financed by the members of the cooperatives.
Today, the cooperatives build larger wind parks, but not as large as commercial parties do. Some still operate self-sufficiently, others partner with larger commercial wind park developers.
Because of the very unproductive state policies for financing wind parks in the Netherlands, the cooperatives have developed a new financing model, where members of a cooperative do not have to pay taxes for the electricity they generate with their community wind park.
In this construction the Zelfleveringsmodel the cooperative operates the wind park, and a traditional energy company only acts as a service provider, for billing and energy balance on the public grid.
This is the new role for energy companies in the future, where production is largely decentralized.
In 2012 a new company launched a new business model for community energy, Windcentrale. The wind turbine is sold in physical shares to families. Every share does not give financial gains, but real power, 500 kWh per year, average. A power company, part of the model, subtracts the generated amount of power, from the yearly power bill. Owners only have to pay for the power they used in excess of the amount their share generated. The Windcentrale started with 2 existing turbines that were sold in about 3 months. 8 months later they sold a turbine in a single evening. By the end of 2016 they were a community of about 17.000 members with 10 turbines and about 15 MW rated power. Every turbine is owned by a separate cooperative, with the Windcentrale doing all organizational work in the cooperative. In three years they grew to the same size, in members, than older wind cooperatives with the average age of 25 years. Two of these older wind cooperatives, DeltaWind and Zeeuwind are run as a business and are building a 100 MW wind farm in Krammer
=== United Kingdom ===
As of 2012, there are 43 communities that are in the process of or already producing renewable energy through co-operative structures in the UK. They are set up and run by everyday people, mostly local residents, who are investing their time and money and together installing large wind turbines, solar panels, or hydro-electric power for their local communities.
Baywind Energy Co-operative was the first co-operative to own wind turbines in the United Kingdom. Baywind was modeled on the similar wind turbine cooperatives and other renewable energy co-operatives that are common in Scandinavia, and was founded as an industrial and provident society in 1996. It grew to exceed 1,300 members, each with one vote.
A proportion of the profits is invested in local community environmental initiatives through the Baywind Energy Conservation Trust. As of 2006, Baywind owns a 2.5 megawatt five-turbine wind farm at Harlock Hill near Ulverston, Cumbria (operational since 29 January 1997), and one of the 600 kilowatt turbines at the Haverigg II wind farm near Millom, Cumbria.
Community-owned schemes in Scotland include schemes Harris in the Outer Hebrides and on the Isle of Gigha. The Heritage Trust set up Gigha Renewable Energy to buy and operate three Vestas V27 wind turbines, known locally as The Dancing Ladies or Creideas, Dòchas is Carthannas (Gaelic for Faith, Hope and Charity). They were commissioned on 21 January 2005 and are capable of generating up to 675 kW of power. Revenue is produced by selling the electricity to the grid via an intermediary called Green Energy UK. Gigha residents control the whole project and profits are reinvested in the community. The North Harris Trust has installed several turbines on Harris.
Another community-owned wind farm, Westmill Wind Farm Cooperative, opened in May 2008 in the Oxfordshire village of Watchfield. It consists of five 1.3 megawatt turbines, and is described by its promoters as the UK's largest community-owned wind farm. It was structured as a cooperative, whose shares and loan stock were sold to the local community. Other businesses, such as Midcounties Co-operative, also invested, and the Co-operative Bank provided a loan.
Community Energy Scotland is an independent Scottish charity established in 2008 that provides advice and financial support for renewable energy projects developed by community groups in Scotland. The stated aim of Community Energy Scotland is 'to build confidence, resilience and wealth at community level in Scotland through sustainable energy development'.
Findhorn Ecovillage has four Vestas wind turbines that can generate up to 750 kW. These make the community net exporters of renewable-generated electricity. Most of the generation is used on-site with any surplus exported to the National Grid.
Boyndie Wind Farm Co-operative is part of the Energy4All group, which promotes community ownership. A number of other schemes supported by Highlands and Islands Community Energy Company are in the pipeline.
Community Renewable Energy (CoRE) has worked with Berwick Community Development Trust who agreed on the installation of a 500 kW Enercon turbine near the A1. The Trust now has an income of £60,000 a year (increasing) after the turbine was installed in 2014. CoRE supported Oakenshaw Community Association setting up a 500 kW wind turbine near Durham. The turbine begun operating in 2014 and the Association now receives substantial yearly income.
Unity Wind Ltd is an industrial and provident society that intends to install two 2MW wind turbines at North Walsham in North Norfolk. Its key aim is community wind turbines and run by community investment and for financial benefit to the community.
=== United States ===
In 2009, the National Renewable Energy Laboratory published a report that identified three different types of community wind projects in the United States. The first model describes a project owned by a municipal utility, such as the Hull Wind Project in Massachusetts. The second model is a wind project that is jointly owned by local community members, such as the MinWind Projects near Luverne, Minnesota. The third type is a flip-style ownership. This model allows local investors to partner with a corporation in order to take advantage of Production Tax Credit federal incentives. Flip projects have been built in Minnesota and Texas.
== Business models ==
=== Community shared ownership ===
In a community-based model, the developer/manager of a wind farm shares ownership of the project with area landowners and other community members. While the renewables sector often spearheads shared ownership initiatives, communities can proactively invite participation from renewable energy firms. This mutually beneficial collaboration can prove advantageous for both sides. Property owners whose land was used for the wind farm are generally given a choice between a monthly cash lease and ownership units in the development.
=== Cooperative ===
A wind turbine cooperative, also known as a wind energy cooperative, is a jointly owned and democratically controlled enterprise that follows the cooperative model, investing in wind turbines or wind farms. The cooperative model was developed in Denmark. The model has also spread to Germany, the Netherlands, Australia and United Kingdom, with isolated examples elsewhere. At a European level, REScoop.eu advocates for renewable energy cooperatives to have fair access to the market, linking individual cooperatives and federations under its umbrella, representing around 1,000,000 citizens and 1,500 cooperatives.
=== Municipal ===
Some places have enacted policies to encourage development of municipally owned and operated wind turbines on town land. These projects are publicly owned and tax exempt. An example is the Hull Wind One project in Massachusetts' Boston Harbor in 2001. A 660 kW wind turbine was installed, and is still a great example of small scale commercial wind.
== Impacts of community wind energy ==
=== Economic ===
Once a wind farm project is established in a community, jobs are needed for: manufacturing the materials needed to build the project, transportation of supplies to the project area, and construction of the project as well as building roads leading to the project. After the project is complete, jobs will be needed to maintain and operate the facility. According to a study by the New York State Energy Research and Development Authority, wind energy produces 27% more jobs per kilowatt-hour than coal plants and 66% more jobs than natural gas plants. 3. Landowners will also collect revenues for hosting turbines on their property. Given a typical wind turbine spacing requirements, a 250-acre farm could increase annual farm income by $14,000 per year with little effect on their normal farming and ranching operations. 4. Community wind energy projects increase local property tax revenue because there was very little to be taxed previously due to the sparse population and vast farm land. Once the wind turbines are in service they are taxed, creating much needed revenue for the local community.
=== Social ===
The Midwest and the Great Plains regions in the United States are ideal areas for community wind energy projects; they are also often prone to drought. Fossil fuel plants use large amounts of water for cooling purposes which is detrimental to communities' water supply if there is a drought. Wind turbines do not use any water since there is no considerable amount of heat produced during energy generation. Wind energy adds power to the electric grid which decreases the amount of oil needed to generate a community's electricity. Local land owners, who produce the wind energy, can also control the amount of energy produced, which expands the regional energy mix. Overall community wind energy reduces the local community's dependence on oil but, because of the subsidies involved, can greatly increase their costs for electricity.
Typically, the ideal form of a community wind energy project is created by and for local people. Community wind energy in a social scope can be seen as strong or weak based on how farms prioritize social motivations, what local benefits they produce, and how well they respond to local energy demand. The planning process for onshore community wind farms has low success rates. Difficulties arise from local government authorities' decisions on what counts as a representative community group, limiting community projects to more minor scales. Developing community wind energy faces barriers such as uncoordinated organizational structures, local authority decisions, and intricate planning requirements. Community-led projects demand substantial efforts and expertise, often comparable to commercial developments. Intermediaries like NGOs or private professionals help bridge relationships between local communities and big companies. Collaboration challenges arise because large companies require majority stakes in projects.
Perceived inequity in the distribution of costs and benefits of wind energy projects often show up in survey responses to new projects. Studies report that rural communities often have concerns they will disproportionately share the burden of energy produced for urban areas. Community-owned wind projects often receive substantially more support from local communities than corporate wind projects due to the perceived even distribution of impacts and economic benefits. Involving residents as investors or shareholders in these projects has increased acceptance and public support. The flexibility of applications for community wind projects may play a role in garnering higher levels of support from residents. An example is Kiowa County Memorial Hospital in Greensburg, Kansas, which installed a second wind turbine. It shows the success and satisfaction that can come with community wind initiatives.
Community wind energy involves diverse activities such as electricity generation, heat generation, energy efficiency, collective purchasing, storage, transport, education, and awareness. There is a debated focus on understanding factors encouraging community participation. A sense of belonging to a place-based community is often noted as necessary for voluntary engagement in community renewable energy projects. Participation experiences and outcomes are not universally positive, and there are accessibility concerns that community wind energy may favor affluent communities.
Community wind projects can offer benefits in stabilizing energy prices for local communities. Due to the absence of fuel costs and relatively low operating expenses, the owners of these projects can accurately predict their energy costs over the project's lifetime. The projects can generate energy utilized locally or sold to local utilities through fixed-rate power purchase agreements, ensuring long-term stability in energy prices. This can be advantageous in regions where high electricity costs result from fuel imports, as community wind projects can help stabilize or even reduce energy expenses. Community wind projects find applications in many sectors, such as schools, hospitals, businesses, farms, ranches, and community facilities, providing a local source of electricity. Ownership of community wind projects can extend to rural electric cooperatives, municipal utilities, or groups of local individuals forming limited liability corporations. This ownership model allows local communities to participate actively and benefit from wind power initiatives.
=== Environmental ===
Compared to the environmental impact of traditional energy sources, the environmental impact of wind power is relatively minor. Wind power consumes no fuel, and emits no air pollution, unlike fossil fuel power sources. The energy consumed to manufacture and transport the materials used to build a wind power plant is equal to the new energy produced by the plant within a few months. While a wind farm may cover a large area of land, many land uses such as agriculture are compatible, with only small areas of turbine foundations and infrastructure made unavailable for use.
There are reports of bird and bat mortality at wind turbines as there are around other artificial structures. The scale of the ecological impact may or may not be significant, depending on specific circumstances. Prevention and mitigation of wildlife fatalities, and protection of peat bogs, affect the siting and operation of wind turbines.
There are anecdotal reports of negative effects from noise on people who live very close to wind turbines. Peer-reviewed research has generally not supported these statements.
== Policy, issues, and legislation ==
In 1992, the renewable energy production tax credit of 2.1 cents per kilowatt-hour was established. In February 2009, through the American Recovery and Reinvestment Act, Congress acted to provide a three-year extension of the PTC through December 31, 2012.
Wind projects that were up and running in 2009 and 2010 can choose to receive a 30% investment tax credit instead of the PTC. The investment tax credit is also an option for wind projects that are in service before 2013 if the final construction is complete before the end of 2010. Smaller wind farms (100 kW or less) can receive a credit for 30% towards the cost of installment of the system. The ITC, written into law through the Emergency Economic Stabilization Act of 2008, is available for equipment installed from October 3, 2008 through December 31, 2016. The value of the credit is now uncapped, through the American Recovery and Reinvestment Act of 2009.
In order to ensure wind energy's future in the energy market, the renewable electricity standard (RES) is a policy in which market mechanisms guarantee a growing percentage of electricity produced comes from renewable sources, like wind energy. The RES exists in 28 states (not at a national level). An example is the Obama-Biden New Energy for America plan, which sets future goals of rapid renewable energy production at 10% by 2012.
A pressing issue of concern is the lack of a modern interstate transmission grid which delivers carbon free electricity to customers. Currently the US Senate and the Natural Resources Committee have reported the bill out of committee on June 17, 2009. A combined energy and climate bill is expected to be considered by the full Senate this fall. In the US House of Representatives the House Energy and Commerce Committee approved a comprehensive energy and climate bill on May 21, 2010.
The clean air and climate change policy is goal to switch from fossil fuel energy sources to renewable carbon-free energy sources for electricity production. Generating 20% of U.S. electricity from wind would be the climate equivalent of removing 140 million vehicles from the roadways. Currently the US Senate Committee on Environmental and Public Works has control over the legislation and will begin to complete a markup by September 25, 2009. The House of Representatives passed the American Clean Energy and Security Act on June 26, 2009, comprising a provision to reduce carbon dioxide emissions 17% below 2005 levels by 2020 and 83% below 2005 levels by 2050. It also allocates a portion of the allowances given away for free to energy efficiency and renewable energy. However, the allowances flow through state governments rather than directly to renewable generators.
Overall federal funding for community wind research and development is insufficient and even more so when compared to other fuels and energy sources. In 2009 the US Department of Energy (DOE) received $118 million from the American Recovery and Reinvestment Act for wind energy research and development. In 2010 the Senate passed a bill granting the DOE $85 million for the DOE wind program. For the same purpose, the House of Representatives allowed the DOE $70 million.
== See also ==
List of onshore wind farms
Native Wind
Community solar farm
== Further reading ==
World Wind Energy Association's community wind website
U.S. Department of Energy Community Wind Fact Sheet
Windustry
AWEA Community Wind Projects
== Notes == | Wikipedia/Community_wind_energy |
The Energy Efficiency Directive 2012/27/EU (abbreviated EED) is a European Union directive which mandates energy efficiency improvements within the European Union. It was approved on 25 October 2012 and entered into force on 4 December 2012.: 2 The directive introduces legally binding measures to encourage efforts to use energy more efficiently in all stages and sectors of the supply chain. It establishes a common framework for the promotion of energy efficiency within the EU in order to meet its energy efficiency headline target of 20% by 2020. It also paves the way for further improvements thereafter.
The directive provides for the establishment of indicative national energy efficiency targets for 2020. Member states were to have submitted their National Energy Efficiency Action Plans (NEEAP) by 30 April 2014, outlining the measures they have implemented to improve energy efficiency and their expected and/or achieved energy savings. In addition, member states are required to report annually on progress toward their national targets. The policy requirements in the directive are minimum obligations and member states may introduce more stringent measures.
The Energy Efficiency Directive 2012/27/EU was preceded by the Energy Services Directive 2006/32/EC. This earlier directive contained a target of a 9% reduction in energy usage within 9 years of the directive coming into force. The earlier directive also required EU members to submit National Energy Efficiency Action Plans, with the first plan to be lodged by 30 June 2007.
On 23 July 2014, the European Commission announced a new target of a 30% improvement in energy efficiency by 2030.
== Development ==
Documents leaked in mid-2012 show that the United Kingdom repeatedly fought to water down key measures during the development of the directive and forced some measures to become voluntary rather than mandatory. As a result, a new version of the directive allows member states to set their own energy efficiency targets, instead of the original requirement of a mandatory EU-wide target of 20% improvement.
== Measures ==
The directive promotes rules to remove barriers in energy markets and to overcome market failures that may impede the uptake of energy efficiency. Under the directive, the public sector is to play an exemplary role and consumers will have a right to know how much energy they consume.
The following categories are covered by the directive:
energy efficiency targets
building renovation
an exemplary role for public buildings
energy efficiency obligation schemes
energy audits and energy management systems
metering and billing information systems and the right to access this data
consumer information and empowerment
promotion of efficiency in heating and cooling
energy transformation, transmission, and distribution
availability of qualification, accreditation, and certification schemes
information and training
energy services
an energy efficiency national fund, financing, and technical support
other measures to promote energy efficiency
== National Energy Efficiency Action Plans and Annual Reports ==
Individual National Energy Efficiency Action Plans (NEEAP) for 2014 and Annual Reports for 2016 are available for download. Some national action plans have Wikipedia articles as well:
German National Action Plan on Energy Efficiency
== Reception and effectiveness ==
A 2014 study finds that, despite the directive being technically complex and lacking binding targets, it is an improvement over earlier European Union policy on energy efficiency. Notwithstanding, the document is weakened by the number of exemptions and the number of passages it contains requiring interpretation. The process of implementation was also subject to problems.: 3–4
In June 2014 the UK government directed through a Procurement Policy Note issued to all government departments that they were to comply after 5 June 2014 with the energy efficiency standards of Article 6 and Annex III to the Directive when purchasing goods and services and when renting or purchasing buildings, as long as this is "consistent with achieving value for money, economic
feasibility, wider sustainability, technical suitability and ensuring sufficient competition". Further information issued in January 2015 made clear that "the obligation under Article 6 is a qualified one" and that public bodies "need only buy to the standards set out in Annex III of the Directive where this is cost effective". Public bodies in the wider public sector outside of central government were "encouraged" to follow the central government example.
A 2016 study examined the treatment of article 7 of the directive: 15 by each of the 28 member states. Titled Energy efficiency obligation schemes, this key article requires that countries "implement energy efficiency obligations and/or alternative policy instruments in order to reach a reduction in final energy use of 1.5% per year".: 1 To fulfill this requirement, the member states have proposed very different policy measures and adopted very different calculation methods and monitoring and verification schemes. The study analyses each national action plan and estimates whether the projected savings are likely to materialise and whether these will be sufficient to meet the article 7 target.
== Future developments ==
Directive 2018/2002/EC was adopted on 21 December 2018. It amends this one.
== See also ==
Energy conservation
Energy efficiency in Europe (study) – a study as part of the Odyssee Mure project
Energy efficiency in Europe § National Energy Efficiency Action Plans
Energy policy of the European Union
Energy Taxation Directive
EU Renewable Energy Directive 2009/28/EC – a similar directive covering renewable energy
European Union directive
German National Action Plan on Energy Efficiency (abbreviated NAPE)
List of European Union directives
White certificates – which certify a reduction in energy consumption
== Further reading ==
Directive 2012/27/EU of the European Parliament and of the Council of 25 October 2012 on energy efficiency, amending Directives 2009/125/EC and 2010/30/EU and repealing Directives 2004/8/EC and 2006/32/EC. Brussels, Belgium: European Council. 14 November 2012. Retrieved 20 September 2016.
== References ==
== External links ==
Complete list of National Energy Efficiency Plans and Annual Reports.
European Commission Energy Efficiency Directive website
Odyssee Mure energy efficiency monitoring project for Europe | Wikipedia/EU_Energy_Efficiency_Directive_2012 |
The term energy input labeling involves producers of goods and services determining the amount of energy used to produce their product and then including that information on their product packaging. Energy input labeling is sometimes known by the acronym EIL. Energy input labeling provides the advantage of knowing how much energy was used to produce a product, but it does not indicate how much energy a product uses to operate, such as the European Union energy label or the Energy rating label used in Australia and New Zealand, and is not in itself a standard for energy efficiency such as Energy Saving Trust Recommended or Energy Star.
== History ==
Energy input labeling originated as a project by several energy and economics activists to explore energy accounting.
== Usage in industry ==
Energy input labeling is intended to be easy for producers to implement, At minimum, they can report and label the energy used by their firm to produce products, which is called "Energy Inputs Added", sometimes merely "Energy Added." If a firm is able to also account for all of the energy imputed by its suppliers, then a firm can report and label "Total Energy Inputs" or "Total Energy", but this is rare. Energy Input Labeling is being used and further developed by the European Organization for Sustainability.
== By country ==
=== Japan ===
In Japan, the Top Runner Program is run, in which new appliances are regularly tested on efficiency, and the most efficient ones are made the standard.
== See also ==
European Union energy label, description of European Union energy label
EnergyGuide, United States energy label
Energy rating label, energy label in Australia and New Zealand
China Energy Label, the energy label used in China
== References ==
== External links ==
Userwww.sfsu.edu
Books.google.com.au | Wikipedia/Energy_input_labeling |
The U.S. Department of Energy’s (DOE's) Building Energy Codes Program (BECP) was established in 1991 (originally called the Building Standards and Guidelines Program), with its activities defined by the Energy Conservation and Production Act (ECPA) (Pub. L. No 94-385), as amended, and the Energy Independence and Security Act (EISA) (Pub. L. No 110-140). These statutes direct DOE to participate in industry processes to develop model building energy codes, issue determinations as to whether updated codes result in energy savings, and provide technical assistance to states to implement and comply with the codes. The BECP is part of DOE's Energy Efficiency and Renewable Energy Building Technologies Office.
== Program Areas ==
BECP focuses on three key building energy code areas: model code development, adoption, and compliance.
=== Model Code Development ===
DOE is directed by statute to review the technical and economic basis of building energy codes and participate in processes for their review and modification, including adoption of all technologically feasible and economically justified energy efficiency measures.
=== Adoption ===
DOE is directed by statute to provide technical assistance to states implementing building energy codes, including the adoption of all technologically feasible and economically justified efficiency measures, as well as encouraging states to adopt updated building energy codes.
=== Compliance ===
DOE is directed by statute to provide technical assistance to states implementing energy codes.
== See also ==
American Society of Heating, Refrigerating and Air-Conditioning Engineers
Building Codes Assistance Project
Energy Conservation and Production Act
International Code Council
International Energy Conservation Code
United States Energy Building Codes
United States Department of Energy
== References ==
== External links ==
http://www.tailoredenergyonline.net
Mapjects provides a management framework for auditing both energy and environmental compliance based on building and LEED codes
Building Energy Codes Program - REScheck
Building Energy Codes Program - COMcheck | Wikipedia/Building_Energy_Codes_Program |
In neuroscience, the default mode network (DMN), also known as the default network, default state network, or anatomically the medial frontoparietal network (M-FPN), is a large-scale brain network primarily composed of the dorsal medial prefrontal cortex, posterior cingulate cortex, precuneus and angular gyrus. It is best known for being active when a person is not focused on the outside world and the brain is at wakeful rest, such as during daydreaming and mind-wandering. It can also be active during detailed thoughts related to external task performance. Other times that the DMN is active include when the individual is thinking about others, thinking about themselves, remembering the past, and planning for the future. The DMN creates a coherent "internal narrative" control to the construction of a sense of self.
The DMN was originally noticed to be deactivated in certain goal-oriented tasks and was sometimes referred to as the task-negative network, in contrast with the task-positive network. This nomenclature is now widely considered misleading, because the network can be active in internal goal-oriented and conceptual cognitive tasks. The DMN has been shown to be negatively correlated with other networks in the brain such as attention networks.
Evidence has pointed to disruptions in the DMN of people with Alzheimer's disease and autism spectrum disorder. Psilocybin produces the largest changes in areas of the DMN associated with neuropsychiatric disorders.
== History ==
Hans Berger, the inventor of the electroencephalogram, was the first to propose the idea that the brain is constantly busy. In a series of papers published in 1929, he showed that the electrical oscillations detected by his device do not cease even when the subject is at rest. However, his ideas were not taken seriously, and a general perception formed among neurologists that only when a focused activity is performed does the brain (or a part of the brain) become active.
But in the 1950s, Louis Sokoloff and his colleagues noticed that metabolism in the brain stayed the same when a person went from a resting state to performing effortful math problems, suggesting active metabolism in the brain must also be happening during rest. In the 1970s, David H. Ingvar and colleagues observed blood flow in the front part of the brain became the highest when a person is at rest. Around the same time, intrinsic oscillatory behavior in vertebrate neurons was observed in cerebellar Purkinje cells, inferior olivary nucleus and thalamus.
In the 1990s, with the advent of positron emission tomography (PET) scans, researchers began to notice that when a person is involved in perception, language, and attention tasks, the same brain areas become less active compared to passive rest, and labeled these areas as becoming "deactivated".
In 1995, Bharat Biswal, a graduate student at the Medical College of Wisconsin in Milwaukee, discovered that the human sensorimotor system displayed "resting-state connectivity," exhibiting synchronicity in functional magnetic resonance imaging (fMRI) scans while not engaged in any task.
Later, experiments by neurologist Marcus E. Raichle's lab at Washington University School of Medicine and other groups showed that the brain's energy consumption is increased by less than 5% of its baseline energy consumption while performing a focused mental task. These experiments showed that the brain is constantly active with a high level of activity even when the person is not engaged in focused mental work. Research thereafter focused on finding the regions responsible for this constant background activity level.
Raichle coined the term "default mode" in 2001 to describe resting state brain function; the concept rapidly became a central theme in neuroscience. Around this time the idea was developed that this network of brain areas is involved in internally directed thoughts and is suspended during specific goal-directed behaviors. In 2003, Greicius and colleagues examined resting state fMRI scans and looked at how correlated different sections in the brain are to each other. Their correlation maps highlighted the same areas already identified by the other researchers. This was important because it demonstrated a convergence of methods all leading to the same areas being involved in the DMN. Since then other networks have been identified, such as visual, auditory, and attention networks. Some of them are often anti-correlated with the default mode network.
Until the mid-2000s, researchers labeled the default mode network as the "task-negative network" because it was deactivated when participants had to perform external goal-directed tasks. DMN was thought to only be active during passive rest and inactive during tasks. However, more recent studies have demonstrated the DMN to be active in certain internal goal-directed tasks such as social working memory and autobiographical tasks.
Around 2007, the number of papers referencing the default mode network skyrocketed. In all years prior to 2007, there were 12 papers published that referenced "default mode network" or "default network" in the title; however, between 2007 and 2014 the number increased to 1,384 papers. One reason for the increase in papers was the robust effect of finding the DMN with resting-state scans and independent component analysis (ICA). Another reason was that the DMN could be measured with short and effortless resting-state scans, meaning they could be performed on any population including young children, clinical populations, and nonhuman primates. A third reason was that the role of the DMN was now understood to be more than just a passive brain network.
== Anatomy ==
The default mode network is an interconnected and anatomically defined set of brain regions. The network can be separated into hubs and subsections:
Functional hubs: Information regarding the self
Posterior cingulate cortex (PCC) & precuneus: Combines bottom-up (not controlled) attention with information from memory and perception. The ventral (lower) part of PCC activates in all tasks which involve the DMN including those related to the self, related to others, remembering the past, thinking about the future, and processing concepts plus spatial navigation. The dorsal (upper) part of PCC involves involuntary awareness and arousal. The precuneus is involved in visual, sensorimotor, and attentional information.
Medial prefrontal cortex (mPFC): Decisions about self-processing such as personal information, autobiographical memories, future goals and events, and decision making regarding those personally very close such as family. The ventral (lower) part is involved in positive emotional information and internally valued reward.
Angular gyrus: Connects perception, attention, spatial cognition, and action and helps with parts of recall of episodic memories.
Dorsal medial subsystem: Thinking about others
Functional hubs: PCC, mPFC, and angular gyrus
Dorsal medial prefrontal cortex (dmPFC): Involved in social directed thought such as determining or inferring the purpose of others' actions
Temporoparietal junction (TPJ): Reflects on beliefs about others, also known as theory of mind
Lateral temporal cortex: Retrieval of social semantic and conceptual knowledge
Anterior temporal pole: Abstract conceptual information particularly social in nature
Medial temporal subsystem: Autobiographical memory and future simulations
Functional hubs: PCC, mPFC, and angular gyrus
Hippocampus (HF+): Formation of new memories as well as remembering the past and imagining the future
Parahippocampus (PHC): Spatial and scene recognition and simulation
Retrosplenial cortex (RSC): Spatial navigation
Posterior inferior parietal lobe (pIPL): Junction of auditory, visual, and somatosensory information and attention
The default mode network is most commonly defined with resting state data by putting a seed in the posterior cingulate cortex and examining which other brain areas most correlate with this area. The DMN can also be defined by the areas deactivated during external directed tasks compared to rest. Independent component analysis (ICA) robustly finds the DMN for individuals and across groups, and has become the standard tool for mapping the default network.
It has been shown that the default mode network exhibits the highest overlap in its structural and functional connectivity, which suggests that the structural architecture of the brain may be built in such a way that this particular network is activated by default. Recent evidence from a population brain-imaging study of 10,000 UK Biobank participants further suggests that each DMN node can be decomposed into subregions with complementary structural and functional properties. It has been a widespread practice in DMN research to treat its constituent nodes to be functionally homogeneous, but the distinction between subnodes within each major DMN node has mostly been neglected. However, the close proximity of subnodes that propagate hippocampal space-time outputs and subnodes that describe the global network architecture may enable default functions, such as autobiographical recall or internally-orientated thinking.
In the infant's brain, there is limited evidence of the default network, but default network connectivity is more consistent in children aged 9–12 years, suggesting that the default network undergoes developmental change.
Functional connectivity analysis in monkeys shows a similar network of regions to the default mode network seen in humans. The PCC is also a key hub in monkeys; however, the mPFC is smaller and less well connected to other brain regions, largely because human's mPFC is much larger and well developed.
Diffusion MRI imaging shows white matter tracts connecting different areas of the DMN together. The structural connections found from diffusion MRI imaging and the functional correlations from resting state fMRI show the highest level of overlap and agreement within the DMN areas. This provides evidence that neurons in the DMN regions are linked to each other through large tracts of axons and this causes activity in these areas to be correlated with one another.
From the point of view of effective connectivity, many studies have attempted to shed some light using dynamic causal modeling, with inconsistent results. However, directionality from the medial prefrontal cortex towards the posterior cingulate gyrus seems confirmed in multiple studies, and the inconsistent results appear to be related to small sample size analysis.
== Function ==
The default mode network is thought to be involved in several different functions:
It is potentially the neurological basis for the self:
Autobiographical information: Memories of collection of events and facts about one's self
Self-reference: Referring to traits and descriptions of one's self
Emotion of one's self: Reflecting about one's own emotional state
Thinking about others:
Theory of mind: Thinking about the thoughts of others and what they might or might not know
Emotions of others: Understanding the emotions of other people and empathizing with their feelings
Moral reasoning: Determining a just and an unjust result of an action
Social evaluations: Good-bad attitude judgements about social concepts
Social categories: Reflecting on important social characteristics and status of a group
Social isolation: A perceived lack of social interaction
Remembering the past and thinking about the future:
Remembering the past: Recalling events that happened in the past
Imagining the future: Envisioning events that might happen in the future
Episodic memory: Detailed memory related to specific events in time
Story comprehension: Understanding and remembering a narrative
Replay: Consolidating recently acquired memory traces
The default mode network is active during passive rest and mind-wandering which usually involves thinking about others, thinking about one's self, remembering the past, and envisioning the future rather than the task being performed. Recent work, however, has challenged a specific mapping between the default mode network and mind-wandering, given that the system is important in maintaining detailed representations of task information during working memory encoding. Electrocorticography studies (which involve placing electrodes on the surface of a subject's cerebral cortex) have shown the default mode network becomes activated within a fraction of a second after participants finish a task. Additionally, during attention demanding tasks, sufficient deactivation of the default mode network at the time of memory encoding has been shown to result in more successful long-term memory consolidation.
Studies have shown that when people watch a movie, listen to a story, or read a story, their DMNs are highly correlated with each other. DMNs are not correlated if the stories are scrambled or are in a language the person does not understand, suggesting that the network is highly involved in the comprehension and the subsequent memory formation of that story. The DMN is shown to even be correlated if the same story is presented to different people in different languages, further suggesting the DMN is truly involved in the comprehension aspect of the story and not the auditory or language aspect.
The default mode network is deactivated during some external goal-oriented tasks such as visual attention or cognitive working memory tasks. However, with internal goal-oriented tasks, such as social working memory or autobiographical tasks, the DMN is positively activated with the task and correlates with other networks such as the network involved in executive function. Regions of the DMN are also activated during cognitively demanding tasks that require higher-order conceptual representations. The DMN shows higher activation when behavioral responses are stable, and this activation is independent of self-reported mind wandering. Meditation, which involves focusing the mind on breathing and relaxation, is associated with reduced activity of the DMN.
Gabrielle et al. (2019) suggests that the DMN is related to the perception of beauty, in which the network becomes activated in a generalized way to aesthetically moving domains such as artworks, landscapes, and architecture. This would explain a deep inner feeling of pleasure related to aesthetics, interconnected with the sense of personal identity, due to the network functions related to the self.
== Clinical significance ==
The default mode network has been hypothesized to be relevant to disorders including Alzheimer's disease, autism, schizophrenia, major depressive disorder (MDD), chronic pain, post-traumatic stress disorder (PTSD) and others. In particular, the DMN has also been reported to show overlapping yet distinct neural activity patterns across different mental health conditions, such as when directly comparing attention deficit hyperactivity disorder (ADHD) and autism.
People with Alzheimer's disease show a reduction in glucose (energy use) within the areas of the default mode network. These reductions start off as slight decreases in patients with mild symptoms and continue to large reductions in those with severe symptoms. Surprisingly, amyloid-beta plaque (one of the major hallmarks of Alzheimer's disease) builds up in the DMN begin even before individuals show symptoms of Alzheimer's disease. This prompted Randy Buckner and colleagues to propose the high metabolic rate from continuous activation of DMN causes more amyloid-beta peptide to accumulate in these DMN areas and to form amyloid-beta plaque. This disrupts the DMN and because the DMN is heavily involved in memory formation and retrieval, this disruption leads to the symptoms of Alzheimer's disease.
DMN is thought to be disrupted in individuals with autism spectrum disorder. These individuals are impaired in social interaction and communication which are tasks central to this network. Studies have shown worse connections between areas of the DMN in individuals with autism, especially between the mPFC (involved in thinking about the self and others) and the PCC (the central core of the DMN). The more severe the autism, the less connected these areas are to each other. It is not clear if this is a cause or a result of autism, or if a third factor is causing both (confounding).
Although it is not clear whether the DMN connectivity is increased or decreased in psychotic bipolar disorder and schizophrenia, several genes correlated with altered DMN connectivity are also risk genes for mood and psychosis disorders.
Rumination, one of the main symptoms of major depressive disorder, is associated with increased DMN connectivity and dominance over other networks during rest. Such DMN hyperconnectivity has been observed in first-episode depression and chronic pain. Altered DMN connectivity may change the way a person perceives events and their social and moral reasoning, thus increasing their susceptibility to depressive symptoms.
Lower connectivity between brain regions was found across the default network in people who have experienced long-term trauma, such as childhood abuse or neglect, and is associated with dysfunctional attachment patterns. Among people experiencing PTSD, lower activation was found in the posterior cingulate gyrus compared to controls, and severe PTSD was characterized by lower connectivity within the DMN.
Adults and children with ADHD show reduced anticorrelation between the DMN and other brain networks. The cause may be a lag in brain maturation. More generally, competing activation between the DMN and other networks during memory encoding may result in poor long-term memory consolidation, which is a symptom of not only ADHD but also depression, anxiety, autism, and schizophrenia.
== Modulation ==
The default mode network (DMN) may be modulated by the following interventions and processes:
Acupuncture – Deactivation of the limbic brain areas and the DMN. It has been suggested that this is due to the pain response.
Antidepressants – Abnormalities in DMN connectivity are reduced following treatment with antidepressant medications in PTSD.
Attention Training Technique - Research shows that even a single session of Attention Training Technique changes functional connectivity of the DMN.
Deep brain stimulation – Alterations in brain activity with deep brain stimulation may be used to balance resting state networks.
Meditation – Structural changes in areas of the DMN such as the temporoparietal junction, posterior cingulate cortex, and precuneus have been found in meditation practitioners. There is reduced activation and reduced functional connectivity of the DMN in long-term practitioners. Various forms of nondirective meditation, including Transcendental Meditation and Acem Meditation, have been found to activate the DMN.
Physical Activity and Exercise – Physical Activity, and more likely Aerobic Training, may alter the DMN. In addition, sports experts are showing networks differences, notably of the DMN.
Psychedelic drugs – Reduced blood flow to the PCC and mPFC was observed under the administration of psilocybin. These two areas are considered to be the main nodes of the DMN. One study on the effects of LSD demonstrated that the drug desynchronizes brain activity within the DMN; the activity of the brain regions that constitute the DMN becomes less correlated.
Psychotherapy – In PTSD, the abnormalities in the default mode network normalize in individuals who respond to psychotherapy interventions.
Sleep deprivation – Functional connectivity between nodes of the DMN in their resting-state is usually strong, but sleep deprivation results in a decrease in connectivity within the DMN. Recent studies suggest a decrease in connectivity between the DMN and the task-positive network as a result of sleep loss.
Sleeping and resting wakefulness
Onset of sleep – Increase in connectivity between the DMN and the task-positive network.
REM sleep – Possible increase in connectivity between nodes of the DMN.
Resting wakefulness – Functional connectivity between nodes of the DMN is strong.
Stage N2 of NREM sleep – Decrease in connectivity between the posterior cingulate cortex and medial prefrontal cortex.
Stage N3 of NREM sleep – Further decrease in connectivity between the PCC and MPFC.
== Criticism ==
Some have argued the brain areas in the default mode network only show up together because of the vascular coupling of large arteries and veins in the brain near these areas, not because these areas are actually functionally connected to each other. Support for this argument comes from studies that show changing in breathing alters oxygen levels in the blood which in turn affects DMN the most. These studies however do not explain why the DMN can also be identified using PET scans by measuring glucose metabolism which is independent of vascular coupling and in electrocorticography studies measuring electrical activity on the surface of the brain, and in MEG by measuring magnetic fields associated with electrophysiological brain activity that bypasses the hemodynamic response.
The idea of a "default network" is not universally accepted. In 2007 the concept of the default mode was criticized as not being useful for understanding brain function, on the grounds that a simpler hypothesis is that a resting brain actually does more processing than a brain doing certain "demanding" tasks, and that there is no special significance to the intrinsic activity of the resting brain.
== Nomenclature ==
The default mode network has also been called the language network, semantic system, or limbic network. Even though the dichotomy is misleading, the term task-negative network is still sometimes used to contrast it against other more externally-oriented brain networks.
In 2019, Uddin et al. proposed that medial frontoparietal network (M-FPN) be used as a standard anatomical name for this network.
== See also ==
Functional magnetic resonance imaging (fMRI)
Mind-wandering
Resting state fMRI
== References ==
== External links == | Wikipedia/Default_mode_network |
Salience (also called saliency, from Latin saliō meaning “leap, spring”) is the property by which some thing stands out. Salient events are an attentional mechanism by which organisms learn and survive; those organisms can focus their limited perceptual and cognitive resources on the pertinent (that is, salient) subset of the sensory data available to them.
Saliency typically arises from contrasts between items and their neighborhood. They might be represented, for example, by a red dot surrounded by white dots, or by a flickering message indicator of an answering machine, or a loud noise in an otherwise quiet environment. Saliency detection is often studied in the context of the visual system, but similar mechanisms operate in other sensory systems. Just what is salient can be influenced by training: for example, for human subjects particular letters can become salient by training. There can be a sequence of necessary events, each of which has to be salient, in turn, in order for successful training in the sequence; the alternative is a failure, as in an illustrated sequence when tying a bowline; in the list of illustrations, even the first illustration is a salient: the rope in the list must cross over, and not under the bitter end of the rope (which can remain fixed, and not free to move); failure to notice that the first salient has not been satisfied means the knot will fail to hold, even when the remaining salient events have been satisfied.
When attention deployment is driven by salient stimuli, it is considered to be bottom-up, memory-free, and reactive. Conversely, attention can also be guided by top-down, memory-dependent, or anticipatory mechanisms, such as when looking ahead of moving objects or sideways before crossing streets. Humans and other animals have difficulty paying attention to more than one item simultaneously, so they are faced with the challenge of continuously integrating and prioritizing different bottom-up and top-down influences.
== Neuroanatomy ==
The brain component named the hippocampus helps with the assessment of salience and context by using past memories to filter new incoming stimuli, and placing those that are most important into long term memory. The entorhinal cortex is the pathway into and out of the hippocampus, and is an important part of the brain's memory network; research shows that it is a brain region that suffers damage early on in Alzheimer's disease, one of the effects of which is altered (diminished) salience.
The pulvinar nuclei (in the thalamus) modulate physical/perceptual salience in attentional selection.
One group of neurons (i.e., D1-type medium spiny neurons) within the nucleus accumbens shell (NAcc shell) assigns appetitive motivational salience ("want" and "desire", which includes a motivational component), aka incentive salience, to rewarding stimuli, while another group of neurons (i.e., D2-type medium spiny neurons) within the NAcc shell assigns aversive motivational salience to aversive stimuli.
The primary visual cortex (V1) generates a bottom-up saliency map from visual inputs to guide reflexive attentional shifts or gaze shifts. According to V1 Saliency Hypothesis, the saliency of a location is higher when V1 neurons give higher responses to that location relative to V1 neurons' responses to other visual locations. For example, a unique red item among green items, or a unique vertical bar among horizontal bars, is salient since it evokes higher V1 responses and attracts attention or gaze. The V1 neural responses are sent to the superior colliculus to guide gaze shifts to the salient locations. A fingerprint of the saliency map in V1 is that attention or gaze can be captured by the location of an eye-of-origin singleton in visual inputs, e.g., a bar uniquely shown to the left eye in a background of many other bars shown to the right eye, even when observers cannot tell the difference between the singleton and the background bars.
== In psychology ==
The term is widely used in the study of perception and cognition to refer to any aspect of a stimulus that, for any of many reasons, stands out from the rest. Salience may be the result of emotional, motivational or cognitive factors and is not necessarily associated with physical factors such as intensity, clarity or size. Although salience is thought to determine attentional selection, salience associated with physical factors does not necessarily influence selection of a stimulus.
=== Salience bias ===
Salience bias (also referred to as perceptual salience) is a cognitive bias that predisposes individuals to focus on or attend to items, information, or stimuli that are more prominent, visible, or emotionally striking. This is as opposed to stimuli that are unremarkable, or less salient, even though this difference is often irrelevant by objective standards. The American Psychological Association (APA) defines the salience hypothesis as a theory regarding perception where “motivationally significant” information is more readily perceived than information with little or less significant motivational importance. Perceptual salience (salience bias) is linked to the vividness effect, whereby a more pronounced response is produced by a more vivid perception of a stimulus than the mere knowledge of the stimulus. Salience bias assumes that more dynamic, conspicuous, or distinctive stimuli engage attention more than less prominent stimuli, disproportionately impacting decision making, it is a bias which favors more salient information.
==== Application ====
===== Cognitive Psychology =====
Salience bias, like all other cognitive biases, is an applicable concept to various disciplines. For example, cognitive psychology investigates cognitive functions and processes, such as perception, attention, memory, problem solving, and decision making, all of which could be influenced by salience bias. Salience bias acts to combat cognitive overload by focusing attention on prominent stimuli, which affects how individuals perceive the world as other, less vivid stimuli that could add to or change this perception, are ignored. Human attention gravitates towards novel and relevant stimuli and unconsciously filters out less prominent information, demonstrating salience bias, which influences behavior as human behavior is affected by what is attended to. Behavioral economists Tversky and Kahneman also suggest that the retrieval of instances is influenced by their salience, such as how witnessing or experiencing an event first-hand has a greater impact than when it is less salient, like if it were read about, implying that memory is affected by salience.
===== Language =====
It is also relevant in language understanding and acquisition. Focusing on more salient phenomena allows people to detect language patterns and dialect variations more easily, making dialect categorization more efficient.
===== Social Behavior =====
Furthermore, social behaviors and interactions can also be influenced by perceptual salience. Changes in the perceptual salience of an individual heavily influences their social behavior and subjective experience of their social interactions, confirming a “social salience effect”. Social salience relates to how individuals perceive and respond to other people.
===== Behavioral Science =====
The connection between salience bias and other heuristics, like availability and representativeness, links it to the fields of behavioral science and behavioral economics. Salience bias is closely related to the availability heuristic in behavioral economics, based on the influence of information vividness and visibility, such as recency or frequency, on judgements, for example:Accessibility and salience are closely related to availability, and they are important as well. If you have personally experienced a serious earthquake, you’re more likely to believe that an earthquake is likely than if you read about it in a weekly magazine. Thus, vivid and easily imagined causes of death (for example, tornadoes) often receive inflated estimates of probability, and less-vivid causes (for example, asthma attacks) receive low estimates, even if they occur with a far greater frequency (here, by a factor of twenty). Timing counts too: more recent events have a greater impact on our behavior, and on our fears, than earlier ones.Humans have bounded rationality, which refers to their limited ability to be rational in decision making, due to a limited capacity to process information and cognitive ability. Heuristics, such as availability, are employed to reduce the complexity of cognitive and social tasks or judgements, in order to decrease the cognitive load that result from bounded rationality. Despite the effectiveness of heuristics in doing so, they are limited by systematic errors that occur, often the result of influencing biases, such as salience. This can lead to misdirected or misinformed judgements, based on an overemphasis or overweighting of certain, more salient information. For example, the irrational behavior of procrastination occurs because costs in the present, like sacrificing free time, are disproportionately salient to future costs, because at that time they are more vivid. The more prominent information is more readily available than the less salient information, and thus has a larger impact on decision making and behavior, resulting in errors in judgement.
Other fields such as philosophy, economics, finance, and political science have also investigated the effects of salience, such as in relation to taxes, where salience bias is applied to real-world behaviors, affecting systems like the economy. The existence of salience bias in humans can make behavior more predictable and this bias can be leveraged to influence behavior, such as through nudges.
==== Evaluation ====
Salience bias is one of many explanations for why humans deviate from rational decision making: by being overly focused on or biased to the most visible data and ignoring other potentially important information that could result in a more reasonable judgment. As a concept it is supported in psychological and economic literature, through its relationship with the availability heuristic outlined by Tversky and Kahneman, and its applicability to behaviors relevant to multiple disciplines, such as economics.
Despite this support, salience bias is limited for various reasons, one example being its difficulty in quantifying, operationalizing, and universally defining. Salience is often confused with other terms in literature, for example, one article states that salience, which is defined as a cognitive bias referring to “visibility and prominence”, is often confused with terms like transparency and complexity in public finance literature. This limits salience bias as the confusion negates its importance as an individual term, and therefore the influence it has on tax related behavior. Likewise, the APA definition of salience refers to motivational importance, which is based on subjective judgement, adding to the difficulty. According to psychologist S. Taylor “some people are more salient than others” and these differences can further bias judgements.
Biased judgements have far-reaching consequences, beyond poor decision making, such as overgeneralizing and stereotyping. Studies into solo status or token integration demonstrate this. The token is an individual in a group different to the other members in that social environment, like a female in an all-male workplace. The token is viewed as symbolic of their social group, whereby judgments made about the solo individual predict judgements of their social group, which can result in inaccurate perceptions of that group and potential stereotyping. The distinctiveness of the individual in that environment “fosters a salience bias” and hence predisposes those generalized judgements, positive or negative.
== In interaction design ==
Salience in design draws from the cognitive aspects of attention, and applies it to the making of 2D and 3D objects. When designing computer and screen interfaces, salience helps draw attention to certain objects like buttons and signify affordance, so designers can utilize this aspect of perception to guide users.
There are several variables used to direct attention:
Color. Hue, saturation, and value can all be used to call attention to areas or objects within an interface, and de-emphasize others.
Size. Object size and proportion to surrounding elements creates visual hierarchy, both in interactive elements like buttons, but also within informative elements like text.
Position. An object's orientation or spatial arrangement in relation to the surrounding objects creates differentiation to invite action.
=== Accessibility ===
A consideration for salience in interaction design is accessibility. Many interfaces used today rely on visual salience for guiding user interaction, and people with disabilities like color-blindness may have trouble interacting with interfaces using color or contrast to create salience.
== Aberrant salience hypothesis of schizophrenia ==
Kapur (2003) proposed that a hyperdopaminergic state, at a "brain" level of description, leads to an aberrant assignment of salience to the elements of one's experience, at a "mind" level. These aberrant salience attributions have been associated with altered activities in the mesolimbic system, including the striatum, the amygdala, the hippocampus, the parahippocampal gyrus., the anterior cingulate cortex and the insula. Dopamine mediates the conversion of the neural representation of an external stimulus from a neutral bit of information into an attractive or aversive entity, i.e. a salient event. Symptoms of schizophrenia may arise out of 'the aberrant assignment of salience to external objects and internal representations', and antipsychotic medications reduce positive symptoms by attenuating aberrant motivational salience via blockade of the dopamine D2 receptors (Kapur, 2003).
Alternative areas of investigation include supplementary motor areas, frontal eye fields and parietal eye fields. These areas of the brain are involved with calculating predictions and visual salience. Changing expectations on where to look restructures these areas of the brain. This cognitive repatterning can result in some of the symptoms found in such disorders.
== Visual saliency modeling ==
In the domain of psychology, efforts have been made in modeling the mechanism of human attention, including the learning of prioritizing the different bottom-up and top-down influences.
In the domain of computer vision, efforts have been made in modeling the mechanism of human attention, especially the bottom-up attentional mechanism, including both spatial and temporal attention. Such a process is also called visual saliency detection.
Generally speaking, there are two kinds of models to mimic the bottom-up saliency mechanism. One way is based on the spatial contrast analysis: for example, a center-surround mechanism is used to define saliency across scales, which is inspired by the putative neural mechanism. The other way is based on the frequency domain analysis. While they used the amplitude spectrum to assign saliency to rarely occurring magnitudes, Guo et al. use the phase spectrum instead.
Recently, Li et al. introduced a system that uses both the amplitude and the phase information.
A key limitation in many such approaches is their computational complexity leading to less than real-time performance, even on modern computer hardware. Some recent work attempts to overcome these issues at the expense of saliency detection quality under some conditions. Other work suggests that saliency and associated speed-accuracy phenomena may be a fundamental mechanisms determined during recognition through gradient descent, needing not be spatial in nature.
== See also ==
Availability heuristic – Bias towards recently acquired information
Dopamine hypothesis of schizophrenia – Scientific model
Latent inhibition – Psychology term
Schizophrenia – Mental disorder with psychotic symptoms
Schizotypy – Concept of personality states ranging from imaginative to psychotic
Sensationalism – Type of editorial tactic used in mass media
Visual spatial attention – Visual sense
Visual temporal attention
== References ==
== External links ==
Itti L, Koch C (March 2001). "Computational modelling of visual attention". Nature Reviews. Neuroscience. 2 (3): 194–203. doi:10.1038/35058500. PMID 11256080. S2CID 2329233.
iLab at the University of Southern California
Scholarpedia article on visual saliency by Prof. Laurent Itti
Huang, J-B; Ahuja, Narendra (2012). Saliency Detection via Divergence Analysis: An Unified Perspective]. 2012 21st International Conference on Pattern Recognition (ICPR). ISBN 978-4-9906441-0-9.
Saliency map at Scholarpedia | Wikipedia/Salience_(neuroscience) |
The sensorimotor network (SMN), also known as somatomotor network, is a large-scale brain network that primarily includes somatosensory (postcentral gyrus) and motor (precentral gyrus) regions and extends to the supplementary motor areas (SMA). The auditory cortex may also be included, as well as the visual cortex. The SMN is activated during motor tasks, such as finger tapping, indicating that the network readies the brain when performing and coordinating motor tasks.
== Clinical significance ==
Dysfunction in the SMN has been implicated in various neuropsychiatric disorders.
Bipolar Disorder: The psychomotor disturbances that characterize the depressive and manic phases of bipolar disorder may be related to dysfunction in the sensorimotor network (SMN) and its balance with other large-scale networks such as the default mode network.
Amyotrophic Lateral Sclerosis: Altered functional connectivity patterns in the SMN may contribute to various symptoms in the neurodegenerative disease .
== Nomenclature ==
In 2019, Uddin et al. proposed that pericentral network (PN) be used as a standard anatomical name for the network.
== References == | Wikipedia/Sensorimotor_network |
The frontoparietal network (FPN), generally also known as the central executive network (CEN) or, more specifically, the lateral frontoparietal network (L-FPN) (see Nomenclature), is a large-scale brain network primarily composed of the dorsolateral prefrontal cortex and posterior parietal cortex, around the intraparietal sulcus. It is involved in sustained attention, complex problem-solving and working memory.
The FPN is one of three networks in the so-called triple-network model, along with the salience network and the default mode network (DMN). The salience network facilitates switching between the FPN and DMN.
== Anatomy ==
The FPN is primarily composed of the rostral lateral and dorsolateral prefrontal cortex (especially the middle frontal gyrus) and the anterior inferior parietal lobule. Additional regions include the middle cingulate gyrus and potentially the dorsal precuneus, posterior inferior temporal lobe, dorsomedial thalamus and the head of the caudate nucleus.
== Function ==
The FPN is involved in executive function and goal-oriented, cognitively demanding tasks. It is crucial for rule-based problem solving, actively maintaining and manipulating information in working memory and making decisions in the context of goal-directed behaviour. Efficient processing in the frontoparietal network during cognitive control tasks enables the fulfillment of cognitive demands. Based on current cognitive demands, the FPN flexibly divides into two subsystems that connect to other networks: the default mode network for introspective processes and the dorsal attention network for perceptual attention.
== Clinical significance ==
Disruption of the nodes of the FPN has been found in virtually every psychiatric and neurological disorder, from autism, schizophrenia and depression to frontotemporal dementia and Alzheimer's disease.
== Nomenclature ==
The term central executive network (CEN) is generally equivalent to the frontoparietal network in literature, distinguishing it from the dorsal attention network (DAN), with which it has several similarities, though sometimes it has been used to include the DAN.
The FPN has fewer similarities with the salience network (which has also been equated with the cingulo-opercular network or ventral attention network). Regardless, it has sometimes been grouped together with either the DAN or the salience network (usually the latter) under the name executive control network (ECN). The term frontoparietal control network (FPCN) has also been used, generally also for a grouping of the FPN and the salience network.
Other names for the FPN have included the multiple-demand system, extrinsic mode network, domain-general system and cognitive control network.
In 2019, Uddin et al. proposed that lateral frontoparietal network (L-FPN) be used as the standard name for this network.
== See also ==
Default mode network
Salience network
== References == | Wikipedia/Frontoparietal_network |
Dynamic causal modeling (DCM) is a framework for specifying models, fitting them to data and comparing their evidence using Bayesian model comparison. It uses nonlinear state-space models in continuous time, specified using stochastic or ordinary differential equations. DCM was initially developed for testing hypotheses about neural dynamics. In this setting, differential equations describe the interaction of neural populations, which directly or indirectly give rise to functional neuroimaging data e.g., functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG) or electroencephalography (EEG). Parameters in these models quantify the directed influences or effective connectivity among neuronal populations, which are estimated from the data using Bayesian statistical methods.
== Procedure ==
DCM is typically used to estimate the coupling among brain regions and the changes in coupling due to experimental changes (e.g., time or context). A model of interacting neural populations is specified, with a level of biological detail dependent on the hypotheses and available data. This is coupled with a forward model describing how neural activity gives rise to measured responses. Estimating the generative model identifies the parameters (e.g. connection strengths) from the observed data. Bayesian model comparison is used to compare models based on their evidence, which can then be characterised in terms of parameters.
DCM studies typically involve the following stages:
Experimental design. Specific hypotheses are formulated and an experiment is conducted.
Data preparation. The acquired data are pre-processed (e.g., to select relevant data features and remove confounds).
Model specification. One or more forward models (DCMs) are specified for each dataset.
Model estimation. The model(s) are fitted to the data to determine their evidence and parameters.
Model comparison. The evidence for each model is used for Bayesian Model Comparison (at the single-subject level or at the group level) to select the best model(s). Bayesian model averaging (BMA) is used to compute a weighted average of parameter estimates over different models.
The key stages are briefly reviewed below.
== Experimental design ==
Functional neuroimaging experiments are typically either task-based or examine brain activity at rest (resting state). In task-based experiments, brain responses are evoked by known deterministic inputs (experimentally controlled stimuli). These experimental variables can change neural activity through direct influences on specific brain regions, such as evoked potentials in the early visual cortex, or via a modulation of coupling among neural populations; for example, the influence of attention. These two types of input - driving and modulatory - are parameterized separately in DCM. To enable efficient estimation of driving and modulatory effects, a 2x2 factorial experimental design is often used - with one factor serving as the driving input and the other as the modulatory input.
Resting state experiments have no experimental manipulations within the period of the neuroimaging recording. Instead, hypotheses are tested about the coupling of endogenous fluctuations in neuronal activity, or in the differences in connectivity between sessions or subjects. The DCM framework includes models and procedures for analysing resting state data, described in the next section.
== Model specification ==
All models in DCM have the following basic form:
z
˙
=
f
(
z
,
u
,
θ
(
n
)
)
y
=
g
(
z
,
θ
(
h
)
)
+
ϵ
{\displaystyle {\begin{aligned}{\dot {z}}&=f(z,u,\theta ^{(n)})\\y&=g(z,\theta ^{(h)})+\epsilon \end{aligned}}}
The first equality describes the change in neural activity
z
{\displaystyle z}
with respect to time (i.e.
z
˙
{\displaystyle {\dot {z}}}
), which cannot be directly observed using non-invasive functional imaging modalities. The evolution of neural activity over time is controlled by a neural function
f
{\displaystyle f}
with parameters
θ
(
n
)
{\displaystyle \theta ^{(n)}}
and experimental inputs
u
{\displaystyle u}
. The neural activity in turn causes the timeseries
y
{\displaystyle y}
(second equality), which are generated via an observation function
g
{\displaystyle g}
with parameters
θ
(
h
)
{\displaystyle \theta ^{(h)}}
. Additive observation noise
ϵ
{\displaystyle \epsilon }
completes the observation model. Usually, the neural parameters
θ
(
n
)
{\displaystyle \theta ^{(n)}}
are of key interest, which for example represent connection strengths that may change under different experimental conditions.
Specifying a DCM requires selecting a neural model
f
{\displaystyle f}
and observation model
g
{\displaystyle g}
and setting appropriate priors over the parameters; e.g. selecting which connections should be switched on or off.
=== Functional MRI ===
The neural model in DCM for fMRI is a Taylor approximation that captures the gross causal influences between brain regions and their change due to experimental inputs (see picture). This is coupled with a detailed biophysical model of the generation of the blood oxygen level dependent (BOLD) response and the MRI signal, based on the Balloon model of Buxton et al., which was supplemented with a model of neurovascular coupling. Additions to the neural model have included interactions between excitatory and inhibitory neural populations and non-linear influences of neural populations on the coupling between other populations.
DCM for resting state studies was first introduced in Stochastic DCM, which estimates both neural fluctuations and connectivity parameters in the time domain, using Generalized Filtering. A more efficient scheme for resting state data was subsequently introduced which operates in the frequency domain, called DCM for Cross-Spectral Density (CSD). Both of these can be applied to large-scale brain networks by constraining the connectivity parameters based on the functional connectivity. Another recent development for resting state analysis is Regression DCM implemented in the Tapas software collection (see Software implementations). Regression DCM operates in the frequency domain, but linearizes the model under certain simplifications, such as having a fixed (canonical) haemodynamic response function. The enables rapid estimation of large-scale brain networks.
=== EEG / MEG ===
DCM for EEG and MEG data use more biologically detailed neural models than fMRI, due to the higher temporal resolution of these measurement techniques. These can be classed into physiological models, which recapitulate neural circuitry, and phenomenological models, which focus on reproducing particular data features. The physiological models can be further subdivided into two classes. Conductance-based models derive from the equivalent circuit representation of the cell membrane developed by Hodgkin and Huxley in the 1950s. Convolution models were introduced by Wilson & Cowan and Freeman in the 1970s and involve a convolution of pre-synaptic input by a synaptic kernel function. Some of the specific models used in DCM are as follows:
Physiological models:
Convolution models:
DCM for evoked responses (DCM for ERP). This is a biologically plausible neural mass model, extending earlier work by Jansen and Rit. It emulates the activity of a cortical area using three neuronal sub-populations (see picture), each of which rests on two operators. The first operator transforms the pre-synaptic firing rate into a Post-Synaptic Potential (PSP), by convolving pre-synaptic input with a synaptic response function (kernel). The second operator, a sigmoid function, transforms the membrane potential into a firing rate of action potentials.
DCM for LFP (Local Field Potentials). Extends DCM for ERP by adding the effects of specific ion channels on spike generation.
Canonical Microcircuit (CMC). Used to address hypotheses about laminar-specific ascending and descending connections in the brain, which underpin the predictive coding account of functional brain architectures. The single pyramidal cell population from DCM for ERP is split into deep and superficial populations (see picture). A version of the CMC has been applied to model multi-modal MEG and fMRI data.
Neural Field Model (NFM). Extends the models above into the spatial domain, modelling continuous changes in current across the cortical sheet.
Conductance models:
Neural Mass Model (NMM) and Mean-field model (MFM). These have the same arrangement of neural populations as DCM for ERP, above, but are based on the Morris-Lecar model of the barnacle muscle fibre, which in turn derives from the Hodgin and Huxley model of the giant squid axon. They enable inference about ligand-gated excitatory (Na+) and inhibitory (Cl-) ion flow, mediated through fast glutamatergic and GABAergic receptors. Whereas DCM for fMRI and the convolution models represent the activity of each neural population by a single number - its mean activity - the conductance models include the full density (probability distribution) of activity within the population. The 'mean-field assumption' used in the MFM version of the model assumes the density of one population's activity depends only on the mean of another. A subsequent extension added voltage-gated NMDA ion channels.
Phenomenological models:
DCM for phase coupling. Models the interaction of brain regions as Weakly Coupled Oscillators (WCOs), in which the rate of change of phase of one oscillator is related to the phase differences between itself and other oscillators.
== Model estimation ==
Model inversion or estimation is implemented in DCM using variational Bayes under the Laplace assumption. This provides two useful quantities: the log marginal likelihood or model evidence
ln
p
(
y
|
m
)
{\displaystyle \ln {p(y|m)}}
is the probability of observing of the data under a given model. Generally, this cannot be calculated explicitly and is approximated by a quantity called the negative variational free energy
F
{\displaystyle F}
, referred to in machine learning as the Evidence Lower Bound (ELBO). Hypotheses are tested by comparing the evidence for different models based on their free energy, a procedure called Bayesian model comparison.
Model estimation also provides estimates of the parameters
p
(
θ
|
y
)
{\displaystyle p(\theta |y)}
, for example connection strengths, which maximise the free energy. Where models differ only in their priors, Bayesian Model Reduction can be used to derive the evidence and parameters of nested or reduced models analytically and efficiently.
== Model comparison ==
Neuroimaging studies typically investigate effects that are conserved at the group level, or which differ between subjects. There are two predominant approaches for group-level analysis: random effects Bayesian Model Selection (BMS) and Parametric Empirical Bayes (PEB). Random Effects BMS posits that subjects differ in terms of which model generated their data - e.g. drawing a random subject from the population, there might be a 25% chance that their brain is structured like model 1 and a 75% chance that it is structured like model 2. The analysis pipeline for the BMS approach procedure follows a series of steps:
Specify and estimate multiple DCMs per subject, where each DCM (or set of DCMs) embodies a hypothesis.
Perform Random Effects BMS to estimate the proportion of subjects whose data were generated by each model
Calculate the average connectivity parameters across models using Bayesian Model Averaging. This average is weighted by the posterior probability for each model, meaning that models with greater probability contribute more to the average than models with lower probability.
Alternatively, Parametric Empirical Bayes (PEB) can be used, which specifies a hierarchical model over parameters (e.g., connection strengths). It eschews the notion of different models at the level of individual subjects, and assumes that people differ in the (parametric) strength of connections. The PEB approach models distinct sources of variability in connection strengths across subjects using fixed effects and between-subject variability (random effects). The PEB procedure is as follows:
Specify a single 'full' DCM per subject, which contains all the parameters of interest.
Specify a Bayesian General Linear Model (GLM) to model the parameters (the full posterior density) from all subjects at the group level.
Test hypotheses by comparing the full group-level model to reduced group-level models where certain combinations of connections have been switched off.
== Validation ==
Developments in DCM have been validated using different approaches:
Face validity establishes whether the parameters of a model can be recovered from simulated data. This is usually performed alongside the development of each new model (E.g.).
Construct validity assesses consistency with other analytical methods. For example, DCM has been compared with Structural Equation Modelling and other neurobiological computational models.
Predictive validity assesses the ability to predict known or expected effects. This has included testing against iEEG / EEG / stimulation and against known pharmacological treatments.
== Limitations / drawbacks ==
DCM is a hypothesis-driven approach for investigating the interactions among pre-defined regions of interest. It is not ideally suited for exploratory analyses. Although methods have been implemented for automatically searching over reduced models (Bayesian Model Reduction) and for modelling large-scale brain networks, these methods require an explicit specification of model space. In neuroimaging, approaches such as psychophysiological interaction (PPI) analysis may be more appropriate for exploratory use; especially for discovering key nodes for subsequent DCM analysis.
The variational Bayesian methods used for model estimation in DCM are based on the Laplace assumption, which treats the posterior over parameters as Gaussian. This approximation can fail in the context of highly non-linear models, where local minima may preclude the free energy from serving as a tight bound on log model evidence. Sampling approaches provide the gold standard; however, they are time-consuming and have typically been used to validate the variational approximations in DCM.
== Software implementations ==
DCM is implemented in the Statistical Parametric Mapping software package, which serves as the canonical or reference implementation (http://www.fil.ion.ucl.ac.uk/spm/software/spm12/). It has been re-implemented and developed in the Tapas software collection (https://www.tnu.ethz.ch/en/software/tapas.html Archived 2019-02-03 at the Wayback Machine) and the VBA toolbox (https://mbb-team.github.io/VBA-toolbox/).
== References ==
== Further reading ==
Dynamic Causal Modelling on Scholarpedia
Understanding DCM: ten simple rules for the clinician
Neural masses and fields in dynamic causal modeling | Wikipedia/Dynamic_causal_modeling |
The salience network (SN), also known anatomically as the midcingulo-insular network (M-CIN) or ventral attention network, is a large scale network of the human brain that is primarily composed of the anterior insula (AI) and dorsal anterior cingulate cortex (dACC). It is involved in detecting and filtering salient stimuli, as well as in recruiting relevant functional networks. Together with its interconnected brain networks, the SN contributes to a variety of complex functions, including communication, social behavior, and self-awareness through the integration of sensory, emotional, and cognitive information.
The network is detectable through independent component analysis of resting state fMRI images, as well as seed based functional connectivity analysis. The functional connectivity has been linked with structural connectivity through diffusion tensor imaging, which reveals white matter tracts between the AI and dACC.
== Anatomy ==
The salience network is primarily anchored at the anterior insula (AI) and dorsal anterior cingulate cortex (dACC). The node in the AI corresponds with the dorsal-anterior division distinguished in meta-analyses of task-positive network related neuroimaging studies. The AI and dACC are linked via a white matter tract along the uncinate fasciculus. Other regions of the network may include the inferior parietal cortex, right temporoparietal junction, and lateral prefrontal cortex.
The subcortical nodes have yet to be structurally linked to the AI and dACC, however both seed-based and resting-state studies have observed intrinsic connectivity of the cortical nodes, with subcortical nodes consisting of the sublenticular extended amygdala, the putamen, the ventral striatum, the dorsomedial thalamus, hypothalamus, and the substantia nigra/ventral tegmental area. The salience network is also distinguished by distinct cellular components, including von Economo neurons in the AI/dACC. Cortico-striatal-thalamic loop circuits contribute to the salience network.
== Function ==
While the function of the salience network is not exactly known, it has been implicated in the detection and integration of emotional and sensory stimuli, as well as in modulating the switch between the internally directed cognition of the default mode network and the externally directed cognition of the central executive network. Evidence that the salience network mediates a switch between the DMN and CEN comes from Granger causality analysis and studies utilizing transcranial magnetic stimulation. The timing of electrophysiological responses during the oddball task is consistent with interaction, as after the initial mismatch negativity response is transmitted "bottom-up" from sensory regions, a "top-down" signal localized to the AI and dACC occurs before a widespread evoked potential that corresponds to attentional shifting. It has also been hypothesized that the AI receives multimodal sensory input and the ACC and the associated dorsomedial prefrontal cortex sends motor output.
== Clinical significance ==
Abnormalities in the salience network have been observed in various psychiatric disorders, including depression, anxiety disorders, post-traumatic stress disorder, schizophrenia, frontotemporal dementia, and Alzheimer's disease.
The frontostriatal salience network is expanded nearly twofold in the cortex of most individuals with depression.
The AI node of the salience network has been observed to be hyperactive in anxiety disorders, which is thought to reflect predictions of aversive bodily states leading to worrisome thoughts and anxious behaviors. In schizophrenia, both structural and functional abnormalities have been observed, thought to reflect excessive salience being ascribed to internally generated stimuli.
In individuals with autism, the relative salience of social stimuli, such as face, eyes, and gaze, may be diminished, leading to poor social skills.
== Nomenclature ==
The cingulo-opercular network (CO) has generally been equated with the salience network, but it may represent a distinct but adjacent network or a part of the SN. The CO may involve more dorsal areas, while the SN involves more ventral and rostral areas of the anterior insula and medial frontal cortex containing von Economo neurons. The CO is sometimes also referred to as the cingulo-insular network.
The ventral attention network (VAN), also known as the ventral frontoparietal network (VFN) or ventral attention system (VAS), has also been equated with the SN. The VAN is commonly defined as a right-hemisphere-dominant network involving the temporoparietal junction and the ventral frontal cortex that responds to unexpected salient stimuli. Some have defined it as a larger, bilateral network that is a combination of the SN and CO, while others have described it as a part of the salience network involving the more dorsal anterior insular cortex.
In 2019, Uddin et al. proposed that midcingulo-insular network (M-CIN) be used as a standard anatomical name for the network that includes the SN, CO, and VAN.
== See also ==
Default mode network
Frontoparietal network
Bottom-up processing
== References == | Wikipedia/Salience_network |
Dynamic functional connectivity (DFC) refers to the observed phenomenon that functional connectivity changes over a short time. Dynamic functional connectivity is a recent expansion on traditional functional connectivity analysis which typically assumes that functional networks are static in time. DFC is related to a variety of different neurological disorders, and has been suggested to be a more accurate representation of functional brain networks. The primary tool for analyzing DFC is fMRI, but DFC has also been observed with several other mediums. DFC is a recent development within the field of functional neuroimaging whose discovery was motivated by the observation of temporal variability in the rising field of steady state connectivity research.
== Overview and history ==
=== Static connectivity ===
Functional connectivity refers to the functionally integrated relationship between spatially separated brain regions. Unlike structural connectivity which looks for physical connections in the brain, functional connectivity is related to similar patterns of activation in different brain regions regardless of the apparent physical connectedness of the regions. This type of connectivity was discovered in the mid-1990s and has been seen primarily using fMRI and Positron emission tomography. Functional connectivity is usually measured during resting state fMRI and is typically analyzed in terms of correlation, coherence, and spatial grouping based on temporal similarities. These methods have been used to show that functional connectivity is related to behavior in a variety of different tasks, and that it has a neural basis. These methods assume the functional connections in the brain remain constant in a short time over a task or period of data collection.
=== The origin of dynamic analysis ===
Studies that showed brain state dependent changes in functional connectivity were the first indicators that temporal variation in functional connectivity may be significant. Several studies in the mid-2000s examined the changes in FC that were related to a variety of different causes such as mental tasks, sleep, and learning. These changes often occur within the same individual and are clearly relevant to behavior. DFC has now been investigated in a variety of different contexts with many analysis tools. It has been shown to be related to both behavior and neural activity. Some researchers believe that it may be heavily related to high level thought or consciousness.
=== Significant findings from DFC ===
Because DFC is such a new field, much of the research related to it is conducted to validate the relevance of these dynamic changes rather than explore their implications; however, many critical findings have been made that help the scientific community better understand the brain.
Analysis of dynamic functional connectivity has shown that far from being completely static, the functional networks of the brain fluctuate on the scale of seconds to minutes. These changes are generally seen as movements from one short term state to another, rather than continuous shifts. Many studies have shown reproducible patterns of network activity that move throughout the brain. These patterns have been seen in both animals and humans, and are present at only certain points during a scanner session.
In addition to showing transient brain states, DFC analysis has shown a distinct hierarchical organization of the networks of the brain. Connectivity between bilaterally symmetric regions is the most stable form of connectivity in the brain, followed by other regions with direct anatomical connections. Steady state functional connectivity networks exist and have physiological relevance, but have less temporal stability than the anatomical networks. Finally, some functional networks are fleeting enough to only be seen with DFC analysis. These networks also possess physiological relevance but are much less temporally stable than the other networks in the brain.
== Methods of analysis ==
=== Sliding window ===
Sliding window analysis is the most common method used in the analysis of functional connectivity, first introduced by Sakoglu and Calhoun in 2009, and applied to schizophrenia.
Sliding window analysis is performed by conducting analysis on a set number of scans in an fMRI session. The number of scans is the length of the sliding window. The defined window is then moved a certain number of scans forward in time and additional analysis is performed. The movement of the window is usually referenced in terms of the degree of overlap between adjacent windows. One of the principle benefits of sliding window analysis is that almost any steady state analysis can also be performed using sliding window if the window length is sufficiently large. Sliding window analysis also has a benefit of being easy to understand and in some ways easier to interpret.
As the most common method of analysis, sliding window analysis has been used in many different ways to investigate a variety of different characteristics and implications of DFC. In order to be accurately interpreted, data from sliding window analysis generally must be compared between two different groups. Researchers have used this type of analysis to show different DFC characteristics in diseased and healthy patients, high and low performers on cognitive tasks, and between large scale brain states.
=== Activation patterns ===
One of the first methods ever used to analyze DFC was pattern analysis of fMRI images to show that there are patterns of activation in spatially separated brain regions that tend to have synchronous activity. It has become clear that there is a spatial and temporal periodicity in the brain that probably reflects some of the constant processes of the brain. Repeating patterns of network information have been suggested to account for 25–50% of the variance in fMRI BOLD data. These patterns of activity have primarily been seen in rats as a propagating wave of synchronized activity along the cortex. These waves have also been shown to be related to underlying neural activity, and has been shown to be present in humans as well as rats.
=== Point process analysis ===
Departing from the traditional approaches, recently an efficient method was introduced to analyze rapidly changing functional activations patterns which transforms the fMRI BOLD data into a point process. This is achieved by selecting for each voxel the points of inflection of the BOLD signal (i.e., the peaks). These few points contain a great portion of the information pertaining functional connectivity, because it has been demonstrated, that despite the tremendous reduction on the data size (> 95%), it compares very well with inferences of functional connectivity obtained with standard methods which uses the full signal.
The large information content of these few points is consistent with the results of Petridou et al. who demonstrated he contribution of these "spontaneous events" to the correlation strength and power spectra of the slow spontaneous fluctuations by deconvolving the task hemodynamic response function from the rest data. Subsequently, similar principles were successfully applied under the name of co-activation patterns (CAP).
=== Other methods ===
Time-frequency analysis has been proposed as an analysis method that is capable of overcoming many of the challenges associated with sliding windows. Unlike sliding window analysis, time frequency analysis allows the researcher to investigate both frequency and amplitude information simultaneously. The wavelet transform has been used to conduct DFC analysis that has validated the existence of DFC by showing its significant changes in time. This same method has recently been used to investigate some of the dynamic characteristics of accepted networks. For example, time frequency analysis has shown that the anticorrelation between the default mode network and the task-positive network is not constant in time but rather is a temporary state.
Independent component analysis has become one of the most common methods of network generation in steady state functional connectivity. ICA divides fMRI signal into several spatial components that have similar temporal patterns. More recently, ICA has been used to divide fMRI data into different temporal components. This has been termed temporal ICA and it has been used to plot network behavior that accounts for 25% of variability in the correlation of anatomical nodes in fMRI.
== Controversy and limitations ==
Several researchers have argued that DFC may be a simple reflection of analysis, scanner, or physiological noise. Noise in fMRI can arise from a variety of different factors including heart beat, changes in the blood brain barrier, characteristics of the acquiring scanner, or unintended effects of analysis. Some researchers have proposed that the variability in functional connectivity in fMRI studies is consistent with the variability that one would expect from simply analyzing random data. This complaint that DFC may reflect only noise has been recently lessened by the observation of electrical basis to fMRI DFC data and behavioral relevance of DFC characteristics.
In addition to complaints that DFC may be a product of scanner noise, observed DFC could be criticized based on the indirect nature of fMRI which is used to observe it. fMRI data is collected by quickly acquiring a sequence of MRI images in time using echo planar imaging. The contrast in these images is heavily influenced by the ratio of oxygenated and deoxygenated blood. Since active neurons require more energy than resting neurons, changes in this contrast is traditionally interpreted an indirect measure of neural activity. Because of its indirect nature, fMRI data in DFC studies could be criticized as potentially being a reflection of non neural information. This concern has been alleviated recently by the observed correlation between fMRI DFC and simultaneously acquired electrophysiology data.
Battaglia and colleagues have tried to address those controversies, linking dynamic functional connectivity to causality or effective connectivity. The scientists claim indeed that dynamic effective connectivity can emerge from transitions in the collective organization of coherent neural activity.
== Physiological evidence ==
fMRI is the primary means of investigating DFC. This presents unique challenges because fMRI has fairly low temporal resolution, typically 0.5 Hz, and is only an indirect measure of neural activity. The indirect nature of fMRI analysis suggests that validation is needed to show that findings from fMRI are actually relevant and reflective of neural activity.
=== Multi modal approach ===
==== Electrophysiology ====
Correlation between DFC and electrophysiology has led some scientists to suggest that DFC could reflect hemodynamic results of dynamic network behavior that has been seen in single cell analysis of neuron populations. Although hemodynamic response is too slow to reflect a one-to-one correspondence with neural network dynamics, it is plausible that DFC is a reflection of the power of some frequencies of electrophysiology data.
Electroencephalography (EEG) has also been used in humans to both validate and interpret observations made in DFC. EEG has poor spatial resolution because it is only able to acquire data on the surface of the scalp, but it is reflective of broad electrical activity from many neurons. EEG has been used simultaneously with fMRI to account for some of the inter scan variance in FC. EEG has also been used to show that changes in FC are related to broad brain states observed in EEG.
==== MEG ====
Magnetoencephalography (MEG) can be used to measure the magnetic fields produced by electrical activity in the brain. MEG has high temporal resolution and has generally higher spatial resolution than EEG. Resting state studies with MEG are still limited by spatial resolution, but the modality has been used to show that resting state networks move through periods of low and high levels of correlation. This observation is consistent with the results seen in other DFC studies such as DFC activation pattern analysis.
=== Neuronal mechanisms ===
Single-unit recording were used in order to explore the extent, strength and plasticity of functional connectivity between individual cortical neurons in cats and monkeys. Such studies revealed correlated activity at various time scales. At the fastest time scale, that of 1 – 20 ms, correlation coefficients were typically < 0.05. These functional connections were found to be plastic – changing the correlation for a conditioning period of Ts (typically a few minutes), by means of spike-triggered sensory stimulations, induced short-term (typically < Ts) lasting changes of the connections. The pre-post conditioning strengthening of a functional connection was typically equal to the square root of its pre-during conditioning strengthening.
Dynamic Functional Connectivity studied using fMRI may be related to a phenomenon previously discovered in macaque prefrontal cortex termed Dynamic Network Connectivity, whereby arousal mechanisms rapidly alter the strength of glutamate synaptic connections onto dendritic spines by opening or closing potassium channels on spines, thus weakening or strengthening connectivity, respectively. For example, dopamine D1 receptor and/or noradrenergic beta-1 receptor stimulation on spines can increase cAMP-PKA-calcium signaling to open HCN, KCNQ2, and/or SK channels to rapidly weaken a connection, e.g. as occurs during stress.
=== Behavioral basis ===
DFC has been shown to be significantly related to human performance, including vigilance and aspects of attention. It has been proposed and supported that the network behavior immediately prior to a task onset is a strong predictor of performance on that task. Traditionally, fMRI studies have focused on the magnitude of activation in brain regions as a predictor of performance, but recent research has shown that correlation between networks as measured with sliding window analysis is an even stronger predictor of performance. Individual differences in functional connectivity variability (FCV) across sliding windows within fMRI scans have been shown to correlate with the tendency to attend to pain. The degree to which a subject is mind wandering away from a sensory stimulus has also been related to FCV.
== Clinical relevance ==
One of the principal motivations of DFC analysis is to better understand, detect and treat neurological diseases. Static functional connectivity has been shown to be significantly related to a variety of diseases such as depression, schizophrenia, and Alzheimer's disease. Because of the newness of the field, DFC has only recently been used to investigate disease states, but since 2012 each of these three diseases has been shown to be correlated to dynamic temporal characteristics in functional connectivity. Most of these differences are related to the amount of time that is spent in different transient states. Patients with Schizophrenia have less frequent state changes than healthy patients, and this result has led to the suggestion that the disease is related to patients being stuck in certain brain states where the brain is unable to respond quickly to different queues. Also, a study in the visual sensory network showed that schizophrenia subjects spent more time than the healthy subjects in a state in which the connectivity between the middle temporal gyrus and other regions of the visual sensory network is highly negative. Studies with Alzheimer's disease have shown that patients with this ailment have altered network connectivity as well as altered time spent in the networks that are present. The observed correlation between DFC and disease does not imply that the changes in DFC are the cause of any of these diseases, but information from DFC analysis may be used to better understand the effects of the disease and to more quickly and accurately diagnose them.
== References == | Wikipedia/Dynamic_functional_connectivity |
The dorsal attention network (DAN), also known anatomically as the dorsal frontoparietal network (D-FPN), is a large-scale brain network of the human brain that is primarily composed of the intraparietal sulcus (IPS) and frontal eye fields (FEF). It is named and most known for its role in voluntary orienting of visuospatial attention.
As the IPS and FEF were noticed to be activated during many attention-demanding tasks, this network was sometimes referred to as the task-positive network to contrast it against the task-negative network, or default mode network. However, this dichotomy is now considered misleading, because the default mode network can be active in certain cognitive tasks.
== Anatomy ==
The core regions of the DAN are the IPS and FEF of each hemisphere. Other regions of the network may include the middle temporal region (MT+), superior parietal lobule (SPL), supplementary eye field (SEF), and ventral premotor cortex.
More recent works indicate that the cerebellum may participate in this network as well. Less studied regions include the right dorsolateral prefrontal cortex and superior colliculus.
== Function ==
The DAN is most prominently involved in goal-directed, voluntary control of visuospatial attention. Corbetta et al., who first defined and named the DAN in the early-to-mid 2000s, suggest that the network is involved in general top-down selection of stimuli and responses, including other modalities (e.g. auditory, tactile). However, evidence that the full DAN is involved in auditory top-down attention has been questioned, as tests that make said claims incorporated both auditory and visual stimuli.
The dorsal attention network dynamically interacts with the ventral attention network (or salience network) according to task demands. The inferior frontal junction configures this interaction between the two networks during task switches or attention shifts.
== Clinical significance ==
Reduced connectivity within the dorsal and ventral attention networks has been linked to higher levels of attention deficit hyperactivity disorder symptoms. Similarly, reduced connectivity between the DAN and the frontoparietal network is associated with major depressive disorder. On the other hand, overactivation of the DAN has been observed in patients with schizophrenia.
== Nomenclature ==
There are several variations of this network's name in neuroscience literature, such as the dorsal attention system, dorsal frontoparietal attention network, and frontoparietal attention network. Until the discovery of other networks, such as the frontoparietal control network, the term task-positive network referred to the DAN. The term task-positive networks is still sometimes used to refer to all non-default-mode networks.
In 2019, Uddin et al. proposed that dorsal frontoparietal network (D-FPN) be used as a standard anatomical name for this network.
== References == | Wikipedia/Task-positive_network |
In neuroscience, tractography is a 3D modeling technique used to visually represent nerve tracts using data collected by diffusion MRI. It uses special techniques of magnetic resonance imaging (MRI) and computer-based diffusion MRI. The results are presented in two- and three-dimensional images called tractograms.
In addition to the long tracts that connect the brain to the rest of the body, there are complicated neural circuits formed by short connections among different cortical and subcortical regions. The existence of these tracts and circuits has been revealed by histochemistry and biological techniques on post-mortem specimens. Nerve tracts are not identifiable by direct exam, CT, or MRI scans. This difficulty explains the paucity of their description in neuroanatomy atlases and the poor understanding of their functions.
The most advanced tractography algorithm can produce 90% of the ground truth bundles, but it still contains a substantial amount of invalid results.
== MRI technique ==
Tractography is performed using data from diffusion MRI. The free water diffusion is termed "isotropic" diffusion. If the water diffuses in a medium with barriers, the diffusion will be uneven, which is termed anisotropic diffusion. In such a case, the relative mobility of the molecules from the origin has a shape different from a sphere. This shape is often modeled as an ellipsoid, and the technique is then called diffusion tensor imaging. Barriers can be many things: cell membranes, axons, myelin, etc.; but in white matter the principal barrier is the myelin sheath of axons. Bundles of axons provide a barrier to perpendicular diffusion and a path for parallel diffusion along the orientation of the fibers.
Anisotropic diffusion is expected to be increased in areas of high mature axonal order. Conditions where the myelin or the structure of the axon are disrupted, such as trauma, tumors, and inflammation reduce anisotropy, as the barriers are affected by destruction or disorganization.
Anisotropy is measured in several ways. One way is by a ratio called fractional anisotropy (FA). An FA of 0 corresponds to a perfect sphere, whereas 1 is an ideal linear diffusion. Few regions have FA larger than 0.90. The number gives information about how aspherical the diffusion is but says nothing of the direction.
Each anisotropy is linked to an orientation of the predominant axis (predominant direction of the diffusion). Post-processing programs are able to extract this directional information.
This additional information is difficult to represent on 2D grey-scaled images. To overcome this problem, a color code is introduced. Basic colors can tell the observer how the fibers are oriented in a 3D coordinate system, this is termed an "anisotropic map". The software could encode the colors in this way:
Red indicates directions in the X axis: right to left or left to right.
Green indicates directions in the Y axis: posterior to anterior or from anterior to posterior.
Blue indicates directions in the Z axis: inferior to superior or vice versa.
The technique is unable to discriminate the "positive" or "negative" direction in the same axis.
== Mathematics ==
Using diffusion tensor MRI, one can measure the apparent diffusion coefficient at each voxel in the image, and after multilinear regression across multiple images, the whole diffusion tensor can be reconstructed.
Suppose there is a fiber tract of interest in the sample. Following the Frenet–Serret formulas, we can formulate the space-path of the fiber tract as a parameterized curve:
d
r
(
s
)
d
s
=
T
(
s
)
,
{\displaystyle {\frac {d\mathbf {r} (s)}{ds}}=\mathbf {T} (s),}
where
T
(
s
)
{\displaystyle \mathbf {T} (s)}
is the tangent vector of the curve. The reconstructed diffusion tensor
D
{\displaystyle D}
can be treated as a matrix, and we can compute its eigenvalues
λ
1
,
λ
2
,
λ
3
{\displaystyle \lambda _{1},\lambda _{2},\lambda _{3}}
and eigenvectors
u
1
,
u
2
,
u
3
{\displaystyle \mathbf {u} _{1},\mathbf {u} _{2},\mathbf {u} _{3}}
. By equating the eigenvector corresponding to the largest eigenvalue with the direction of the curve:
d
r
(
s
)
d
s
=
u
1
(
r
(
s
)
)
{\displaystyle {\frac {d\mathbf {r} (s)}{ds}}=\mathbf {u} _{1}(\mathbf {r} (s))}
we can solve for
r
(
s
)
{\displaystyle \mathbf {r} (s)}
given the data for
u
1
(
s
)
{\displaystyle \mathbf {u} _{1}(s)}
. This can be done using numerical integration, e.g., using Runge–Kutta, and by interpolating the principal eigenvectors.
== See also ==
Connectome
Diffusion MRI
Connectogram
== References == | Wikipedia/Tractography |
The dorsal attention network (DAN), also known anatomically as the dorsal frontoparietal network (D-FPN), is a large-scale brain network of the human brain that is primarily composed of the intraparietal sulcus (IPS) and frontal eye fields (FEF). It is named and most known for its role in voluntary orienting of visuospatial attention.
As the IPS and FEF were noticed to be activated during many attention-demanding tasks, this network was sometimes referred to as the task-positive network to contrast it against the task-negative network, or default mode network. However, this dichotomy is now considered misleading, because the default mode network can be active in certain cognitive tasks.
== Anatomy ==
The core regions of the DAN are the IPS and FEF of each hemisphere. Other regions of the network may include the middle temporal region (MT+), superior parietal lobule (SPL), supplementary eye field (SEF), and ventral premotor cortex.
More recent works indicate that the cerebellum may participate in this network as well. Less studied regions include the right dorsolateral prefrontal cortex and superior colliculus.
== Function ==
The DAN is most prominently involved in goal-directed, voluntary control of visuospatial attention. Corbetta et al., who first defined and named the DAN in the early-to-mid 2000s, suggest that the network is involved in general top-down selection of stimuli and responses, including other modalities (e.g. auditory, tactile). However, evidence that the full DAN is involved in auditory top-down attention has been questioned, as tests that make said claims incorporated both auditory and visual stimuli.
The dorsal attention network dynamically interacts with the ventral attention network (or salience network) according to task demands. The inferior frontal junction configures this interaction between the two networks during task switches or attention shifts.
== Clinical significance ==
Reduced connectivity within the dorsal and ventral attention networks has been linked to higher levels of attention deficit hyperactivity disorder symptoms. Similarly, reduced connectivity between the DAN and the frontoparietal network is associated with major depressive disorder. On the other hand, overactivation of the DAN has been observed in patients with schizophrenia.
== Nomenclature ==
There are several variations of this network's name in neuroscience literature, such as the dorsal attention system, dorsal frontoparietal attention network, and frontoparietal attention network. Until the discovery of other networks, such as the frontoparietal control network, the term task-positive network referred to the DAN. The term task-positive networks is still sometimes used to refer to all non-default-mode networks.
In 2019, Uddin et al. proposed that dorsal frontoparietal network (D-FPN) be used as a standard anatomical name for this network.
== References == | Wikipedia/Dorsal_attention_network |
Public Understanding of Science is a bimonthly peer-reviewed academic journal established in 1992 and published by SAGE Publications. It covers topics in the popular perception of science, the role of science in society, philosophy of science, science education, and science in public policy. The editor-in-chief is Hans-Peter Peters (Research Center Jülich & Free University of Berlin, Germany).
== Abstracting and indexing ==
Public Understanding of Science is abstracted and indexed in Scopus and the Social Sciences Citation Index. According to the Journal Citation Reports, its 2019 2-year impact factor is 2.754, ranking it 13 out of 88 journals in the category "Communication" and 2 out of 46 journals in the category "History & Philosophy of Science".
== Criticism ==
Public Understanding of Science has been criticised for its lack of commitment to open access, given that it publishes research about public understanding and access to scientific knowledge. Journal editors have published reasons for their position in the journal. However debate continues even within the journal's editorial team.
== Editors ==
John Durant, 1992-1997
Bruce V. Lewenstein, 1998-2003
Edna F. Einsiedel, 2004-2009
Martin W. Bauer, 2010-2015
Massimiano Bucchi, 2016-2019
Hans-Peter Peters, 2020–present
== References ==
== External links ==
Official website | Wikipedia/Public_Understanding_of_Science_(journal) |
Public Understanding of Science is a bimonthly peer-reviewed academic journal established in 1992 and published by SAGE Publications. It covers topics in the popular perception of science, the role of science in society, philosophy of science, science education, and science in public policy. The editor-in-chief is Hans-Peter Peters (Research Center Jülich & Free University of Berlin, Germany).
== Abstracting and indexing ==
Public Understanding of Science is abstracted and indexed in Scopus and the Social Sciences Citation Index. According to the Journal Citation Reports, its 2019 2-year impact factor is 2.754, ranking it 13 out of 88 journals in the category "Communication" and 2 out of 46 journals in the category "History & Philosophy of Science".
== Criticism ==
Public Understanding of Science has been criticised for its lack of commitment to open access, given that it publishes research about public understanding and access to scientific knowledge. Journal editors have published reasons for their position in the journal. However debate continues even within the journal's editorial team.
== Editors ==
John Durant, 1992-1997
Bruce V. Lewenstein, 1998-2003
Edna F. Einsiedel, 2004-2009
Martin W. Bauer, 2010-2015
Massimiano Bucchi, 2016-2019
Hans-Peter Peters, 2020–present
== References ==
== External links ==
Official website | Wikipedia/Public_Understanding_of_Science |
Uses and gratifications theory is a communication theory that describes the reasons and means by which people seek out media to meet specific needs. The theory postulates that media is a highly available product, that audiences are the consumers of the product, and that audiences choose media to satisfy given needs as well as social and psychological uses, such as knowledge, relaxation, social relationships, and diversion.
Uses and gratifications theory was developed from a number of prior communication theories and research conducted by fellow theorists. The theory has a heuristic value because it gives communication scholars a "perspective through which a number of ideas and theories about media choice, consumption, and even impact can be viewed".
== History ==
=== 1940s: Basic premise ===
Beginning in the 1940s, researchers began to see patterns under the perspective of the uses and gratifications theory in radio listeners. Early research was concerned with topics such as children's use of comics and the absence of newspapers during a newspaper strike. An interest in more psychological interpretations emerged during this time period. By 1944, researchers began to look into the earliest forms of uses and gratifications with their work classifying the reasons why people chose specific types of media. Herta Herzog interviewed various soap opera fans and was able to identify three types of gratifications based on why people listened to soap operas: emotional, wishful thinking, and learning. Then, in 1948, Lasswell introduced a four-functional interpretation of the media on a macro-sociological level: media served the functions of surveillance, correlation, entertainment and cultural transmission for both society and individuals.
2 According to Richard West and Lynn Turner, UGT is an extension of Maslow's Hierarchy of Needs that argues that people actively look to satisfy their needs based on a hierarchy. These needs are organized as a pyramid with the largest, most fundamental needs at the base and the need for self-actualization at the top. Wilbur Schramm developed the fraction of selection, a formula for determining which form of mass media an individual would select. The formula helped to decide the amount of gratification an individual would expect to gain from the medium over how much effort they had to make to achieve gratification. Elihu Katz, Jay Blumler, and Michael Gurevitch synthesized that UGT's approach was focused on "the social and psychological origins of needs, which generate expectations of the mass media or other sources, which lead to differential patterns of media exposure (or engagement in other activities), resulting in need gratifications and some other consequences, perhaps mostly unintended ones."
=== 1970s: Five assumptions proposed ===
In 1969 Jay Blumler and Denis McQuail studied the 1964 election in the United Kingdom by examining people's motives for watching certain political programs on television. By categorizing the audience's motives for viewing a certain program, they aimed to understand any potential mass-media effects by classifying viewers according to their needs. The audience motivations they were able to identify helped lay the groundwork for their research in 1972 and eventually uses and gratifications theory. McQuail, Blumler and Joseph Brown suggested that the uses of different types of media could be grouped into 4 categories: diversion, personal relationships, personal identity, surveillance (i.e. forms of information seeking).
McQuail, Blumler and Brown were joined in their media exploration by Elihu Katz, Michael Gurevitch and Hadassah Haas, and their collaborative research began to indicate how people saw the mass media. A 1974 study by Katz, Blumler, and Gurevitch stated five basic assumptions for a framework for understanding the correlation between media and audiences. These assumptions are:
The audience is conceived as active.
In the mass communication process, much initiative in linking gratification and media choice lies with the audience member.
The media compete with other sources of satisfaction.
Methodologically speaking, many of the goals of mass media use can be derived from data supplied by individual audience members themselves.
Value judgments about the cultural significance of mass communication should be suspended while audience orientations are explored on their own terms.
According to their research, goals for media use can be grouped into five uses. The audience wants to:
Be informed or educated
Identify with characters of the situation in the media environment
Simple entertainment
Enhance social interaction
Escape from the stresses of daily life
=== Applications of UGT since 1980s ===
Rehman (1983) applied UGT to study the relationship between movie audience expectations and the satisfaction they derived from going to the movies. The following year Alan Rubin identified two main types of television viewers: ritualized (or, habitual) users and instrumental (or, non-habitual) users. Rubin defined the ritualized users as individuals who had a high regard for television, used television often, and primarily used it for the purpose of a diversion. Meanwhile, the instrumental users were defined as having a lower regard for television, did not use it often, and when they would use television it was for the purpose of acquiring information. Mark Levy and Sven Windahl identified three types of audience activity, which they labeled as preactivity, duractivity, and postactivity. Levy and Windahl described preactivity as seeking out certain media to gratify intellectual needs, duractivity as focusing on deciphering and interpreting messages, and postactivity as seeking out a message for personal or interpersonal benefit.
A year later, in 1985, Levy and Windahl provided a description of what it means to be an "active consumer" of media:
As commonly understood by gratifications researchers, the term "audience activity" postulates a voluntaristic and selective orientation by audiences toward the communication process. In brief, it suggests that media use is motivated by needs and goals that are defined by audience members themselves, and that active participation in the communication process may facilitate, limit, or otherwise influence the gratifications and effects associated with exposure. Current thinking also suggests that audience activity is best conceptualized as a variable construct, with audiences exhibiting varying kinds and degrees of activity.
Then, in 1987, researchers Lewis Donohew, Philip Palmgreen, and J.D. Rayburn identified four different lifestyle types of television viewers, each with a variety of differences from the degrees to which the audience member watches TV, why they watch it, what their income and gender is, their marriage status, and so on. The four types are: disengaged homemaker, outgoing activist, restrained activist, and working class climber
The most recent interest surrounding UGT is the link between the reason why media is used and the achieved gratification. UGT researchers are developing the theory to be more predictive and explanatory by connecting the needs, goals, benefits, consequences of media consumption and use along with individual factors. Work in UGT was trailblazed by the research of Katz, Blumler, and Gurevitch which built on Herzog's research and caused a paradigm shift from how media influences people to how audiences use media, diminishing the dominance of the limited effects approach to mass media studies.
== Research issues ==
In the 1980s, Palmgreen and Rayburn proposed the model of gratifications sought (GS) and gratifications obtained (GO). GS are the rewards people seek from media, while GO are the rewards people receive from media. In their study, they found that correlations between individual GS and non-corresponding GOs were generally much lower, indicating considerable promise for a sought versus obtained conceptualization of uses and gratifications.
Palmgreen et al. conducted an investigation in 1985 that provides support for a process model of uses and gratifications based upon an expectancy-value approach. Results of the study supported the hypothesis that gratifications obtained are strongly related to the beliefs about media attributes but are not related to evaluations of those attributes. Further, the results demonstrated that gratifications sought and obtained may be measured at the same level of abstraction, contrary to earlier speculation.
== Modern applications ==
The studies of Katz and his colleagues laid a theoretical foundation for building the uses and gratifications approach. Since then, the research on this subject has been strengthened and extended. The current status of uses and gratifications is still based on Katz's first analysis, particularly as new media forms have emerged in an electronic information age when people have more options of media use.
=== Mobile phone usage ===
Mobile phones, a comparatively new technology, have many uses and gratifications attached to them. Due to their nature of mobility, constant access, and options to both add and access content, this field is expanding with new research on the motivations behind using mobile phones. In general, people use mobile phones for the following uses and gratifications: sociability, entertainment, status, immediate access, instrumentality, mobility, and psychological reassurance. Researchers have also identified that the uses and gratifications for contributing mobile content differ from those for retrieving mobile content.
The specific function of text messaging has also been studied to find its uses and gratifications and explore any potential gender differences. Seven uses and gratifications, in order of importance, have been proposed: accessibility, relaxation, escape, entertainment, information seeking, coordination for business, socialization, status seeking. The results also displayed gender differences, implying that social and societal expectations for females around independence and connection were a factor in their uses and gratification seeking. A study on instant messaging found that women chatted longer and for sociability; men chatted for less time per session and for entertainment and relaxation.
=== Internet usage ===
The Internet provides a new and deep field for exploring UGT. It was found to have three main categories of gratifications: content gratification, process gratification, and social gratification. Content uses and gratification include the need for researching or finding specific information or material, which are gratified with content. Process uses and gratification involve the experience of purposeful navigating or random browsing of the Internet in its functional process. Social uses and gratification encompass a wide range of forming and deepening social ties.
Scholars like LaRose utilize UGT to understand Internet usage via a socio-cognitive framework. This reduces uncertainties that arise from homogenizing an Internet audience and explaining media usage in terms of only positive gratifications. LaRose also created measures for self-efficacy and self-disparagement and related UGT to negative outcomes of online behavior, such as internet addiction.
=== Social media usage ===
Whereas basic research finds that socialization motivates use of friend-networking sites, uses and gratifications theory suggests that individual users will continue to be engaged with social networking sites if their gratifications and needs are fulfilled by such tools. Some further exploration has demonstrated that although emotional, cognitive, social, and habitual uses are motivational to use social media, not all uses are consistently gratified. By 2013, research has looked at social networking services, personal and subject-based blogs, and internet forums. The relationship between gratifications and narcissism, and the effects of age on this relationship and corresponding gratifications have also been studied. Overall, users have the following motivations: social and affection, need to vent negative feelings, recognition, entertainment, cognitive needs.
Users who share news are motivated by the uses and gratifications of socializing and status seeking, especially if they have had prior experience with social media. Users also engage in cyberbullying in order to fulfil a need to be vengeful and malicious, while avoiding face-to-face contact.
=== Online gaming ===
Achievement, enjoyment and social interaction are all motivations for starting to play an online game, with success at the game and the extent to which gamers' uses were gratified predicting continuance in playing. In 2017, researchers applied UGT to study user behavior among Pokémon Go players. Results show that enjoyment, physical activity, nostalgia, image, normative influences and flow drive various forms of user behavior. In addition, perceived physical risks, but not perceived privacy risks, lead to weaker forms of usage.
=== Entertainment media ===
Research has shown that media taken in for entertainment purposes have a wide range of uses and emotional gratifications, and that these are not mutually exclusive but can overlap with each other. Rehman (1983) demonstrated a relationship between gratifications sought and obtained from the movies and movie attendance. The most prominently cited emotional gratification of media use of mood management. UGT proposes that people prefer to maintain a state of intermediate arousal. When in a bad mood, bored, or over-aroused, people will seek media as regulation for or distraction from their mood. Another emotional gratification is affective disposition, which involves people experiencing gratificaition when rooting for characters depicted as good and moral. Other emotional gratifications include excitation transfer, sensation seeking, downward social comparison, mood adjustment, and competence.
Additionally, the modes of reception of entertainment media correlates with emotion involvement and can facilitate the pursuit of other goals. Entertainment media allows users to live out gender-socialised roles, satisfy parasocial relationships, live vicariously through fictional characters, and find meaning and purpose.
== Related theories ==
=== Media system dependency theory ===
Media system dependency theory (MSDT or media dependency theory) has been studied as an offshoot of UGT. However, media dependency theory focuses on audiences' goals for media consumption as the source of their dependency; while uses and gratification theory focuses on audience's needs as drivers for media consumption. MSDT states that as a person becomes increasingly dependent on media to satisfy their needs, that media will become more important in a person's life and thereby have increased influence and effects on that person. MSDT acknowledges and builds upon UGT because it is based on the assumptions that people have different uses for media that arise from their needs.
=== Social cognitive theory ===
Building on UGT, Social Cognitive Theory helped distinguish GS versus GO stimulus for media consumption. Social cognitive theory explains behavior in terms of the reciprocal causation between individuals, environments, and behaviors. This allows for a more personal application of UGT instead of a large, blanketing assumption about a large audience of mass media. If GO is greater than GS then there will be more audience satisfaction. Lastly, audiences' GS are not always the reality of their GO.
=== Cultivation theory ===
Cultivation theory is concerned with understanding the role that media – specifically television – plays in shaping a person's world view. Whereas UGT tries to understand the motivations that drive media usage, cultivation theory focuses on the psychological effects of media. Cultivation theory is used especially to study violence in television and how it shapes audience's understanding of the reality of violence in society. Often, because of media's influence, audiences have a more heightened and unrealistic perception of the amount of violence. A UGT approach may be implemented to Cultivation theory cases to understand why an audience would seek violent media and if audiences seek television violence to satisfy the need of confirmation of their worldview.
=== Hypodermic needle model ===
Hypodermic needle model (known as the hypodermic-syringe model, transmission-belt model, or magic bullet theory) is a model of communication suggesting that an intended message is directly received and wholly accepted by the receiver. The model was originally rooted in 1930s behaviourism and was largely considered obsolete for a long time, but big data analytics-based mass customisation has led to a modern revival of the basic idea. After that, a shift which rediscovered the relationship between media and people occurred and led to establishment of uses and gratifications approach.
=== Mass media ===
In media studies, mass communication, media psychology, communication theory, and sociology, media influence and media effects are topics relating to mass media and media culture's effects on individual or an audience's thoughts, attitudes, and behavior. Whether it is written, televised, or spoken, mass media reaches a large audience. Mass media's role and effect in shaping modern culture are central issues for study of culture.
== Theory criticism ==
Uses and gratifications theory has, almost since its inception, been viewed critics as not meeting the standards necessary to be a theory. Critics argue that it instead is more of an approach to analysis or a data-collecting strategy. Common criticism include that gratifications are more dependent on input by researchers than on decisions made by research subjects; that early research utilized flawed methodologies that led findings to be overstimated; that audiences of different ages likely have different motivations for using identical media, and also likely have different gratifications; that most research relies on pure recollection of memory rather than data; and that it goes too far in claiming that people are free to choose the media and the interpretations they desire.
As a sociologically based theory, UGT has little to no benefit to psychology due to its weakness in operational definitions and weak analytical mode. It also is focused too narrowly on the individual and neglects the social structure and place of the media in that structure. Ruggiero wrote that "most scholars agree that early research had little theoretical coherence and was primarily behaviorist and individualist in its methodological tendencies." Blumler and other critics have argued that the line between gratification and satisfaction is blurred, and Blumler wrote that "the nature of the theory underlying uses and gratifications research is not totally clear." McQuail criticized the UGT as too cumbersome and tried to do too much, arguing that there is no real way of testing the theory through content analysis or surveys.
Among the most criticized tenets of uses and gratifications as theory is the assumption of an active audience. Ruggerio noted three assumptions necessary to the idea of active audience: First, media selection is initiated by the individual. Second, expectations regarding the use of media must be a product of individual predispositions, social interactions and environmental factors. And third, the active audience exhibits goal-directed behavior. This concept of active audience finds, at best, limited acceptance outside of the United States.
Jay Blumler presented a number of points as to why UGT cannot measure an active audience. He stated, "The issue to be considered here is whether what has been thought about Uses and Gratifications Theory has been an article of faith and if it could now be converted into an empirical question such as: How to measure an active audience?" Blumler then offered suggestions about the kinds of activity the audiences were engaging with in the different types of media: utility, intentionality, selectivity, and imperviousness to influence. In 1973, Blumler, McQuail and Brown extended Lasswell's four groups to include four more primary factors for media usage: diversion, personal relationships, personal identity, and surveillance.
Severin and Tankard also argued that most of the data collection method used in uses and gratification studies are self-report questionnaires, which is not a reliable way to ascertain the genuine reason for using the media because they believe that individuals can not respond accurately to questions about their own feelings and behavior.
== See also ==
Influence of mass media
Outline of communication
== References ==
== Further reading ==
Menon, D. (2022). Uses and gratifications of photo sharing on Instagram. International Journal of Human-Computer Studies, 168, 102917.https://doi.org/10.1016/j.ijhcs.2022.102917
Blumler, J.; Katz, E. (1974). The Uses of Mass Communication: Current Perspectives on Gratification Research. London: SAGE Publications.
Straubhaar, Joseph D.; LaRose, Robert; Straubhaar, Josheph (2010). Media now: communications media in the information age (6 ed.). Belmont: Wadsworth. ISBN 978-0-495-57008-0.
Melvin Defleur Ball-Rokeach, S. J. (1989). Theories of Mass Communication.
Grant, A. E. (April 1998). Dependency and control. Paper presented to the Annual Convention of the Association of Educators in Journalism and Mass Communications, Baltimore, Maryland (Report).
Menon, D., & Meghana, H. R. (2021). Unpacking the uses and gratifications of Facebook: A study among college teachers in India. Computers in Human Behavior Reports, 3, 100066.https://doi.org/10.1016/j.chbr.2021.100066
Infante, Dominic A.; Rancer, Andrew S.; Womack, Deanna F. (1993). Building Communication Theory. pp. 204–412.
Infante, Dominic A.; Rancer, Andrew S.; Avtgis, Theodore A. (2009). Contemporary Communication Theory. Kendall Hunt Publishing Company. ISBN 978-0-7575-6634-9.
Katz, E. (1987). "Communication research since Lazarsfeld". Public Opinion Quarterly. 51 (4 PART 2): 525–545. doi:10.1093/poq/51.4_PART_2.S25.
Menon, D. (2022). Uses and gratifications of educational apps: A study during COVID-19 pandemic. Computers and Education Open, 3, 100076.https://doi.org/10.1016/j.caeo.2022.100076
Katz, E. (1959). "Mass communication research and the study of culture". Studies in Public Communication. 2: 1–6.
Katz, E.; Blumler, J. G.; Gurevitch, M. (1974). Utilization of mass communication by the individual. In J. G. Blumler, & E. Katz (Eds.), The uses of mass communications: Current perspectives on gratifications research. Beverly Hills: Sage. pp. 19–32.
Katz, E.; Haas, H.; Gurevitch, M. (1973). "On the use of the mass media for important things". American Sociological Review. 38 (2): 164–181. doi:10.2307/2094393. JSTOR 2094393. S2CID 14263420.
Laughey, Dan. Key Themes in Media Theory. pp. 26–27 – via Behaviourism and Media Effects.
Lazarsfeld, P.F. (1940). "Radio and the Printed Page.". New York: Dvell, Sloan, Pearce.
McQuail, D.; Blumler, J. G.; Brown, J. (1972). The television audience: A revised perspective. Middlesex, England: Penguin. pp. 135–165 – via In D. McQuail (Ed.), Sociology of Mass Communication.
McQuail, D. (1983). With Benefits to Hindsight : Reflections on Uses and Gratifications Research. SAGE Publications – via Critical Studies in Mass Communication Theory: And Introduction.
McQuail, D. (2010). McQuails Mass Communication Theory (6 ed.). London: SAGE Publications.
Menon, Devadas; Meghana, H.R. (January 2021). "Unpacking the uses and gratifications of Facebook: A study among college teachers in India". Computers in Human Behavior Reports. 3: 100066. doi:10.1016/j.chbr.2021.100066.
Palmgreen, Philip; Rayburn, J. D. (December 1985). "A comparison of gratification models of media satisfaction". Communication Monographs. 52 (4): 334–346. doi:10.1080/03637758509376116.
Rehman, S. (1983). Correlation between gratifications sought and obtained from the movies. Doctoral dissertation, Bowling Green State University, Ohio (Report).
Roger, Tony (28 August 2019). "Are Newspapers Dying?". ThoughtCo. Archived from the original on 20 March 2023. Retrieved 25 September 2023.
Rubin, A. M.; Windahl, S. (1982). Mass media uses and dependency: A social systems approach to uses and gratifications. Paper presented to the meeting of the International Communication Association, Boston, MA. | Wikipedia/Uses_and_gratifications_theory |
Science in popular culture is the treatment and use of scientific terms and issues in popular media such as cinema, music, television, and novels. Science fiction (SciFi), in particular, is a branch of literature that uses scientific ideas as a basis.: 172 In the creation of these works, scientific knowledge and theories are occasionally manipulated or distorted to align with the narrative content.
== History ==
Before the 19th century, the impact of scientific advancements on society was not consistently widespread. The general populace often remained unaware of new scientific discoveries, and even if they did become aware, comprehension of the underlying principles and the implications of these discoveries was limited. As industrialization and urbanization rose, people migrated from rural areas to work in large factories, leading to increased socialization which in turn exposed them to scientific ideas, challenging their traditional beliefs. One of these ideas is the theory of evolution, which provided a scientific theory for the origin of humankind that ran counter to many religious beliefs.
Beginning in the 19th century, there was a societal change where people were increasingly exposed to scientific and technological knowledge in their everyday lives. This was due to not only the increasing appeal for new science and technology, but the entrepreneurs, who capitalized on this appeal and would advertise those ideas to the general public. One example of such idea is the lobotomy, a medical procedure that was extensively used in the 1940s to treat mental illnesses, though it remains controversial for its effect on brain functioning and its supposed use to control minorities. A greater number of scientific discoveries made scientific research the foremost actor that people turned to in society, to help solve problems.
By the mid-19th century, knowledge became more specialized and institutionalized, such that only those that had spent years studying an academic discipline could fully grasp its knowledge and contribute to it. As more research was produced on a subject, the deeper researchers had to delve into it to produce something that hadn't been done before, which resulted in different sub-fields being created. For example, in some biological research is concerned with classification, where biologists create a taxonomies to classify biological organisms, and show the perceived relationships between different species. Other biological research focuses more on the building blocks of organisms, concerning itself with DNA sequences and proteins that are involved in the complex functions of life. As scientific research progressed, the specialization within fields meant that two biologists that studied these fields would have little to discuss regarding their respective discoveries to one another. Specialization of science also discouraged non-academic citizens from contributing to it. Due to the increasing gap between scientific discovery and its perceived usefulness by the general public, people began viewing some scientific discoveries as irrelevant. For instance, the general public wouldn't have experienced as much unrest about a recently discovered protein as they had at On the Origin of Species.
This gap led to the development of popular science (also pop-science), which intends to inform the general public about scientific fields, while combatting the perceived irrelevancy of specific sciences. Usually in the form of written media, popular science has allowed scientific ideas to be presented to the public in a way intuitively understandable. From popular science stemmed science fiction, a genre of speculative fiction that incorporated elements of science to add to its appeal.
== Examples ==
=== Alternative worlds ===
Fictional worlds refer to conceptual realms with imaginary characters and settings. These realms may parallel aspects of the real world, albeit with distinctive fantastical elements, such as in The Wizard of Oz. They may also present altered versions of historical periods, as seen in J.R.R. Tolkien's The Lord of the Rings trilogy. Additionally, fictional worlds can diverge from reality by introducing an alternate history. For example, in Harry Harrison's Eden trilogy, a fictionalized account unfolds in a reality where the dinosaur mass extinction event never occurs.
=== Androids ===
The focus of androids is the invention and use of robots that look and act like humans. As of June 2018, there has been development of some prototype androids like Hanson Robotics' Sophia, who can interact with humans and engage in sophisticated but limited movement.
== See also ==
Science portal
Social effects of evolutionary theory
Reactions to On the Origin of Species
== References == | Wikipedia/Science_in_popular_culture |
Public awareness of science (PAS) is everything relating to the awareness, attitudes, behaviors, opinions, and activities that comprise the relations between the general public or lay society as a whole to scientific knowledge and organization. This concept is also known as public understanding of science (PUS), or more recently, public engagement with science and technology (PEST). It is a comparatively new approach to the task of exploring the multitude of relations and linkages science, technology, and innovation have among the general public. While early work in the discipline focused on increasing or augmenting the public's knowledge of scientific topics, in line with the information deficit model of science communication, the deficit model has largely been abandoned by science communication researchers. Instead, there is an increasing emphasis on understanding how the public chooses to use scientific knowledge and on the development of interfaces to mediate between expert and lay understandings of an issue. Newer frameworks of communicating science include the dialogue and the participation models. The dialogue model aims to create spaces for conversations between scientists and non-scientists to occur while the participation model aims to include non-scientists in the process of science.
== Major themes ==
The area integrates a series of fields and themes such as:
Citizen science
Consumer education
Fixed and mobile science exhibits
Media and science (medialisation of science)
Public controversies over science and technology
Public tours of research and development (R&D) parks, manufacturing companies, etc.
Science and art
Science communication in the mass media, Internet, radio, films and television programs
Science education for adults
Science fairs in schools and social groups
Science festivals
Science in popular culture
Science in text books and classrooms
Science museums, aquaria, planetaria, zoological parks, botanical gardens, etc.
Science social movements
Important lines of research are how to raise public awareness and public understanding of science and technology. Also, learning how the public feels and knows about science generally as well as individual subjects, such as genetic engineering, or bioethics. Research by Matthew Nisbet highlights several challenges in science communication, including the paradox that scientific success can create either trust or distrust in experts in different populations and that attitudes of trust are shaped by mostly socioeconomic rather than religious or ideological differences. A 2020 survey by the Pew Research Center found varying levels of trust in science by country, political leanings, and other factors.
== Bodmer report ==
The publication of the Royal Society's' report The Public Understanding of Science (or Bodmer Report) in 1985 is widely held to be the birth of the Public Understanding of Science movement in Britain. The report led to the founding of the Committee on the Public Understanding of Science and a cultural change in the attitude of scientists to outreach activities.
== Models of engagement ==
=== Contextualist model ===
In the 1990s, a new perspective emerged in the field with the classic study of Cumbrian Sheep Farmers' interaction with the Nuclear scientists in England. Brian Wynne demonstrated how the experts were ignorant or disinterested in taking into account the lay knowledge of the sheep farmers while conducting field experiments on the impact of the Chernobyl nuclear fallout on the sheep in the region. Because of this shortcoming from the side of the scientists, local farmers lost their trust in them. The experts were unaware of the local environmental conditions and the behaviour of sheep and this has eventually led to the failure of their experimental models. Following this study, scholars have studies similar micro-sociological contexts of expert-lay interaction and proposed that the context of knowledge communication is important to understand public engagement with science. Instead of large scale public opinion surveys, researchers proposed studies informed by sociology of scientific knowledge (SSK). The contextualist model focuses on the social impediments in the bidirectional flow of scientific knowledge between experts and laypersons/communities.
=== Deliberative model ===
Scholars like Sheila Jasanoff have advanced the debate around public engagement with science by leveraging the theory of deliberative democracy to analyze the public deliberation of and participation in science through various institutional forms. Proponents of greater public deliberation argue it is a basic condition for decision making in democratic societies, even on science and technology issues. There are also attempts to develop more inclusive participatory models of technological governance in the form of consensus conferences, citizen juries, extended peer reviews, and deliberative mapping.
=== Civic science model ===
Some scholars have identified a new era of "post-normal science" (PNS) in which many scientific discoveries carry high stakes if risks are estimated incorrectly within a broader social context that has a high degree of uncertainty. This PNS era requires a new approach to public engagement efforts and requires a reevaluation of the underlying assumptions of "public engagement", especially with emerging science and technology issues, like CRISPR gene editing, that have the potential to become "wicked problems". These "wicked" issues often require regulatory and policy decisions that have no single correct solution and often involve numerous interest groups – none of whom are clearly positioned to decide and resolve the problem. Policy and regulatory decisions around these scientific issues are inherently political and must balance trade-offs between the scientific research, perceptions of risk, societal needs, and ethical values. While scientists can provide factual answers to research questions and mathematical estimates of risk, many considerations surrounding these wicked science and technology issues have no factual answer. The unidirectional deficit model of simply educating the public on theses issues is insufficient to address these complex questions, and some scholars have proposed scientists adopt a culture of civic science: "broad public engagement with issues that arise at the many intersections between science and society." An emphasis is placed on developing an iterative engagement model that actively seeks to incorporate groups who stand to be adversely effected by a new technology and conducting this engagement away from universities so that it can be done on the public's terms with the public's terms. Other scholars have emphasized that this model of public engagement requires that the public be able to influence science, not merely be engaged by it, up to the point of being able to say "no" to research that does not align with the broader public's values. Under the civic science model, there are five key lessons for scientists committed to public engagement:
Establish why you want to engage with the public and clearly identify your goals.
Seek out and engage with a broad, diverse range of groups and perspectives and center engagement on listening to these groups.
Work cooperatively with groups to establish common definitions to avoid the perception that researchers are being disingenuous by relying on semantic differences between expert and lay interpretations of vocabulary to ensure the public "supports" their position.
Working to tilt public debates in favor of the priorities and values of researchers will not lead to consistent "best" decisions because wicked science and technology problems will have different considerations and perspectives depending on the application and cultural context.
Meaningfully engage as early as possible; engagement must begin early enough in the research process that the public's views can shape both the research and implementation of findings
== Public understanding of science ==
Social scientists use various metrics to measure public understanding of science, including:
=== Factual knowledge ===
The key assumptions is that the more individual pieces of information a person is able to retrieve, the more that person is considered to have learned.
Examples of measurement:
Recognition: Answering a specific question by selecting the correct answer out a list
Cued recall: Answering a specific question without a list of choices
Free recall: After exposure to information, the study participant produces a list of as much of the information as they can remember
=== Self-reported knowledge, perceived knowledge, or perceived familiarity ===
The key assumption is that emphasizes the value of knowledge of one's knowledge.
Examples of measurement:
Scaled survey responses to questions such as, "How well informed you would say you are about this topic?", this can be also used to assess perceived knowledge before and after events
=== Structural knowledge ===
The nature of connections among different pieces of information in memory.
The key assumption is that the use of elaboration increases the likelihood of remembering information.
Examples of measurement:
Asking study participants to assess relationships among concepts. For example, participants free recall concepts onto the first row and column of a matrix, then indicate whether the concepts are related to each other by placing an "X" in the cell if they are not. Participants then rank the remaining open cells by their relatedness from 1 (only very weakly) to 7 (very strongly related).
Study participants answer questions designed to measure elaboration involved in a task, such as, "I tried to relate the ideas I read about to my own past experiences."
=== Trust and credibility ===
People may trust science or scientists to different degrees, or may find specific scientists or specific research to be more or less credible. These factors can be related to how science can be used to advance knowledge, and may also be related to how science is communicated.
Examples of measurement:
The 21-item Trust in Science and Scientists Inventory, which measures agreement/disagreement with statements like, "We can trust scientists to share their discoveries even if we don't like their findings."
Scientist-specific measures of agreement, such as "I would trust scientific information if I knew it came from this author."
=== Mixed use of measures ===
While some studies purport that factual and perceived knowledge can be viewed as the same construct, a 2012 study investigating public knowledge of nanotechnology supports separating their use in communications research, as they "do not reflect the same underlying knowledge structures". Correlations between them were found to be low and they were not predicted by the same factors. For example different types of science media use, television versus online, predicted different constructs.
Factual knowledge has been shown to be empirically distinct from structural knowledge.
== Project example ==
Government and private-led campaigns and events, such as Dana Foundation's "Brain Awareness Week", are becoming a strong focus of programmes which try to promote public awareness of science.
The UK PAWS Foundation dramatically went as far as establishing a Drama Fund with the BBC in 1994. The purpose was to encourage and support the creation of new drama for television, drawing on the world of science and technology.
The Vega Science Trust was set up in 1994 to promote science through the media of television and the internet with the aim of giving scientists a platform from which to communicate to the general public.
The Simonyi Professorship for the Public Understanding of Science chair at The University of Oxford was established in 1995 for the ethologist Richard Dawkins by an endowment from Charles Simonyi. Mathematician Marcus du Sautoy has held the chair since Dawkins' retirement in 2008. Similar professorships have since been created at other British universities. Professorships in the field have been held by well-known academics including Richard Fortey and Kathy Sykes at the University of Bristol, Brian Cox at Manchester University, Tanya Byron at Edge Hill University, Jim Al-Khalili at the University of Surrey, and Alice Roberts at the University of Birmingham.
== See also ==
== References ==
== Further reading ==
Bensaude-vincent, Bernadette (2001). "A Genealogy of the Increasing Gap between Science and the Public". Public Understanding of Science. 10 (1): 99–113. doi:10.1088/0963-6625/10/1/307.
Bijker, Wiebe E., Bal, Roland and Hendriks, Ruud. 2009. The Paradox of Scientific Authority: The Role of Scientific Advice in Democracies. Cambridge and London: The MIT Press.
Bucchi, Massimiano (1996). "When Scientists Turn to the Public: Alternative Routes in Science Communication". Public Understanding of Science. 5 (4): 375–394. doi:10.1088/0963-6625/5/4/005. S2CID 143374883.
Dash, Biswanath (2014a). "Public Understanding of Cyclone Warning in India: Can Wind be Predicted?". Public Understanding of Science. 24 (8): 970–987. doi:10.1177/0963662514553203. PMID 25313142. S2CID 22226217.
Davenport, Sally and Leitch, Shirley. 2005. "Agoras, Ancient and Modern, and a Framework for Science-Society Debate", Science and Public Policy 32(2), April, pp. 137–153.
Dryzek, John S. 2000. Deliberative Democracy and Beyond: Liberals, Critics, Contestations. New York and Oxford: Oxford University Press.
Felt, Ulrike; Fochler, Maximilian (2010). "Machineries for Making Publics: Inscribing and De-scribing Publics in Public Engagement". Minerva. 48 (3): 219–239. doi:10.1007/s11024-010-9155-x. S2CID 144227502.
Fischer, Frank. 2005. Citizens, Experts, and the Environment. Durham: Duke University Press.
Gregory, Jane & Miller, Steve (1998); Science in Public: Communication, Culture & Credibility (Cambridge, Massachusetts USA: Perseus Publishing)
Hess, David J (2011). "To Tell the Truth: On Scientific Counter Publics". Public Understanding of Science. 20 (5): 627–641. doi:10.1177/0963662509359988. S2CID 145627603.
Hilgartner, Stephen (1990). "The Dominant View of Popularisation: Conceptual Problems, Political Uses". Social Studies of Science. 20 (3): 519–539. doi:10.1177/030631290020003006. S2CID 144068473.
Irwin, Alan and Wynne, Brian. (eds.) 1996. Misunderstanding Science? The Public Reconstruction of Science and Technology. Cambridge: Cambridge University Press.
Irwin, Alan. 1995. Citizen Science: A Study of People, Expertise and Sustainable Development. London and New York: Routledge.
Jasanoff, Sheila (2003c). "Technologies of Humility: Citizen Participation in Governing Science". Minerva. 41 (3): 223–244. doi:10.1023/A:1025557512320. S2CID 14370392.
Jasanoff, Sheila. 2005. Designs on Nature: Science and Democracy in Europe and the United States. Princeton and Oxford: Princeton University Press.
Leach, Melissa, Scoones, Ian and Wynne, Brian. (eds.) 2005. Science and Citizens: Globalisation and the Challenge of Engagement. London and New York: Zed Books.
Public Understanding of Science, specialist journal.
Shapin, Steven. 1990. 'Science and the Public' in R.C. Olby et al. (eds). Companion to the History of Modern Science. London and New York: Routledge. Pp. 990–1007.
The Royal Academy of Science's 2006 "Factors affecting science communication: a survey of scientists and engineers" report.
Southwell, Brian G. (2013). "Social Networks and Popular Understanding of Science and Health". Baltimore, MD: Johns Hopkins University Press.
Southwell, Brian G.; Torres, Alicia (2006). "Connecting interpersonal and mass communication: Science news exposure, perceived ability to understand science, and conversation". Communication Monographs. 73 (3): 334–350. doi:10.1080/03637750600889518. S2CID 143644528.
Varughese, Shiju Sam (2012). "Where are the missing masses? The Quasi-publics and Non-publics of Technoscience". Minerva. 50 (2): 239–254. doi:10.1007/s11024-012-9197-3. S2CID 144319733.
Varughese, Shiju Sam (2017). Contested Knowledge: Science, Media, and Democracy in Kerala. Oxford University Press. doi:10.1093/acprof:oso/9780199469123.001.0001. ISBN 9780199469123.
== External links ==
Science.gov
Vega Science Trust | Wikipedia/Public_understanding_of_science |
The United Nations Educational, Scientific and Cultural Organization (UNESCO ) is a specialized agency of the United Nations (UN) with the aim of promoting world peace and security through international cooperation in education, arts, sciences and culture. It has 194 member states and 12 associate members, as well as partners in the non-governmental, intergovernmental and private sector. Headquartered in Paris, France, UNESCO has 53 regional field offices and 199 national commissions.
UNESCO was founded in 1945 as the successor to the League of Nations' International Committee on Intellectual Cooperation. UNESCO's founding mission, which was shaped by the events of World War II, is to advance peace, sustainable development and human rights by facilitating collaboration and dialogue among nations. It pursues this objective through five major programme areas: education, natural sciences, social/human sciences, culture and communication/information. UNESCO sponsors projects that improve literacy, provide technical training and education, advance science, protect independent media and press freedom, preserve regional and cultural history, and promote cultural diversity. The organization prominently helps establish and secure World Heritage Sites of cultural and natural importance.
UNESCO is governed by the General Conference composed of member states and associate members, which meets biannually to set the agency's programs and budget. It also elects members of the executive board, which manages UNESCO's work, and appoints every four years a Director-General, who serves as UNESCO's chief administrator.
== History ==
=== Origins ===
UNESCO and its mandate for international cooperation can be traced back to a League of Nations resolution on 21 September 1921, to elect a commission to study the feasibility of having nations freely share cultural, educational and scientific achievements. This new body, the International Committee on Intellectual Cooperation (ICIC), was created in 1922 and counted such figures as Henri Bergson, Albert Einstein, Marie Curie, Robert A. Millikan, and Gonzague de Reynold among its members (being thus a small commission of the League of Nations essentially centred on Western Europe). The International Institute for Intellectual Cooperation (IIIC) was then created in Paris in September 1924, to act as the executing agency for the ICIC. However, the onset of World War II largely interrupted the work of these predecessor organizations. As for private initiatives, the International Bureau of Education (IBE) began to work as a non-governmental organization in the service of international educational development since December 1925 and joined UNESCO in 1969, after having established a joint commission in 1952.
=== Creation ===
After the signing of the Atlantic Charter and the Declaration of the United Nations, the Conference of Allied Ministers of Education (CAME) began meetings in London which continued from 16 November 1942 to 5 December 1945. On 30 October 1943, the necessity for an international organization was expressed in the Moscow Declaration, agreed upon by China, the United Kingdom, the United States and the USSR. This was followed by the Dumbarton Oaks Conference proposals of 9 October 1944. Upon the proposal of CAME and in accordance with the recommendations of the United Nations Conference on International Organization (UNCIO), held in San Francisco from April to June 1945, a United Nations Conference for the establishment of an educational and cultural organization (ECO/CONF) was convened in London from 1 to 16 November 1945 with 44 governments represented. The idea of UNESCO was largely developed by Rab Butler, the Minister of Education for the United Kingdom, who had a great deal of influence in its development. At the ECO/CONF, the Constitution of UNESCO was introduced and signed by 37 countries, and a Preparatory Commission was established. The Preparatory Commission operated between 16 November 1945, and 4 November 1946 — the date when UNESCO's Constitution came into force with the deposit of the twentieth ratification by a member state.
The first General Conference took place from 19 November to 10 December 1946, and elected Julian Huxley to Director-General. United States Army colonel, university president and civil rights advocate Blake R. Van Leer joined as a member as well. The Constitution was amended in November 1954 when the General Conference resolved that members of the executive board would be representatives of the governments of the States of which they are nationals and would not, as before, act in their personal capacity. This change in governance distinguished UNESCO from its predecessor, the ICIC, in how member states would work together in the organization's fields of competence. As member states worked together over time to realize UNESCO's mandate, political and historical factors have shaped the organization's operations in particular during the Cold War, the decolonization process, and the dissolution of the Soviet Union.
=== Development ===
Among the major achievements of the organization is its work against racism, for example through influential statements on race starting with a declaration of anthropologists (among them was Claude Lévi-Strauss) and other scientists in 1950 and concluding with the 1978 Declaration on Race and Racial Prejudice.
In 1955, the Republic of South Africa withdrew from UNESCO saying that some of the organization's publications amounted to "interference" in the country's "racial problems". It rejoined the organization in 1994 under the leadership of Nelson Mandela.
One of the early work of UNESCO in the education field was a pilot project on fundamental education in the Marbial Valley, Haiti, which was launched in 1947. Following this project one of expert missions to other countries, included a 1949 mission to Afghanistan. UNESCO recommended in 1948 that Member countries should make free primary education compulsory and universal. The World Conference on Education for All, in Jomtien, Thailand, started a global movement in 1990 to provide basic education for all children, youths and adults. In 2000, World Education Forum in Dakar, Senegal, led member governments to commit for achieving basic education for all in 2015.
The World Declaration on Higher Education was adopted by UNESCO's World Conference on Higher Education on 9 October 1998, with the aim of setting global standards on the ideals and accessibility of higher education.
UNESCO's early activities in culture included the International Campaign to Save the Monuments of Nubia, launched in 1960. The purpose of the campaign was to move the Great Temple of Abu Simbel to keep it from being swamped by the Nile after the construction of the Aswan Dam. During the 20-year campaign, 22 monuments and architectural complexes were relocated. This was the first and largest in a series of campaigns including Mohenjo-daro (Pakistan), Fes (Morocco), Kathmandu (Nepal), Borobudur (Indonesia) and the Acropolis of Athens (Greece). The organization's work on heritage led to the adoption, in 1972, of the Convention concerning the Protection of the World Cultural and Natural Heritage. In 1976, the World Heritage Committee was established and the first sites were included on the World Heritage List in 1978. Since then important legal instruments on cultural heritage and diversity have been adopted by UNESCO member states in 2003 (Convention for the Safeguarding of the Intangible Cultural Heritage) and 2005 (Convention on the Protection and Promotion of the Diversity of Cultural Expressions).
An intergovernmental meeting of UNESCO in Paris in December 1951 led to the creation of the European Council for Nuclear Research, which was responsible for establishing the European Organization for Nuclear Research (CERN) later on, in 1954.
Arid Zone programming, 1948–1966, is another example of an early major UNESCO project in the field of natural sciences.
In 1968, UNESCO organized the first intergovernmental conference aimed at reconciling the environment and development, a problem that continues to be addressed in the field of sustainable development. The main outcome of the 1968 conference was the creation of UNESCO's Man and the Biosphere Programme.
UNESCO has been credited with the diffusion of national science bureaucracies.
In the field of communication, the "free flow of ideas by word and image" has been in UNESCO's constitution since it was established, following the experience of the Second World War when control of information was a factor in indoctrinating populations for aggression. In the years immediately following World War II, efforts were concentrated on reconstruction and on the identification of needs for means of mass communication around the world. UNESCO started organizing training and education for journalists in the 1950s. In response to calls for a "New World Information and Communication Order" in the late 1970s, UNESCO established the International Commission for the Study of Communication Problems, which produced the 1980 MacBride report (named after the chair of the commission, the Nobel Peace Prize laureate Seán MacBride). The same year, UNESCO created the International Programme for the Development of Communication (IPDC), a multilateral forum designed to promote media development in developing countries. In 1993, UNESCO's General Conference endorsed the Windhoek Declaration on media independence and pluralism, which led the UN General Assembly to declare the date of its adoption, 3 May, as World Press Freedom Day. Since 1997, UNESCO has awarded the UNESCO / Guillermo Cano World Press Freedom Prize every 3 May.
=== 21st century ===
UNESCO admitted Palestine as a member in 2011.
Laws passed in the United States after Palestine applied for UNESCO and WHO membership in April 1989 mean that the United States cannot contribute financially to any UN organization that accepts Palestine as a full member. As a result, the United States withdrew its funding, which had accounted for about 22% of UNESCO's budget. Israel also reacted to Palestine's admittance to UNESCO by freezing Israeli payments to UNESCO and imposing sanctions on the Palestinian Authority, stating that Palestine's admittance would be detrimental "to potential peace talks". Two years after stopping payment of its dues to UNESCO, the United States and Israel lost UNESCO voting rights in 2013 without losing the right to be elected; thus, the United States was elected as a member of the executive board for the period 2016–19. In 2019, Israel left UNESCO after 69 years of membership, with Israel's ambassador to the UN Danny Danon writing: "UNESCO is the body that continually rewrites history, including by erasing the Jewish connection to Jerusalem... it is corrupted and manipulated by Israel's enemies... we are not going to be a member of an organization that deliberately acts against us".
2023 saw Russia excluded from the executive committee for the first time, after failing to get sufficient votes.
The United States stated its intent to rejoin UNESCO in 2023, 5 years after leaving, and to pay its $600 million in back dues. The United States was readmitted by the UNESCO General Conference that July.
== Activities ==
UNESCO implements its activities through five programme areas: education, natural sciences, social and human sciences, culture, and communication and information.
UNESCO supports research in comparative education, provides expertise and fosters partnerships to strengthen national educational leadership and the capacity of countries to offer quality education for all. This includes the
UNESCO Chairs, an international network of 644 UNESCO chairs, involving more than 770 institutions in 126 countries
Environmental Conservation Organization
Convention against Discrimination in Education adopted in 1960
Organization of the International Conference on Adult Education (CONFINTEA) in an interval of 12 years
Publication of the Education for All Global Monitoring Report
Publication of the Four Pillars of Learning seminal document
UNESCO ASPNet, an international network of more than 12,000 schools in 182 countries
UNESCO does not accredit institutions of higher learning.
UNESCO also issues public statements to educate the public:
Seville Statement on Violence: A statement adopted by UNESCO in 1989 to refute the notion that humans are biologically predisposed to organized violence.
Designating projects and places of cultural and scientific significance, such as:
Global Geoparks Network
Biosphere reserves, through the Programme on Man and the Biosphere (MAB), since 1971
City of Literature; in 2007, the first city to be given this title was Edinburgh, the site of Scotland's first circulating library. In 2008, Iowa City, Iowa, became the City of Literature.
Endangered languages and linguistic diversity projects (UNESCO Atlas of the World's Languages in Danger)
Masterpieces of the Oral and Intangible Heritage of Humanity
Memory of the World International Register, since 1997, plus a number of national and regional registers
Water resources management, through the International Hydrological Programme (IHP), since 1965
World Heritage Sites
World Digital Library
Encouraging the "free flow of ideas by images and words" by:
Promoting freedom of expression, including freedom of the press and freedom of information legislation, through the Division of Freedom of Expression and Media Development, including the International Programme for the Development of Communication
Promoting the safety of journalists and combatting impunity for those who attack them, through coordination of the UN Plan of Action on the Safety of Journalists and the Issue of Impunity
Promoting universal access to and preservation of information and open solutions for sustainable development through the Knowledge Societies Division, including the Memory of the World Programme and Information for All Programme
Promoting pluralism, gender equality and cultural diversity in the media
Promoting Internet Universality and its principles, that the Internet should be (I) human Rights-based, (ii) Open, (iii) Accessible to all, and (iv) nurtured by Multi-stakeholder participation (summarized as the acronym R.O.A.M.)
Generating knowledge through publications such as World Trends in Freedom of Expression and Media Development, the UNESCO Series on Internet Freedom, and the Media Development Indicators, as well as other indicator-based studies.
Promoting events, such as:
International Decade for the Promotion of a Culture of Peace and Non-Violence for the Children of the World: 2001–2010, proclaimed by the UN in 1998
World Press Freedom Day, 3 May each year, to promote freedom of expression and freedom of the press as a basic human right and as crucial components of any healthy, democratic and free society.
Criança Esperança in Brazil, in partnership with Rede Globo, to raise funds for community-based projects that foster social integration and violence prevention.
International Literacy Day, 8 September each year
International Year for the Culture of Peace, 2000
Health Education for Behavior Change programme in partnership with the Ministry of Education of Kenya which was financially supported by the Government of Azerbaijan to promote health education among 10-19-year-old young people who live in informal camp in Kibera, Nairobi. The project was carried out between September 2014 – December 2016.
World Day for Cultural Diversity for Dialogue and Development 21 May each year
Founding and funding projects, such as:
Migration Museums Initiative: Promoting the establishment of museums for cultural dialogue with migrant populations.
UNESCO-CEPES, the European Centre for Higher Education: established in 1972 in Bucharest, Romania, as a decentralized office to promote international co-operation in higher education in Europe as well as Canada, USA and Israel. Higher Education in Europe is its official journal.
Free Software Directory: since 1998 UNESCO and the Free Software Foundation have jointly funded this project cataloguing free software.
FRESH, Focusing Resources on Effective School Health
OANA, Organization of Asia-Pacific News Agencies
International Council of Science
UNESCO Goodwill Ambassadors
ASOMPS, Asian Symposium on Medicinal Plants and Spices, a series of scientific conferences held in Asia
Botany 2000, a programme supporting taxonomy, and biological and cultural diversity of medicinal and ornamental plants, and their protection against environmental pollution
The UNESCO Collection of Representative Works, translating works of world literature both to and from multiple languages, from 1948 to 2005
GoUNESCO, an umbrella of initiatives to make heritage fun supported by UNESCO, New Delhi Office
UNESCO-CHIC BIRUP, UNESCO-CHIC Group (China) Biosphere Rural and Urbanization Programme
The UNESCO transparency portal has been designed to enable public access to information regarding the Organization's activities, such as its aggregate budget for a biennium, as well as links to relevant programmatic and financial documents. These two distinct sets of information are published on the IATI registry, respectively based on the IATI Activity Standard and the IATI Organization Standard.
There have been proposals to establish two new UNESCO lists. The first proposed list will focus on movable cultural heritage such as artifacts, paintings, and biofacts. The list may include cultural objects, such as the Jōmon Venus of Japan, the Mona Lisa of France, the Gebel el-Arak Knife of Egypt, The Ninth Wave of Russia, the Seated Woman of Çatalhöyük of Turkey, the David (Michelangelo) of Italy, the Mathura Herakles of India, the Manunggul Jar of the Philippines, the Crown of Baekje of South Korea, The Hay Wain of the United Kingdom and the Benin Bronzes of Nigeria. The second proposed list will focus on the world's living species.
== Media ==
UNESCO and its specialized institutions issue a number of magazines.
Created in 1945, The UNESCO Courier magazine states its mission to "promote UNESCO's ideals, maintain a platform for the dialogue between cultures and provide a forum for international debate". Since March 2006 it has been available free online, with limited printed issues. Its articles express the opinions of the authors which are not necessarily the opinions of UNESCO. There was a hiatus in publishing between 2012 and 2017.
In 1950, UNESCO initiated the quarterly review Impact of Science on Society (also known as Impact) to discuss the influence of science on society. The journal ceased publication in 1992.
== Official UNESCO NGOs ==
UNESCO has official relations with 322 international non-governmental organizations (NGOs). Most of these are what UNESCO calls "operational"; a select few are "formal". The highest form of affiliation to UNESCO is "formal associate", and the 22 NGOs with formal associate (ASC) relations occupying offices at UNESCO are:
== Institutes and centres ==
The institutes are specialized departments of the organization that support UNESCO's programme, providing specialized support for cluster and national offices.
== Prizes ==
UNESCO awards 26 prizes in education, natural sciences, social and human sciences, culture, communication and information as well as peace:
=== Education ===
UNESCO/King Sejong Literacy Prize
UNESCO/Confucius Prize for Literacy
UNESCO-Japan Prize on Education for Sustainable Development
UNESCO Prize for Girls' and Women's Education
UNESCO/Hamdan Bin Rashid Al-Maktoum Prize for Outstanding Practice and Performance in Enhancing the Effectiveness of Teachers
UNESCO King Hamad Bin Isa Al-Khalifa Prize for the Use of Information and Communication Technologies in Education
=== Natural Sciences ===
L'Oréal-UNESCO Awards for Women in Science
UNESCO/Kalinga Prize for the Popularization of Science
UNESCO-Equatorial Guinea International Prize for Research in the Life Sciences
Carlos J. Finlay Prize for Microbiology
UNESCO/Sultan Qaboos Prize for Environmental Preservation
UNESCO-Russia Mendeleev International Prize in the Basic Sciences
UNESCO-Al Fozan International Prize for the Promotion of Young Scientists in STEM
Michel Batisse Award for Biosphere Reserve Management
=== Social and Human Sciences ===
UNESCO Avicenna Prize for Ethics in Science
UNESCO/Juan Bosch Prize for the Promotion of Social Science Research in Latin America and the Caribbean
UNESCO-Madanjeet Singh Prize for the Promotion of Tolerance and Non-Violence
UNESCO-Sharjah Prize for Arab Culture
UNESCO/International José Martí Prize
UNESCO-UNAM / Jaime Torres Bodet Prize in social sciences, humanities and arts
=== Culture ===
Melina Mercouri International Prize for the Safeguarding and Management of Cultural Landscapes (UNESCO-Greece)
=== Communication and Information ===
UNESCO/Guillermo Cano World Press Freedom Prize
UNESCO/Emir Jaber al-Ahmad al-Jaber al-Sabah Prize to promote Quality Education for Persons with Intellectual Disabilities
UNESCO/Jikji Memory of the World Prize
=== Peace ===
Félix Houphouët-Boigny Peace Prize
=== Inactive prizes ===
International Simón Bolívar Prize (inactive since 2004)
UNESCO Prize for Human Rights Education
UNESCO/Obiang Nguema Mbasogo International Prize for Research in the Life Sciences (inactive since 2010)
UNESCO Prize for the Promotion of the Arts
== International Days observed at UNESCO ==
International Days observed at UNESCO are provided in the table below:
== Member states ==
As of July 2023, UNESCO has 194 member states and 12 associate members. Some members are not independent states and some members have additional National Organizing Committees from some of their dependent territories. UNESCO state parties are the United Nations member states (except Israel and Liechtenstein), as well as Cook Islands, Niue and Palestine. The United States and Israel left UNESCO on 31 December 2018, but the United States rejoined in 2023.
== Governing bodies ==
=== Director-General ===
As of June 2023, there have been 11 Directors-General of UNESCO since its inception – nine men and two women. The 11 Directors-General of UNESCO have come from six regions within the organization: West Europe (5), Central America (1), North America (2), West Africa (1), East Asia (1), and East Europe (1).
To date, there has been no elected Director-General from the remaining ten regions within UNESCO: Southeast Asia, South Asia, Central and North Asia, Middle East, North Africa, East Africa, Central Africa, South Africa, Australia-Oceania, and South America.
The list of the Directors-General of UNESCO since its establishment in 1946 is as follows:
=== General Conference ===
This is the list of the sessions of the UNESCO General Conference held since 1946:
=== Executive Board ===
Biennial elections are held, with 58 elected representatives holding office for four years.
== Offices and headquarters ==
The UNESCO headquarters is located at Place de Fontenoy in Paris, France. Several architects collaborated on the construction of the headquarters, including Bernard Zehrfuss, Marcel Breuer and Luigi Nervi. It includes a Garden of Peace which was donated by the Government of Japan. This garden was designed by American-Japanese sculptor artist Isamu Noguchi in 1958 and installed by Japanese gardener Toemon Sano. In 1994–1995, in memory of the 50th anniversary of UNESCO, a meditation room was built by Tadao Ando.
UNESCO's field offices across the globe are categorized into four primary office types based upon their function and geographic coverage: cluster offices, national offices, regional bureaus and liaison offices.
=== Field offices by region ===
The following list of all UNESCO Field Offices is organized geographically by UNESCO Region and identifies the members states and associate members of UNESCO which are served by each office.
==== Africa ====
Abidjan – National Office to Côte d'Ivoire
Abuja – National Office to Nigeria
Accra – Cluster Office for Benin, Côte d'Ivoire, Ghana, Liberia, Nigeria, Sierra Leone and Togo
Addis Ababa – Liaison Office with the African Union and with the Economic Commission for Africa
Bamako – Cluster Office for Burkina Faso, Guinea, Mali and Niger
Brazzaville – National Office to the Republic of the Congo
Bujumbura – National Office to Burundi
Dakar – Regional Bureau for Education in Africa and Cluster Office for Cape Verde, Gambia, Guinea-Bissau, and Senegal
Dar es Salaam – Cluster Office for Comoros, Madagascar, Mauritius, Seychelles and Tanzania
Harare – Cluster Office for Botswana, Malawi, Mozambique, Zambia and Zimbabwe
Juba – National Office to South Sudan
Kinshasa – National Office to the Democratic Republic of the Congo
Libreville – Cluster Office for the Republic of the Congo, Democratic Republic of the Congo, Equatorial Guinea, Gabon and São Tomé and Príncipe
Maputo – National Office to Mozambique
Nairobi – Regional Bureau for Sciences in Africa and Cluster Office for Burundi, Djibouti, Eritrea, Kenya, Rwanda, Somalia, South Sudan and Uganda
Windhoek – National Office to Namibia
Yaoundé – Cluster Office to Cameroon, Central African Republic and Chad
==== Arab States ====
Amman – National Office to Jordan
Beirut – Regional Bureau for Education in the Arab States and Cluster Office to Lebanon, Syria, Jordan, Iraq and Palestine
Cairo – Regional Bureau for Sciences in the Arab States and Cluster Office for Egypt and Sudan
Doha – Cluster Office to Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, United Arab Emirates and Yemen
Iraq – National Office for Iraq (currently located in Amman, Jordan)
Khartoum – National Office to Sudan
Manama – Arab Regional Centre for World Heritage
Rabat – Cluster Office to Algeria, Libya, Mauritania, Morocco and Tunisia
Ramallah – National Office to the Palestinian Territories
==== Asia and Pacific ====
Almaty – Cluster Office to Kazakhstan, Kyrgyzstan, Tajikistan and Uzbekistan
Apia – Cluster Office to Australia, Cook Islands, Fiji, Kiribati, Marshall Islands, Federated States of Micronesia, Nauru, New Zealand, Niue, Palau, Papua New Guinea, Samoa, Solomon Islands, Tonga, Tuvalu, Vanuatu and Tokelau (Associate Member)
Bangkok – Regional Bureau for Education in Asia and the Pacific and Cluster Office to Thailand, Burma, Laos, Singapore and Vietnam
Beijing – Cluster Office to North Korea, Japan, Mongolia, the People's Republic of China and South Korea
Dhaka – National Office to Bangladesh
Hanoi – National Office to Vietnam
Islamabad – National Office to Pakistan
Jakarta – Regional Bureau for Sciences in Asia and the Pacific and Cluster Office to the Philippines, Brunei, Indonesia, Malaysia, and East Timor
Manila – National Office to the Philippines
Kabul – National Office to Afghanistan
Kathmandu – National Office to Nepal
New Delhi – Cluster Office to Bangladesh, Bhutan, India, Maldives and Sri Lanka
Phnom Penh – National Office to Cambodia
Tashkent – National Office to Uzbekistan
Tehran – Cluster Office to Afghanistan, Iran, Pakistan and Turkmenistan
==== Europe and North America ====
Brussels – Liaison Office to the European Union and its subsidiary bodies in Brussels
Geneva – Liaison Office to the United Nations in Geneva
New York City – Liaison Office to the United Nations in New York
Venice – Regional Bureau for Sciences and Culture in Europe
==== Latin America and the Caribbean ====
Brasília – National Office to Brazil
Guatemala City – National Office to Guatemala
Havana – Regional Bureau for Culture in Latin America and the Caribbean and Cluster Office to Cuba, Dominican Republic, Haiti and Aruba
Kingston – Cluster Office to Antigua and Barbuda, Bahamas, Barbados, Belize, Dominica, Grenada, Guyana, Jamaica, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Suriname and Trinidad and Tobago as well as the associate member states of British Virgin Islands, Cayman Islands, Curaçao and Sint Maarten
Lima – National Office to Peru
Mexico City – National Office to Mexico
Montevideo – Regional Bureau for Sciences in Latin America and the Caribbean and Cluster Office to Argentina, Brazil, Chile, Paraguay and Uruguay
Port-au-Prince – National Office to Haiti
Quito – Cluster Office to Bolivia, Colombia, Ecuador and Venezuela
San José – Cluster Office to Costa Rica, El Salvador, Guatemala, Honduras, Mexico, Nicaragua and Panama
Santiago de Chile – Regional Bureau for Education in Latin America and the Caribbean and National Office to Chile
=== Partner organizations ===
International Committee of the Red Cross (ICRC)
Blue Shield International (BSI)
International Council of Museums (ICOM)
International Council on Monuments and Sites (ICOMOS)
International Institute of Humanitarian Law (IIHL)
== Controversies ==
=== New World Information and Communication Order ===
UNESCO has been the centre of controversy in the past, particularly in its relationships with the United States, the United Kingdom, Singapore and the former Soviet Union. During the 1970s and 1980s, UNESCO's support for a "New World Information and Communication Order" and its MacBride report calling for democratization of the media and more egalitarian access to information was condemned in these countries as attempts to curb freedom of the press. UNESCO was perceived as a platform for communists and Third World dictators to attack the West, in contrast to accusations made by the USSR in the late 1940s and early 1950s. In 1984, the United States withheld its contributions and withdrew from the organization in protest, followed by the United Kingdom in 1985. Singapore withdrew also at the end of 1985, citing rising membership fees. Following a change of government in 1997, the UK rejoined. The United States rejoined in 2003, followed by Singapore on 8 October 2007.
=== China ===
UNESCO has been criticized as being used by the People's Republic of China to present a Chinese Communist Party version of history and to dilute the contributions of ethnic minorities in China such as Uyghurs and Tibetans.
=== Israel ===
Israel was admitted to UNESCO in 1949, one year after its creation. Israel has maintained its membership since then. In 2010, Israel designated the Cave of the Patriarchs in Hebron and Rachel's Tomb in Bethlehem – both in the West Bank – as National Heritage Sites and announced restoration work, prompting criticism from the Obama administration and protests from Palestinians. In October 2010, UNESCO's executive board voted to declare the sites as "al-Haram al-Ibrahimi/Tomb of the Patriarchs" and "Bilal bin Rabah Mosque/Rachel's Tomb" and stated that they were "an integral part of the occupied Palestinian Territories" and any unilateral Israeli action was a violation of international law.
UNESCO described the sites as significant to "people of the Muslim, Christian and Jewish traditions", and accused Israel of highlighting only the Jewish character of the sites.
Israel in turn accused UNESCO of "detach[ing] the Nation of Israel from its heritage", and accused it of being politically motivated.
The Rabbi of the Western Wall said that Rachel's tomb had not previously been declared a holy Muslim site. Israel partially suspended ties with UNESCO. Israeli Deputy Foreign Minister Danny Ayalon declared that the resolution was a "part of Palestinian escalation".
Zevulun Orlev, chairman of the Knesset Education and Culture Committee, referred to the resolutions as an attempt to undermine the mission of UNESCO as a scientific and cultural organization that promotes cooperation throughout the world.
On 28 June 2011, UNESCO's World Heritage Committee, at Jordan's insistence, censured Israel's decision to demolish and rebuild the Mughrabi Gate Bridge in Jerusalem for safety reasons. Israel stated that Jordan had signed an agreement with Israel stipulating that the existing bridge must be dismantled for safety reasons; Jordan disputed the agreement, saying that it was only signed under U.S. pressure. Israel was also unable to address the UNESCO committee over objections from Egypt.
In January 2014, days before it was scheduled to open, UNESCO Director-General, Irina Bokova, "indefinitely postponed" and effectively cancelled an exhibit created by the Simon Wiesenthal Centre entitled "The People, The Book, The Land: The 3,500-year relationship between the Jewish people and the Land of Israel". The event was scheduled to run from 21 January through 30 January in Paris. Bokova cancelled the event after representatives of Arab states at UNESCO argued that its display would "harm the peace process". The author of the exhibition, professor Robert Wistrich of the Hebrew University's Vidal Sassoon International Centre for the Study of Anti-Semitism, called the cancellation an "appalling act", and characterized Bokova's decision as "an arbitrary act of total cynicism and, really, contempt for the Jewish people and its history". UNESCO amended the decision to cancel the exhibit within the year, and it quickly achieved popularity and was viewed as a great success.
On 1 January 2019, Israel formally left UNESCO in pursuance of the US withdrawal over perceived continuous anti-Israel bias.
==== Occupied Palestine Resolution ====
On 13 October 2016, UNESCO passed a resolution on East Jerusalem that condemned Israel for "aggressions" by Israeli police and soldiers and "illegal measures" against the freedom of worship and Muslims' access to their holy sites, while also recognizing Israel as the occupying power. Palestinian leaders welcomed the decision. While the text acknowledged the "importance of the Old City of Jerusalem and its walls for the three monotheistic religions", it referred to the sacred hilltop compound in Jerusalem's Old City only by its Muslim name "Al-Haram al-Sharif", Arabic for Noble Sanctuary. In response, Israel denounced the UNESCO resolution for its omission of the words "Temple Mount" or "Har HaBayit", stating that it denies Jewish ties to the key holy site. After receiving criticism from numerous Israeli politicians and diplomats, including Benjamin Netanyahu and Ayelet Shaked, Israel froze all ties with the organization. The resolution was condemned by Ban Ki-moon and the Director-General of UNESCO, Irina Bokova, who said that Judaism, Islam and Christianity have clear historical connections to Jerusalem and "to deny, conceal or erase any of the Jewish, Christian or Muslim traditions undermines the integrity of the site. "Al-Aqsa Mosque [or] Al-Haram al-Sharif" is also Temple Mount, whose Western Wall is the holiest place in Judaism." It was also rejected by the Czech Parliament which said the resolution reflects a "hateful anti-Israel sentiment", and hundreds of Italian Jews demonstrated in Rome over Italy's abstention. On 26 October, UNESCO approved a reviewed version of the resolution, which also criticized Israel for its continuous "refusal to let the body's experts access Jerusalem's holy sites to determine their conservation status". Despite containing some softening of language following Israeli protests over a previous version, Israel continued to denounce the text. The resolution refers to the site Jews and Christians refer to as the Temple Mount, or Har HaBayit in Hebrew, only by its Arab name – a significant semantic decision also adopted by UNESCO's executive board, triggering condemnation from Israel and its allies. U.S. Ambassador Crystal Nix Hines stated: "This item should have been defeated. These politicized and one-sided resolutions are damaging the credibility of UNESCO."
In October 2017, the United States and Israel announced they would withdraw from the organization, citing in-part anti-Israel bias.
=== Palestine ===
==== Palestinian youth magazine controversy ====
In February 2011, an article was published in a Palestinian youth magazine in which a teenage girl described one of her four role models as Adolf Hitler. In December 2011, UNESCO, which partly funded the magazine, condemned the material and subsequently withdrew support.
==== Islamic University of Gaza controversy ====
In 2012, UNESCO decided to establish a chair at the Islamic University of Gaza in the field of astronomy, astrophysics, and space sciences, fueling controversy and criticism. Israel bombed the school in 2008 stating that they develop and store weapons there, which Israel restated in criticizing UNESCO's move.
The head, Kamalain Shaath, defended UNESCO, stating that "the Islamic University is a purely academic university that is interested only in education and its development". Israeli ambassador to UNESCO Nimrod Barkan planned to submit a letter of protest with information about the university's ties to Hamas, especially angry that this was the first Palestinian university that UNESCO chose to cooperate with. The Jewish organization B'nai B'rith criticized the move as well.
=== Listing Nanjing Massacre documents ===
In 2015, Japan threatened to halt funding of UNESCO because of the organization's decision to include documents related to the 1937 Nanjing massacre in the latest listing for its "Memory of the World" program. In October 2016, Japanese Foreign Minister Fumio Kishida confirmed that Japan's 2016 annual funding of ¥4.4 billion had been suspended, although he denied any direct link with the Nanjing document controversy.
=== US withdrawals ===
The United States withdrew from UNESCO in 1984, citing the "highly politicized" nature of the organization, its ostensible "hostility toward the basic institutions of a free society, especially a free market and a free press", as well as its "unrestrained budgetary expansion", and poor management under then Director-General Amadou-Mahtar M'Bow of Senegal.
On 19 September 1989, US Congressman Jim Leach stated before a congressional subcommittee:
The reasons for the withdrawal of the United States from UNESCO in 1984 are well-known; my view is that we overreacted to the calls of some who wanted to radicalize UNESCO, and the calls of others who wanted the United States to lead in emasculating the UN system. The fact is UNESCO is one of the least dangerous international institutions ever created. While some member countries within UNESCO attempted to push journalistic views antithetical to the values of the west, and engage in Israel bashing, UNESCO itself never adopted such radical postures. The United States opted for empty-chair diplomacy, after winning, not losing, the battles we engaged in... It was nuts to get out, and would be nuttier not to rejoin.
Leach concluded that the record showed Israel bashing, a call for a new world information order, money management, and arms control policy to be the impetuses behind the withdrawal; he asserted that before departing from UNESCO, a withdrawal from the IAEA had been pushed on him. On 1 October 2003, the United States rejoined UNESCO.
On 12 October 2017, the United States notified UNESCO it would again withdraw from the organization, on 31 December 2018; Israel followed suit. The Department of State cited "mounting arrears at UNESCO, the need for fundamental reform in the organization, and continuing anti-Israel bias at UNESCO".
The United States has not paid over $600 million in dues since it stopped paying its $80 million annual UNESCO dues when Palestine became a full member in 2011. Israel and the United States were among the 14 votes against the membership out of 194 member countries. When the United States announced it was rejoining the body in 2023, it also pledged to pay all past-due payments.
=== Kurdish–Turkish conflict ===
On 25 May 2016, Turkish poet and human rights activist Zülfü Livaneli resigned as Turkey's only UNESCO goodwill ambassador. He highlighted the human rights situation in Turkey and the destruction of the historical Sur district of Diyarbakir, the largest city in Kurdish-majority southeast Turkey, during fighting between the Turkish army and Kurdish militants as the main reasons for his resignation. Livaneli said: "To pontificate on peace while remaining silent against such violations is a contradiction of the fundamental ideals of UNESCO."
=== Campaigns against illicit art trading ===
In 2020 UNESCO stated that the size of the illicit trade in cultural property amounted to 10 billion dollars a year. A report that same year by the Rand Organization suggested the actual market is "not likely to be larger than a few hundred million dollars each year". An expert cited by UNESCO as attributing the 10 billion figure denied it, saying he had "no idea" where the figure came from. Art dealers were particularly critical of the UNESCO figure because it amounted to 15% of the total world art market.
In November 2020, part of a UNESCO advertising campaign intended to highlight international trafficking in looted artefacts had to be withdrawn after it falsely presented a series of museum-held artworks with known provenances as recently looted objects held in private collections. The adverts claimed that a head of Buddha in the Metropolitan Museum's collection since 1930 had been looted from a Kabul Museum in 2001 and then smuggled into the US art market, that a funerary monument from Palmyra that the Met had acquired in 1901 had been recently looted from the Palmyra Museum by Islamic State militants and then smuggled into the European antiquities market, and that an Ivory Coast mask with a provenance that indicates it was in the United States by 1954 was looted during armed clashes in 2010–2011. After complaints by the Met, the adverts were withdrawn.
== Products and services ==
UNESDOC Database – Contains more than 146,000 UNESCO documents in full text published since 1945 as well as metadata from the collections of the UNESCO Library and documentation centres in field offices and institutes.
=== Information processing tools ===
UNESCO develops, maintains, and disseminates, free of charge, two interrelated software packages for database management (CDS/ISIS [not to be confused with UK police software package ISIS]) and data mining/statistical analysis (IDAMS).
CDS/ISIS – a generalized information storage and retrieval system. The Windows version may run on a single computer or in a local area network. The JavaISIS client/server components allow remote database management over the Internet and are available for Windows, Linux, and Macintosh. Furthermore, GenISIS allows users to produce HTML Web forms for CDS/ISIS database searching. The ISIS_DLL provides an API for developing CDS/ISIS based applications.
OpenIDAMS – a software package for processing and analysing numerical data developed, maintained and disseminated by UNESCO. The original package was proprietary, but UNESCO has initiated a project to provide it as open source.
IDIS – a tool for direct data exchange between CDS/ISIS and IDAMS
== See also ==
Academic mobility network
League of Nations archives
UNESCO Intangible Cultural Heritage Lists
UNESCO Reclining Figure 1957–58, sculpture by Henry Moore
UniRef
International Charter of Physical Education, Physical Activity and Sport
== Notes ==
== References ==
== Further reading ==
Finnemore, Martha. 1993. "International Organizations as Teachers of Norms: The United Nations Educational, Scientific, and Cutural [sic] Organization and Science Policy." International Organization Vol. 47, No. 4 (Autumn, 1993), pp. 565–597
== External links ==
Official website | Wikipedia/World_Science_Day_for_Peace_and_Development |
In studies of science communication, the information deficit model, also known as the deficit model or science literacy/knowledge deficit model, theorizes that scientific literacy can be improved with increased public engagement by the scientific community. As a result, the public may then be able to make more decisions that are science-informed. The model implies that communication should focus on improving the transfer of information from experts to non-experts.
Currently, many studies challenge the information deficit model as it ignores the cognitive, social, and affective factors that influence one’s formation of attitude and judgements toward science and technology.
== Deficit model of science communication ==
The original term 'deficit model' was believed to be coined in the 1930s, and sometimes attributed to the work of Jon D. Miller, though his widely cited work on scientific literacy does not employ the term. The deficit model sees the general population as the receiver of information and scientific knowledge. The information they receive, through whatever medium, has been prearranged according to what the distributors believe to be in the public's interest. Due to the recent growth of scientific research and subsequent discoveries, the deficit model suggests that this has led to a decrease in interest surrounding certain areas of science. This may be a result of the public feeling overwhelmed with information and disengaging, as it appears too much to take in.
There are two aspects to the deficit model. The first is the idea that public uncertainty and skepticism towards modern science, including environmental issues and technology, is caused primarily by a lack of sufficient knowledge about science and related subjects. The second aspect relates to the idea that by providing adequate information to overcome this lack of knowledge, also known as a 'knowledge deficit', the general public opinion will change based on the information being reliable and accurate.
Supporters of the deficit model in science communication argue that a better-informed public would increase their support for scientific exploration and technologies. In the deficit model, scientists assume that there is a knowledge deficit that can be 'fixed' by giving the public more information: scientists often assume that "given the facts (whatever they are), the public will happily support new technologies."
=== Controversy of the deficit model ===
The deficit model of scientific understanding perceives the public to be "blank slates" where their knowledge of scientific discourse and research is almost non-existent. The knowledge deficit is then informed by a reliable, knowledgeable, and hierarchical scientific community. But the increase in new information systems, such as the Internet and their ease of accessibility, has led to a greater cumulative knowledge of scientific research and the public's understanding.
However, critics state that the deficit model can also produce an unintended cumulative advantage system: growing inequality between and within the knowledge-attitude-practice (KAP) gap of individuals and groups due to a wide variety of possible moderators. Over time, these effects can exacerbate gaps between individuals’ and groups’ levels of KAP. With this in mind, this can also be a good thing in terms of the members of the public that can actively increase their own knowledge base, decrease the knowledge deficit and assess the truth and validity of what mass media outlets and governments are telling them. This should enhance and increase the relationship between the passive "blank slates" of the public, with the minority of the population who hold the 'knowledge surplus'.
The deficit model, however, has been discredited by a wealth of literature that shows that simply giving more information to people does not necessarily change their views. This is in part due to people wanting to feel that they have had their say (and have been heard) in any decision-making process and people making decisions based on a host of factors. These factors include ethical, political, and religious beliefs, in addition to culture, history, and personal experience.
Put another way, people's sense of risk extends beyond the purely scientific considerations of conventional risk analysis, and the deficit model marginalizes these 'externalities'. It is now widely accepted that the best alternative to deficit model thinking is to genuinely engage with the public and take these externalities into account.
=== Examples of externalities ===
Externalities can influence one’s views and behaviors towards science and technology. For example, a survey of US public in 2004 found that religiosity correlates with support of nanotechnology. Additionally, in climate communication, even though today the majority of people worldwide believe climate change is a global emergency, climate action has been impeded by other factors, such as political opposition, corruption and oil company interest.
It has been also observed that sociodemographic factors such as education and age affect individuals' use of and access to communication channels; individuals' trust in and selection of health information from the program content and their changing health behaviors (as a result of the health information) are related to both their perception of the mass communication process and to sociodemographic factors but are more strongly related to the former.
With the challenges to the deficit model in science communication in health, caution is advised with the increasing role of technology and social media, and how these may affect the legitimacy of healthcare information flows away from the healthcare professional.
Furthermore, science communicators, particularly those seeking to address unsubstantiated beliefs, to look for alternative methods of persuasion. A 2019 study, for example, showed that exposure to the stories of an individual converted from opposing to supporting genetically modified organisms led to more positive attitudes toward GMOs.
=== Evidence for a deficit affecting opinion ===
A 2008 meta-analysis of 193 studies sought to interpret the link between science knowledge and attitude towards science. The studies included were taken using nonuniform methods across the world between 1989 and 2004 to provide a cross-cultural analysis. Broad and specific science knowledge and attitude categories were correlated. General science and general biology knowledge was gauged using questions similar to those by the National Science Foundation used to capture "civil scientific literacy". Data on general science and biology knowledge was then compared with attitudes towards general science, nuclear power, genetic medicine, genetically modified food, and environmental science. From the raw data, it was found that a small positive correlation exists between general science knowledge and attitude towards science, indicating that increased scientific knowledge is related to a favorable attitude towards a science topic and that this was not related to the socioeconomic or technological status of a country, but rather the number of individuals enrolled in tertiary education. However, some studies have found that high levels of science knowledge may indicate highly positive and highly negative attitudes towards specific topics such as agriculture biotechnology. Thus knowledge may be a predictor of the attitude strength and not necessarily if the attitude is positive or negative.
=== Evidence against the deficit model ===
While knowledge may influence attitude strengths, other studies have shown that merely increasing knowledge does not effectively augment public trust in science. In addition to scientific knowledge, the public uses other values (e.g. religion) to form heuristics and make decisions about scientific technology. These same values may cloud responses to questions probing the public's scientific understanding, an example being evolution. On the National Science Foundation Indicators, less than half (~45%) of Americans agreed that humans evolved from other species. This is much lower than reports from other countries and was interpreted as a deficit in scientific literacy. However, when a qualifier was added ("according to the theory of evolution..."), 72% of Americans correctly answered that humans evolved from other species. Therefore, knowledge alone does not explain public opinions with regard to science. Scientists must take other values and heuristics into account when communicating with the public in order to maintain trust and deference. In fact, some have called for more democratic accountability for bioethicists and scientists, meaning public values would feedback onto the progression/acceptance of scientific technology. Emerging evidence suggests that this public/science collaboration may even be rewarding for researchers: 82% of faculty surveyed in a 2019 study agreed that getting "food for thought" from their public audiences was a positive outcome from public engagement activities. As attention among the academics starts shifting back towards an emphasis on public engagement, organizations like the American Association for the Advancement of Science (AAAS) have therefore called for "intentional, meaningful interactions that provide opportunities for mutual learning between scientists and members of the public".
== The role of the media ==
Mass media representations, ranging from news to entertainment, are critical links between the everyday realities of how people experience certain issues and the ways in which these are discussed at a distance between science, policy, and public actors. Numerous studies show that the public frequently learns about science and more specifically issues such as climate change from the mass media. Heuristics (see low-information rationality and cognitive miser) also play a role in decision-making where the way.
The actual processes behind the communication and dissemination of information from experts to the public may be far more complex and deep-running than the deficit model suggests. In mass communication, the communicator (source) is always a part of an organized group and is most often a member of an institution that has functions other than communication. A receiver is always an individual; however, receivers are often seen by communicator organizations as members of a group that share some general characteristics. The channel includes large-scale technologically based distribution devices and systems.
=== 'Spinning', Heuristics, and Framing ===
There is perceived to be a trend within the world's media to commit to report the full facts, Factual reporting has given way to a more obvious, less reliable method to concentrate coverage on interpretations of the facts. This so-called 'spin' (see Frank Luntz) is reported by the world's press under a combination of commercial and political pressure. In other words, the media provides the public with cognitive shortcuts or heuristics to quickly digest new information. The way message is framed may influence one’s attitudes. The subjects of anthropogenic global warming and climate change is repeatedly exemplified. However, in all cases it is becoming increasingly difficult to separate out the factual basis of what is being reported from the 'spin' that is exerted on the way a story is reported and presented.
Framing can be used to reduce the complexity of an issue, or to persuade audiences, and can play into the underlying religious beliefs, moral values, prior knowledge, and even trust in scientists or political individuals. Further, the transmission of scientific ideas and technological adoption may be strongly linked to the passage of information between easily influenced individuals, versus the widely accepted "two-step flow" theory where a few opinion leaders acted as intermediaries between mass media and the general public. Decreasing the knowledge deficit is a complicated task, but if we know how the general public thinks, or how they go about learning and interpreting new information, we can better communicate our message to them in the most unbiased, objective way possible.
== Alternative models ==
A supported alternative to the knowledge deficit model, the low-information rationality model states humans minimize costs associated with making decisions and forming attitudes, thereby avoiding developing in-depth understandings.
In food safety risk communication, the deficit model was widely followed by food safety authorities in the last decades, even after more developed risk communication models, such as the dialogue model and the partnership model appeared.
== See also ==
Cultural cognition
Low-information rationality
Thinking, Fast and Slow
Heuristics
== Notes and references == | Wikipedia/Information_deficit_model |
The Committee on the Public Understanding of Science or Copus was founded in 1985 by the British Association for the Advancement of Science (BAAS), the Royal Institution and the Royal Society. Copus came about as a result of the 'Bodmer Report' by the eminent geneticist Walter Bodmer. The aim of Copus was to interpret scientific advances and make them more accessible to non-scientists.
It played a part in developing the public understanding of science it establishing standards for communicating science and technology
The Copus Grant Schemes was set up in 1987 and the last round of grants was for 2003/4. The scheme was funded by the Office of Science and Technology and the Royal Society. 25 grants worth a total of over £750,000 were awarded in 2003/2004.
In 2000 The new Copus Council was formed to be a more inclusive partnership for science communication in the UK. In 2002 following a report commissioned by the Office of Science and Technology the Copus Council was discontinued.
== References == | Wikipedia/Committee_on_the_Public_Understanding_of_Science |
The Simonyi Professorship for the Public Understanding of Science is a chair at the University of Oxford. The chair was established in 1995 for the ethologist Richard Dawkins by an endowment from Charles Simonyi. The aim of the Professorship is 'to communicate science to the public without, in doing so, losing those elements of scholarship which constitute the essence of true understanding'. It is a position that had been endowed by Charles Simonyi with the express intention that the holder "be expected to make important contributions to the public understanding of some scientific field", and that its first holder should be Richard Dawkins.
== History ==
[...] if I am asked for a single phrase to characterize my role as Professor of the Public Understanding of Science, I think I would claim Advocate for Disinterested Truth.
Richard Dawkins explained the history of the creation of the chair in a chapter of his memoirs, Brief Candle in the Dark: My Life in Science. In 2008, Dawkins retired and the Oxford mathematician Marcus du Sautoy was elected to the chair.
== List of Simonyi Professors ==
1995–2008: Richard Dawkins, biological science
Since 2008: Marcus du Sautoy, mathematical science
== List of Simonyi Lectures ==
Richard Dawkins established an annual "Charles Simonyi Lecture" at the University of Oxford. He invited the following speakers:
Marcus du Sautoy, second Simonyi Professor, invited:
== Notes and references ==
== Bibliography ==
Richard Dawkins, Brief Candle in the Dark: My Life in Science, Bantam Press, 2015 (ISBN 978-0-59307-256-1). Chapter "Simonyi Professor", pages 271-307.
== External links ==
Official website
Charles Simonyi's manifesto | Wikipedia/Simonyi_Professorship_for_the_Public_Understanding_of_Science |
Sense about Science is a United Kingdom charitable organization that promotes the public understanding of science. Sense about Science was founded in 2002 by Lord Taverne, Bridget Ogilvie and others to promote respect for scientific evidence and good science. It was established as a charitable trust in 2003, with 14 trustees, an advisory council and a small office staff. Tracey Brown has been the director since 2002.
The organisation works with scientists and journalists to put scientific evidence in public discussions about science, and to correct unscientific misinformation. They encourage and assist scientists to engage in public debates about their area of expertise, to respond to scientifically inaccurate claims in the media, to help people contact scientists with appropriate expertise, and to prepare briefings about the scientific background to issues of public concern.
== Projects ==
Sense about Science publishes guides to different areas of science in partnership with experts. These include: Responsible Handover Framework, Data Science: A Guide for Society, Making Sense of Nuclear, Making Sense of Uncertainty, Making Sense of Allergies, Making Sense of Drug Safety Science, Making Sense of Testing, Making Sense of Crime, Making Sense of Statistics, Making Sense of Screening and Making Sense of GM.
Sense about Science runs the Voice of Young Science programme to help early career scientists engage in public debates.
Since its founding, Sense about Science has contributed to UK public debates about such subjects as alternative medicine, "detoxification" products and detox diets, genetically modified food, avian influenza, chemicals and health, "electrosmog", vaccination, weather and climate, nuclear power, and the use and utility of peer review. Sense about Science encourages scientists to explain to the public the value of peer review in determining which reports should be taken seriously. Director Tracey Brown describes such critical thinking as crucial to preventing public health scares based on unpublished information.
== Causes ==
=== AllTrials ===
The AllTrials campaign calls for all past and present clinical trials to be registered and their full methods and summary results reported.
AllTrials is an international initiative of Bad Science, BMJ, Centre for Evidence-based Medicine, Cochrane Collaboration, James Lind Initiative, PLOS and Sense About Science and is being led in the US by Sense About Science USA, Dartmouth's Geisel School of Medicine and the Dartmouth Institute for Health Policy & Clinical Practice.
As of January 2018, the AllTrials petition has been signed by 91,989 people and 737 organisations.
=== Ask for Evidence ===
Ask for Evidence was launched by Sense About Science in 2011. It is a campaign that helps people request for themselves the evidence behind news stories, marketing claims and policies. When challenged in this way, organisations may withdraw their claims or send evidence to support them. The campaign is supported by more than 6000 volunteer scientists who are available to review the evidence provided and determine whether it supports the original claim or story. The campaign has received funding from The Wellcome Trust and is endorsed by figures such as Dara Ó Briain and Derren Brown.
=== Keep Libel Laws Out of Science ===
Sense About Science launched the Keep Libel Laws out of Science campaign in June 2009 in defence of a member of its board of trustees, author and journalist Simon Singh, who has been sued for libel by the British Chiropractic Association. They issued a statement entitled "The law has no place in scientific disputes", which was signed by many people representing science, medicine, journalism, publishing, arts, humanities, entertainment, sceptics, campaign groups and law. In April 2010, the BCA lost this case with the court accepting that criticism of the BCA concerning its promotion of bogus treatments was fair comment.
In December 2009, Sense About Science, Index on Censorship and English PEN launched the Libel Reform Campaign. The Defamation Act 2013 received Royal Assent on 25 April 2013 and came into force on 1 January 2014.
The Trust actively campaigns in support of various causes. It has issued a statement signed by over 35 scientists asking the WHO to condemn homeopathy for diseases such as HIV.
== Reception ==
Sense about Science and their publications have been cited a number of times in the popular press,
most notably for encouraging celebrities and the public to think critically about scientific claims,
criticizing marketing unsupported by research,
decrying the unsubstantiated claims of homeopathy,
supporting genetically modified crops,
criticising "do-it-yourself" health testing,
denouncing detox products,
warning against "miracle cures",
and promoting public understanding of peer review.
They have received positive coverage in publications from the Royal Society
and the U.S. National Science Foundation,
and in the writings of scientists such as Ben Goldacre and Steven Novella.
Lord Taverne, chairman of Sense About Science, has criticised campaigns to ban plastic bags as counter-productive and being based on "bad science".
Anti-genetic-modification campaigners and academics have criticised Sense About Science for what they view as a failure to disclose industry connections of some advisers,
and Private Eye reported that it had seen a draft of the Making Sense of GM guide that included Monsanto Company's former director of scientific affairs as an author.
Tracey Brown, managing director of Sense About Science, rebutted these claims on the Science about Science website.
Homeopath Peter Fisher criticised Sense About Science, who have been working closely with NHS primary care trusts on the issue of funding for homeopathy, for being funded by the pharmaceutical industry; Sense About Science responded in a statement to Channel 4 News that "Peter Fisher's desperate comments show about as much grasp of reality as the homeopathic medicine he sells."
A 2016 piece in The Intercept was critical of Sense About Science's data on and support for flame retardant chemicals.
== References ==
== External links ==
Official website
Interviews with Tracey Brown on Little Atoms, the official podcast of The Skeptic magazine, on Resonance FM
Alan Sokal giving the 2008 Sense About Science lecture
"Sense About Science", The Guardian, 5 January 2010
Tracey Brown, What would a ‘super-majority’ government mean for parliamentary scrutiny?[1] | Wikipedia/Sense_about_Science |
The Coalition on the Public Understanding of Science (COPUS) is a United States grassroots effort linking universities, scientific societies, science advocacy groups, science media, science educators, businesses, and industry in a consortium having as its goal a greater public understanding of the nature of science and its value to society. Its premise is that full public engagement in science is critical to the long-term social well-being of the American people.
COPUS is organizing the Year of Science 2009, in cooperation with the National Academy of Sciences.
COPUS is sponsored by the American Institute of Biological Sciences and the Geological Society of America.
The COPUS national office is located in Washington, D.C., hosted by the American Institute of Biological Sciences (AIBS).
Participants in the COPUS network, as of March 19, 2007 include:
Alaska Division of Geological & Geophysical Surveys
Alliance for Science
American Association of Physics Teachers
American Fisheries Society
American Institute of Biological Sciences
American Society of Human Genetics
American Society of Plant Biologists
American Sociological Association
Arizona Geological Survey
Arkansas State University
Berkeley Natural History Museums
BioOne
Biotechnology Institute
Botanical Society of America
Colorado Science Forum
Denver Museum of Nature and Science
Geological Society of America
HMS Beagle Project
Louisiana State University Museum of Natural Science
Lyme Regis Fossil Festival - Rising Seas
Massachusetts Society for Medical Research
National Academy of Sciences
National Center for Ecological Analysis and Synthesis
National Institute of General Medical Sciences
National Institutes of Health
National Science Teachers Association
New York State Museum
Peabody Museum of Natural History at Yale University
Pinellas County Environmental Management
Science Education Solutions
Society for Developmental Biology
University of California Museum of Paleontology
University of California Press
University of Connecticut
Visionlearning
Wonderfest
== External links ==
COPUS | Wikipedia/Coalition_on_the_Public_Understanding_of_Science |
Kirsten "Kiki" Sanford is an American neurophysiologist and science communicator. After working at the University of California, Davis as a research scientist, she left research work to pursue a career in science communication. Her work has included multiple audio and video programs, including the This Week in Science radio program and podcast and Dr. Kiki's Science Hour, a podcast involving interviews with experts in a given scientific field.
== Personal life ==
Sanford was born in Santa Rosa, California and raised near Stockton, California. She holds a B.S. in conservation biology and Ph.D. in Molecular, Cellular, and Integrative Physiology from U.C. Davis. She is a specialist in learning and memory. While attending graduate school at U.C. Davis, she found academic bureaucracy unappealing and decided to shift her career path from research to science communication. Sanford holds a black belt in taekwondo. She says martial arts was "something concrete to escape to" when faced with research hardships during graduate school. Sanford lived in San Francisco with her husband until moving to Portland, Oregon in April 2015.
== Science communication ==
Sanford, known as "Dr. Kiki," produces and appears in a number of science education programs. Sanford says of her work, "My shtick is: Dr. Kiki reaches out to people who don't necessarily like science to get them to see it as something enjoyable. My goal is to get people who maybe flunked chemistry or didn't do well on their science fair project to say, 'This is really interesting.'"
Sanford is the host and editor of the This Week in Science radio show/podcast, which she founded in 1999. This Week in Science is a weekly program formerly streamed live from the This Week in Tech Network (TWiT), and then rebroadcast from U.C. Davis' KDVS, 90.3 FM. This Week in Science currently records every Wednesday night using Hangouts on Air which are streamed live on both Youtube and the This Week in Science live page.
Starting in late 2007, Sanford expanded her work, starring in On Network's successful series Food Science. The program explores the science of cooking as well as at-home experiments involving food. In 2008, she began co-hosting Revision3's variety show PopSiren. PopSiren described itself as offering a "feminine perspective" on pop culture and technology.
In May 2008, Sanford along with several other skeptics and scientists created a pilot for a TV series titled The Skeptologists. The premise was that claimed experts in a field of pseudoscience or the paranormal would present their claims, which would then be investigated by the team.
On April 30, 2009, Dr. Kiki's Science Hour started broadcasting on TWiT.tv. The show, recorded live on TWiT, became a podcast with episode 24. Guests included scientists, skeptics, and science communicators such as astronomer Phil Plait and neurologist Steven Novella. The last episode aired on June 29, 2012. While at TWiT she also co-hosted Green Tech Today, a show about environmentally friendly technology, and Science News Weekly a five-minute show.
Sanford has produced and hosted various segments for The Science Channel's science program Brink.
In February 2015, Sanford launched a new company to help researchers and other scientists have better communication. The company, named Broader Impacts, does video production and social media outreach.
== Awards ==
In 2005, Sanford was awarded the American Association for the Advancement of Science Mass Media Science & Engineering Fellowship, in recognition for her work with her radio show This Week in Science. Through the fellowship she worked as a television news producer at WNBC News in New York City, alongside noted health and science reporter Max Gomez.
== References ==
== External links ==
The Bird's Brain, Sanford's blog
This Week in Science
Dr. Kiki's Science Hour
PopSiren
Dr Kiki interviewed on the TV show Triangulation on the TWiT.tv network | Wikipedia/This_Week_in_Science |
The people's science movement (PSM) aims to popularise science and scientific outlook among common people. Kerala Sasthra Sahithya Parishad, Bharat Gyan Vigyan Samiti, Assam Science Society, Bigyan Prachar Samiti (Orissa), We the Sapiens and the All India Peoples Science Network are some popular people's science movements in India.
== People's science movements in India ==
Kerala Sasthra Sahithya Parishad
Pondicherry Science Forum
Bharat Gyan Vigyan Samiti
Tamil Nadu Science Forum
Jan Vignana Vedika
Delhi Science Forum
Assam Science Society
Tripura Science Forum
Bigyan Prachar Samiti, Odisha
Bharat Gyan Vigyan Samiti Uttar Pradesh
Bharat Gyan Vigyan Samiti Haryana
Bharat Gyan Vigyan Samiti Utharkhand
We, the Sapiens
All India Peoples Science Network
== References ==
"Secularism and People's Science Movement in India" and "Towards a People's Science Movement" from Economic and Political Weekly
"People's Science Movement" from Science, technology, imperialism, and war
"The People's Science Movements" from Knowing Nature
"Science for social change" | Wikipedia/People's_science_movement |
The biochemistry of Alzheimer's disease, the most common cause of dementia, is not yet very well understood. Alzheimer's disease (AD) has been identified as a proteopathy: a protein misfolding disease due to the accumulation of abnormally folded amyloid beta (Aβ) protein in the brain. Amyloid beta is a short peptide that is an abnormal proteolytic byproduct of the transmembrane protein amyloid-beta precursor protein (APP), whose function is unclear but thought to be involved in neuronal development. The presenilins are components of proteolytic complex involved in APP processing and degradation.
Amyloid beta monomers are soluble and contain short regions of beta sheet and polyproline II helix secondary structures in solution, though they are largely alpha helical in membranes; however, at sufficiently high concentration, they undergo a dramatic conformational change to form a beta sheet-rich tertiary structure that aggregates to form amyloid fibrils. These fibrils and oligomeric forms of Aβ deposit outside neurons in formations known as senile plaques. There are different types of plaques, including the diffuse, compact, cored or neuritic plaque types, as well as Aβ deposits in the walls of small blood vessel walls in the brain called cerebral amyloid angiopathy.
AD is also considered a tauopathy due to abnormal aggregation of the tau protein, a microtubule-associated protein expressed in neurons that normally acts to stabilize microtubules in the cell cytoskeleton. Like most microtubule-associated proteins, tau is normally regulated by phosphorylation; however, in Alzheimer's disease, hyperphosphorylated tau accumulates as paired helical filaments that in turn aggregate into masses inside nerve cell bodies known as neurofibrillary tangles and as dystrophic neurites associated with amyloid plaques. Although little is known about the process of filament assembly, depletion of a prolyl isomerase protein in the parvulin family has been shown to accelerate the accumulation of abnormal tau.
Neuroinflammation is also involved in the complex cascade leading to AD pathology and symptoms. Considerable pathological and clinical evidence documents immunological changes associated with AD, including increased pro-inflammatory cytokine concentrations in the blood and cerebrospinal fluid. Whether these changes may be a cause or consequence of AD remains to be fully understood, but inflammation within the brain, including increased reactivity of the resident microglia towards amyloid deposits, has been implicated in the pathogenesis and progression of AD. Much of the known biochemistry of Alzheimer's disease has been deciphered through research using experimental models of Alzheimer's disease.
== Neuropathology ==
At a macroscopic level, AD is characterized by loss of neurons and synapses in the cerebral cortex and certain subcortical regions. This results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus.
Both amyloid plaques and neurofibrillary tangles are clearly visible by microscopy in AD brains. Plaques are dense, mostly insoluble deposits of protein and cellular material outside and around neurons. Tangles are insoluble twisted fibers that build up inside the nerve cell. Though many older people develop some plaques and tangles, the brains of AD patients have them to a much greater extent and in different brain locations.
== Biochemical characteristics ==
Fundamental to the understanding of Alzheimer's disease is the biochemical events that leads to accumulation of the amyloid-beta plaques and tau-protein tangles. A delicate balance of the enzymes secretases regulate the amyloid-beta accumulation. Recently, a link between cholinergic neuronal activity and the activity of alpha-secretase has been highlighted, which can discourage amyloid-beta proteins deposition in brain of patients with Alzheimer's disease.
Alzheimer's disease has been identified as a protein misfolding disease, or proteopathy, due to the accumulation of abnormally folded amyloid-beta proteins in the brains of AD patients. Abnormal amyloid-beta accumulation can first be detected using cerebrospinal fluid analysis and later using positron emission tomography (PET).
Although AD shares pathophysiological mechanisms with prion diseases, it is not transmissible in the wild, as prion diseases are. Any transmissibility that it may have is limited solely to extremely rare iatrogenic events from donor-derived therapies that are no longer used. Amyloid-beta, also written Aβ, is a short peptide that is a proteolytic byproduct of the transmembrane protein amyloid precursor protein (APP), whose function is unclear but thought to be involved in neuronal development. The presenilins are components of a proteolytic complex involved in APP processing and degradation.
Although amyloid beta monomers are harmless, they undergo a dramatic conformational change at sufficiently high concentration to form a beta sheet-rich tertiary structure that aggregates to form amyloid fibrils that deposit outside neurons in dense formations known as senile plaques or neuritic plaques, in less dense aggregates as diffuse plaques, and sometimes in the walls of small blood vessels in the brain in a process called amyloid angiopathy or congophilic angiopathy.
AD is also considered a tauopathy due to abnormal aggregation of the tau protein, a microtubule-associated protein expressed in neurons that normally acts to stabilize microtubules in the cell cytoskeleton. Like most microtubule-associated proteins, tau is normally regulated by phosphorylation; however, in AD patients, hyperphosphorylated tau accumulates as paired helical filaments that in turn aggregate into masses inside nerve cell bodies known as neurofibrillary tangles and as dystrophic neurites associated with amyloid plaques.
Levels of the neurotransmitter acetylcholine (ACh) are reduced. Levels of other neurotransmitters serotonin, norepinephrine, and somatostatin are also often reduced. Replenishing the ACh by anti-cholinesterases is an approved mode of treatment by FDA. An alternative method of stimulating ACh receptors of M1-M3 types by synthetic agonists that have a slower rate of dissociation from the receptor has been proposed as next generation cholinomimetic in Alzheimer's disease[15].
== Disease mechanisms ==
While the gross histological features of AD in the brain have been well characterized, several different hypotheses have been advanced regarding the primary cause. Among the oldest hypotheses is the cholinergic hypothesis, which suggests that deficiency in cholinergic signaling initiates the progression of the disease. Current theories establish that both misfolding tau protein inside the cell and aggregation of amyloid beta outside the cell initiates the cascade leading to AD pathology. Newer potential hypotheses propose metabolic factors, vascular disturbance, lipid invasion and chronically elevated inflammation in the brain as contributing factors to AD. The amyloid beta hypothesis of molecular initiation have become dominant among many researchers to date. The amyloid and tau hypothesis are the most widely accepted.
=== Tau hypothesis ===
The hypothesis that tau is the primary causative factor has long been grounded in the observation that deposition of amyloid plaques does not correlate well with neuron loss. A mechanism for neurotoxicity has been proposed based on the loss of microtubule-stabilizing tau protein that leads to the degradation of the cytoskeleton. However, consensus has not been reached on whether tau hyperphosphorylation precedes or is caused by the formation of the abnormal helical filament aggregates. Support for the tau hypothesis also derives from the existence of other diseases known as tauopathies in which the same protein is identifiably misfolded. However, a majority of researchers support the alternative hypothesis that amyloid is the primary causative agent.
=== Amyloid hypothesis ===
The amyloid hypothesis was proposed because the gene for the amyloid beta precursor APP is located on chromosome 21, and patients with trisomy 21 – better known as Down syndrome – who have an extra gene copy exhibit AD-like disorders by 40 years of age. The amyloid hypothesis points to the cytotoxicity of mature aggregated amyloid fibrils, which are believed to be the toxic form of the protein responsible for disrupting the cell's calcium ion homeostasis and thus inducing apoptosis. This hypothesis is supported by the observation that higher levels of a variant of the beta amyloid protein known to form fibrils faster in vitro correlate with earlier onset and greater cognitive impairment in mouse models and with AD diagnosis in humans. However, mechanisms for the induced calcium influx, or proposals for alternative cytotoxic mechanisms, by mature fibrils are not obvious.
A more recent variation of the amyloid hypothesis identifies the cytotoxic species as an intermediate misfolded form of amyloid beta, neither a soluble monomer nor a mature aggregated polymer but an oligomeric species, possibly toroidal or star-shaped with a central channel that may induce apoptosis by physically piercing the cell membrane. This ion channel hypothesis postulates that oligomers of soluble, non-fibrillar Aβ form membrane ion channels allowing unregulated calcium influx into neurons. A related alternative suggests that a globular oligomer localized to dendritic processes and axons in neurons is the cytotoxic species. The prefibrillar aggregates were shown to be able to disrupt the membrane.
The cytotoxic-fibril hypothesis presents a clear target for drug development: inhibit the fibrillization process. Much early development work on lead compounds has focused on this inhibition; most are also reported to reduce neurotoxicity, but the toxic-oligomer theory would imply that prevention of oligomeric assembly is the more important process
or that a better target lies upstream, for example in the inhibition of APP processing to amyloid beta. For example, apomorphine was seen to significantly improve memory function through the increased successful completion of the Morris Water Maze.
Soluble intracellular (o)Aβ42
Two papers have shown that oligomeric (o)Aβ42 (a species of Aβ), in soluble intracellular form, acutely inhibits synaptic transmission, a pathophysiology that characterizes AD (in its early stages), by activating casein kinase 2.
=== Inflammatory hypothesis ===
Converging evidence suggests that a sustained inflammatory response in the brain is a core modifying feature of AD pathology and may be a key modifying factor in AD pathogenesis. The brains of AD patients exhibit several markers of increased inflammatory signaling. The inflammatory hypothesis proposes that chronically elevated inflammation in the brain is a crucial component to the amyloid cascade in the early phases of AD and magnifies disease severity in later stages of AD. Aβ is present in healthy brains and serves a vital physiological function in recovery from neuronal injury, protection from infection, and repair of the blood-brain barrier, however it is unknown how Aβ production starts to exceed the clearance capacity of the brain and initiates AD progression. A possible explanation is that Aβ causes microglia, the resident immune cell of the brain, to become activated and secrete pro-inflammatory signaling molecules, called cytokines, which recruit other local microglia. While acute microglial activation, as in response to injury, is beneficial and allows microglia to clear Aβ and other cellular debris via phagocytosis, chronically activated microglia exhibit decreased efficiency in Aβ clearance. Despite this reduced AB clearance capacity, activated microglia continue to secrete pro-inflammatory cytokines like interleukins 1β and 6 (IL-6, IL-1β) and tumor necrosis factor-alpha (TNF-a), as well as reactive oxygen species which disrupt healthy synaptic functioning and eventually cause neuronal death. The loss of synaptic functioning and later neuronal death is responsible for the cognitive impairments and loss of volume in key brain regions which are associated with AD. IL-1B, IL-6, and TNF-a cause further production of Aβ oligomers, as well as tau hyperphosphorylation, leading to continued microglia activation and creating a feed forward mechanism in which Aβ production is increased and Aβ clearance is decreased eventually causing the formation of Aβ plaques.
=== Historical cholinergic hypothesis ===
The cholinergic hypothesis of AD development was first proposed in 1976 by Peter Davies and A.J.F Maloney. It claimed that Alzheimer's begins as a deficiency in the production of acetylcholine, a vital neurotransmitter. Much early therapeutic research was based on this hypothesis, including restoration of the "cholinergic nuclei". The possibility of cell-replacement therapy was investigated on the basis of this hypothesis. All of the first-generation anti-Alzheimer's medications are based on this hypothesis and work to preserve acetylcholine by inhibiting acetylcholinesterases (enzymes that break down acetylcholine). These medications, though sometimes beneficial, have not led to a cure. In all cases, they have served to only treat symptoms of the disease and have neither halted nor reversed it. These results and other research have led to the conclusion that acetylcholine deficiencies may not be directly causal, but are a result of widespread brain tissue damage, damage so widespread that cell-replacement therapies are likely to be impractical.
More recent findings center on the effects of the misfolded and aggregated proteins, amyloid beta and tau: tau protein abnormalities may initiate the disease cascade, then beta amyloid deposits progress the disease.
=== Glucose consumption ===
The human brain is one of the most metabolically active organs in the body and metabolizes a large amount of glucose to produce cellular energy in the form of adenosine triphosphate (ATP). Despite its high energy demands, the brain is relatively inflexible in its ability to utilize substrates for energy production and relies almost entirely on circulating glucose for its energy needs. This dependence on glucose puts the brain at risk if the supply of glucose is interrupted, or if its ability to metabolize glucose becomes defective. If the brain is not able to produce ATP, synapses cannot be maintained and cells cannot function, ultimately leading to impaired cognition.
Imaging studies have shown decreased utilization of glucose in the brains of Alzheimer's disease patients early in the disease, before clinical signs of cognitive impairment occur. This decrease in glucose metabolism worsens as clinical symptoms develop and the disease progresses. Studies have found a 17%-24% decline in cerebral glucose metabolism in patients with Alzheimer's disease, compared with age-matched controls. Numerous imaging studies have since confirmed this observation.
Abnormally low rates of cerebral glucose metabolism are found in a characteristic pattern in the Alzheimer's disease brain, particularly in the posterior cingulate, parietal, temporal, and prefrontal cortices. These brain regions are believed to control multiple aspects of memory and cognition. This metabolic pattern is reproducible and has even been proposed as a diagnostic tool for Alzheimer's disease. Moreover, diminished cerebral glucose metabolism (DCGM) correlates with plaque density and cognitive deficits in patients with more advanced disease.
Diminished cerebral glucose metabolism (DCGM) may not be solely an artifact of brain cell loss since it occurs in asymptomatic patients at risk for Alzheimer's disease, such as patients homozygous for the epsilon 4 variant of the apolipoprotein E gene (APOE4, a genetic risk factor for Alzheimer's disease), as well as in inherited forms of Alzheimer's disease. Given that DCGM occurs before other clinical and pathological changes occur, it is unlikely to be due to the gross cell loss observed in Alzheimer's disease.
In imaging studies involving young adult APOE4 carriers, where there were no signs of cognitive impairment, diminished cerebral glucose metabolism (DCGM) was detected in the same areas of the brain as older subjects with Alzheimer's disease. However, DCGM is not exclusive to APOE4 carriers. By the time Alzheimer's has been diagnosed, DCGM occurs in genotypes APOE3/E4, APOE3/E3, and APOE4/E4. Thus, DCGM is a metabolic biomarker for the disease state.
=== Insulin signaling ===
A connection has been established between Alzheimer's disease and diabetes during the past decade, as insulin resistance, which is a characteristic hallmark of diabetes, has also been observed in brains of subjects with Alzheimer's disease. Neurotoxic oligomeric amyloid-β species decrease the expression of insulin receptors on the neuronal cell surface and abolish neuronal insulin signaling. It has been suggested that neuronal gangliosides, which take part in the formation of membrane lipid microdomains, facilitate amyloid-β-induced removal of the insulin receptors from the neuronal surface. In Alzheimer's disease, oligomeric amyloid-β species trigger TNF-α signaling. c-Jun N-terminal kinase activation by TNF-α in turn activates stress-related kinases and results in IRS-1 serine phosphorylation, which subsequently blocks downstream insulin signaling. The resulting insulin resistance contributes to cognitive impairment. Consequently, increasing neuronal insulin sensitivity and signaling may constitute a novel therapeutic approach to treat Alzheimer's disease.
=== Oxidative stress ===
Oxidative stress is emerging as a key factor in the pathogenesis of AD. Reactive oxygen species (ROS) over-production is thought to play a critical role in the accumulation and deposition of amyloid beta in AD. Brains of AD patients have elevated levels of oxidative DNA damage in both nuclear and mitochondrial DNA, but the mitochondrial DNA has approximately 10-fold higher levels than nuclear DNA. Aged mitochondria may be the critical factor in the origin of neurodegeneration in AD. Even individuals with mild cognitive impairment, the phase between normal aging and early dementia, have increased oxidative damage in their nuclear and mitochondrial brain DNA (see Aging brain). Naturally occurring DNA double-strand breaks (DSBs) arise in human cells largely from single-strand breaks induced by various processes including the activity of reactive oxygen species, topoisomerases, and hydrolysis due to thermal fluctuations. In neurons DSBs are induced by a type II topoisomerase as part of the physiologic process of memory formation. DSBs are present in both neurons and astrocytes in the postmortem human hippocampus of AD patients at a higher level than in non-AD individuals. AD is associated with an accumulation of DSBs in neurons and astrocytes in the hippocampus and frontal cortex from early stages onward. DSBs are increased in the vicinity of amyloid plaques in the hippocampus, indicating a potential role for Aβ in DSB accumulation or vice versa. The predominant mechanism for repairing DNA double-strand breaks is non-homologous end joining (NHEJ), a mechanism that utilizes the DNA-dependent protein kinase (DNA-PK) complex. The end joining activity and protein levels of DNA-PK catalytic subunit are significantly lower in AD brains than in normal brains.
=== Cholesterol hypothesis ===
The cholesterol hypothesis is a combination of the amyloid hypothesis, tau hypothesis, and potentially the inflammatory hypothesis. Cholesterol was shown to be upstream of both amyloid and tau production. The cholesterol is produced in the astrocytes and shipped to neurons where it activates amyloid production through a process called substrate presentation. The process required apoE. Cholesterol's regulation of Tau production is less well understood, but knocking out the cholesterol synthesis enzyme SREBP2 decreased Tau phosphorylation. Innate immunity triggers cholesterol synthesis and cells take up the cholesterol. Presumably a cell in the brain dies with old age and this triggers innate immunity. More studies are needed to directly tie the inflammatory hypothesis to cholesterol synthesis in the brain.
=== Lipid invasion hypothesis ===
The Lipid Invasion Model (LIM) is a hypothesis for AD published in 2022, which argues that AD is a result of external lipid invasion to the brain, following damage to the blood-brain barrier (BBB). The LIM provides a comprehensive explanation of the observed neuropathologies associated with the disease, including the lipid irregularities first described by Alois Alzheimer himself, and accounts for the wide range of risk factors now identified with AD (including old age, ApoE4, Aβ, brain trauma, high blood pressure, smoking, type 2 diabetes, obesity, alcohol, stress and sleep deprivation), most of which are also associated with damage to the BBB.
The LIM can be viewed as a development of the cholesterol hypothesis, and incorporates and extends the amyloid hypothesis, the current dominant explanation of the disease. It goes back a step to argue that the cause of the amyloid plaques, neurofibrillary/tau tangles and many other features of the disease is the invasion of Low-density lipoprotein (LDL) and other forms of 'bad cholesterol' along with free fatty acids (FFAs) into the brain, following breakdown of the BBB. Such lipids would normally be excluded from the brain by the BBB.
The LIM argues that the influx of 'bad cholesterol' is the primary cause of the excess Aβ, plaque formation and neurofibrillary/tau tangles in Late Onset AD (LOAD), due to changes in lipid raft composition and endosomal-lysosomal trafficking. This concurs with a large body of evidence showing an association of excess cholesterol with increased Aβ production, amyloid plaques and neurofibrillary/tau tangles.
Plaques and tangles are thought to contribute to memory loss in AD. However, not all AD brains display plaques or tangles, and plaques and tangles do not always lead to AD. Therefore, the LIM proposes that it is the FFAs, rather than cholesterol-driven Aβ, that could be the primary drivers of AD. FFAs can account for all the common features of AD, including amnesia, synaptic disruption, neuroinflammation, brain shrinkage, body clock disruption, changes in brain energy production from glucose to ketone bodies, mitochondrial toxicity and oxidative stress within neurons. The LIM argues that the impact of the FFAs could cause most of the memory loss in AD, in addition to the spatial confusion, sleep disruption and sometimes paranoia also associated with the disease.
The Lipid Invasion Model is the only model of AD that explains both the plaques and neurofibrillary/tau tangles commonly seen in LOAD (which accounts for 95% of AD cases), as well as all the other standard features of AD. It also explains why AD so disproportionally affects older people, and the high instance in contact sports players. By arguing that the root cause of AD is primarily damage to the BBB and the subsequent invasion of harmful lipids, the model offers new insights into the fundamental causes of AD, and potential new pathways for remedies for the disease. The LIM may also provide insights into other dementias and neurological diseases, such as Parkinson’s and ALS/Motor Neurone Disease.
=== Reelin hypothesis ===
A 1994 study showed that the isoprenoid changes in Alzheimer's disease differ from those occurring during normal aging and that this disease cannot, therefore, be regarded as a result of premature aging. During aging the human brain shows a progressive increase in levels of dolichol, a reduction in levels of ubiquinone, but relatively unchanged concentrations of cholesterol and dolichyl phosphate. In Alzheimer's disease, the situation is reversed with decreased levels of dolichol and increased levels of ubiquinone. The concentrations of dolichyl phosphate are also increased, while cholesterol remains unchanged. The increase in the sugar carrier dolichyl phosphate may reflect an increased rate of glycosylation in the diseased brain and the increase in the endogenous anti-oxidant ubiquinone an attempt to protect the brain from oxidative stress, for instance induced by lipid peroxidation. Ropren, identified previously in Russia, is neuroprotective in a rat model of Alzheimer's disease.
A relatively recent hypothesis based mainly on rodent experiments links the onset of Alzheimer's disease to the hypofunction of the large extracellular protein reelin. A decrease of reelin in the human entorhinal cortex where the disease typically initiates is evident while compensatory increase of reelin levels in other brain structures of the patients is also reported. Of key importance, overexpression of reelin rescues the cognitive capacities of Alzheimer's disease model mice and τ-protein overexpressing mice. A recent circuit level model proposed a mechanism of how reelin depletion leads to the early deterioration of episodic memory thereby laying the theoretical foundation of the reelin hypothesis.
=== Large gene instability hypothesis ===
A bioinformatics analysis in 2017 revealed that extremely large human genes are significantly over-expressed in brain and take part in the postsynaptic architecture. These genes are also highly enriched in cell adhesion Gene Ontology (GO) terms and often map to chromosomal fragile sites. The majority of known Alzheimer's disease risk gene products including the amyloid precursor protein (APP) and gamma-secretase, as well as the APOE receptors and GWAS risk loci take part in similar cell adhesion mechanisms. It was concluded that dysfunction of cell and synaptic adhesion is central to Alzheimer's disease pathogenesis, and mutational instability of large synaptic adhesion genes may be the etiological trigger of neurotransmission disruption and synaptic loss in brain aging. As a typical example, this hypothesis explains the APOE risk locus of AD in context of signaling of its giant lipoprotein receptor, LRP1b which is a large tumor-suppressor gene with brain-specific expression and also maps to an unstable chromosomal fragile site. The large gene instability hypothesis puts the DNA damage mechanism at the center of Alzheimer's disease pathophysiology.
== References == | Wikipedia/Biochemistry_of_Alzheimer's_disease |
Medium spiny neurons (MSNs), also known as spiny projection neurons (SPNs), are a special type of inhibitory GABAergic neuron representing approximately 90% of neurons within the human striatum, a basal ganglia structure. Medium spiny neurons have two primary phenotypes (characteristic types): D1-type MSNs of the direct pathway and D2-type MSNs of the indirect pathway. Most striatal MSNs contain only D1-type or D2-type dopamine receptors, but a subpopulation of MSNs exhibit both phenotypes.
Direct pathway MSNs excite their ultimate basal ganglia output structure (such as the thalamus) and promote associated behaviors; these neurons express D1-type dopamine receptors, adenosine A1 receptors, dynorphin peptides, and substance P peptides. Indirect pathway MSNs inhibit their output structure and in turn inhibit associated behaviors; these neurons express D2-type dopamine receptors, adenosine A2A receptors (A2A), DRD2–A2A heterotetramers, and enkephalin. Both types express glutamate receptors (NMDAR and AMPAR), cholinergic receptors (M1 and M4) and CB1 receptors are expressed on the somatodendritic area of both MSN types. A subpopulation of MSNs contain both D1-type and D2-type receptors, with approximately 40% of striatal MSNs expressing both DRD1 and DRD2 mRNA. In the nucleus accumbens (NAcc), these mixed-type MSNs that contain both D1-type and D2-type receptors are mostly contained in the NAcc shell.
The dorsal striatal MSNs play a key role in initiating and controlling movements of the body, limbs, and eyes. The ventral striatal MSNs play a key role in motivation, reward, reinforcement, and aversion. Dorsal and ventral medium spiny neuron subtypes (i.e., direct D1-type and indirect D2-type) are identical phenotypes, but their output connections differ.
== Appearance and location ==
The medium spiny neurons are medium-sized projection neurons with extensively branched dendrites. The cell body is 15–18 μm and has five primary dendrites that become branched. At first the dendrites are without spines but at about the first branch point they become densely spined. The branches produce almost spherical dendritic fields of between 200–300 μm.
About 90% of neurons in the striatum are medium projection neurons, the other 10% are interneurons. In the direct pathway the neurons project directly to the globus pallidus internal (GPi) and the substantia nigra pars reticulata (SNpr). In the indirect pathway the MSNs ultimately project to these two structures via an intermediate connection to the globus pallidus external (GPe) and ventral pallidum (VP). The GPe and VP send a GABAergic projection to the subthalamic nucleus, which then sends glutamatergic projections to the GPi and SNpr. Both the GPi and SNpr send inhibitory projections to nuclei within the thalamus.
== Function ==
MSNs are inhibitory GABAergic neurons, but the effect of direct MSNs (dMSNs) and indirect MSNs (iMSNs) on their ultimate output structures differs: dMSNs excite, while iMSNs inhibit, their basal ganglia output structures (e.g., the thalamus). Within the basal ganglia, there are several complex circuits of neuronal loops all of which include medium spiny neurons.
The cortical, thalamic, and brain-stem inputs that arrive at the medium spiny neurons show a vast divergence in that each incoming axon forms contacts with many spiny neurons and each spiny neuron receives a vast amount of input from different incoming axons. Since these inputs are glutamatergic they exhibit an excitatory influence on the inhibitory medium spiny neurons.
There are also interneurons in the striatum which regulate the excitability of the medium spiny neurons. The synaptic connections between a particular GABAergic interneuron, the parvalbumin expressing fast-spiking interneuron, and spiny neurons are close to the spiny neurons' soma, or cell body. Recall that excitatory postsynaptic potentials caused by glutamatergic inputs at the dendrites of the spiny neurons only cause an action potential when the depolarization wave is strong enough upon entering the cell soma. Since the fast-spiking interneurons influence is located so closely to this critical gate between the dendrites and the soma, they can readily regulate the generation of an action potential. Additionally, other types of GABAergic interneurons make connections with the spiny neurons. These include interneurons that express tyrosine hydroxylase and neuropeptide Y.
== Dorsal striatal MSNs ==
=== Direct pathway ===
==== Anatomy ====
The direct pathway within the basal ganglia receives excitatory input from the cortex, thalamus, and other brain regions. In the direct pathway, medium spiny neurons project to the internal division of the globus pallidus (GPi) or the substantia nigra pars reticula (SNpr or SNr). These nuclei project to the deep layer of the superior colliculus and control fast eye movements (saccades), and also project to the ventral thalamus, which in turn projects to upper motor neurons in the primary motor cortex (precentral gyrus). The SNr and GPi outputs are both tonically active inhibitory nuclei and are thus constantly inhibiting the thalamus (and thus motor cortex). However, transient activity in (inhibitory) direct pathway medium spiny neurons ultimately disinhibits thalamus projections to the motor cortex and enables movement.
=== Indirect pathway ===
==== Anatomy ====
The indirect pathway also receives excitatory input from various brain regions. Indirect pathway medium spiny neurons project to the external segment of the globus pallidus (GPe). Like the GPi, the GPe is a tonically active inhibitory nucleus. The GPe projects to the excitatory subthalamic nucleus (STN), which in turn projects to the GPi and SNr. When the indirect pathway is not activated, activity in the STN is suppressed by the GPe, which translates to decreased SNr/GPi activity downstream and thus increased thalamic and motor cortex neuron activity. When indirect pathway neurons fire, GPe neurons are inhibited, which disinhibits the STN. The STN then excites SNr/GPi neurons, suppressing thalamus/motor cortex activity.
=== Functional distinctions ===
Classic models of striatal function have posited that activation of the direct pathway leads to movement, whereas activation of the indirect pathway leads to the termination of movement. This model is supported by experiments demonstrating that optogenetically stimulating direct pathway medium spiny neurons increases locomotion, whereas stimulating indirect pathway medium spiny neurons inhibits locomotion. The balance of direct/indirect activity in movement is supported by evidence from neurodegenerative disorders, including Parkinson's disease (PD), which is characterized by loss of dopamine neurons projecting to the striatum, hypoactivity in direct pathway and hyperactivity in indirect pathway neurons, along with motor dysfunction. This results in loss of normal action selection, as loss of dopamine drives activity in the indirect pathway, globally inhibiting all motor paradigms. This may explain impaired action initiation, slowed actions (bradykinesia), and impaired voluntary motor initiation in Parkinson's patients. On the other hand, Huntington's disease, which is characterized by preferential degradation of indirect pathway medium spiny neurons, results in unwanted movements (chorea) that may result from impaired movement inhibition and predominant direct pathway activity. An alternative related hypothesis is that the striatum controls action initiation and selection via a ’center-surround’ architecture, where activation of a subset of direct pathway neurons initiates movements while closely related motor patterns represented by surrounding neurons are inhibited by lateral inhibition via indirect pathway neurons. This specific hypothesis is supported by recent calcium-imaging work showing that direct and indirect pathway medium spiny neurons encoding specific actions are located in spatially organized ensembles.
Despite the abundance of evidence for the initiation/termination model, recent evidence using transgenic mice expressing calcium indicators in either the direct or indirect pathway demonstrated that both pathways are active at action initiation, but neither are active during inactivity, a finding which has been replicated using simultaneous two-channel calcium imaging. This has led to somewhat of a paradigm shift in models of striatal functioning, such that newer models posit that the direct pathway facilitates wanted movements, whereas the indirect pathway simultaneously inhibits unwanted movements. Indeed, more sophisticated techniques and analyses, such as state-dependent optogenetics, have revealed that both pathways are heavily involved in action sequence execution, and that specifically, both striatal pathways are involved in element-level action control. However, direct pathway medium spiny neurons mostly signal sequence initiation/termination and indirect pathway medium spiny neurons may signal switching between subsequences of a given action sequence. Other evidence suggests that the direct and indirect pathway oppositely influence the termination of movement—specifically, the relative timing of their activity determines if an action will be terminated.
Recent experiments have established that the direct and indirect pathways of the dorsal striatum are not solely involved in movement. Initial experiments in an intracranial self-stimulation paradigm suggested opposing roles in reinforcement for the two pathways; specifically, stimulation of direct pathway medium spiny neurons was found to be reinforcing, whereas stimulation of indirect pathway medium spiny neurons was aversive. However, a subsequent study (using more physiologically relevant stimulation parameters) found that direct and indirect pathway stimulation was reinforcing, but that pathway-specific stimulation resulted in the development of different action strategies. Regardless, these studies suggest a critical role for reinforcement in the dorsal striatum, as opposed to the striatum only serving a role in movement control.
== Ventral striatal MSNs ==
=== Direct pathway ===
The direct pathway of the ventral striatum within the basal ganglia mediates reward-based learning and appetitive incentive salience, which is assigned to rewarding stimuli.
=== Indirect pathway ===
The indirect pathway of the ventral striatum within the basal ganglia mediates aversion-based learning and aversive motivational salience, which is assigned to aversive stimuli.
== See also ==
List of distinct cell types in the adult human body
== References ==
== Further reading ==
== External links ==
NIF Search – Medium Spiny Neuron via the Neuroscience Information Framework | Wikipedia/Medium_spiny_neurons |
Upper motor neurons (UMNs) is a term introduced by William Gowers in 1886. They are found in the cerebral cortex and brainstem and carry information down to activate interneurons and lower motor neurons, which in turn directly signal muscles to contract or relax. UMNs represent the major origin point for voluntary somatic movement.
Upper motor neurons represent the largest pyramidal cells in the motor regions of the cerebral cortex. The major cell type of the UMNs is the Betz cells residing in layer V of the primary motor cortex, located on the precentral gyrus in the posterior frontal lobe. The cell bodies of Betz cell neurons are the largest in the brain, approaching nearly 0.1 mm in diameter. The axons of the upper motor neurons project out of the precentral gyrus travelling through to the brainstem, where they will decussate (intersect) within the lower medulla oblongata to form the lateral corticospinal tract on each side of the spinal cord. The fibers that do not decussate will pass through the medulla and continue on to form the anterior corticospinal tracts.
The upper motor neuron descends in the spinal cord to the level of the appropriate spinal nerve root. At this point, the upper motor neuron synapses with the lower motor neuron or interneurons within the ventral horn of the spinal cord, each of whose axons innervate a fiber of skeletal muscle.
These neurons connect the brain to the appropriate level in the spinal cord, from which point nerve signals continue to the muscles by means of the lower motor neurons. The neurotransmitter glutamate transmits the nerve impulses from upper to lower motor neurons, where it is detected by glutamate receptors.
== Pathways ==
Upper motor neurons travel in several neural pathways through the central nervous system (CNS):
== Lesions ==
Any upper motor neuron lesion, also known as pyramidal insufficiency, occurs in the neural pathway above the anterior horn of the spinal cord. Such lesions can arise as a result of stroke, multiple sclerosis, spinal cord injury or other acquired brain injury. The resulting changes in muscle performance that can be wide and varied are described overall as upper motor neuron syndrome. Symptoms can include muscle weakness, decreased motor control including a loss of the ability to perform fine movements, increased vigor (and decreased threshold) of spinal reflexes including spasticity, clonus (involuntary, successive cycles of contraction/relaxation of a muscle), and an extensor plantar response known as the Babinski sign.
== See also ==
Lower motor neuron
Upper motor neuron lesion
Lower motor neuron lesion
== References ==
== External links ==
"motoneuron" at Dorland's Medical Dictionary | Wikipedia/Upper_motor_neurons |
In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes that impact the body, then works in tandem with the endocrine system to respond to such events. Nervous tissue first arose in wormlike organisms about 550 to 600 million years ago. In vertebrates, it consists of two main parts, the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS consists of the brain and spinal cord. The PNS consists mainly of nerves, which are enclosed bundles of the long fibers, or axons, that connect the CNS to every other part of the body. Nerves that transmit signals from the brain are called motor nerves (efferent), while those nerves that transmit information from the body to the CNS are called sensory nerves (afferent). The PNS is divided into two separate subsystems, the somatic and autonomic nervous systems. The autonomic nervous system is further subdivided into the sympathetic, parasympathetic and enteric nervous systems. The sympathetic nervous system is activated in cases of emergencies to mobilize energy, while the parasympathetic nervous system is activated when organisms are in a relaxed state. The enteric nervous system functions to control the gastrointestinal system. Nerves that exit from the brain are called cranial nerves while those exiting from the spinal cord are called spinal nerves.
The nervous system consists of nervous tissue which, at a cellular level, is defined by the presence of a special type of cell, called the neuron. Neurons have special structures that allow them to send signals rapidly and precisely to other cells. They send these signals in the form of electrochemical impulses traveling along thin fibers called axons, which can be directly transmitted to neighboring cells through electrical synapses or cause chemicals called neurotransmitters to be released at chemical synapses. A cell that receives a synaptic signal from a neuron may be excited, inhibited, or otherwise modulated. The connections between neurons can form neural pathways, neural circuits, and larger networks that generate an organism's perception of the world and determine its behavior. Along with neurons, the nervous system contains other specialized cells called glial cells (or simply glia), which provide structural and metabolic support. Many of the cells and vasculature channels within the nervous system make up the neurovascular unit, which regulates cerebral blood flow in order to rapidly satisfy the high energy demands of activated neurons.
Nervous systems are found in most multicellular animals, but vary greatly in complexity. The only multicellular animals that have no nervous system at all are sponges, placozoans, and mesozoans, which have very simple body plans. The nervous systems of the radially symmetric organisms ctenophores (comb jellies) and cnidarians (which include anemones, hydras, corals and jellyfish) consist of a diffuse nerve net. All other animal species, with the exception of a few types of worm, have a nervous system containing a brain, a central cord (or two cords running in parallel), and nerves radiating from the brain and central cord. The size of the nervous system ranges from a few hundred cells in the simplest worms, to around 300 billion cells in African elephants.
The central nervous system functions to send signals from one cell to others, or from one part of the body to others and to receive feedback. Malfunction of the nervous system can occur as a result of genetic defects, physical damage due to trauma or toxicity, infection, or simply senescence. The medical specialty of neurology studies disorders of the nervous system and looks for interventions that can prevent or treat them. In the peripheral nervous system, the most common problem is the failure of nerve conduction, which can be due to different causes including diabetic neuropathy and demyelinating disorders such as multiple sclerosis and amyotrophic lateral sclerosis. Neuroscience is the field of science that focuses on the study of the nervous system.
== Structure ==
The nervous system derives its name from nerves, which are cylindrical bundles of fibers (the axons of neurons), that emanate from the brain and spinal cord, and branch repeatedly to innervate every part of the body. Nerves are large enough to have been recognized by the ancient Egyptians, Greeks, and Romans, but their internal structure was not understood until it became possible to examine them using a microscope. The author Michael Nikoletseas wrote:
"It is difficult to believe that until approximately year 1900 it was not known that neurons are the basic units of the brain (Santiago Ramón y Cajal). Equally surprising is the fact that the concept of chemical transmission in the brain was not known until around 1930 (Henry Hallett Dale and Otto Loewi). We began to understand the basic electrical phenomenon that neurons use in order to communicate among themselves, the action potential, in the 1950s (Alan Lloyd Hodgkin, Andrew Huxley and John Eccles). It was in the 1960s that we became aware of how basic neuronal networks code stimuli and thus basic concepts are possible (David H. Hubel and Torsten Wiesel). The molecular revolution swept across US universities in the 1980s. It was in the 1990s that molecular mechanisms of behavioral phenomena became widely known (Eric Richard Kandel)." A microscopic examination shows that nerves consist primarily of axons, along with different membranes that wrap around them and segregate them into fascicles. The neurons that give rise to nerves do not lie entirely within the nerves themselves—their cell bodies reside within the brain, spinal cord, or peripheral ganglia.
All animals more advanced than sponges have nervous systems. However, even sponges, unicellular animals, and non-animals such as slime molds have cell-to-cell signalling mechanisms that are precursors to those of neurons. In radially symmetric animals such as the jellyfish and hydra, the nervous system consists of a nerve net, a diffuse network of isolated cells. In bilaterian animals, which make up the great majority of existing species, the nervous system has a common structure that originated early in the Ediacaran period, over 550 million years ago.
=== Cells ===
The nervous system contains two main categories or types of cells: neurons and glial cells.
==== Neurons ====
The nervous system is defined by the presence of a special type of cell—the neuron (sometimes called "neurone" or "nerve cell"). Neurons can be distinguished from other cells in a number of ways, but their most fundamental property is that they communicate with other cells via synapses, which are membrane-to-membrane junctions containing molecular machinery that allows rapid transmission of signals, either electrical or chemical. Many types of neuron possess an axon, a protoplasmic protrusion that can extend to distant parts of the body and make thousands of synaptic contacts; axons typically extend throughout the body in bundles called nerves.
Even in the nervous system of a single species such as humans, hundreds of different types of neurons exist, with a wide variety of morphologies and functions. These include sensory neurons that transmute physical stimuli such as light and sound into neural signals, and motor neurons that transmute neural signals into activation of muscles or glands; however in many species the great majority of neurons participate in the formation of centralized structures (the brain and ganglia) and they receive all of their input from other neurons and send their output to other neurons.
==== Glial cells ====
Glial cells (named from the Greek for "glue") are non-neuronal cells that provide support and nutrition, maintain homeostasis, form myelin, and participate in signal transmission in the nervous system. In the human brain, it is estimated that the total number of glia roughly equals the number of neurons, although the proportions vary in different brain areas. Among the most important functions of glial cells are to support neurons and hold them in place; to supply nutrients to neurons; to insulate neurons electrically; to destroy pathogens and remove dead neurons; and to provide guidance cues directing the axons of neurons to their targets. A very important type of glial cell (oligodendrocytes in the central nervous system, and Schwann cells in the peripheral nervous system) generates layers of a fatty substance called myelin that wraps around axons and provides electrical insulation which allows them to transmit action potentials much more rapidly and efficiently. Recent findings indicate that glial cells, such as microglia and astrocytes, serve as important resident immune cells within the central nervous system.
=== Anatomy in vertebrates ===
The nervous system of vertebrates (including humans) is divided into the central nervous system (CNS) and the peripheral nervous system (PNS).
The CNS is the major division, and consists of the brain and the spinal cord. The spinal canal contains the spinal cord, while the cranial cavity contains the brain. The CNS is enclosed and protected by the meninges, a three-layered system of membranes, including a tough, leathery outer layer called the dura mater. The brain is also protected by the skull, and the spinal cord by the vertebrae.
The peripheral nervous system (PNS) is a collective term for the nervous system structures that do not lie within the CNS. The large majority of the axon bundles called nerves are considered to belong to the PNS, even when the cell bodies of the neurons to which they belong reside within the brain or spinal cord. The PNS is divided into somatic and visceral parts. The somatic part consists of the nerves that innervate the skin, joints, and muscles. The cell bodies of somatic sensory neurons lie in dorsal root ganglia of the spinal cord. The visceral part, also known as the autonomic nervous system, contains neurons that innervate the internal organs, blood vessels, and glands. The autonomic nervous system itself consists of two parts: the sympathetic nervous system and the parasympathetic nervous system. Some authors also include sensory neurons whose cell bodies lie in the periphery (for senses such as hearing) as part of the PNS; others, however, omit them.
The vertebrate nervous system can also be divided into areas called gray matter and white matter. Gray matter (which is only gray in preserved tissue, and is better described as pink or light brown in living tissue) contains a high proportion of cell bodies of neurons. White matter is composed mainly of myelinated axons, and takes its color from the myelin. White matter includes all of the nerves, and much of the interior of the brain and spinal cord. Gray matter is found in clusters of neurons in the brain and spinal cord, and in cortical layers that line their surfaces. There is an anatomical convention that a cluster of neurons in the brain or spinal cord is called a nucleus, whereas a cluster of neurons in the periphery is called a ganglion. There are, however, a few exceptions to this rule, notably including the part of the forebrain called the basal ganglia.
=== Comparative anatomy and evolution ===
==== Neural precursors in sponges ====
Sponges have no cells connected to each other by synaptic junctions, that is, no neurons, and therefore no nervous system. They do, however, have homologs of many genes that play key roles in synaptic function. Recent studies have shown that sponge cells express a group of proteins that cluster together to form a structure resembling a postsynaptic density (the signal-receiving part of a synapse). However, the function of this structure is currently unclear. Although sponge cells do not show synaptic transmission, they do communicate with each other via calcium waves and other impulses, which mediate some simple actions such as whole-body contraction.
==== Radiata ====
Jellyfish, comb jellies, and related animals have diffuse nerve nets rather than a central nervous system. In most jellyfish the nerve net is spread more or less evenly across the body; in comb jellies it is concentrated near the mouth. The nerve nets consist of sensory neurons, which pick up chemical, tactile, and visual signals; motor neurons, which can activate contractions of the body wall; and intermediate neurons, which detect patterns of activity in the sensory neurons and, in response, send signals to groups of motor neurons. In some cases groups of intermediate neurons are clustered into discrete ganglia.
The development of the nervous system in radiata is relatively unstructured. Unlike bilaterians, radiata only have two primordial cell layers, endoderm and ectoderm. Neurons are generated from a special set of ectodermal precursor cells, which also serve as precursors for every other ectodermal cell type.
==== Bilateria ====
The vast majority of existing animals are bilaterians, meaning animals with left and right sides that are approximate mirror images of each other. All bilateria are thought to have descended from a common wormlike ancestor that appear as fossils beginning in the Ediacaran period, 550–600 million years ago. The fundamental bilaterian body form is a tube with a hollow gut cavity running from mouth to anus, and a nerve cord with an enlargement (a "ganglion") for each body segment, with an especially large ganglion at the front, called the "brain".
Even mammals, including humans, show the segmented bilaterian body plan at the level of the nervous system. The spinal cord contains a series of segmental ganglia, each giving rise to motor and sensory nerves that innervate a portion of the body surface and underlying musculature. On the limbs, the layout of the innervation pattern is complex, but on the trunk it gives rise to a series of narrow bands. The top three segments belong to the brain, giving rise to the forebrain, midbrain, and hindbrain.
Bilaterians can be divided, based on events that occur very early in embryonic development, into two groups (superphyla) called protostomes and deuterostomes. Deuterostomes include vertebrates as well as echinoderms, hemichordates (mainly acorn worms), and Xenoturbellidans. Protostomes, the more diverse group, include arthropods, molluscs, and numerous phyla of "worms". There is a basic difference between the two groups in the placement of the nervous system within the body: protostomes possess a nerve cord on the ventral (usually bottom) side of the body, whereas in deuterostomes the nerve cord is on the dorsal (usually top) side. In fact, numerous aspects of the body are inverted between the two groups, including the expression patterns of several genes that show dorsal-to-ventral gradients. Most anatomists now consider that the bodies of protostomes and deuterostomes are "flipped over" with respect to each other, a hypothesis that was first proposed by Geoffroy Saint-Hilaire for insects in comparison to vertebrates. Thus insects, for example, have nerve cords that run along the ventral midline of the body, while all vertebrates have spinal cords that run along the dorsal midline.
==== Worms ====
Worms are the simplest bilaterian animals, and reveal the basic structure of the bilaterian nervous system in the most straightforward way. As an example, earthworms have dual nerve cords running along the length of the body and merging at the tail and the mouth. These nerve cords are connected by transverse nerves like the rungs of a ladder. These transverse nerves help coordinate the two sides of the animal. Two ganglia at the head (the "nerve ring") end function similar to a simple brain. Photoreceptors on the animal's eyespots provide sensory information on light and dark.
The nervous system of one very small roundworm, the nematode Caenorhabditis elegans, has been completely mapped out in a connectome including its synapses. Every neuron and its cellular lineage has been recorded and most, if not all, of the neural connections are known. In this species, the nervous system is sexually dimorphic; the nervous systems of the two sexes, males and female hermaphrodites, have different numbers of neurons and groups of neurons that perform sex-specific functions. In C. elegans, males have exactly 383 neurons, while hermaphrodites have exactly 302 neurons.
==== Arthropods ====
Arthropods, such as insects and crustaceans, have a nervous system made up of a series of ganglia, connected by a ventral nerve cord made up of two parallel connectives running along the length of the belly. Typically, each body segment has one ganglion on each side, though some ganglia are fused to form the brain and other large ganglia. The head segment contains the brain, also known as the supraesophageal ganglion. In the insect nervous system, the brain is anatomically divided into the protocerebrum, deutocerebrum, and tritocerebrum. Immediately behind the brain is the subesophageal ganglion, which is composed of three pairs of fused ganglia. It controls the mouthparts, the salivary glands and certain muscles. Many arthropods have well-developed sensory organs, including compound eyes for vision and antennae for olfaction and pheromone sensation. The sensory information from these organs is processed by the brain.
In insects, many neurons have cell bodies that are positioned at the edge of the brain and are electrically passive—the cell bodies serve only to provide metabolic support and do not participate in signalling. A protoplasmic fiber runs from the cell body and branches profusely, with some parts transmitting signals and other parts receiving signals. Thus, most parts of the insect brain have passive cell bodies arranged around the periphery, while the neural signal processing takes place in a tangle of protoplasmic fibers called neuropil, in the interior.
==== Molluscs ====
==== "Identified" neurons ====
A neuron is called identified if it has properties that distinguish it from every other neuron in the same animal—properties such as location, neurotransmitter, gene expression pattern, and connectivity—and if every individual organism belonging to the same species has one and only one neuron with the same set of properties. In vertebrate nervous systems very few neurons are "identified" in this sense—in humans, there are believed to be none—but in simpler nervous systems, some or all neurons may be thus unique. In the roundworm C. elegans, whose nervous system is the most thoroughly described of any animal's, every neuron in the body is uniquely identifiable, with the same location and the same connections in every individual worm. One notable consequence of this fact is that the form of the C. elegans nervous system is completely specified by the genome, with no experience-dependent plasticity.
The brains of many molluscs and insects also contain substantial numbers of identified neurons. In vertebrates, the best known identified neurons are the gigantic Mauthner cells of fish. Every fish has two Mauthner cells, in the bottom part of the brainstem, one on the left side and one on the right. Each Mauthner cell has an axon that crosses over, innervating neurons at the same brain level and then travelling down through the spinal cord, making numerous connections as it goes. The synapses generated by a Mauthner cell are so powerful that a single action potential gives rise to a major behavioral response: within milliseconds the fish curves its body into a C-shape, then straightens, thereby propelling itself rapidly forward. Functionally this is a fast escape response, triggered most easily by a strong sound wave or pressure wave impinging on the lateral line organ of the fish. Mauthner cells are not the only identified neurons in fish—there are about 20 more types, including pairs of "Mauthner cell analogs" in each spinal segmental nucleus. Although a Mauthner cell is capable of bringing about an escape response individually, in the context of ordinary behavior other types of cells usually contribute to shaping the amplitude and direction of the response.
Mauthner cells have been described as command neurons. A command neuron is a special type of identified neuron, defined as a neuron that is capable of driving a specific behavior individually. Such neurons appear most commonly in the fast escape systems of various species—the squid giant axon and squid giant synapse, used for pioneering experiments in neurophysiology because of their enormous size, both participate in the fast escape circuit of the squid. The concept of a command neuron has, however, become controversial, because of studies showing that some neurons that initially appeared to fit the description were really only capable of evoking a response in a limited set of circumstances.
== Function ==
At the most basic level, the function of the nervous system is to send signals from one cell to others, or from one part of the body to others. There are multiple ways that a cell can send signals to other cells. One is by releasing chemicals called hormones into the internal circulation, so that they can diffuse to distant sites. In contrast to this "broadcast" mode of signaling, the nervous system provides "point-to-point" signals—neurons project their axons to specific target areas and make synaptic connections with specific target cells. Thus, neural signaling is capable of a much higher level of specificity than hormonal signaling. It is also much faster: the fastest nerve signals travel at speeds that exceed 100 meters per second.
At a more integrative level, the primary function of the nervous system is to control the body. It does this by extracting information from the environment using sensory receptors, sending signals that encode this information into the central nervous system, processing the information to determine an appropriate response, and sending output signals to muscles or glands to activate the response. The evolution of a complex nervous system has made it possible for various animal species to have advanced perception abilities such as vision, complex social interactions, rapid coordination of organ systems, and integrated processing of concurrent signals. In humans, the sophistication of the nervous system makes it possible to have language, abstract representation of concepts, transmission of culture, and many other features of human society that would not exist without the human brain.
=== Neurons and synapses ===
Most neurons send signals via their axons, although some types are capable of dendrite-to-dendrite communication. (In fact, the types of neurons called amacrine cells have no axons, and communicate only via their dendrites.) Neural signals propagate along an axon in the form of electrochemical waves called action potentials, which produce cell-to-cell signals at points where axon terminals make synaptic contact with other cells.
Synapses may be electrical or chemical. Electrical synapses make direct electrical connections between neurons, but chemical synapses are much more common, and much more diverse in function. At a chemical synapse, the cell that sends signals is called presynaptic, and the cell that receives signals is called postsynaptic. Both the presynaptic and postsynaptic areas are full of molecular machinery that carries out the signalling process. The presynaptic area contains large numbers of tiny spherical vessels called synaptic vesicles, packed with neurotransmitter chemicals. When the presynaptic terminal is electrically stimulated, an array of molecules embedded in the membrane are activated, and cause the contents of the vesicles to be released into the narrow space between the presynaptic and postsynaptic membranes, called the synaptic cleft. The neurotransmitter then binds to receptors embedded in the postsynaptic membrane, causing them to enter an activated state. Depending on the type of receptor, the resulting effect on the postsynaptic cell may be excitatory, inhibitory, or modulatory in more complex ways. For example, release of the neurotransmitter acetylcholine at a synaptic contact between a motor neuron and a muscle cell induces rapid contraction of the muscle cell. The entire synaptic transmission process takes only a fraction of a millisecond, although the effects on the postsynaptic cell may last much longer (even indefinitely, in cases where the synaptic signal leads to the formation of a memory trace).
There are literally hundreds of different types of synapses. In fact, there are over a hundred known neurotransmitters, and many of them have multiple types of receptors. Many synapses use more than one neurotransmitter—a common arrangement is for a synapse to use one fast-acting small-molecule neurotransmitter such as glutamate or GABA, along with one or more peptide neurotransmitters that play slower-acting modulatory roles. Molecular neuroscientists generally divide receptors into two broad groups: chemically gated ion channels and second messenger systems. When a chemically gated ion channel is activated, it forms a passage that allows specific types of ions to flow across the membrane. Depending on the type of ion, the effect on the target cell may be excitatory or inhibitory. When a second messenger system is activated, it starts a cascade of molecular interactions inside the target cell, which may ultimately produce a wide variety of complex effects, such as increasing or decreasing the sensitivity of the cell to stimuli, or even altering gene transcription.
According to a rule called Dale's principle, which has only a few known exceptions, a neuron releases the same neurotransmitters at all of its synapses. This does not mean, though, that a neuron exerts the same effect on all of its targets, because the effect of a synapse depends not on the neurotransmitter, but on the receptors that it activates. Because different targets can (and frequently do) use different types of receptors, it is possible for a neuron to have excitatory effects on one set of target cells, inhibitory effects on others, and complex modulatory effects on others still. Nevertheless, it happens that the two most widely used neurotransmitters, glutamate and GABA, each have largely consistent effects. Glutamate has several widely occurring types of receptors, but all of them are excitatory or modulatory. Similarly, GABA has several widely occurring receptor types, but all of them are inhibitory. Because of this consistency, glutamatergic cells are frequently referred to as "excitatory neurons", and GABAergic cells as "inhibitory neurons". Strictly speaking, this is an abuse of terminology—it is the receptors that are excitatory and inhibitory, not the neurons—but it is commonly seen even in scholarly publications.
One very important subset of synapses are capable of forming memory traces by means of long-lasting activity-dependent changes in synaptic strength. The best-known form of neural memory is a process called long-term potentiation (abbreviated LTP), which operates at synapses that use the neurotransmitter glutamate acting on a special type of receptor known as the NMDA receptor. The NMDA receptor has an "associative" property: if the two cells involved in the synapse are both activated at approximately the same time, a channel opens that permits calcium to flow into the target cell. The calcium entry initiates a second messenger cascade that ultimately leads to an increase in the number of glutamate receptors in the target cell, thereby increasing the effective strength of the synapse. This change in strength can last for weeks or longer. Since the discovery of LTP in 1973, many other types of synaptic memory traces have been found, involving increases or decreases in synaptic strength that are induced by varying conditions, and last for variable periods of time. The reward system, that reinforces desired behaviour for example, depends on a variant form of LTP that is conditioned on an extra input coming from a reward-signalling pathway that uses dopamine as neurotransmitter. All these forms of synaptic modifiability, taken collectively, give rise to neural plasticity, that is, to a capability for the nervous system to adapt itself to variations in the environment.
=== Neural circuits and systems ===
The basic neuronal function of sending signals to other cells includes a capability for neurons to exchange signals with each other. Networks formed by interconnected groups of neurons are capable of a wide variety of functions, including feature detection, pattern generation and timing, and there are seen to be countless types of information processing possible. Warren McCulloch and Walter Pitts showed in 1943 that even artificial neural networks formed from a greatly simplified mathematical abstraction of a neuron are capable of universal computation.
Historically, for many years the predominant view of the function of the nervous system was as a stimulus-response associator. In this conception, neural processing begins with stimuli that activate sensory neurons, producing signals that propagate through chains of connections in the spinal cord and brain, giving rise eventually to activation of motor neurons and thereby to muscle contraction, i.e., to overt responses. Descartes believed that all of the behaviors of animals, and most of the behaviors of humans, could be explained in terms of stimulus-response circuits, although he also believed that higher cognitive functions such as language were not capable of being explained mechanistically. Charles Sherrington, in his influential 1906 book The Integrative Action of the Nervous System, developed the concept of stimulus-response mechanisms in much more detail, and behaviorism, the school of thought that dominated psychology through the middle of the 20th century, attempted to explain every aspect of human behavior in stimulus-response terms.
However, experimental studies of electrophysiology, beginning in the early 20th century and reaching high productivity by the 1940s, showed that the nervous system contains many mechanisms for maintaining cell excitability and generating patterns of activity intrinsically, without requiring an external stimulus. Neurons were found to be capable of producing regular sequences of action potentials, or sequences of bursts, even in complete isolation. When intrinsically active neurons are connected to each other in complex circuits, the possibilities for generating intricate temporal patterns become far more extensive. A modern conception views the function of the nervous system partly in terms of stimulus-response chains, and partly in terms of intrinsically generated activity patterns—both types of activity interact with each other to generate the full repertoire of behavior.
==== Reflexes and other stimulus-response circuits ====
The simplest type of neural circuit is a reflex arc, which begins with a sensory input and ends with a motor output, passing through a sequence of neurons connected in series. This can be shown in the "withdrawal reflex" causing a hand to jerk back after a hot stove is touched. The circuit begins with sensory receptors in the skin that are activated by harmful levels of heat: a special type of molecular structure embedded in the membrane causes heat to change the electrical field across the membrane. If the change in electrical potential is large enough to pass the given threshold, it evokes an action potential, which is transmitted along the axon of the receptor cell, into the spinal cord. There the axon makes excitatory synaptic contacts with other cells, some of which project (send axonal output) to the same region of the spinal cord, others projecting into the brain. One target is a set of spinal interneurons that project to motor neurons controlling the arm muscles. The interneurons excite the motor neurons, and if the excitation is strong enough, some of the motor neurons generate action potentials, which travel down their axons to the point where they make excitatory synaptic contacts with muscle cells. The excitatory signals induce contraction of the muscle cells, which causes the joint angles in the arm to change, pulling the arm away.
In reality, this straightforward schema is subject to numerous complications. Although for the simplest reflexes there are short neural paths from sensory neuron to motor neuron, there are also other nearby neurons that participate in the circuit and modulate the response. Furthermore, there are projections from the brain to the spinal cord that are capable of enhancing or inhibiting the reflex.
Although the simplest reflexes may be mediated by circuits lying entirely within the spinal cord, more complex responses rely on signal processing in the brain. For example, when an object in the periphery of the visual field moves, and a person looks toward it many stages of signal processing are initiated. The initial sensory response, in the retina of the eye, and the final motor response, in the oculomotor nuclei of the brainstem, are not all that different from those in a simple reflex, but the intermediate stages are completely different. Instead of a one or two step chain of processing, the visual signals pass through perhaps a dozen stages of integration, involving the thalamus, cerebral cortex, basal ganglia, superior colliculus, cerebellum, and several brainstem nuclei. These areas perform signal-processing functions that include feature detection, perceptual analysis, memory recall, decision-making, and motor planning.
Feature detection is the ability to extract biologically relevant information from combinations of sensory signals. In the visual system, for example, sensory receptors in the retina of the eye are only individually capable of detecting "points of light" in the outside world. Second-level visual neurons receive input from groups of primary receptors, higher-level neurons receive input from groups of second-level neurons, and so on, forming a hierarchy of processing stages. At each stage, important information is extracted from the signal ensemble and unimportant information is discarded. By the end of the process, input signals representing "points of light" have been transformed into a neural representation of objects in the surrounding world and their properties. The most sophisticated sensory processing occurs inside the brain, but complex feature extraction also takes place in the spinal cord and in peripheral sensory organs such as the retina.
==== Intrinsic pattern generation ====
Although stimulus-response mechanisms are the easiest to understand, the nervous system is also capable of controlling the body in ways that do not require an external stimulus, by means of internally generated rhythms of activity. Because of the variety of voltage-sensitive ion channels that can be embedded in the membrane of a neuron, many types of neurons are capable, even in isolation, of generating rhythmic sequences of action potentials, or rhythmic alternations between high-rate bursting and quiescence. When neurons that are intrinsically rhythmic are connected to each other by excitatory or inhibitory synapses, the resulting networks are capable of a wide variety of dynamical behaviors, including attractor dynamics, periodicity, and even chaos. A network of neurons that uses its internal structure to generate temporally structured output, without requiring a corresponding temporally structured stimulus, is called a central pattern generator.
Internal pattern generation operates on a wide range of time scales, from milliseconds to hours or longer. One of the most important types of temporal pattern is circadian rhythmicity—that is, rhythmicity with a period of approximately 24 hours. All animals that have been studied show circadian fluctuations in neural activity, which control circadian alternations in behavior such as the sleep-wake cycle. Experimental studies dating from the 1990s have shown that circadian rhythms are generated by a "genetic clock" consisting of a special set of genes whose expression level rises and falls over the course of the day. Animals as diverse as insects and vertebrates share a similar genetic clock system. The circadian clock is influenced by light but continues to operate even when light levels are held constant and no other external time-of-day cues are available. The clock genes are expressed in many parts of the nervous system as well as many peripheral organs, but in mammals, all of these "tissue clocks" are kept in synchrony by signals that emanate from a master timekeeper in a tiny part of the brain called the suprachiasmatic nucleus.
=== Mirror neurons ===
A mirror neuron is a neuron that fires both when an animal acts and when the animal observes the same action performed by another. Thus, the neuron "mirrors" the behavior of the other, as though the observer were itself acting. Such neurons have been directly observed in primate species. Birds have been shown to have imitative resonance behaviors and neurological evidence suggests the presence of some form of mirroring system. In humans, brain activity consistent with that of mirror neurons has been found in the premotor cortex, the supplementary motor area, the primary somatosensory cortex and the inferior parietal cortex. The function of the mirror system is a subject of much speculation. Many researchers in cognitive neuroscience and cognitive psychology consider that this system provides the physiological mechanism for the perception/action coupling (see the common coding theory). They argue that mirror neurons may be important for understanding the actions of other people, and for learning new skills by imitation. Some researchers also speculate that mirror systems may simulate observed actions, and thus contribute to theory of mind skills, while others relate mirror neurons to language abilities. However, to date, no widely accepted neural or computational models have been put forward to describe how mirror neuron activity supports cognitive functions such as imitation. There are neuroscientists who caution that the claims being made for the role of mirror neurons are not supported by adequate research.
== Development ==
In vertebrates, landmarks of embryonic neural development include the birth and differentiation of neurons from stem cell precursors, the migration of immature neurons from their birthplaces in the embryo to their final positions, outgrowth of axons from neurons and guidance of the motile growth cone through the embryo towards postsynaptic partners, the generation of synapses between these axons and their postsynaptic partners, and finally the lifelong changes in synapses which are thought to underlie learning and memory.
All bilaterian animals at an early stage of development form a gastrula, which is polarized, with one end called the animal pole and the other the vegetal pole. The gastrula has the shape of a disk with three layers of cells, an inner layer called the endoderm, which gives rise to the lining of most internal organs, a middle layer called the mesoderm, which gives rise to the bones and muscles, and an outer layer called the ectoderm, which gives rise to the skin and nervous system.
In vertebrates, the first sign of the nervous system is the appearance of a thin strip of cells along the center of the back, called the neural plate. The inner portion of the neural plate (along the midline) is destined to become the central nervous system (CNS), the outer portion the peripheral nervous system (PNS). As development proceeds, a fold called the neural groove appears along the midline. This fold deepens, and then closes up at the top. At this point the future CNS appears as a cylindrical structure called the neural tube, whereas the future PNS appears as two strips of tissue called the neural crest, running lengthwise above the neural tube. The sequence of stages from neural plate to neural tube and neural crest is known as neurulation.
In the early 20th century, a set of famous experiments by Hans Spemann and Hilde Mangold showed that the formation of nervous tissue is "induced" by signals from a group of mesodermal cells called the organizer region. For decades, though, the nature of neural induction defeated every attempt to figure it out, until finally it was resolved by genetic approaches in the 1990s. Induction of neural tissue requires inhibition of the gene for a so-called bone morphogenetic protein, or BMP. Specifically the protein BMP4 appears to be involved. Two proteins called Noggin and Chordin, both secreted by the mesoderm, are capable of inhibiting BMP4 and thereby inducing ectoderm to turn into neural tissue. It appears that a similar molecular mechanism is involved for widely disparate types of animals, including arthropods as well as vertebrates. In some animals, however, another type of molecule called Fibroblast Growth Factor or FGF may also play an important role in induction.
Induction of neural tissues causes formation of neural precursor cells, called neuroblasts. In Drosophila, neuroblasts divide asymmetrically, so that one product is a "ganglion mother cell" (GMC), and the other is a neuroblast. A GMC divides once, to give rise to either a pair of neurons or a pair of glial cells. In all, a neuroblast is capable of generating an indefinite number of neurons or glia.
As shown in a 2008 study, one factor common to all bilateral organisms (including humans) is a family of secreted signaling molecules called neurotrophins which regulate the growth and survival of neurons. Zhu et al. identified DNT1, the first neurotrophin found in flies. DNT1 shares structural similarity with all known neurotrophins and is a key factor in the fate of neurons in Drosophila. Because neurotrophins have now been identified in both vertebrate and invertebrates, this evidence suggests that neurotrophins were present in an ancestor common to bilateral organisms and may represent a common mechanism for nervous system formation.
== Pathology ==
The central nervous system is protected by major physical and chemical barriers. Physically, the brain and spinal cord are surrounded by tough meningeal membranes, and enclosed in the bones of the skull and vertebral column, which combine to form a strong physical shield. Chemically, the brain and spinal cord are isolated by the blood–brain barrier, which prevents most types of chemicals from moving from the bloodstream into the interior of the CNS. These protections make the CNS less susceptible in many ways than the PNS; the flip side, however, is that damage to the CNS tends to have more serious consequences.
Although nerves tend to lie deep under the skin except in a few places such as the ulnar nerve near the elbow joint, they are still relatively exposed to physical damage, which can cause pain, loss of sensation, or loss of muscle control. Damage to nerves can also be caused by swelling or bruises at places where a nerve passes through a tight bony channel, as happens in carpal tunnel syndrome. If a nerve is completely transected, it will often regenerate, but for long nerves this process may take months to complete. In addition to physical damage, peripheral neuropathy may be caused by many other medical problems, including genetic conditions, metabolic conditions such as diabetes, inflammatory conditions such as Guillain–Barré syndrome, vitamin deficiency, infectious diseases such as leprosy or shingles, or poisoning by toxins such as heavy metals. Many cases have no cause that can be identified, and are referred to as idiopathic. It is also possible for nerves to lose function temporarily, resulting in numbness as stiffness—common causes include mechanical pressure, a drop in temperature, or chemical interactions with local anesthetic drugs such as lidocaine.
Physical damage to the spinal cord may result in loss of sensation or movement. If an injury to the spine produces nothing worse than swelling, the symptoms may be transient, but if nerve fibers in the spine are actually destroyed, the loss of function is usually permanent. Experimental studies have shown that spinal nerve fibers attempt to regrow in the same way as nerve fibers, but in the spinal cord, tissue destruction usually produces scar tissue that cannot be penetrated by the regrowing nerves.
Neurological practice draws heavily on the fields of neuroscience and psychiatry to treat diseases of the nervous system using various techniques of neurotherapy.
== See also ==
Circulatory system
Digestive system
Muscular system
Sentience
== References ==
== Further reading ==
Nervous system. William E. Skaggs. Scholarpedia.
== External links ==
The Nervous System at Wikibooks (human)
Nervous System at Wikibooks (non-human)
The Human Brain Project Homepage | Wikipedia/Nervous_systems |
An autoradiograph is an image on an X-ray film or nuclear emulsion produced by the pattern of decay emissions (e.g., beta particles or gamma rays) from a distribution of a radioactive substance. Alternatively, the autoradiograph is also available as a digital image (digital autoradiography), due to the recent development of scintillation gas detectors or rare-earth phosphorimaging systems. The film or emulsion is apposed to the labeled tissue section to obtain the autoradiograph (also called an autoradiogram). The auto- prefix indicates that the radioactive substance is within the sample, as distinguished from the case of historadiography or microradiography, in which the sample is marked using an external source. Some autoradiographs can be examined microscopically for localization of silver grains (such as on the interiors or exteriors of cells or organelles) in which the process is termed micro-autoradiography. For example, micro-autoradiography was used to examine whether atrazine was being metabolized by the hornwort plant or by epiphytic microorganisms in the biofilm layer surrounding the plant.
== Applications ==
In biology, this technique may be used to determine the tissue (or cell) localization of a radioactive substance, either introduced into a metabolic pathway, bound to a receptor or enzyme, or hybridized to a nucleic acid. Applications for autoradiography are broad, ranging from biomedical to environmental sciences to industry.
=== Receptor autoradiography ===
The use of radiolabeled ligands to determine the tissue distributions of receptors is termed either in vivo or in vitro receptor autoradiography if the ligand is administered into the circulation (with subsequent tissue removal and sectioning) or applied to the tissue sections, respectively. Once the receptor density is known, in vitro autoradiography can also be used to determine the anatomical distribution and affinity of a radiolabeled drug towards the receptor. For in vitro autoradiography, radioligand was directly applying on frozen tissue sections without administration to the subject. Thus it cannot follow the distribution, metabolism and degradation situation completely in the living body. But because target in the cryosections is widely exposed and can direct contact with radioligand, in vitro autoradiography is still a quick and easy method to screen drug candidates, PET and SPECT ligands. The ligands are generally labeled with 3H (tritium), 18F (fluorine), 11C (carbon) or 125I (radioiodine). Compare to in vitro, ex vivo autoradiography were performed after administration of radioligand in the body, which can decrease the artifacts and are closer to the inner environment.
The distribution of RNA transcripts in tissue sections by the use of radiolabeled, complementary oligonucleotides or ribonucleic acids ("riboprobes") is called in situ hybridization histochemistry. Radioactive precursors of DNA and RNA, [3H]-thymidine and [3H]-uridine respectively, may be introduced to living cells to determine the timing of several phases of the cell cycle. RNA or DNA viral sequences can also be located in this fashion. These probes are usually labeled with 32P, 33P, or 35S. In the realm of behavioral endocrinology, autoradiography can be used to determine hormonal uptake and indicate receptor location; an animal can be injected with a radiolabeled hormone, or the study can be conducted in vitro.
=== Rate of DNA replication ===
The rate of DNA replication in a mouse cell growing in vitro was measured by autoradiography as 33 nucleotides per second. The rate of phage T4 DNA elongation in phage-infected E. coli was also measured by autoradiography as 749 nucleotides per second during the period of exponential DNA increase at 37 °C (99 °F).
=== Detection of protein phosphorylation ===
Phosphorylation means the posttranslational addition of a phosphate group to specific amino acids of proteins, and such modification can lead to a drastic change in the stability or the function of a protein in the cell. Protein phosphorylation can be detected on an autoradiograph, after incubating the protein in vitro with the appropriate kinase and γ-32P-ATP. The radiolabeled phosphate of latter is incorporated into the protein which is isolated via SDS-PAGE and visualized on an autoradiograph of the gel. (See figure 3. of a recent study showing that CREB-binding protein is phosphorylated by HIPK2.)
=== Detection of sugar movement in plant tissue ===
In plant physiology, autoradiography can be used to determine sugar accumulation in leaf tissue. Sugar accumulation, as it relates to autoradiography, can described the phloem-loading strategy used in a plant. For example, if sugars accumulate in the minor veins of a leaf, it is expected that the leaves have few plasmodesmatal connections which is indicative of apoplastic movement, or an active phloem-loading strategy. Sugars, such as sucrose, fructose, or mannitol, are radiolabeled with [14-C], and then absorbed into leaf tissue by simple diffusion. The leaf tissue is then exposed to autoradiographic film (or emulsion) to produce an image. Images will show distinct vein patterns if sugar accumulation is concentrated in leaf veins (apoplastic movement), or images will show a static-like pattern if sugar accumulation is uniform throughout the leaf (symplastic movement).
=== Other techniques ===
This autoradiographic approach contrasts to techniques such as PET and SPECT where the exact 3-dimensional localization of the radiation source is provided by careful use of coincidence counting, gamma counters and other devices.
Krypton-85 is used to inspect aircraft components for small defects. Krypton-85 is allowed to penetrate small cracks, and then its
presence is detected by autoradiography. The method is called "krypton gas penetrant imaging". The gas penetrates smaller openings than the liquids used in dye penetrant inspection and fluorescent penetrant inspection.
== Historical events ==
The task of radioactive decontamination following the Baker nuclear test at Bikini Atoll during Operation Crossroads in 1946 was far more difficult than the U.S. Navy had prepared for. Though the task's futility became apparent and the danger to cleanup crews mounted, Colonel Stafford Warren, in charge of radiation safety, had difficulty persuading Vice Admiral William H. P. Blandy to abandon the cleanup and with it the surviving target ships. On August 10, Warren showed Blandy an autoradiograph made by a surgeonfish from the lagoon that was left on a photographic plate overnight. The film was exposed by alpha radiation produced from the fish's scales, evidence that plutonium, mimicking calcium, had been distributed throughout the fish. Blandy promptly ordered that all further decontamination work be discontinued. Warren wrote home, "A self X ray of a fish ... did the trick."
== References ==
=== General references ===
Original publication by sole inventor
Askins, Barbara S. (1 November 1976). "Photographic image intensification by autoradiography". Applied Optics. 15 (11): 2860–2865. Bibcode:1976ApOpt..15.2860A. doi:10.1364/ao.15.002860.
=== Inline citations ===
== Further reading ==
Rogers, Andrew W (1979). Techniques of Autoradiography (3rd ed.). New York: Elsevier North Holland. ISBN 978-0-444-80063-3.
"Patent US4101780 Treating silver with a radioactive sulfur compound such as thiourea or derivatives". Google Patents. Retrieved 26 June 2014. | Wikipedia/Autoradiography |
A cDNA library is a combination of cloned cDNA (complementary DNA) fragments inserted into a collection of host cells, which constitute some portion of the transcriptome of the organism and are stored as a "library". cDNA is produced from fully transcribed mRNA found in the nucleus and therefore contains only the expressed genes of an organism. Similarly, tissue-specific cDNA libraries can be produced. In eukaryotic cells the mature mRNA is already spliced, hence the cDNA produced lacks introns and can be readily expressed in a bacterial cell. While information in cDNA libraries is a powerful and useful tool since gene products are easily identified, the libraries lack information about enhancers, introns, and other regulatory elements found in a genomic DNA library.
== cDNA Library Construction ==
cDNA is created from a mature mRNA from a eukaryotic cell with the use of reverse transcriptase. In eukaryotes, a poly-(A) tail (consisting of a long sequence of adenine nucleotides) distinguishes mRNA from tRNA and rRNA and can therefore be used as a primer site for reverse transcription. This has the problem that not all transcripts, such as those for the histone, encode a poly-A tail.
=== mRNA extraction ===
Firstly, mRNA template needs to be isolated for the creation of cDNA libraries. Since mRNA only contains exons, the integrity of the isolated mRNA should be considered so that the protein encoded can still be produced. Isolated mRNA should range from 500 bp to 8 kb. Several methods exist for purifying RNA such as trizol extraction and column purification. Column purification can be done using oligomeric dT nucleotide coated resins, and features of mRNA such as having a poly-A tail can be exploited where only mRNA sequences containing said feature will bind. The desired mRNA bound to the column is then eluted.
=== cDNA construction ===
Once mRNA is purified, an oligo-dT primer (a short sequence of deoxy-thymidine nucleotides) is bound to the poly-A tail of the RNA. The primer is required to initiate DNA synthesis by the enzyme reverse transcriptase. This results in the creation of RNA-DNA hybrids where a single strand of complementary DNA is bound to a strand of mRNA. To remove the mRNA, the RNAse H enzyme is used to cleave the backbone of the mRNA and generate free 3'-OH groups, which is important for the replacement of mRNA with DNA. DNA polymerase I is then added, the cleaved RNA acts as a primer the DNA polymerase I can identify and initiate replacement of RNA nucleotides with those of DNA. This is provided by the sscDNA itself by coiling on itself at the 3' end, generating a hairpin loop. The polymerase extends the 3'-OH end, and later the loop at 3' end is opened by the scissoring action of S1 nuclease. Restriction endonucleases and DNA ligase are then used to clone the sequences into bacterial plasmids.
The cloned bacteria are then selected, commonly through the use of antibiotic selection. Once selected, stocks of the bacteria are created which can later be grown and sequenced to compile the cDNA library.
== cDNA Library uses ==
cDNA libraries are commonly used when reproducing eukaryotic genomes, as the amount of information is reduced to remove the large numbers of non-coding regions from the library. cDNA libraries are used to express eukaryotic genes in prokaryotes. Prokaryotes do not have introns in their DNA and therefore do not possess any enzymes that can cut it out during transcription process. cDNA does not have introns and therefore can be expressed in prokaryotic cells. cDNA libraries are most useful in reverse genetics where the additional genomic information is of less use. Additionally, cDNA libraries are frequently used in functional cloning to identify genes based on the encoded protein's function. When studying eukaryotic DNA, expression libraries are constructed using complementary DNA (cDNA) to help ensure the insert is truly a gene.
=== cDNA Library vs. Genomic DNA Library ===
cDNA library lacks the non-coding and regulatory elements found in genomic DNA. Genomic DNA libraries provide more detailed information about the organism, but are more resource-intensive to generate and keep.
== Cloning of cDNA ==
cDNA molecules can be cloned by using restriction site linkers. Linkers are short, double stranded pieces of DNA (oligodeoxyribonucleotide) about 8 to 12 nucleotide pairs long that include a restriction endonuclease cleavage site e.g. BamHI. Both the cDNA and the linker have blunt ends which can be ligated together using a high concentration of T4 DNA ligase. Then sticky ends are produced in the cDNA molecule by cleaving the cDNA ends (which now have linkers with an incorporated site) with the appropriate endonuclease. A cloning vector (plasmid) is then also cleaved with the appropriate endonuclease. Following "sticky end" ligation of the insert into the vector the resulting recombinant DNA molecule is transferred into E. coli host cell for cloning.
== See also ==
Functional cloning
== References ==
== External links ==
Functional Annotation of the Mouse database (FANTOM)
examples of cDNA synthesis and cloning
Preparation of cDNA libraries for high-throughput RNA sequencing analysis of RNA 5′ ends | Wikipedia/CDNA_library |
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. They are coupled with G proteins. They pass through the cell membrane seven times in the form of six loops (three extracellular loops interacting with ligand molecules, three intracellular loops interacting with G proteins, an N-terminal extracellular region and a C-terminal intracellular region) of amino acid residues, which is why they are sometimes referred to as seven-transmembrane receptors. Ligands can bind either to the extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (rhodopsin-like family). They are all activated by agonists, although a spontaneous auto-activation of an empty receptor has also been observed.
G protein-coupled receptors are found only in eukaryotes, including yeast, and choanoflagellates. The ligands that bind and activate these receptors include light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters. They vary in size from small molecules to peptides, to large proteins. G protein-coupled receptors are involved in many diseases.
There are two principal signal transduction pathways involving the G protein-coupled receptors:
the cAMP signal pathway and
the phosphatidylinositol signal pathway.
When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a guanine nucleotide exchange factor (GEF). The GPCR can then activate an associated G protein by exchanging the GDP bound to the G protein for a GTP. The G protein's α subunit, together with the bound GTP, can then dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type (Gαs, Gαi/o, Gαq/11, Gα12/13).: 1160
GPCRs are an important drug target, and approximately 34% of all Food and Drug Administration (FDA) approved drugs target 108 members of this family. The global sales volume for these drugs is estimated to be 180 billion US dollars as of 2018. It is estimated that GPCRs are targets for about 50% of drugs currently on the market, mainly due to their involvement in signaling pathways related to many diseases i.e. mental, metabolic including endocrinological disorders, immunological including viral infections, cardiovascular, inflammatory, senses disorders, and cancer. The long ago discovered association between GPCRs and many endogenous and exogenous substances, resulting in e.g. analgesia, is another dynamically developing field of the pharmaceutical research.
== History and significance ==
With the determination of the first structure of the complex between a G-protein coupled receptor (GPCR) and a G-protein trimer (Gαβγ) in 2011 a new chapter of GPCR research was opened for structural investigations of global switches with more than one protein being investigated. The previous breakthroughs involved determination of the crystal structure of the first GPCR, rhodopsin, in 2000 and the crystal structure of the first GPCR with a diffusible ligand (β2AR) in 2007. The way in which the seven transmembrane helices of a GPCR are arranged into a bundle was suspected based on the low-resolution model of frog rhodopsin from cryogenic electron microscopy studies of the two-dimensional crystals. The crystal structure of rhodopsin, that came up three years later, was not a surprise apart from the presence of an additional cytoplasmic helix H8 and a precise location of a loop covering retinal binding site. However, it provided a scaffold which was hoped to be a universal template for homology modeling and drug design for other GPCRs – a notion that proved to be too optimistic.
Results 7 years later were surprising because the crystallization of β2-adrenergic receptor (β2AR) with a diffusible ligand revealed quite a different shape of the receptor extracellular side than that of rhodopsin. This area is important because it is responsible for the ligand binding and is targeted by many drugs. Moreover, the ligand binding site was much more spacious than in the rhodopsin structure and was open to the exterior. In the other receptors crystallized shortly afterwards the binding side was even more easily accessible to the ligand. New structures complemented with biochemical investigations uncovered mechanisms of action of molecular switches which modulate the structure of the receptor leading to activation states for agonists or to complete or partial inactivation states for inverse agonists.
The 2012 Nobel Prize in Chemistry was awarded to Brian Kobilka and Robert Lefkowitz for their work that was "crucial for understanding how G protein-coupled receptors function". There have been at least seven other Nobel Prizes awarded for some aspect of G protein–mediated signaling. As of 2012, two of the top ten global best-selling drugs (Advair Diskus and Abilify) act by targeting G protein-coupled receptors.
== Classification ==
The exact size of the GPCR superfamily is unknown, but at least 831 different human genes (or about 4% of the entire protein-coding genome) have been predicted to code for them from genome sequence analysis. Although numerous classification schemes have been proposed, the superfamily was classically divided into three main classes (A, B, and C) with no detectable shared sequence homology between classes.
The largest class by far is class A, which accounts for nearly 85% of the GPCR genes. Of class A GPCRs, over half of these are predicted to encode olfactory receptors, while the remaining receptors are liganded by known endogenous compounds or are classified as orphan receptors. Despite the lack of sequence homology between classes, all GPCRs have a common structure and mechanism of signal transduction. The very large rhodopsin A group has been further subdivided into 19 subgroups (A1-A19).
According to the classical A-F system, GPCRs can be grouped into six classes based on sequence homology and functional similarity:
Class A (or 1) (Rhodopsin-like)
Class B (or 2) (Secretin receptor family)
Class C (or 3) (Metabotropic glutamate/pheromone)
Class D (or 4) (Fungal mating pheromone receptors)
Class E (or 5) (Cyclic AMP receptors)
Class F (or 6) (Frizzled/Smoothened)
More recently, an alternative classification system called GRAFS (Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2, Secretin) has been proposed for vertebrate GPCRs. They correspond to classical classes C, A, B2, F, and B.
An early study based on available DNA sequence suggested that the human genome encodes roughly 750 G protein-coupled receptors, about 350 of which detect hormones, growth factors, and other endogenous ligands. Approximately 150 of the GPCRs found in the human genome have unknown functions.
Some web-servers and bioinformatics prediction methods have been used for predicting the classification of GPCRs according to their amino acid sequence alone, by means of the pseudo amino acid composition approach.
== Physiological roles ==
GPCRs are involved in a wide variety of physiological processes. Some examples of their physiological roles include:
The visual sense: The opsins use a photoisomerization reaction to translate electromagnetic radiation into cellular signals. Rhodopsin, for example, uses the conversion of 11-cis-retinal to all-trans-retinal for this purpose.
The gustatory sense (taste): GPCRs in taste cells mediate release of gustducin in response to bitter-, umami- and sweet-tasting substances.
The sense of smell: Receptors of the olfactory epithelium bind odorants (olfactory receptors) and pheromones (vomeronasal receptors)
Behavioral and mood regulation: Receptors in the mammalian brain bind several different neurotransmitters, including serotonin, dopamine, histamine, GABA, and glutamate
Regulation of immune system activity and inflammation: chemokine receptors bind ligands that mediate intercellular communication between cells of the immune system; receptors such as histamine receptors bind inflammatory mediators and engage target cell types in the inflammatory response. GPCRs are also involved in immune-modulation, e. g. regulating interleukin induction or suppressing TLR-induced immune responses from T cells.
Autonomic nervous system transmission: Both the sympathetic and parasympathetic nervous systems are regulated by GPCR pathways, responsible for control of many automatic functions of the body such as blood pressure, heart rate, and digestive processes
Cell density sensing: A novel GPCR role in regulating cell density sensing.
Homeostasis modulation (e.g., water balance).
Involved in growth and metastasis of some types of tumors.
Used in the endocrine system for peptide and amino-acid derivative hormones that bind to GCPRs on the cell membrane of a target cell. This activates cAMP, which in turn activates several kinases, allowing for a cellular response, such as transcription.
== Receptor structure ==
GPCRs are integral membrane proteins that possess seven membrane-spanning domains or transmembrane helices. The extracellular parts of the receptor can be glycosylated. These extracellular loops also contain two highly conserved cysteine residues that form disulfide bonds to stabilize the receptor structure. Some seven-transmembrane helix proteins (channelrhodopsin) that resemble GPCRs may contain ion channels, within their protein.
In 2000, the first crystal structure of a mammalian GPCR, that of bovine rhodopsin (1F88), was solved. In 2007, the first structure of a human GPCR was solved This human β2-adrenergic receptor GPCR structure proved highly similar to the bovine rhodopsin. The structures of activated or agonist-bound GPCRs have also been determined. These structures indicate how ligand binding at the extracellular side of a receptor leads to conformational changes in the cytoplasmic side of the receptor. The biggest change is an outward movement of the cytoplasmic part of the 5th and 6th transmembrane helix (TM5 and TM6). The structure of activated beta-2 adrenergic receptor in complex with Gs confirmed that the Gα binds to a cavity created by this movement.
GPCRs exhibit a similar structure to some other proteins with seven transmembrane domains, such as microbial rhodopsins and adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2). However, these 7TMH (7-transmembrane helices) receptors and channels do not associate with G proteins. In addition, ADIPOR1 and ADIPOR2 are oriented oppositely to GPCRs in the membrane (i.e. GPCRs usually have an extracellular N-terminus, cytoplasmic C-terminus, whereas ADIPORs are inverted).
== Structure–function relationships ==
In terms of structure, GPCRs are characterized by an extracellular N-terminus, followed by seven transmembrane (7-TM) α-helices (TM-1 to TM-7) connected by three intracellular (IL-1 to IL-3) and three extracellular loops (EL-1 to EL-3), and finally an intracellular C-terminus. The GPCR arranges itself into a tertiary structure resembling a barrel, with the seven transmembrane helices forming a cavity within the plasma membrane that serves a ligand-binding domain that is often covered by EL-2. Ligands may also bind elsewhere, however, as is the case for bulkier ligands (e.g., proteins or large peptides), which instead interact with the extracellular loops, or, as illustrated by the class C metabotropic glutamate receptors (mGluRs), the N-terminal tail. The class C GPCRs are distinguished by their large N-terminal tail, which also contains a ligand-binding domain. Upon glutamate-binding to an mGluR, the N-terminal tail undergoes a conformational change that leads to its interaction with the residues of the extracellular loops and TM domains. The eventual effect of all three types of agonist-induced activation is a change in the relative orientations of the TM helices (likened to a twisting motion) leading to a wider intracellular surface and "revelation" of residues of the intracellular helices and TM domains crucial to signal transduction function (i.e., G-protein coupling). Inverse agonists and antagonists may also bind to a number of different sites, but the eventual effect must be prevention of this TM helix reorientation.
The structure of the N- and C-terminal tails of GPCRs may also serve important functions beyond ligand-binding. For example, The C-terminus of M3 muscarinic receptors is sufficient, and the six-amino-acid polybasic (KKKRRK) domain in the C-terminus is necessary for its preassembly with Gq proteins. In particular, the C-terminus often contains serine (Ser) or threonine (Thr) residues that, when phosphorylated, increase the affinity of the intracellular surface for the binding of scaffolding proteins called β-arrestins (β-arr). Once bound, β-arrestins both sterically prevent G-protein coupling and may recruit other proteins, leading to the creation of signaling complexes involved in extracellular-signal regulated kinase (ERK) pathway activation or receptor endocytosis (internalization). As the phosphorylation of these Ser and Thr residues often occurs as a result of GPCR activation, the β-arr-mediated G-protein-decoupling and internalization of GPCRs are important mechanisms of desensitization. In addition, internalized "mega-complexes" consisting of a single GPCR, β-arr(in the tail conformation), and heterotrimeric G protein exist and may account for protein signaling from endosomes.
A final common structural theme among GPCRs is palmitoylation of one or more sites of the C-terminal tail or the intracellular loops. Palmitoylation is the covalent modification of cysteine (Cys) residues via addition of hydrophobic acyl groups, and has the effect of targeting the receptor to cholesterol- and sphingolipid-rich microdomains of the plasma membrane called lipid rafts. As many of the downstream transducer and effector molecules of GPCRs (including those involved in negative feedback pathways) are also targeted to lipid rafts, this has the effect of facilitating rapid receptor signaling.
GPCRs respond to extracellular signals mediated by a huge diversity of agonists, ranging from proteins to biogenic amines to protons, but all transduce this signal via a mechanism of G-protein coupling. This is made possible by a guanine-nucleotide exchange factor (GEF) domain primarily formed by a combination of IL-2 and IL-3 along with adjacent residues of the associated TM helices.
== Mechanism ==
The G protein-coupled receptor is activated by an external signal in the form of a ligand or other signal mediator. This creates a conformational change in the receptor, causing activation of a G protein. Further effect depends on the type of G protein. G proteins are subsequently inactivated by GTPase activating proteins, known as RGS proteins.
=== Ligand binding ===
GPCRs include one or more receptors for the following ligands:
sensory signal mediators (e.g., light and olfactory stimulatory molecules);
adenosine, bombesin, bradykinin, endothelin, γ-aminobutyric acid (GABA), hepatocyte growth factor (HGF), melanocortins, neuropeptide Y, opioid peptides, opsins, somatostatin, GH, tachykinins, members of the vasoactive intestinal peptide family, and vasopressin;
biogenic amines (e.g., dopamine, epinephrine, norepinephrine, histamine, serotonin, and melatonin);
glutamate (metabotropic effect);
glucagon;
acetylcholine (muscarinic effect);
chemokines;
lipid mediators of inflammation (e.g., prostaglandins, prostanoids, platelet-activating factor, and leukotrienes);
peptide hormones (e.g., calcitonin, C5a anaphylatoxin, follicle-stimulating hormone [FSH], gonadotropin-releasing hormone [GnRH], neurokinin, thyrotropin-releasing hormone [TRH], and oxytocin);
and endocannabinoids.
GPCRs that act as receptors for stimuli that have not yet been identified are known as orphan receptors.
However, in contrast to other types of receptors that have been studied, wherein ligands bind externally to the membrane, the ligands of GPCRs typically bind within the transmembrane domain. However, protease-activated receptors are activated by cleavage of part of their extracellular domain.
=== Conformational change ===
The transduction of the signal through the membrane by the receptor is not completely understood. It is known that in the inactive state, the GPCR is bound to a heterotrimeric G protein complex. Binding of an agonist to the GPCR results in a conformational change in the receptor that is transmitted to the bound Gα subunit of the heterotrimeric G protein via protein domain dynamics. The activated Gα subunit exchanges GTP in place of GDP which in turn triggers the dissociation of Gα subunit from the Gβγ dimer and from the receptor. The dissociated Gα and Gβγ subunits interact with other intracellular proteins to continue the signal transduction cascade while the freed GPCR is able to rebind to another heterotrimeric G protein to form a new complex that is ready to initiate another round of signal transduction.
It is believed that a receptor molecule exists in a conformational equilibrium between active and inactive biophysical states. The binding of ligands to the receptor may shift the equilibrium toward the active receptor states. Three types of ligands exist: Agonists are ligands that shift the equilibrium in favour of active states; inverse agonists are ligands that shift the equilibrium in favour of inactive states; and neutral antagonists are ligands that do not affect the equilibrium. It is not yet known how exactly the active and inactive states differ from each other.
=== G-protein activation/deactivation cycle ===
When the receptor is inactive, the GEF domain may be bound to an also inactive α-subunit of a heterotrimeric G-protein. These "G-proteins" are a trimer of α, β, and γ subunits (known as Gα, Gβ, and Gγ, respectively) that is rendered inactive when reversibly bound to Guanosine diphosphate (GDP) (or, alternatively, no guanine nucleotide) but active when bound to guanosine triphosphate (GTP). Upon receptor activation, the GEF domain, in turn, allosterically activates the G-protein by facilitating the exchange of a molecule of GDP for GTP at the G-protein's α-subunit. The cell maintains a 10:1 ratio of cytosolic GTP:GDP so exchange for GTP is ensured. At this point, the subunits of the G-protein dissociate from the receptor, as well as each other, to yield a Gα-GTP monomer and a tightly interacting Gβγ dimer, which are now free to modulate the activity of other intracellular proteins. The extent to which they may diffuse, however, is limited due to the palmitoylation of Gα and the presence of an isoprenoid moiety that has been covalently added to the C-termini of Gγ.
Because Gα also has slow GTP→GDP hydrolysis capability, the inactive form of the α-subunit (Gα-GDP) is eventually regenerated, thus allowing reassociation with a Gβγ dimer to form the "resting" G-protein, which can again bind to a GPCR and await activation. The rate of GTP hydrolysis is often accelerated due to the actions of another family of allosteric modulating proteins called regulators of G-protein signaling, or RGS proteins, which are a type of GTPase-activating protein, or GAP. In fact, many of the primary effector proteins (e.g., adenylate cyclases) that become activated/inactivated upon interaction with Gα-GTP also have GAP activity. Thus, even at this early stage in the process, GPCR-initiated signaling has the capacity for self-termination.
=== Crosstalk ===
GPCRs downstream signals have been shown to possibly interact with integrin signals, such as FAK. Integrin signaling will phosphorylate FAK, which can then decrease GPCR Gαs activity.
== Signaling ==
If a receptor in an active state encounters a G protein, it may activate it. Some evidence suggests that receptors and G proteins are actually pre-coupled. For example, binding of G proteins to receptors affects the receptor's affinity for ligands. Activated G proteins are bound to GTP.
Further signal transduction depends on the type of G protein. The enzyme adenylate cyclase is an example of a cellular protein that can be regulated by a G protein, in this case the G protein Gs. Adenylate cyclase activity is activated when it binds to a subunit of the activated G protein. Activation of adenylate cyclase ends when the G protein returns to the GDP-bound state.
Adenylate cyclases (of which 9 membrane-bound and one cytosolic forms are known in humans) may also be activated or inhibited in other ways (e.g., Ca2+/calmodulin binding), which can modify the activity of these enzymes in an additive or synergistic fashion along with the G proteins.
The signaling pathways activated through a GPCR are limited by the primary sequence and tertiary structure of the GPCR itself but ultimately determined by the particular conformation stabilized by a particular ligand, as well as the availability of transducer molecules. Currently, GPCRs are considered to utilize two primary types of transducers: G-proteins and β-arrestins. Because β-arr's have high affinity only to the phosphorylated form of most GPCRs (see above or below), the majority of signaling is ultimately dependent upon G-protein activation. However, the possibility for interaction does allow for G-protein-independent signaling to occur.
=== G-protein-dependent signaling ===
There are three main G-protein-mediated signaling pathways, mediated by four sub-classes of G-proteins distinguished from each other by sequence homology (Gαs, Gαi/o, Gαq/11, and Gα12/13). Each sub-class of G-protein consists of multiple proteins, each the product of multiple genes or splice variations that may imbue them with differences ranging from subtle to distinct with regard to signaling properties, but in general they appear reasonably grouped into four classes. Because the signal transducing properties of the various possible βγ combinations do not appear to radically differ from one another, these classes are defined according to the isoform of their α-subunit.: 1163
While most GPCRs are capable of activating more than one Gα-subtype, they also show a preference for one subtype over another. When the subtype activated depends on the ligand that is bound to the GPCR, this is called functional selectivity (also known as agonist-directed trafficking, or conformation-specific agonism). However, the binding of any single particular agonist may also initiate activation of multiple different G-proteins, as it may be capable of stabilizing more than one conformation of the GPCR's GEF domain, even over the course of a single interaction. In addition, a conformation that preferably activates one isoform of Gα may activate another if the preferred is less available. Furthermore, feedback pathways may result in receptor modifications (e.g., phosphorylation) that alter the G-protein preference. Regardless of these various nuances, the GPCR's preferred coupling partner is usually defined according to the G-protein most obviously activated by the endogenous ligand under most physiological or experimental conditions.
==== Gα signaling ====
The effector of both the Gαs and Gαi/o pathways is the cyclic-adenosine monophosphate (cAMP)-generating enzyme adenylate cyclase, or AC. While there are ten different AC gene products in mammals, each with subtle differences in tissue distribution or function, all catalyze the conversion of cytosolic adenosine triphosphate (ATP) to cAMP, and all are directly stimulated by G-proteins of the Gαs class. In contrast, however, interaction with Gα subunits of the Gαi/o type inhibits AC from generating cAMP. Thus, a GPCR coupled to Gαs counteracts the actions of a GPCR coupled to Gαi/o, and vice versa. The level of cytosolic cAMP may then determine the activity of various ion channels as well as members of the ser/thr-specific protein kinase A (PKA) family. Thus cAMP is considered a second messenger and PKA a secondary effector.
The effector of the Gαq/11 pathway is phospholipase C-β (PLCβ), which catalyzes the cleavage of membrane-bound phosphatidylinositol 4,5-bisphosphate (PIP2) into the second messengers inositol (1,4,5) trisphosphate (IP3) and diacylglycerol (DAG). IP3 acts on IP3 receptors found in the membrane of the endoplasmic reticulum (ER) to elicit Ca2+ release from the ER, while DAG diffuses along the plasma membrane where it may activate any membrane localized forms of a second ser/thr kinase called protein kinase C (PKC). Since many isoforms of PKC are also activated by increases in intracellular Ca2+, both these pathways can also converge on each other to signal through the same secondary effector. Elevated intracellular Ca2+ also binds and allosterically activates proteins called calmodulins, which in turn tosolic small GTPase, Rho. Once bound to GTP, Rho can then go on to activate various proteins responsible for cytoskeleton regulation such as Rho-kinase (ROCK). Most GPCRs that couple to Gα12/13 also couple to other sub-classes, often Gαq/11.
==== Gβγ signaling ====
The above descriptions ignore the effects of Gβγ–signalling, which can also be important, in particular in the case of activated Gαi/o-coupled GPCRs. The primary effectors of Gβγ are various ion channels, such as G-protein-regulated inwardly rectifying K+ channels (GIRKs), P/Q- and N-type voltage-gated Ca2+ channels, as well as some isoforms of AC and PLC, along with some phosphoinositide-3-kinase (PI3K) isoforms.
=== G-protein-independent signaling ===
Although they are classically thought of working only together, GPCRs may signal through G-protein-independent mechanisms, and heterotrimeric G-proteins may play functional roles independent of GPCRs. GPCRs may signal independently through many proteins already mentioned for their roles in G-protein-dependent signaling such as β-arrs, GRKs, and Srcs. Such signaling has been shown to be physiologically relevant, for example, β-arrestin signaling mediated by the chemokine receptor CXCR3 was necessary for full efficacy chemotaxis of activated T cells. In addition, further scaffolding proteins involved in subcellular localization of GPCRs (e.g., PDZ-domain-containing proteins) may also act as signal transducers. Most often the effector is a member of the MAPK family.
==== Examples ====
In the late 1990s, evidence began accumulating to suggest that some GPCRs are able to signal without G proteins. The ERK2 mitogen-activated protein kinase, a key signal transduction mediator downstream of receptor activation in many pathways, has been shown to be activated in response to cAMP-mediated receptor activation in the slime mold D. discoideum despite the absence of the associated G protein α- and β-subunits.
In mammalian cells, the much-studied β2-adrenoceptor has been demonstrated to activate the ERK2 pathway after arrestin-mediated uncoupling of G-protein-mediated signaling. Therefore, it seems likely that some mechanisms previously believed related purely to receptor desensitisation are actually examples of receptors switching their signaling pathway, rather than simply being switched off.
In kidney cells, the bradykinin receptor B2 has been shown to interact directly with a protein tyrosine phosphatase. The presence of a tyrosine-phosphorylated ITIM (immunoreceptor tyrosine-based inhibitory motif) sequence in the B2 receptor is necessary to mediate this interaction and subsequently the antiproliferative effect of bradykinin.
==== GPCR-independent signaling by heterotrimeric G-proteins ====
Although it is a relatively immature area of research, it appears that heterotrimeric G-proteins may also take part in non-GPCR signaling. There is evidence for roles as signal transducers in nearly all other types of receptor-mediated signaling, including integrins, receptor tyrosine kinases (RTKs), cytokine receptors (JAK/STATs), as well as modulation of various other "accessory" proteins such as GEFs, guanine-nucleotide dissociation inhibitors (GDIs) and protein phosphatases. There may even be specific proteins of these classes whose primary function is as part of GPCR-independent pathways, termed activators of G-protein signalling (AGS). Both the ubiquity of these interactions and the importance of Gα vs. Gβγ subunits to these processes are still unclear.
== Details of cAMP and PIP2 pathways ==
There are two principal signal transduction pathways involving the G protein-linked receptors: the cAMP signal pathway and the phosphatidylinositol signal pathway.
=== cAMP signal pathway ===
The cAMP signal transduction contains five main characters: stimulative hormone receptor (Rs) or inhibitory hormone receptor (Ri); stimulative regulative G-protein (Gs) or inhibitory regulative G-protein (Gi); adenylyl cyclase; protein kinase A (PKA); and cAMP phosphodiesterase.
Stimulative hormone receptor (Rs) is a receptor that can bind with stimulative signal molecules, while inhibitory hormone receptor (Ri) is a receptor that can bind with inhibitory signal molecules.
Stimulative regulative G-protein is a G-protein linked to stimulative hormone receptor (Rs), and its α subunit upon activation could stimulate the activity of an enzyme or other intracellular metabolism. On the contrary, inhibitory regulative G-protein is linked to an inhibitory hormone receptor, and its α subunit upon activation could inhibit the activity of an enzyme or other intracellular metabolism.
Adenylyl cyclase is a 12-transmembrane glycoprotein that catalyzes the conversion of ATP to cAMP with the help of cofactor Mg2+ or Mn2+. The cAMP produced is a second messenger in cellular metabolism and is an allosteric activator of protein kinase A.
Protein kinase A is an important enzyme in cell metabolism due to its ability to regulate cell metabolism by phosphorylating specific committed enzymes in the metabolic pathway. It can also regulate specific gene expression, cellular secretion, and membrane permeability. The protein enzyme contains two catalytic subunits and two regulatory subunits. When there is no cAMP, the complex is inactive. When cAMP binds to the regulatory subunits, their conformation is altered, causing the dissociation of the regulatory subunits, which activates protein kinase A and allows further biological effects.
These signals then can be terminated by cAMP phosphodiesterase, which is an enzyme that degrades cAMP to 5'-AMP and inactivates protein kinase A.
=== Phosphatidylinositol signal pathway ===
In the phosphatidylinositol signal pathway, the extracellular signal molecule binds with the G-protein receptor (Gq) on the cell surface and activates phospholipase C, which is located on the plasma membrane. The lipase hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into two second messengers: inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 binds with the IP3 receptor in the membrane of the smooth endoplasmic reticulum and mitochondria to open Ca2+ channels. DAG helps activate protein kinase C (PKC), which phosphorylates many other proteins, changing their catalytic activities, leading to cellular responses.
The effects of Ca2+ are also remarkable: it cooperates with DAG in activating PKC and can activate the CaM kinase pathway, in which calcium-modulated protein calmodulin (CaM) binds Ca2+, undergoes a change in conformation, and activates CaM kinase II, which has unique ability to increase its binding affinity to CaM by autophosphorylation, making CaM unavailable for the activation of other enzymes. The kinase then phosphorylates target enzymes, regulating their activities. The two signal pathways are connected together by Ca2+-CaM, which is also a regulatory subunit of adenylyl cyclase and phosphodiesterase in the cAMP signal pathway.
== Receptor regulation ==
GPCRs become desensitized when exposed to their ligand for a long period of time. There are two recognized forms of desensitization: 1) homologous desensitization, in which the activated GPCR is downregulated; and 2) heterologous desensitization, wherein the activated GPCR causes downregulation of a different GPCR. The key reaction of this downregulation is the phosphorylation of the intracellular (or cytoplasmic) receptor domain by protein kinases.
=== Phosphorylation by cAMP-dependent protein kinases ===
Cyclic AMP-dependent protein kinases (protein kinase A) are activated by the signal chain coming from the G protein (that was activated by the receptor) via adenylate cyclase and cyclic AMP (cAMP). In a feedback mechanism, these activated kinases phosphorylate the receptor. The longer the receptor remains active the more kinases are activated and the more receptors are phosphorylated. In β2-adrenoceptors, this phosphorylation results in the switching of the coupling from the Gs class of G-protein to the Gi class. cAMP-dependent PKA mediated phosphorylation can cause heterologous desensitisation in receptors other than those activated.
=== Phosphorylation by GRKs ===
The G protein-coupled receptor kinases (GRKs) are protein kinases that phosphorylate only active GPCRs. G-protein-coupled receptor kinases (GRKs) are key modulators of G-protein-coupled receptor (GPCR) signaling. They constitute a family of seven mammalian serine-threonine protein kinases that phosphorylate agonist-bound receptor. GRKs-mediated receptor phosphorylation rapidly initiates profound impairment of receptor signaling and desensitization. Activity of GRKs and subcellular targeting is tightly regulated by interaction with receptor domains, G protein subunits, lipids, anchoring proteins and calcium-sensitive proteins.
Phosphorylation of the receptor can have two consequences:
Translocation: The receptor is, along with the part of the membrane it is embedded in, brought to the inside of the cell, where it is dephosphorylated within the acidic vesicular environment and then brought back. This mechanism is used to regulate long-term exposure, for example, to a hormone, by allowing resensitisation to follow desensitisation. Alternatively, the receptor may undergo lysozomal degradation, or remain internalised, where it is thought to participate in the initiation of signalling events, the nature of which depending on the internalised vesicle's subcellular localisation.
Arrestin linking: The phosphorylated receptor can be linked to arrestin molecules that prevent it from binding (and activating) G proteins, in effect switching it off for a short period of time. This mechanism is used, for example, with rhodopsin in retina cells to compensate for exposure to bright light. In many cases, arrestin's binding to the receptor is a prerequisite for translocation. For example, beta-arrestin bound to β2-adrenoreceptors acts as an adaptor for binding with clathrin, and with the beta-subunit of AP2 (clathrin adaptor molecules); thus, the arrestin here acts as a scaffold assembling the components needed for clathrin-mediated endocytosis of β2-adrenoreceptors.
=== Mechanisms of GPCR signal termination ===
As mentioned above, G-proteins may terminate their own activation due to their intrinsic GTP→GDP hydrolysis capability. However, this reaction proceeds at a slow rate (≈0.02 times/sec) and, thus, it would take around 50 seconds for any single G-protein to deactivate if other factors did not come into play. Indeed, there are around 30 isoforms of RGS proteins that, when bound to Gα through their GAP domain, accelerate the hydrolysis rate to ≈30 times/sec. This 1500-fold increase in rate allows for the cell to respond to external signals with high speed, as well as spatial resolution due to limited amount of second messenger that can be generated and limited distance a G-protein can diffuse in 0.03 seconds. For the most part, the RGS proteins are promiscuous in their ability to deactivate G-proteins, while which RGS is involved in a given signaling pathway seems more determined by the tissue and GPCR involved than anything else. In addition, RGS proteins have the additional function of increasing the rate of GTP-GDP exchange at GPCRs, (i.e., as a sort of co-GEF) further contributing to the time resolution of GPCR signaling.
In addition, the GPCR may be desensitized itself. This can occur as:
a direct result of ligand occupation, wherein the change in conformation allows recruitment of GPCR-Regulating Kinases (GRKs), which go on to phosphorylate various serine/threonine residues of IL-3 and the C-terminal tail. Upon GRK phosphorylation, the GPCR's affinity for β-arrestin (β-arrestin-1/2 in most tissues) is increased, at which point β-arrestin may bind and act to both sterically hinder G-protein coupling as well as initiate the process of receptor internalization through clathrin-mediated endocytosis. Because only the liganded receptor is desensitized by this mechanism, it is called homologous desensitization
the affinity for β-arrestin may be increased in a ligand occupation and GRK-independent manner through phosphorylation of different ser/thr sites (but also of IL-3 and the C-terminal tail) by PKC and PKA. These phosphorylations are often sufficient to impair G-protein coupling on their own as well.
PKC/PKA may, instead, phosphorylate GRKs, which can also lead to GPCR phosphorylation and β-arrestin binding in an occupation-independent manner. These latter two mechanisms allow for desensitization of one GPCR due to the activities of others, or heterologous desensitization. GRKs may also have GAP domains and so may contribute to inactivation through non-kinase mechanisms as well. A combination of these mechanisms may also occur.
Once β-arrestin is bound to a GPCR, it undergoes a conformational change allowing it to serve as a scaffolding protein for an adaptor complex termed AP-2, which in turn recruits another protein called clathrin. If enough receptors in the local area recruit clathrin in this manner, they aggregate and the membrane buds inwardly as a result of interactions between the molecules of clathrin, in a process called opsonization. Once the pit has been pinched off the plasma membrane due to the actions of two other proteins called amphiphysin and dynamin, it is now an endocytic vesicle. At this point, the adapter molecules and clathrin have dissociated, and the receptor is either trafficked back to the plasma membrane or targeted to lysosomes for degradation.
At any point in this process, the β-arrestins may also recruit other proteins—such as the non-receptor tyrosine kinase (nRTK), c-SRC—which may activate ERK1/2, or other mitogen-activated protein kinase (MAPK) signaling through, for example, phosphorylation of the small GTPase, Ras, or recruit the proteins of the ERK cascade directly (i.e., Raf-1, MEK, ERK-1/2) at which point signaling is initiated due to their close proximity to one another. Another target of c-SRC are the dynamin molecules involved in endocytosis. Dynamins polymerize around the neck of an incoming vesicle, and their phosphorylation by c-SRC provides the energy necessary for the conformational change allowing the final "pinching off" from the membrane.
=== GPCR cellular regulation ===
Receptor desensitization is mediated through a combination phosphorylation, β-arr binding, and endocytosis as described above. Downregulation occurs when endocytosed receptor is embedded in an endosome that is trafficked to merge with an organelle called a lysosome. Because lysosomal membranes are rich in proton pumps, their interiors have low pH (≈4.8 vs. the pH≈7.2 cytosol), which acts to denature the GPCRs. In addition, lysosomes contain many degradative enzymes, including proteases, which can function only at such low pH, and so the peptide bonds joining the residues of the GPCR together may be cleaved. Whether or not a given receptor is trafficked to a lysosome, detained in endosomes, or trafficked back to the plasma membrane depends on a variety of factors, including receptor type and magnitude of the signal.
GPCR regulation is additionally mediated by gene transcription factors. These factors can increase or decrease gene transcription and thus increase or decrease the generation of new receptors (up- or down-regulation) that travel to the cell membrane.
== Receptor oligomerization ==
G-protein-coupled receptor oligomerisation is a widespread phenomenon. One of the best-studied examples is the metabotropic GABAB receptor. This so-called constitutive receptor is formed by heterodimerization of GABABR1 and GABABR2 subunits. Expression of the GABABR1 without the GABABR2 in heterologous systems leads to retention of the subunit in the endoplasmic reticulum. Expression of the GABABR2 subunit alone, meanwhile, leads to surface expression of the subunit, although with no functional activity (i.e., the receptor does not bind agonist and cannot initiate a response following exposure to agonist). Expression of the two subunits together leads to plasma membrane expression of functional receptor. It has been shown that GABABR2 binding to GABABR1 causes masking of a retention signal of functional receptors.
== Origin and diversification of the superfamily ==
Signal transduction mediated by the superfamily of GPCRs dates back to the origin of multicellularity. Mammalian-like GPCRs are found in fungi, and have been classified according to the GRAFS classification system based on GPCR fingerprints. Identification of the superfamily members across the eukaryotic domain, and comparison of the family-specific motifs, have shown that the superfamily of GPCRs have a common origin. Characteristic motifs indicate that three of the five GRAFS families, Rhodopsin, Adhesion, and Frizzled, evolved from the Dictyostelium discoideum cAMP receptors before the split of opisthokonts. Later, the Secretin family evolved from the Adhesion GPCR receptor family before the split of nematodes. Insect GPCRs appear to be in their own group and Taste2 is identified as descending from Rhodopsin. Note that the Secretin/Adhesion split is based on presumed function rather than signature, as the classical Class B (7tm_2, Pfam PF00002) is used to identify both in the studies.
== See also ==
G protein-coupled receptors database
List of MeSH codes (D12.776)
Metabotropic receptor
Orphan receptor
Pepducins, a class of drug candidates targeted at GPCRs
Receptor activated solely by a synthetic ligand, a technique for control of cell signaling through synthetic GPCRs
TOG superfamily
== References ==
== Further reading ==
Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, et al. (April 2003). "The G protein-coupled receptor repertoires of human and mouse". Proceedings of the National Academy of Sciences of the United States of America. 100 (8): 4903–8. Bibcode:2003PNAS..100.4903V. doi:10.1073/pnas.0230374100. PMC 153653. PMID 12679517.
"GPCR Reference Library". Retrieved 11 August 2008. Reference for molecular and mathematical models for the initial receptor response
"The Nobel Prize in Chemistry 2012" (PDF). Archived (PDF) from the original on 18 October 2012. Retrieved 10 October 2012.
== External links ==
G-protein-coupled+receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
GPCR Cell Line Archived 3 April 2015 at the Wayback Machine
"IUPHAR/BPS Guide to PHARMACOLOGY Database (GPCRs)". IUPHAR Database. University of Edinburgh / International Union of Basic and Clinical Pharmacology. Retrieved 6 February 2019.
"GPCRdb". Data, diagrams and web tools for G protein-coupled receptors (GPCRs).; Munk C, Isberg V, Mordalski S, Harpsøe K, Rataj K, Hauser AS, et al. (July 2016). "GPCRdb: the G protein-coupled receptor database - an introduction". British Journal of Pharmacology. 173 (14): 2195–207. doi:10.1111/bph.13509. PMC 4919580. PMID 27155948.
"G Protein-Coupled Receptors on the NET". Archived from the original on 23 July 2011. Retrieved 10 November 2010. a classification of GPCRs
"PSI GPCR Network Center". Archived from the original on 25 July 2013. Retrieved 11 July 2013. a Protein Structure Initiative:Biology Network Center aimed at determining the 3D structures of representative GPCR family proteins
GPCR-HGmod Archived 1 February 2016 at the Wayback Machine, a database of 3D structural models of all human G-protein coupled receptors, built by the GPCR-I-TASSER pipeline Zhang J, Yang J, Jang R, Zhang Y (August 2015). "GPCR-I-TASSER: A Hybrid Approach to G Protein-Coupled Receptor Structure Modeling and the Application to the Human Genome". Structure. 23 (8): 1538–1549. doi:10.1016/j.str.2015.06.007. PMC 4526412. PMID 26190572. | Wikipedia/G-protein_linked_receptors |
Reticular theory is an obsolete scientific theory in neurobiology that stated that everything in the nervous system, such as the brain, is a single continuous network. The concept was postulated by a German anatomist Joseph von Gerlach in 1871, and was most popularised by the Nobel laureate Italian physician Camillo Golgi.
However, the theory was refuted by later observations of Spanish pathologist Santiago Ramón y Cajal, using a staining technique discovered by Golgi, which showed that nervous tissue, like other tissues, is made of discrete cells. This neuron doctrine turned out to be the correct description of the nervous system, whereas the reticular theory was discredited.
The proponents of the two contrasting theories, Golgi and Ramón y Cajal were jointly awarded the Nobel Prize in Physiology or Medicine in 1906, "in recognition of their work on the structure of the nervous system".
== Development ==
In 1863 a German anatomist Otto Friedrich Karl Deiters described the existence of an unbranched tubular process (the axon) extending from some cells in the central nervous system, specifically from the lateral vestibular nucleus. In 1871 Gerlach proposed that the brain is composed of "protoplasmic network", hence the basis of reticular theory. According to Gerlach, the nervous system simply consisted of a single continuous network called the reticulum. In 1873 Golgi invented a revolutionary method for microscopic research based on a specific technique for staining nerve cells, which he called "la reazione nera" (the "black reaction"). He was able to provide an intricate description of nerve cells in various regions of the cerebro-spinal axis, clearly distinguishing the axon from the dendrites. He drew up a new classification of cells on the basis of the structure of their nervous prolongation, and he criticized Gerlach's theory of the "protoplasmic network". Golgi claimed to observe in the gray matter an extremely dense and intricate network, composed of a web of intertwined branches of axons coming from different cell layers ("diffuse nervous network"). This structure, which emerges from the axons and is therefore essentially different from that hypothesized by Gerlach, appeared in his view to be the main organ of the nervous system, the organ that connected different cerebral areas both anatomically and functionally by means of the transmission of an electric nervous impulse. Although Golgi's earlier works between 1873 and 1885 clearly depicted the axonal connections of cerebellar cortex and olfactory bulb as independent of one another, his later works including the Nobel Lecture showed the entire granular layer of the cerebellar cortex occupied by a network of branching and anastomosing nerve processes. This was due to his strong conviction in the reticular theory.
== Decline ==
In 1877 an English physiologist Edward Schäfer described the absence of connections between the nerve elements in the mantles of the jellyfish. The Norwegian zoologist Fridtjof Nansen also reported in 1887 that he found no connections between the processes of the ganglion cells of aquatic animals in his doctoral research (The Structure and Combination of Histological Elements of the Central Nervous System). By the late 1880s, serious opposition to the reticular theory began to emerge. Wilhelm His in Leipzig studied the embryological development of the central nervous system and concluded that his observations were consistent with the classic cell theory (that nerve cells were individual cells), and not the reticular theory. In 1891, another German anatomist Wilhelm Waldeyer also supported the theory by stating that the nervous system, as other tissues, was composed of cells, which he named "neurons." Using the very same Golgi's technique, Ramón y Cajal confirmed that discrete neurons did exist, thereby strengthening the concept of the growing neuron doctrine. Golgi, however, never accepted these new findings, and a controversy and rivalry between the two scientists lasted even after they were jointly awarded the Nobel Prize in 1906. The Nobel award is even dubbed as creating the "storm center of histological controversy". Ramón y Cajal even commented that: "What a cruel irony of fate to pair, like Siamese twins united by the shoulders, scientific adversaries of such contrasting character!".
In the 1950s electron microscopy finally confirmed the existence of individual neurons in the central nervous system, and the existence of gaps in between neurons called synapse. The reticular theory was finally put to rest.
== References ==
== External links ==
SOME HISTORICAL LANDMARKS IN CELL THEORY OF THE BRAIN
NEURON DOCTRINE VS. RETICULAR THEORY
Who Is Camillo Golgi? | Wikipedia/Reticular_theory |
Decision theory or the theory of rational choice is a branch of probability, economics, and analytic philosophy that uses expected utility and probability to model how individuals would behave rationally under uncertainty. It differs from the cognitive and behavioral sciences in that it is mainly prescriptive and concerned with identifying optimal decisions for a rational agent, rather than describing how people actually make decisions. Despite this, the field is important to the study of real human behavior by social scientists, as it lays the foundations to mathematically model and analyze individuals in fields such as sociology, economics, criminology, cognitive science, moral philosophy and political science.
== History ==
The roots of decision theory lie in probability theory, developed by Blaise Pascal and Pierre de Fermat in the 17th century, which was later refined by others like Christiaan Huygens. These developments provided a framework for understanding risk and uncertainty, which are central to decision-making.
In the 18th century, Daniel Bernoulli introduced the concept of "expected utility" in the context of gambling, which was later formalized by John von Neumann and Oskar Morgenstern in the 1940s. Their work on Game Theory and Expected Utility Theory helped establish a rational basis for decision-making under uncertainty.
After World War II, decision theory expanded into economics, particularly with the work of economists like Milton Friedman and others, who applied it to market behavior and consumer choice theory. This era also saw the development of Bayesian decision theory, which incorporates Bayesian probability into decision-making models.
By the late 20th century, scholars like Daniel Kahneman and Amos Tversky challenged the assumptions of rational decision-making. Their work in behavioral economics highlighted cognitive biases and heuristics that influence real-world decisions, leading to the development of prospect theory, which modified expected utility theory by accounting for psychological factors.
== Branches ==
Normative decision theory is concerned with identification of optimal decisions where optimality is often determined by considering an ideal decision maker who is able to calculate with perfect accuracy and is in some sense fully rational. The practical application of this prescriptive approach (how people ought to make decisions) is called decision analysis and is aimed at finding tools, methodologies, and software (decision support systems) to help people make better decisions.
In contrast, descriptive decision theory is concerned with describing observed behaviors often under the assumption that those making decisions are behaving under some consistent rules. These rules may, for instance, have a procedural framework (e.g. Amos Tversky's elimination by aspects model) or an axiomatic framework (e.g. stochastic transitivity axioms), reconciling the Von Neumann-Morgenstern axioms with behavioral violations of the expected utility hypothesis, or they may explicitly give a functional form for time-inconsistent utility functions (e.g. Laibson's quasi-hyperbolic discounting).
Prescriptive decision theory is concerned with predictions about behavior that positive decision theory produces to allow for further tests of the kind of decision-making that occurs in practice. In recent decades, there has also been increasing interest in "behavioral decision theory", contributing to a re-evaluation of what useful decision-making requires.
== Types of decisions ==
=== Choice under uncertainty ===
The area of choice under uncertainty represents the heart of decision theory. Known from the 17th century (Blaise Pascal invoked it in his famous wager, which is contained in his Pensées, published in 1670), the idea of expected value is that, when faced with a number of actions, each of which could give rise to more than one possible outcome with different probabilities, the rational procedure is to identify all possible outcomes, determine their values (positive or negative) and the probabilities that will result from each course of action, and multiply the two to give an "expected value", or the average expectation for an outcome; the action to be chosen should be the one that gives rise to the highest total expected value. In 1738, Daniel Bernoulli published an influential paper entitled Exposition of a New Theory on the Measurement of Risk, in which he uses the St. Petersburg paradox to show that expected value theory must be normatively wrong. He gives an example in which a Dutch merchant is trying to decide whether to insure a cargo being sent from Amsterdam to St. Petersburg in winter. In his solution, he defines a utility function and computes expected utility rather than expected financial value.
In the 20th century, interest was reignited by Abraham Wald's 1939 paper pointing out that the two central procedures of sampling-distribution-based statistical-theory, namely hypothesis testing and parameter estimation, are special cases of the general decision problem. Wald's paper renewed and synthesized many concepts of statistical theory, including loss functions, risk functions, admissible decision rules, antecedent distributions, Bayesian procedures, and minimax procedures. The phrase "decision theory" itself was used in 1950 by E. L. Lehmann.
The revival of subjective probability theory, from the work of Frank Ramsey, Bruno de Finetti, Leonard Savage and others, extended the scope of expected utility theory to situations where subjective probabilities can be used. At the time, von Neumann and Morgenstern's theory of expected utility proved that expected utility maximization followed from basic postulates about rational behavior.
The work of Maurice Allais and Daniel Ellsberg showed that human behavior has systematic and sometimes important departures from expected-utility maximization (Allais paradox and Ellsberg paradox). The prospect theory of Daniel Kahneman and Amos Tversky renewed the empirical study of economic behavior with less emphasis on rationality presuppositions. It describes a way by which people make decisions when all of the outcomes carry a risk. Kahneman and Tversky found three regularities – in actual human decision-making, "losses loom larger than gains"; people focus more on changes in their utility-states than they focus on absolute utilities; and the estimation of subjective probabilities is severely biased by anchoring.
=== Intertemporal choice ===
Intertemporal choice is concerned with the kind of choice where different actions lead to outcomes that are realized at different stages over time. It is also described as cost-benefit decision making since it involves the choices between rewards that vary according to magnitude and time of arrival. If someone received a windfall of several thousand dollars, they could spend it on an expensive holiday, giving them immediate pleasure, or they could invest it in a pension scheme, giving them an income at some time in the future. What is the optimal thing to do? The answer depends partly on factors such as the expected rates of interest and inflation, the person's life expectancy, and their confidence in the pensions industry. However even with all those factors taken into account, human behavior again deviates greatly from the predictions of prescriptive decision theory, leading to alternative models in which, for example, objective interest rates are replaced by subjective discount rates.
=== Interaction of decision makers ===
Some decisions are difficult because of the need to take into account how other people in the situation will respond to the decision that is taken. The analysis of such social decisions is often treated under decision theory, though it involves mathematical methods. In the emerging field of socio-cognitive engineering, the research is especially focused on the different types of distributed decision-making in human organizations, in normal and abnormal/emergency/crisis situations.
=== Complex decisions ===
Other areas of decision theory are concerned with decisions that are difficult simply because of their complexity, or the complexity of the organization that has to make them. Individuals making decisions are limited in resources (i.e. time and intelligence) and are therefore boundedly rational; the issue is thus, more than the deviation between real and optimal behavior, the difficulty of determining the optimal behavior in the first place. Decisions are also affected by whether options are framed together or separately; this is known as the distinction bias.
== Heuristics ==
Heuristics are procedures for making a decision without working out the consequences of every option. Heuristics decrease the amount of evaluative thinking required for decisions, focusing on some aspects of the decision while ignoring others. While quicker than step-by-step processing, heuristic thinking is also more likely to involve fallacies or inaccuracies.
One example of a common and erroneous thought process that arises through heuristic thinking is the gambler's fallacy — believing that an isolated random event is affected by previous isolated random events. For example, if flips of a fair coin give repeated tails, the coin still has the same probability (i.e., 0.5) of tails in future turns, though intuitively it might seems that heads becomes more likely. In the long run, heads and tails should occur equally often; people commit the gambler's fallacy when they use this heuristic to predict that a result of heads is "due" after a run of tails. Another example is that decision-makers may be biased towards preferring moderate alternatives to extreme ones. The compromise effect operates under a mindset that the most moderate option carries the most benefit. In an incomplete information scenario, as in most daily decisions, the moderate option will look more appealing than either extreme, independent of the context, based only on the fact that it has characteristics that can be found at either extreme.
== Alternatives ==
A highly controversial issue is whether one can replace the use of probability in decision theory with something else.
=== Probability theory ===
Advocates for the use of probability theory point to:
the work of Richard Threlkeld Cox for justification of the probability axioms,
the Dutch book paradoxes of Bruno de Finetti as illustrative of the theoretical difficulties that can arise from departures from the probability axioms, and
the complete class theorems, which show that all admissible decision rules are equivalent to the Bayesian decision rule for some utility function and some prior distribution (or for the limit of a sequence of prior distributions). Thus, for every decision rule, either the rule may be reformulated as a Bayesian procedure (or a limit of a sequence of such), or there is a rule that is sometimes better and never worse.
=== Alternatives to probability theory ===
The proponents of fuzzy logic, possibility theory, Dempster–Shafer theory, and info-gap decision theory maintain that probability is only one of many alternatives and point to many examples where non-standard alternatives have been implemented with apparent success. Notably, probabilistic decision theory can sometimes be sensitive to assumptions about the probabilities of various events, whereas non-probabilistic rules, such as minimax, are robust in that they do not make such assumptions.
=== Ludic fallacy ===
A general criticism of decision theory based on a fixed universe of possibilities is that it considers the "known unknowns", not the "unknown unknowns": it focuses on expected variations, not on unforeseen events, which some argue have outsized impact and must be considered – significant events may be "outside model". This line of argument, called the ludic fallacy, is that there are inevitable imperfections in modeling the real world by particular models, and that unquestioning reliance on models blinds one to their limits.
== See also ==
== References ==
== Further reading == | Wikipedia/Decision_sciences |
A physical neural network is a type of artificial neural network in which an electrically adjustable material is used to emulate the function of a neural synapse or a higher-order (dendritic) neuron model. "Physical" neural network is used to emphasize the reliance on physical hardware used to emulate neurons as opposed to software-based approaches. More generally the term is applicable to other artificial neural networks in which a memristor or other electrically adjustable resistance material is used to emulate a neural synapse.
== Types of physical neural networks ==
=== ADALINE ===
In the 1960s Bernard Widrow and Ted Hoff developed ADALINE (Adaptive Linear Neuron) which used electrochemical cells called memistors (memory resistors) to emulate synapses of an artificial neuron. The memistors were implemented as 3-terminal devices operating based on the reversible electroplating of copper such that the resistance between two of the terminals is controlled by the integral of the current applied via the third terminal. The ADALINE circuitry was briefly commercialized by the Memistor Corporation in the 1960s enabling some applications in pattern recognition. However, since the memistors were not fabricated using integrated circuit fabrication techniques the technology was not scalable and was eventually abandoned as solid-state electronics became mature.
=== Analog VLSI ===
In 1989 Carver Mead published his book Analog VLSI and Neural Systems, which spun off perhaps the most common variant of analog neural networks. The physical realization is implemented in analog VLSI. This is often implemented as field effect transistors in low inversion. Such devices can be modelled as translinear circuits. This is a technique described by Barrie Gilbert in several papers around mid 1970th, and in particular his Translinear Circuits from 1981. With this method circuits can be analyzed as a set of well-defined functions in steady-state, and such circuits assembled into complex networks.
=== Physical Neural Network ===
Alex Nugent describes a physical neural network as one or more nonlinear neuron-like nodes used to sum signals and nanoconnections formed from nanoparticles, nanowires, or nanotubes which determine the signal strength input to the nodes. Alignment or self-assembly of the nanoconnections is determined by the history of the applied electric field performing a function analogous to neural synapses. Numerous applications for such physical neural networks are possible. For example, a temporal summation device can be composed of one or more nanoconnections having an input and an output thereof, wherein an input signal provided to the input causes one or more of the nanoconnection to experience an increase in connection strength thereof over time. Another example of a physical neural network is taught by U.S. Patent No. 7,039,619 entitled "Utilized nanotechnology apparatus using a neural network, a solution and a connection gap," which issued to Alex Nugent by the U.S. Patent & Trademark Office on May 2, 2006.
A further application of physical neural network is shown in U.S. Patent No. 7,412,428 entitled "Application of hebbian and anti-hebbian learning to nanotechnology-based physical neural networks," which issued on August 12, 2008.
Nugent and Molter have shown that universal computing and general-purpose machine learning are possible from operations available through simple memristive circuits operating the AHaH plasticity rule.
More recently, it has been argued that also complex networks of purely memristive circuits can serve as neural networks.
=== Phase change neural network ===
In 2002, Stanford Ovshinsky described an analog neural computing medium in which phase-change material has the ability to cumulatively respond to multiple input signals. An electrical alteration of the resistance of the phase change material is used to control the weighting of the input signals.
=== Memristive neural network ===
Greg Snider of HP Labs describes a system of cortical computing with memristive nanodevices. The memristors (memory resistors) are implemented by thin film materials in which the resistance is electrically tuned via the transport of ions or oxygen vacancies within the film. DARPA's SyNAPSE project has funded IBM Research and HP Labs, in collaboration with the Boston University Department of Cognitive and Neural Systems (CNS), to develop neuromorphic architectures which may be based on memristive systems.
=== Protonic artificial synapses ===
In 2022, researchers reported the development of nanoscale brain-inspired artificial synapses, using the ion proton (H+), for 'analog deep learning'.
== See also ==
AI accelerator
Brain simulation
Neuromorphic engineering
Optical neural network
Quantum neural network
== References ==
== External links ==
Information on DARPA's SyNAPSE project 2009 | Wikipedia/Physical_neural_network |
Neuron is a simulation environment for modeling individual and networks of neurons. It was primarily developed by Michael Hines, John W. Moore, and Ted Carnevale at Yale and Duke.
Neuron models individual neurons via the use of sections that are automatically subdivided into individual compartments, instead of requiring the user to manually create compartments. The primary scripting language is hoc but a Python interface is also available. Programs can be written interactively in a shell, or loaded from a file. Neuron supports parallelization via the MPI protocol.
Neuron is capable of handling diffusion-reaction models, and integrating diffusion functions into models of synapses and cellular networks. Parallelization is possible via internal multithreaded routines, for use on multi-core computers. The properties of the membrane channels of the neuron are simulated using compiled mechanisms written using the NMODL language or by compiled routines operating on internal data structures that are set up with Channel Builder.
Along with the analogous software platform GENESIS, Neuron is the basis for instruction in computational neuroscience in many courses and laboratories around the world.
== User interface ==
Neuron features a graphical user interface (GUI), for use by individuals with minimal programming experience. The GUI comes equipped with a builder for single and multiple compartment cells, networks, network cells, channels and linear electric circuits. Single and multiple compartment cells differ in that multiple compartment cells features several "sections", each with potentially distinct parameters for dimensions and kinetics. Tutorials are available on the Neuron website, including for getting basic models out of the cell, channel and network builders. With these builders, the user can form the basis of all simulations and models.
=== Cell Builder ===
Cell Builder allows the user to generate and modify stick figure cell structures. These sections form the basis of functionally distinct areas of the neuron.
The user can define functionally distinct groups of sections. Sections branching from one another can be labeled "dendrites," while another, single section that projects from the same central one can be labeled as the "axon." The user can define parameters along which certain values are variable as a function across a section. For instance, path length along a subset can be defined as a domain, the functions along which can then be defined later.
The user can select either individual sections, or groups and set precise parameters for length, diameter, area and length for that group or section. Any of these values can be set as a function of length or some other parameter of the corresponding section. The user can set the number of functional segments in a section, which is a strategy for spatial resolution. The higher the number of segments, the more precisely Neuron can handle a function in a section. Segments are the points where point process managers can be associated.
Users can define kinetic and electro-physiological functions across both subsets and sections. Neuron comes equipped with a probabilistic model of Hodgkin-Huxley Model giant squid axon kinetics, as well as a function to model passive leak channel kinetics. Both of these functions, and the features they describe, can be added to the membrane of the constructed cell. Values for leak rate, sodium conductance and potassium conductance can be set for modeling these kinetics can be set as functions over a parameterized domain. Channels become available for implementation in a cell membrane.
=== Channel Builder ===
The user can generate both voltage- and ligand-gated channel models. Channel Builder supports local point channels, generally used for single, large channels whose function is to be modeled, and general channels whose density across the cell can be defined. Maximum conductance, reversal potential, ligand sensitivity, ion permeability, as well as precise dynamics of transitional states using activation and inactivation variables, and including differential conductance, can be defined.
=== Network and Network Cell Builder ===
Neuron allows for the generation of mixed models, populated with both artificial cells and neurons. Artificial cells essentially function as point processes, implemented into the network. Artificial cells require only a point process, with defined parameters. The user can create the structure and dynamics of network cells. The user can create synapses, using simulated synapse point processes as archetypes. Parameters on these point processes can be manipulated to simulate both inhibitory and excitatory responses. Synapses can be placed on specific segments of the constructed cell, wherein, again, they will behave as point processes, except that they are sensitive to the activity of a pre-synaptic element. Cells can be managed. The user creates the basic grid of network cells, taking previously completed network cells as archetypes. Connections can be defined between source cells and target synapses on other cells. The cell containing the target synapse becomes the post-synaptic element, whereas the source cells function as pre-synaptic elements. Weights can be added to define strength of activation of a synapse by the pre-synaptic cell. A plot option can be activated to open a graph of spikes across time for individual neurons.
=== Simulation and recording ===
Neuron comes equipped with a slew of simulation tools. Most notably, it includes several "point processes," which are simple functions at a particular segment of a cell. Point processes include simulations of voltage, patch, single electrode and current clamps, as well as several simulated synapses. Synapse point processes are distinct for their ability to model stimulation intensities that vary non-linearly across time. These can be placed on any segment of any section of a built cell, individual or network, and their precise values, including amplitude and duration of stimulation, delay time of activation in a run and time decay parameters (for synapses), can be defined from the point process manager module. When implemented into a network as synapses, point process parameters are defined in the synapse builder for a particular network cell. Graphs describing voltage, conductance, and current axes over time can be used to describe changes in electrical state at the location of any segment on the cell. Neuron allows for graphs of change at both individual points over time, and across an entire section through time. Duration of run can be set. All point processes, including those standing for cells or synapses of artificial neurons, and all graphs reflect the duration.
== Examples ==
This example creates a simple cell, with a single compartment soma and a multi compartment axon. It has the dynamics of the cell membrane simulated using Hodgkin-Huxley squid axon kinetics. The simulator stimulates the cell and runs for 50 ms.
A plot can be generated showing the voltage traces starting from the soma and the distal end of the axon. The action potential at the end of the axon arrives slightly later than it appears in the soma at the point of stimulation. The plot is membrane voltage versus time.
== References ==
== External links ==
The NEURON Book
A Neuron tutorial
NEURON documentation at Yale University
Screenshot of the network builder, displaying a completed simple network | Wikipedia/Neuron_(software) |
Computational and Systems Neuroscience (COSYNE or CoSyNe) is an annual scientific conference for the exchange of experimental and theoretical/computational approaches to problems in systems neuroscience. It is an important meeting for computational neuroscientists where many levels of approaches are discussed. It is a single track-meeting with oral and poster sessions and attracts about 800-900 participants from a variety of disciplines, including neuroscience, computer science and machine learning. Until 2018, the 3-day long main meeting was held in Salt Lake City, followed by two days of workshops at Snowbird, Utah. In 2018, COSYNE moved to Denver (3 days) and Breckenridge (2 days).
== History ==
COSYNE grew out of the Neural Information and Coding (NIC) meetings founded by Anthony Zador in 1996. The first COSYNE was organized in 2004 by Michael Shadlen, Alexandre Pouget, Carlos Brody and Anthony Zador. The current Executive Committee consists of Alexandre Pouget, Zachary Mainen, Stephanie Palmer and Anthony Zador.
== Meetings ==
== Related Meetings ==
Neural Information Processing Systems (since 1987)
Annual meeting of the Organization for Computational Neuroscience (since 1990/1992)
Conference on Cognitive Computational Neuroscience (since 2017)
Bernstein Conference (since 2005)
== References == | Wikipedia/Computational_and_Systems_Neuroscience |
The Goldman–Hodgkin–Katz voltage equation, sometimes called the Goldman equation, is used in cell membrane physiology to determine the resting potential across a cell's membrane, taking into account all of the ions that are permeant through that membrane.
The discoverers of this are David E. Goldman of Columbia University, and the Medicine Nobel laureates Alan Lloyd Hodgkin and Bernard Katz.
== Equation for monovalent ions ==
The GHK voltage equation for
M
{\displaystyle M}
monovalent positive ionic species and
A
{\displaystyle A}
negative:
E
m
=
R
T
F
ln
(
∑
i
n
P
M
i
+
[
M
i
+
]
o
u
t
+
∑
j
m
P
A
j
−
[
A
j
−
]
i
n
∑
i
n
P
M
i
+
[
M
i
+
]
i
n
+
∑
j
m
P
A
j
−
[
A
j
−
]
o
u
t
)
{\displaystyle E_{m}={\frac {RT}{F}}\ln {\left({\frac {\sum _{i}^{n}P_{M_{i}^{+}}[M_{i}^{+}]_{\mathrm {out} }+\sum _{j}^{m}P_{A_{j}^{-}}[A_{j}^{-}]_{\mathrm {in} }}{\sum _{i}^{n}P_{M_{i}^{+}}[M_{i}^{+}]_{\mathrm {in} }+\sum _{j}^{m}P_{A_{j}^{-}}[A_{j}^{-}]_{\mathrm {out} }}}\right)}}
This results in the following if we consider a membrane separating two
K
x
N
a
1
−
x
C
l
{\displaystyle \mathrm {K} _{x}\mathrm {Na} _{1-x}\mathrm {Cl} }
-solutions:
E
m
,
K
x
Na
1
−
x
C
l
=
R
T
F
ln
(
P
Na
[
Na
+
]
o
u
t
+
P
K
[
K
+
]
o
u
t
+
P
Cl
[
Cl
−
]
i
n
P
Na
[
Na
+
]
i
n
+
P
K
[
K
+
]
i
n
+
P
Cl
[
Cl
−
]
o
u
t
)
{\displaystyle E_{m,\mathrm {K} _{x}\mathrm {\text{Na}} _{1-x}\mathrm {Cl} }={\frac {RT}{F}}\ln {\left({\frac {P_{\text{Na}}[{\text{Na}}^{+}]_{\mathrm {out} }+P_{\text{K}}[{\text{K}}^{+}]_{\mathrm {out} }+P_{\text{Cl}}[{\text{Cl}}^{-}]_{\mathrm {in} }}{P_{\text{Na}}[{\text{Na}}^{+}]_{\mathrm {in} }+P_{\text{K}}[{\text{K}}^{+}]_{\mathrm {in} }+P_{\text{Cl}}[{\text{Cl}}^{-}]_{\mathrm {out} }}}\right)}}
It is "Nernst-like" but has a term for each permeant ion:
E
m
,
Na
=
R
T
F
ln
(
P
Na
[
Na
+
]
o
u
t
P
Na
[
Na
+
]
i
n
)
=
R
T
F
ln
(
[
Na
+
]
o
u
t
[
Na
+
]
i
n
)
{\displaystyle E_{m,{\text{Na}}}={\frac {RT}{F}}\ln {\left({\frac {P_{\text{Na}}[{\text{Na}}^{+}]_{\mathrm {out} }}{P_{\text{Na}}[{\text{Na}}^{+}]_{\mathrm {in} }}}\right)}={\frac {RT}{F}}\ln {\left({\frac {[{\text{Na}}^{+}]_{\mathrm {out} }}{[{\text{Na}}^{+}]_{\mathrm {in} }}}\right)}}
E
m
{\displaystyle E_{m}}
= the membrane potential (in volts, equivalent to joules per coulomb)
P
i
o
n
{\displaystyle P_{\mathrm {ion} }}
= the selectivity for that ion (in meters per second)
[
i
o
n
]
o
u
t
{\displaystyle [\mathrm {ion} ]_{\mathrm {out} }}
= the extracellular concentration of that ion (in moles per cubic meter, to match the other SI units)
[
i
o
n
]
i
n
{\displaystyle [\mathrm {ion} ]_{\mathrm {in} }}
= the intracellular concentration of that ion (in moles per cubic meter)
R
{\displaystyle R}
= the ideal gas constant (joules per kelvin per mole)
T
{\displaystyle T}
= the temperature in kelvins
F
{\displaystyle F}
= Faraday's constant (coulombs per mole)
R
T
F
{\displaystyle {\frac {RT}{F}}}
is approximately 26.7 mV at human body temperature (37 °C); when factoring in the change-of-base formula between the natural logarithm, ln, and logarithm with base 10
(
[
log
10
exp
(
1
)
]
−
1
=
ln
(
10
)
=
2.30258...
)
{\displaystyle ([\log _{10}\exp(1)]^{-1}=\ln(10)=2.30258...)}
, it becomes
26.7
m
V
⋅
2.303
=
61.5
m
V
{\displaystyle 26.7\,\mathrm {mV} \cdot 2.303=61.5\,\mathrm {mV} }
, a value often used in neuroscience.
E
X
=
61.5
m
V
⋅
log
(
[
X
+
]
o
u
t
[
X
+
]
i
n
)
=
−
61.5
m
V
⋅
log
(
[
X
−
]
o
u
t
[
X
−
]
i
n
)
{\displaystyle E_{X}=61.5\,\mathrm {mV} \cdot \log {\left({\frac {[X^{+}]_{\mathrm {out} }}{[X^{+}]_{\mathrm {in} }}}\right)}=-61.5\,\mathrm {mV} \cdot \log {\left({\frac {[X^{-}]_{\mathrm {out} }}{[X^{-}]_{\mathrm {in} }}}\right)}}
The ionic charge determines the sign of the membrane potential contribution. During an action potential, although the membrane potential changes about 100mV, the concentrations of ions inside and outside the cell do not change significantly. They are always very close to their respective concentrations when the membrane is at their resting potential.
=== Calculating the first term ===
Using
R
≈
8.3
J
K
⋅
m
o
l
{\displaystyle R\approx {\frac {8.3\ \mathrm {J} }{\mathrm {K} \cdot \mathrm {mol} }}}
,
F
≈
9.6
×
10
4
J
m
o
l
⋅
V
{\displaystyle F\approx {\frac {9.6\times 10^{4}\ \mathrm {J} }{\mathrm {mol} \cdot \mathrm {V} }}}
, (assuming body temperature)
T
=
37
∘
C
=
310
K
{\displaystyle T=37\ ^{\circ }\mathrm {C} =310\ \mathrm {K} }
and the fact that one volt is equal to one joule of energy per coulomb of charge, the equation
E
X
=
R
T
z
F
ln
X
o
X
i
{\displaystyle E_{X}={\frac {RT}{zF}}\ln {\frac {X_{o}}{X_{i}}}}
can be reduced to
E
X
≈
0.0267
V
z
ln
X
o
X
i
=
26.7
m
V
z
ln
X
o
X
i
≈
61.5
m
V
z
log
X
o
X
i
since
ln
10
≈
2.303
{\displaystyle {\begin{aligned}E_{X}&\approx {\frac {0.0267\ \mathrm {V} }{z}}\ln {\frac {X_{o}}{X_{i}}}\\&={\frac {26.7\ \mathrm {mV} }{z}}\ln {\frac {X_{o}}{X_{i}}}\\&\approx {\frac {61.5\ \mathrm {mV} }{z}}\log {\frac {X_{o}}{X_{i}}}&{\text{ since }}\ln 10\approx 2.303\end{aligned}}}
which is the Nernst equation.
== Derivation ==
Goldman's equation seeks to determine the voltage Em across a membrane. A Cartesian coordinate system is used to describe the system, with the z direction being perpendicular to the membrane. Assuming that the system is symmetrical in the x and y directions (around and along the axon, respectively), only the z direction need be considered; thus, the voltage Em is the integral of the z component of the electric field across the membrane.
According to Goldman's model, only two factors influence the motion of ions across a permeable membrane: the average electric field and the difference in ionic concentration from one side of the membrane to the other. The electric field is assumed to be constant across the membrane, so that it can be set equal to Em/L, where L is the thickness of the membrane. For a given ion denoted A with valence nA, its flux jA—in other words, the number of ions crossing per time and per area of the membrane—is given by the formula
j
A
=
−
D
A
(
d
[
A
]
d
z
−
n
A
F
R
T
E
m
L
[
A
]
)
{\displaystyle j_{\mathrm {A} }=-D_{\mathrm {A} }\left({\frac {d\left[\mathrm {A} \right]}{dz}}-{\frac {n_{\mathrm {A} }F}{RT}}{\frac {E_{m}}{L}}\left[\mathrm {A} \right]\right)}
The first term corresponds to Fick's law of diffusion, which gives the flux due to diffusion down the concentration gradient, i.e., from high to low concentration. The constant DA is the diffusion constant of the ion A. The second term reflects the flux due to the electric field, which increases linearly with the electric field; Formally, it is [A] multiplied by the drift velocity of the ions, with the drift velocity expressed using the Stokes–Einstein relation applied to electrophoretic mobility. The constants here are the charge valence nA of the ion A (e.g., +1 for K+, +2 for Ca2+ and −1 for Cl−), the temperature T (in kelvins), the molar gas constant R, and the faraday F, which is the total charge of a mole of electrons.
This is a first-order ODE of the form y' = ay + b, with y = [A] and y' = d[A]/dz; integrating both sides from z=0 to z=L with the boundary conditions [A](0) = [A]in and [A](L) = [A]out, one gets the solution
j
A
=
μ
n
A
P
A
[
A
]
o
u
t
−
[
A
]
i
n
e
n
A
μ
1
−
e
n
A
μ
{\displaystyle j_{\mathrm {A} }=\mu n_{\mathrm {A} }P_{\mathrm {A} }{\frac {\left[\mathrm {A} \right]_{\mathrm {out} }-\left[\mathrm {A} \right]_{\mathrm {in} }e^{n_{\mathrm {A} }\mu }}{1-e^{n_{\mathrm {A} }\mu }}}}
where μ is a dimensionless number
μ
=
F
E
m
R
T
{\displaystyle \mu ={\frac {FE_{m}}{RT}}}
and PA is the ionic permeability, defined here as
P
A
=
D
A
L
{\displaystyle P_{\mathrm {A} }={\frac {D_{\mathrm {A} }}{L}}}
The electric current density JA equals the charge qA of the ion multiplied by the flux jA
J
A
=
q
A
j
A
{\displaystyle J_{A}=q_{\mathrm {A} }j_{\mathrm {A} }}
Current density has units of (Amperes/m2). Molar flux has units of (mol/(s m2)). Thus, to get current density from molar flux one needs to multiply by Faraday's constant F (Coulombs/mol). F will then cancel from the equation below. Since the valence has already been accounted for above, the charge qA of each ion in the equation above, therefore, should be interpreted as +1 or −1 depending on the polarity of the ion.
There is such a current associated with every type of ion that can cross the membrane; this is because each type of ion would require a distinct membrane potential to balance diffusion, but there can only be one membrane potential. By assumption, at the Goldman voltage Em, the total current density is zero
J
t
o
t
=
∑
A
J
A
=
0
{\displaystyle J_{tot}=\sum _{A}J_{A}=0}
(Although the current for each ion type considered here is nonzero, there are other pumps in the membrane, e.g. Na+/K+-ATPase, not considered here which serve to balance each individual ion's current, so that the ion concentrations on either side of the membrane do not change over time in equilibrium.) If all the ions are monovalent—that is, if all the nA equal either +1 or −1—this equation can be written
w
−
v
e
μ
=
0
{\displaystyle w-ve^{\mu }=0}
whose solution is the Goldman equation
F
E
m
R
T
=
μ
=
ln
w
v
{\displaystyle {\frac {FE_{m}}{RT}}=\mu =\ln {\frac {w}{v}}}
where
w
=
∑
c
a
t
i
o
n
s
C
P
C
[
C
+
]
o
u
t
+
∑
a
n
i
o
n
s
A
P
A
[
A
−
]
i
n
{\displaystyle w=\sum _{\mathrm {cations\ C} }P_{\mathrm {C} }\left[\mathrm {C} ^{+}\right]_{\mathrm {out} }+\sum _{\mathrm {anions\ A} }P_{\mathrm {A} }\left[\mathrm {A} ^{-}\right]_{\mathrm {in} }}
v
=
∑
c
a
t
i
o
n
s
C
P
C
[
C
+
]
i
n
+
∑
a
n
i
o
n
s
A
P
A
[
A
−
]
o
u
t
{\displaystyle v=\sum _{\mathrm {cations\ C} }P_{\mathrm {C} }\left[\mathrm {C} ^{+}\right]_{\mathrm {in} }+\sum _{\mathrm {anions\ A} }P_{\mathrm {A} }\left[\mathrm {A} ^{-}\right]_{\mathrm {out} }}
If divalent ions such as calcium are considered, terms such as e2μ appear, which is the square of eμ; in this case, the formula for the Goldman equation can be solved using the quadratic formula.
== See also ==
Bioelectronics
Cable theory
GHK current equation
Hindmarsh–Rose model
Hodgkin–Huxley model
Morris–Lecar model
Nernst equation
Saltatory conduction
== References ==
== External links ==
Subthreshold membrane phenomena Includes a well-explained derivation of the Goldman-Hodgkin-Katz equation
Nernst/Goldman Equation Simulator Archived 2010-08-08 at the Wayback Machine
Goldman-Hodgkin-Katz Equation Calculator
Nernst/Goldman interactive Java applet The membrane voltage is calculated interactively as the number of ions are changed between the inside and outside of the cell.
Potential, Impedance, and Rectification in Membranes by Goldman (1943) | Wikipedia/Goldman_equation |
Biological neuron models, also known as spiking neuron models, are mathematical descriptions of the conduction of electrical signals in neurons. Neurons (or nerve cells) are electrically excitable cells within the nervous system, able to fire electric signals, called action potentials, across a neural network. These mathematical models describe the role of the biophysical and geometrical characteristics of neurons on the conduction of electrical activity.
Central to these models is the description of how the membrane potential (that is, the difference in electric potential between the interior and the exterior of a biological cell) across the cell membrane changes over time. In an experimental setting, stimulating neurons with an electrical current generates an action potential (or spike), that propagates down the neuron's axon. This axon can branch out and connect to a large number of downstream neurons at sites called synapses. At these synapses, the spike can cause the release of neurotransmitters, which in turn can change the voltage potential of downstream neurons. This change can potentially lead to even more spikes in those downstream neurons, thus passing down the signal. As many as 95% of neurons in the neocortex, the outermost layer of the mammalian brain, consist of excitatory pyramidal neurons, and each pyramidal neuron receives tens of thousands of inputs from other neurons. Thus, spiking neurons are a major information processing unit of the nervous system.
One such example of a spiking neuron model may be a highly detailed mathematical model that includes spatial morphology. Another may be a conductance-based neuron model that views neurons as points and describes the membrane voltage dynamics as a function of trans-membrane currents. A mathematically simpler "integrate-and-fire" model significantly simplifies the description of ion channel and membrane potential dynamics (initially studied by Lapique in 1907).
== Biological background, classification, and aims of neuron models ==
Non-spiking cells, spiking cells, and their measurement
Not all the cells of the nervous system produce the type of spike that defines the scope of the spiking neuron models. For example, cochlear hair cells, retinal receptor cells, and retinal bipolar cells do not spike. Furthermore, many cells in the nervous system are not classified as neurons but instead are classified as glia.
Neuronal activity can be measured with different experimental techniques, such as the "Whole cell" measurement technique, which captures the spiking activity of a single neuron and produces full amplitude action potentials.
With extracellular measurement techniques, one or more electrodes are placed in the extracellular space. Spikes, often from several spiking sources, depending on the size of the electrode and its proximity to the sources, can be identified with signal processing techniques. Extracellular measurement has several advantages:
It is easier to obtain experimentally;
It is robust and lasts for a longer time;
It can reflect the dominant effect, especially when conducted in an anatomical region with many similar cells.
Overview of neuron models
Neuron models can be divided into two categories according to the physical units of the interface of the model. Each category could be further divided according to the abstraction/detail level:
Electrical input–output membrane voltage models – These models produce a prediction for membrane output voltage as a function of electrical stimulation given as current or voltage input. The various models in this category differ in the exact functional relationship between the input current and the output voltage and in the level of detail. Some models in this category predict only the moment of occurrence of the output spike (also known as "action potential"); other models are more detailed and account for sub-cellular processes. The models in this category can be either deterministic or probabilistic.
Natural stimulus or pharmacological input neuron models – The models in this category connect the input stimulus, which can be either pharmacological or natural, to the probability of a spike event. The input stage of these models is not electrical but rather has either pharmacological (chemical) concentration units, or physical units that characterize an external stimulus such as light, sound, or other forms of physical pressure. Furthermore, the output stage represents the probability of a spike event and not an electrical voltage.
Although it is not unusual in science and engineering to have several descriptive models for different abstraction/detail levels, the number of different, sometimes contradicting, biological neuron models is exceptionally high. This situation is partly the result of the many different experimental settings, and the difficulty to separate the intrinsic properties of a single neuron from measurement effects and interactions of many cells (network effects).
Aims of neuron models
Ultimately, biological neuron models aim to explain the mechanisms underlying the operation of the nervous system. However, several approaches can be distinguished, from more realistic models (e.g., mechanistic models) to more pragmatic models (e.g., phenomenological models). Modeling helps to analyze experimental data and address questions. Models are also important in the context of restoring lost brain functionality through neuroprosthetic devices.
== Electrical input–output membrane voltage models ==
The models in this category describe the relationship between neuronal membrane currents at the input stage and membrane voltage at the output stage. This category includes (generalized) integrate-and-fire models and biophysical models inspired by the work of Hodgkin–Huxley in the early 1950s using an experimental setup that punctured the cell membrane and allowed to force a specific membrane voltage/current.
Most modern electrical neural interfaces apply extra-cellular electrical stimulation to avoid membrane puncturing, which can lead to cell death and tissue damage. Hence, it is not clear to what extent the electrical neuron models hold for extra-cellular stimulation (see e.g.).
=== Hodgkin–Huxley ===
The Hodgkin–Huxley model (H&H model)
is a model of the relationship between the flow of ionic currents across the neuronal cell membrane and the membrane voltage of the cell. It consists of a set of nonlinear differential equations describing the behavior of ion channels that permeate the cell membrane of the squid giant axon. Hodgkin and Huxley were awarded the 1963 Nobel Prize in Physiology or Medicine for this work.
It is important to note the voltage-current relationship, with multiple voltage-dependent currents charging the cell membrane of capacity Cm
C
m
d
V
(
t
)
d
t
=
−
∑
i
I
i
(
t
,
V
)
.
{\displaystyle C_{\mathrm {m} }{\frac {dV(t)}{dt}}=-\sum _{i}I_{i}(t,V).}
The above equation is the time derivative of the law of capacitance, Q = CV where the change of the total charge must be explained as the sum over the currents. Each current is given by
I
(
t
,
V
)
=
g
(
t
,
V
)
⋅
(
V
−
V
e
q
)
{\displaystyle I(t,V)=g(t,V)\cdot (V-V_{\mathrm {eq} })}
where g(t,V) is the conductance, or inverse resistance, which can be expanded in terms of its maximal conductance ḡ and the activation and inactivation fractions m and h, respectively, that determine how many ions can flow through available membrane channels. This expansion is given by
g
(
t
,
V
)
=
g
¯
⋅
m
(
t
,
V
)
p
⋅
h
(
t
,
V
)
q
{\displaystyle g(t,V)={\bar {g}}\cdot m(t,V)^{p}\cdot h(t,V)^{q}}
and our fractions follow the first-order kinetics
d
m
(
t
,
V
)
d
t
=
m
∞
(
V
)
−
m
(
t
,
V
)
τ
m
(
V
)
=
α
m
(
V
)
⋅
(
1
−
m
)
−
β
m
(
V
)
⋅
m
{\displaystyle {\frac {dm(t,V)}{dt}}={\frac {m_{\infty }(V)-m(t,V)}{\tau _{\mathrm {m} }(V)}}=\alpha _{\mathrm {m} }(V)\cdot (1-m)-\beta _{\mathrm {m} }(V)\cdot m}
with similar dynamics for h, where we can use either τ and m∞ or α and β to define our gate fractions.
The Hodgkin–Huxley model may be extended to include additional ionic currents. Typically, these include inward Ca2+ and Na+ input currents, as well as several varieties of K+ outward currents, including a "leak" current.
The result can be at the small end of 20 parameters which one must estimate or measure for an accurate model. In a model of a complex system of neurons, numerical integration of the equations are computationally expensive. Careful simplifications of the Hodgkin–Huxley model are therefore needed.
The model can be reduced to two dimensions thanks to the dynamic relations which can be established between the gating variables. it is also possible to extend it to take into account the evolution of the concentrations (considered fixed in the original model).
=== Perfect Integrate-and-fire ===
One of the earliest models of a neuron is the perfect integrate-and-fire model (also called non-leaky integrate-and-fire), first investigated in 1907 by Louis Lapicque. A neuron is represented by its membrane voltage V which evolves in time during stimulation with an input current I(t) according
I
(
t
)
=
C
d
V
(
t
)
d
t
{\displaystyle I(t)=C{\frac {dV(t)}{dt}}}
which is just the time derivative of the law of capacitance, Q = CV. When an input current is applied, the membrane voltage increases with time until it reaches a constant threshold Vth, at which point a delta function spike occurs and the voltage is reset to its resting potential, after which the model continues to run. The firing frequency of the model thus increases linearly without bound as input current increases.
The model can be made more accurate by introducing a refractory period tref that limits the firing frequency of a neuron by preventing it from firing during that period. For constant input I(t)=I the threshold voltage is reached after an integration time tint=CVthr/I after starting from zero. After a reset, the refractory period introduces a dead time so that the total time until the next firing is tref+tint . The firing frequency is the inverse of the total inter-spike interval (including dead time). The firing frequency as a function of a constant input current, is therefore
f
(
I
)
=
I
C
V
t
h
+
t
r
e
f
I
.
{\displaystyle \,\!f(I)={\frac {I}{C_{\mathrm {} }V_{\mathrm {th} }+t_{\mathrm {ref} }I}}.}
A shortcoming of this model is that it describes neither adaptation nor leakage. If the model receives a below-threshold short current pulse at some time, it will retain that voltage boost forever - until another input later makes it fire. This characteristic is not in line with observed neuronal behavior. The following extensions make the integrate-and-fire model more plausible from a biological point of view.
=== Leaky integrate-and-fire ===
The leaky integrate-and-fire model, which can be traced back to Louis Lapicque, contains a "leak" term in the membrane potential equation that reflects the diffusion of ions through the membrane, unlike the non-leaky integrate-and-fire model. The model equation looks like
C
m
d
V
m
(
t
)
d
t
=
I
(
t
)
−
V
m
(
t
)
R
m
{\displaystyle C_{\mathrm {m} }{\frac {dV_{\mathrm {m} }(t)}{dt}}=I(t)-{\frac {V_{\mathrm {m} }(t)}{R_{\mathrm {m} }}}}
where Vm is the voltage across the cell membrane and Rm is the membrane resistance. (The non-leaky integrate-and-fire model is retrieved in the limit Rm to infinity, i.e. if the membrane is a perfect insulator). The model equation is valid for arbitrary time-dependent input until a threshold Vth is reached; thereafter the membrane potential is reset.
For constant input, the minimum input to reach the threshold is Ith = Vth / Rm. Assuming a reset to zero, the firing frequency thus looks like
f
(
I
)
=
{
0
,
I
≤
I
t
h
[
t
r
e
f
−
R
m
C
m
log
(
1
−
V
t
h
I
R
m
)
]
−
1
,
I
>
I
t
h
{\displaystyle f(I)={\begin{cases}0,&I\leq I_{\mathrm {th} }\\\left[t_{\mathrm {ref} }-R_{\mathrm {m} }C_{\mathrm {m} }\log \left(1-{\tfrac {V_{\mathrm {th} }}{IR_{\mathrm {m} }}}\right)\right]^{-1},&I>I_{\mathrm {th} }\end{cases}}}
which converges for large input currents to the previous leak-free model with the refractory period. The model can also be used for inhibitory neurons.
The most significant disadvantage of this model is that it does not contain neuronal adaptation, so that it cannot describe an experimentally measured spike train in response to constant input current. This disadvantage is removed in generalized integrate-and-fire models that also contain one or several adaptation-variables and are able to predict spike times of cortical neurons under current injection to a high degree of accuracy.
=== Adaptive integrate-and-fire ===
Neuronal adaptation refers to the fact that even in the presence of a constant current injection into the soma, the intervals between output spikes increase. An adaptive integrate-and-fire neuron model combines the leaky integration of voltage V with one or several adaptation variables wk (see Chapter 6.1. in the textbook Neuronal Dynamics)
τ
m
d
V
m
(
t
)
d
t
=
R
I
(
t
)
−
[
V
m
(
t
)
−
E
m
]
−
R
∑
k
w
k
{\displaystyle \tau _{\mathrm {m} }{\frac {dV_{\mathrm {m} }(t)}{dt}}=RI(t)-[V_{\mathrm {m} }(t)-E_{\mathrm {m} }]-R\sum _{k}w_{k}}
τ
k
d
w
k
(
t
)
d
t
=
−
a
k
[
V
m
(
t
)
−
E
m
]
−
w
k
+
b
k
τ
k
∑
f
δ
(
t
−
t
f
)
{\displaystyle \tau _{k}{\frac {dw_{k}(t)}{dt}}=-a_{k}[V_{\mathrm {m} }(t)-E_{\mathrm {m} }]-w_{k}+b_{k}\tau _{k}\sum _{f}\delta (t-t^{f})}
where
τ
m
{\displaystyle \tau _{m}}
is the membrane time constant, wk is the adaptation current number, with index k,
τ
k
{\displaystyle \tau _{k}}
is the time constant of adaptation current wk, Em is the resting potential and tf is the firing time of the neuron and the Greek delta denotes the Dirac delta function. Whenever the voltage reaches the firing threshold the voltage is reset to a value Vr below the firing threshold. The reset value is one of the important parameters of the model. The simplest model of adaptation has only a single adaptation variable w and the sum over k is removed.
Integrate-and-fire neurons with one or several adaptation variables can account for a variety of neuronal firing patterns in response to constant stimulation, including adaptation, bursting, and initial bursting. Moreover, adaptive integrate-and-fire neurons with several adaptation variables are able to predict spike times of cortical neurons under time-dependent current injection into the soma.
=== Fractional-order leaky integrate-and-fire ===
Recent advances in computational and theoretical fractional calculus lead to a new form of model called Fractional-order leaky integrate-and-fire. An advantage of this model is that it can capture adaptation effects with a single variable. The model has the following form
I
(
t
)
−
V
m
(
t
)
R
m
=
C
m
d
α
V
m
(
t
)
d
α
t
{\displaystyle I(t)-{\frac {V_{\mathrm {m} }(t)}{R_{\mathrm {m} }}}=C_{\mathrm {m} }{\frac {d^{\alpha }V_{\mathrm {m} }(t)}{d^{\alpha }t}}}
Once the voltage hits the threshold it is reset. Fractional integration has been used to account for neuronal adaptation in experimental data.
=== 'Exponential integrate-and-fire' and 'adaptive exponential integrate-and-fire' ===
In the exponential integrate-and-fire model, spike generation is exponential, following the equation:
d
V
d
t
−
R
τ
m
I
(
t
)
=
1
τ
m
[
E
m
−
V
+
Δ
T
exp
(
V
−
V
T
Δ
T
)
]
.
{\displaystyle {\frac {dV}{dt}}-{\frac {R}{\tau _{m}}}I(t)={\frac {1}{\tau _{m}}}\left[E_{m}-V+\Delta _{T}\exp \left({\frac {V-V_{T}}{\Delta _{T}}}\right)\right].}
where
V
{\displaystyle V}
is the membrane potential,
V
T
{\displaystyle V_{T}}
is the intrinsic membrane potential threshold,
τ
m
{\displaystyle \tau _{m}}
is the membrane time constant,
E
m
{\displaystyle E_{m}}
is the resting potential, and
Δ
T
{\displaystyle \Delta _{T}}
is the sharpness of action potential initiation, usually around 1 mV for cortical pyramidal neurons. Once the membrane potential crosses
V
T
{\displaystyle V_{T}}
, it diverges to infinity in finite time. In numerical simulation the integration is stopped if the membrane potential hits an arbitrary threshold (much larger than
V
T
{\displaystyle V_{T}}
) at which the membrane potential is reset to a value Vr . The voltage reset value Vr is one of the important parameters of the model. Importantly, the right-hand side of the above equation contains a nonlinearity that can be directly extracted from experimental data. In this sense the exponential nonlinearity is strongly supported by experimental evidence.
In the adaptive exponential integrate-and-fire neuron the above exponential nonlinearity of the voltage equation is combined with an adaptation variable w
τ
m
d
V
d
t
=
R
I
(
t
)
+
[
E
m
−
V
+
Δ
T
exp
(
V
−
V
T
Δ
T
)
]
−
R
w
{\displaystyle \tau _{m}{\frac {dV}{dt}}=RI(t)+\left[E_{m}-V+\Delta _{T}\exp \left({\frac {V-V_{T}}{\Delta _{T}}}\right)\right]-Rw}
τ
d
w
(
t
)
d
t
=
−
a
[
V
m
(
t
)
−
E
m
]
−
w
+
b
τ
δ
(
t
−
t
f
)
{\displaystyle \tau {\frac {dw(t)}{dt}}=-a[V_{\mathrm {m} }(t)-E_{\mathrm {m} }]-w+b\tau \delta (t-t^{f})}
where w denotes the adaptation current with time scale
τ
{\displaystyle \tau }
. Important model parameters are the voltage reset value Vr, the intrinsic threshold
V
T
{\displaystyle V_{T}}
, the time constants
τ
{\displaystyle \tau }
and
τ
m
{\displaystyle \tau _{m}}
as well as the coupling parameters a and b. The adaptive exponential integrate-and-fire model inherits the experimentally derived voltage nonlinearity of the exponential integrate-and-fire model. But going beyond this model, it can also account for a variety of neuronal firing patterns in response to constant stimulation, including adaptation, bursting, and initial bursting. However, since the adaptation is in the form of a current, aberrant hyperpolarization may appear. This problem was solved by expressing it as a conductance.
=== Adaptive Threshold Neuron Model ===
In this model, a time-dependent function
θ
(
t
)
{\displaystyle \theta (t)}
is added to the fixed threshold,
v
t
h
0
{\displaystyle v_{th0}}
, after every spike, causing an adaptation of the threshold. The threshold potential,
v
t
h
{\displaystyle v_{th}}
, gradually returns to its steady state value depending on the threshold adaptation time constant
τ
θ
{\displaystyle \tau _{\theta }}
. This is one of the simpler techniques to achieve spike frequency adaptation. The expression for the adaptive threshold is given by:
v
t
h
(
t
)
=
v
t
h
0
+
∑
θ
(
t
−
t
f
)
f
=
v
t
h
0
+
∑
θ
0
exp
[
−
(
t
−
t
f
)
τ
θ
]
f
{\displaystyle v_{th}(t)=v_{th0}+{\frac {\sum \theta (t-t_{f})}{f}}=v_{th0}+{\frac {\sum \theta _{0}\exp \left[-{\frac {(t-t_{f})}{\tau _{\theta }}}\right]}{f}}}
where
θ
(
t
)
{\displaystyle \theta (t)}
is defined by:
θ
(
t
)
=
θ
0
exp
[
−
t
τ
θ
]
{\displaystyle \theta (t)=\theta _{0}\exp \left[-{\frac {t}{\tau _{\theta }}}\right]}
When the membrane potential,
u
(
t
)
{\displaystyle u(t)}
, reaches a threshold, it is reset to
v
r
e
s
t
{\displaystyle v_{rest}}
:
u
(
t
)
≥
v
t
h
(
t
)
⇒
v
(
t
)
=
v
rest
{\displaystyle u(t)\geq v_{th}(t)\Rightarrow v(t)=v_{\text{rest}}}
A simpler version of this with a single time constant in threshold decay with an LIF neuron is realized in to achieve LSTM like recurrent spiking neural networks to achieve accuracy nearer to ANNs on few spatio temporal tasks.
=== Double Exponential Adaptive Threshold (DEXAT) ===
The DEXAT neuron model is a flavor of adaptive neuron model in which the threshold voltage decays with a double exponential having two time constants. Double exponential decay is governed by a fast initial decay and then a slower decay over a longer period of time. This neuron used in SNNs through surrogate gradient creates an adaptive learning rate yielding higher accuracy and faster convergence, and flexible long short-term memory compared to existing counterparts in the literature. The membrane potential dynamics are described through equations and the threshold adaptation rule is:
v
t
h
(
t
)
=
b
0
+
β
1
b
1
(
t
)
+
β
2
b
2
(
t
)
{\displaystyle v_{th}(t)=b_{0}+\beta _{1}b_{1}(t)+\beta _{2}b_{2}(t)}
The dynamics of
b
1
(
t
)
{\displaystyle b_{1}(t)}
and
b
2
(
t
)
{\displaystyle b_{2}(t)}
are given by
b
1
(
t
+
δ
t
)
=
p
j
1
b
1
(
t
)
+
(
1
−
p
j
1
)
z
(
t
)
δ
(
t
)
{\displaystyle b_{1}(t+\delta t)=p_{j1}b_{1}(t)+(1-p_{j1})z(t)\delta (t)}
,
b
2
(
t
+
δ
t
)
=
p
j
2
b
2
(
t
)
+
(
1
−
p
j
2
)
z
(
t
)
δ
(
t
)
{\displaystyle b_{2}(t+\delta t)=p_{j2}b_{2}(t)+(1-p_{j2})z(t)\delta (t)}
,
where
p
j
1
=
exp
[
−
δ
t
τ
b
1
]
{\displaystyle p_{j1}=\exp \left[-{\frac {\delta t}{\tau _{b1}}}\right]}
and
p
j
2
=
exp
[
−
δ
t
τ
b
2
]
{\displaystyle p_{j2}=\exp \left[-{\frac {\delta t}{\tau _{b2}}}\right]}
.
Further, multi-time scale adaptive threshold neuron model showing more complex dynamics is shown in.
== Stochastic models of membrane voltage and spike timing ==
The models in this category are generalized integrate-and-fire models that include a certain level of stochasticity. Cortical neurons in experiments are found to respond reliably to time-dependent input, albeit with a small degree of variations between one trial and the next if the same stimulus is repeated. Stochasticity in neurons has two important sources. First, even in a very controlled experiment where input current is injected directly into the soma, ion channels open and close stochastically and this channel noise leads to a small amount of variability in the exact value of the membrane potential and the exact timing of output spikes. Second, for a neuron embedded in a cortical network, it is hard to control the exact input because most inputs come from unobserved neurons somewhere else in the brain.
Stochasticity has been introduced into spiking neuron models in two fundamentally different forms: either (i) a noisy input current is added to the differential equation of the neuron model; or (ii) the process of spike generation is noisy. In both cases, the mathematical theory can be developed for continuous time, which is then, if desired for the use in computer simulations, transformed into a discrete-time model.
The relation of noise in neuron models to the variability of spike trains and neural codes is discussed in Neural Coding and in Chapter 7 of the textbook Neuronal Dynamics.
=== Noisy input model (diffusive noise) ===
A neuron embedded in a network receives spike input from other neurons. Since the spike arrival times are not controlled by an experimentalist they can be considered as stochastic. Thus a (potentially nonlinear) integrate-and-fire model with nonlinearity f(v) receives two inputs: an input
I
(
t
)
{\displaystyle I(t)}
controlled by the experimentalists and a noisy input current
I
n
o
i
s
e
(
t
)
{\displaystyle I^{\rm {noise}}(t)}
that describes the uncontrolled background input.
τ
m
d
V
d
t
=
f
(
V
)
+
R
I
(
t
)
+
R
I
noise
(
t
)
{\displaystyle \tau _{m}{\frac {dV}{dt}}=f(V)+RI(t)+RI^{\text{noise}}(t)}
Stein's model is the special case of a leaky integrate-and-fire neuron and a stationary white noise current
I
n
o
i
s
e
(
t
)
=
ξ
(
t
)
{\displaystyle I^{\rm {noise}}(t)=\xi (t)}
with mean zero and unit variance. In the subthreshold regime, these assumptions yield the equation of the Ornstein–Uhlenbeck process
τ
m
d
V
d
t
=
[
E
m
−
V
]
+
R
I
(
t
)
+
R
ξ
(
t
)
{\displaystyle \tau _{m}{\frac {dV}{dt}}=[E_{m}-V]+RI(t)+R\xi (t)}
However, in contrast to the standard Ornstein–Uhlenbeck process, the membrane voltage is reset whenever V hits the firing threshold Vth . Calculating the interval distribution of the Ornstein–Uhlenbeck model for constant input with threshold leads to a first-passage time problem. Stein's neuron model and variants thereof have been used to fit interspike interval distributions of spike trains from real neurons under constant input current.
In the mathematical literature, the above equation of the Ornstein–Uhlenbeck process is written in the form
d
V
=
[
E
m
−
V
+
R
I
(
t
)
]
d
t
τ
m
+
σ
d
W
{\displaystyle dV=[E_{m}-V+RI(t)]{\frac {dt}{\tau _{m}}}+\sigma \,dW}
where
σ
{\displaystyle \sigma }
is the amplitude of the noise input and dW are increments of a Wiener process. For discrete-time implementations with time step dt the voltage updates are
Δ
V
=
[
E
m
−
V
+
R
I
(
t
)
]
Δ
t
τ
m
+
σ
τ
m
y
{\displaystyle \Delta V=[E_{m}-V+RI(t)]{\frac {\Delta t}{\tau _{m}}}+\sigma {\sqrt {\tau _{m}}}y}
where y is drawn from a Gaussian distribution with zero mean unit variance. The voltage is reset when it hits the firing threshold Vth .
The noisy input model can also be used in generalized integrate-and-fire models. For example, the exponential integrate-and-fire model with noisy input reads
τ
m
d
V
d
t
=
E
m
−
V
+
Δ
T
exp
(
V
−
V
T
Δ
T
)
+
R
I
(
t
)
+
R
ξ
(
t
)
{\displaystyle \tau _{m}{\frac {dV}{dt}}=E_{m}-V+\Delta _{T}\exp \left({\frac {V-V_{T}}{\Delta _{T}}}\right)+RI(t)+R\xi (t)}
For constant deterministic input
I
(
t
)
=
I
0
{\displaystyle I(t)=I_{0}}
it is possible to calculate the mean firing rate as a function of
I
0
{\displaystyle I_{0}}
. This is important because the frequency-current relation (f-I-curve) is often used by experimentalists to characterize a neuron.
The leaky integrate-and-fire with noisy input has been widely used in the analysis of networks of spiking neurons. Noisy input is also called 'diffusive noise' because it leads to a diffusion of the subthreshold membrane potential around the noise-free trajectory (Johannesma, The theory of spiking neurons with noisy input is reviewed in Chapter 8.2 of the textbook Neuronal Dynamics.
=== Noisy output model (escape noise) ===
In deterministic integrate-and-fire models, a spike is generated if the membrane potential V(t) hits the threshold
V
t
h
{\displaystyle V_{th}}
. In noisy output models, the strict threshold is replaced by a noisy one as follows. At each moment in time t, a spike is generated stochastically with instantaneous stochastic intensity or 'escape rate'
ρ
(
t
)
=
f
(
V
(
t
)
−
V
t
h
)
{\displaystyle \rho (t)=f(V(t)-V_{th})}
that depends on the momentary difference between the membrane voltage V(t) and the threshold
V
t
h
{\displaystyle V_{th}}
. A common choice for the 'escape rate'
f
{\displaystyle f}
(that is consistent with biological data) is
f
(
V
−
V
t
h
)
=
1
τ
0
exp
[
β
(
V
−
V
t
h
)
]
{\displaystyle f(V-V_{th})={\frac {1}{\tau _{0}}}\exp[\beta (V-V_{th})]}
where
τ
0
{\displaystyle \tau _{0}}
is a time constant that describes how quickly a spike is fired once the membrane potential reaches the threshold and
β
{\displaystyle \beta }
is a sharpness parameter. For
β
→
∞
{\displaystyle \beta \to \infty }
the threshold becomes sharp and spike firing occurs deterministically at the moment when the membrane potential hits the threshold from below. The sharpness value found in experiments is
1
/
β
≈
4
m
V
{\displaystyle 1/\beta \approx 4mV}
which means that neuronal firing becomes non-negligible as soon as the membrane potential is a few mV below the formal firing threshold.
The escape rate process via a soft threshold is reviewed in Chapter 9 of the textbook Neuronal Dynamics.
For models in discrete time, a spike is generated with probability
P
F
(
t
n
)
=
F
[
V
(
t
n
)
−
V
t
h
]
{\displaystyle P_{F}(t_{n})=F[V(t_{n})-V_{th}]}
that depends on the momentary difference between the membrane voltage V at time
t
n
{\displaystyle t_{n}}
and the threshold
V
t
h
{\displaystyle V_{th}}
. The function F is often taken as a standard sigmoidal
F
(
x
)
=
0.5
[
1
+
tanh
(
γ
x
)
]
{\displaystyle F(x)=0.5[1+\tanh(\gamma x)]}
with steepness parameter
γ
{\displaystyle \gamma }
, similar to the update dynamics in artificial neural networks. But the functional form of F can also be derived from the stochastic intensity
f
{\displaystyle f}
in continuous time introduced above as
F
(
y
n
)
≈
1
−
exp
[
y
n
Δ
t
]
{\displaystyle F(y_{n})\approx 1-\exp[y_{n}\Delta t]}
where
y
n
=
V
(
t
n
)
−
V
t
h
{\displaystyle y_{n}=V(t_{n})-V_{th}}
is the threshold distance.
Integrate-and-fire models with output noise can be used to predict the peristimulus time histogram (PSTH) of real neurons under arbitrary time-dependent input. For non-adaptive integrate-and-fire neurons, the interval distribution under constant stimulation can be calculated from stationary renewal theory.
=== Spike response model (SRM) ===
main article: Spike response model
The spike response model (SRM) is a generalized linear model for the subthreshold membrane voltage combined with a nonlinear output noise process for spike generation. The membrane voltage V(t) at time t is
V
(
t
)
=
∑
f
η
(
t
−
t
f
)
+
∫
0
∞
κ
(
s
)
I
(
t
−
s
)
d
s
+
V
r
e
s
t
{\displaystyle V(t)=\sum _{f}\eta (t-t^{f})+\int \limits _{0}^{\infty }\kappa (s)I(t-s)\,ds+V_{\mathrm {rest} }}
where tf is the firing time of spike number f of the neuron, Vrest is the resting voltage in the absence of input, I(t-s) is the input current at time t-s and
κ
(
s
)
{\displaystyle \kappa (s)}
is a linear filter (also called kernel) that describes the contribution of an input current pulse at time t-s to the voltage at time t. The contributions to the voltage caused by a spike at time
t
f
{\displaystyle t^{f}}
are described by the refractory kernel
η
(
t
−
t
f
)
{\displaystyle \eta (t-t^{f})}
. In particular,
η
(
t
−
t
f
)
{\displaystyle \eta (t-t^{f})}
describes the reset after the spike and the time course of the spike-afterpotential following a spike. It therefore expresses the consequences of refractoriness and adaptation. The voltage V(t) can be interpreted as the result of an integration of the differential equation of a leaky integrate-and-fire model coupled to an arbitrary number of spike-triggered adaptation variables.
Spike firing is stochastic and happens with a time-dependent stochastic intensity (instantaneous rate)
f
(
V
−
ϑ
(
t
)
)
=
1
τ
0
exp
[
β
(
V
−
ϑ
(
t
)
)
]
{\displaystyle f(V-\vartheta (t))={\frac {1}{\tau _{0}}}\exp[\beta (V-\vartheta (t))]}
with parameters
τ
0
{\displaystyle \tau _{0}}
and
β
{\displaystyle \beta }
and a dynamic threshold
ϑ
(
t
)
{\displaystyle \vartheta (t)}
given by
ϑ
(
t
)
=
ϑ
0
+
∑
f
θ
1
(
t
−
t
f
)
{\displaystyle \vartheta (t)=\vartheta _{0}+\sum _{f}\theta _{1}(t-t^{f})}
Here
ϑ
0
{\displaystyle \vartheta _{0}}
is the firing threshold of an inactive neuron and
θ
1
(
t
−
t
f
)
{\displaystyle \theta _{1}(t-t^{f})}
describes the increase of the threshold after a spike at time
t
f
{\displaystyle t^{f}}
. In case of a fixed threshold, one sets
θ
1
(
t
−
t
f
)
=
0
{\displaystyle \theta _{1}(t-t^{f})=0}
. For
β
→
∞
{\displaystyle \beta \to \infty }
the threshold process is deterministic.
The time course of the filters
η
,
κ
,
θ
1
{\displaystyle \eta ,\kappa ,\theta _{1}}
that characterize the spike response model can be directly extracted from experimental data. With optimized parameters the SRM describes the time course of the subthreshold membrane voltage for time-dependent input with a precision of 2mV and can predict the timing of most output spikes with a precision of 4ms. The SRM is closely related to linear-nonlinear-Poisson cascade models (also called Generalized Linear Model). The estimation of parameters of probabilistic neuron models such as the SRM using methods developed for Generalized Linear Models is discussed in Chapter 10 of the textbook Neuronal Dynamics.
The name spike response model arises because, in a network, the input current for neuron i is generated by the spikes of other neurons so that in the case of a network the voltage equation becomes
V
i
(
t
)
=
∑
f
η
i
(
t
−
t
i
f
)
+
∑
j
=
1
N
w
i
j
∑
f
′
ε
i
j
(
t
−
t
j
f
′
)
+
V
r
e
s
t
{\displaystyle V_{i}(t)=\sum _{f}\eta _{i}(t-t_{i}^{f})+\sum _{j=1}^{N}w_{ij}\sum _{f'}\varepsilon _{ij}(t-t_{j}^{f'})+V_{\mathrm {rest} }}
where
t
j
f
′
{\displaystyle t_{j}^{f'}}
is the firing times of neuron j (i.e., its spike train);
η
i
(
t
−
t
i
f
)
{\displaystyle \eta _{i}(t-t_{i}^{f})}
describes the time course of the spike and the spike after-potential for neuron i; and
w
i
j
{\displaystyle w_{ij}}
and
ε
i
j
(
t
−
t
j
f
′
)
{\displaystyle \varepsilon _{ij}(t-t_{j}^{f'})}
describe the amplitude and time course of an excitatory or inhibitory postsynaptic potential (PSP) caused by the spike
t
j
f
′
{\displaystyle t_{j}^{f'}}
of the presynaptic neuron j. The time course
ε
i
j
(
s
)
{\displaystyle \varepsilon _{ij}(s)}
of the PSP results from the convolution of the postsynaptic current
I
(
t
)
{\displaystyle I(t)}
caused by the arrival of a presynaptic spike from neuron j with the membrane filter
κ
(
s
)
{\displaystyle \kappa (s)}
.
=== SRM0 ===
The SRM0 is a stochastic neuron model related to time-dependent nonlinear renewal theory and a simplification of the Spike Response Model (SRM). The main difference to the voltage equation of the SRM introduced above is that in the term containing the refractory kernel
η
(
s
)
{\displaystyle \eta (s)}
there is no summation sign over past spikes: only the most recent spike (denoted as the time
t
^
{\displaystyle {\hat {t}}}
) matters. Another difference is that the threshold is constant. The model SRM0 can be formulated in discrete or continuous time. For example, in continuous time, the single-neuron equation is
V
(
t
)
=
η
(
t
−
t
^
)
+
∫
0
∞
κ
(
s
)
I
(
t
−
s
)
d
s
+
V
r
e
s
t
{\displaystyle V(t)=\eta (t-{\hat {t}})+\int _{0}^{\infty }\kappa (s)I(t-s)\,ds+V_{\mathrm {rest} }}
and the network equations of the SRM0 are
V
i
(
t
∣
t
^
i
)
=
η
i
(
t
−
t
^
i
)
+
∑
j
w
i
j
∑
f
ε
i
j
(
t
−
t
^
i
,
t
−
t
f
)
+
V
r
e
s
t
{\displaystyle V_{i}(t\mid {\hat {t}}_{i})=\eta _{i}(t-{\hat {t}}_{i})+\sum _{j}w_{ij}\sum _{f}\varepsilon _{ij}(t-{\hat {t}}_{i},t-t^{f})+V_{\mathrm {rest} }}
where
t
^
i
{\displaystyle {\hat {t}}_{i}}
is the last firing time neuron i. Note that the time course of the postsynaptic potential
ε
i
j
{\displaystyle \varepsilon _{ij}}
is also allowed to depend on the time since the last spike of neuron i to describe a change in membrane conductance during refractoriness. The instantaneous firing rate (stochastic intensity) is
f
(
V
−
ϑ
)
=
1
τ
0
exp
[
β
(
V
−
V
t
h
)
]
{\displaystyle f(V-\vartheta )={\frac {1}{\tau _{0}}}\exp[\beta (V-V_{th})]}
where
V
t
h
{\displaystyle V_{th}}
is a fixed firing threshold. Thus spike firing of neuron i depends only on its input and the time since neuron i has fired its last spike.
With the SRM0, the interspike-interval distribution for constant input can be mathematically linked to the shape of the refractory kernel
η
{\displaystyle \eta }
. Moreover the stationary frequency-current relation can be calculated from the escape rate in combination with the refractory kernel
η
{\displaystyle \eta }
. With an appropriate choice of the kernels, the SRM0 approximates the dynamics of the Hodgkin-Huxley model to a high degree of accuracy. Moreover, the PSTH response to arbitrary time-dependent input can be predicted.
=== Galves–Löcherbach model ===
The Galves–Löcherbach model is a stochastic neuron model closely related to the spike response model SRM0 and the leaky integrate-and-fire model. It is inherently stochastic and, just like the SRM0, it is linked to time-dependent nonlinear renewal theory. Given the model specifications, the probability that a given neuron
i
{\displaystyle i}
spikes in a period
t
{\displaystyle t}
may be described by
P
r
o
b
(
X
t
(
i
)
=
1
∣
F
t
−
1
)
=
φ
i
(
∑
j
∈
I
W
j
→
i
∑
s
=
L
t
i
t
−
1
g
j
(
t
−
s
)
X
s
(
j
)
,
t
−
L
t
i
)
,
{\displaystyle \mathop {\mathrm {Prob} } (X_{t}(i)=1\mid {\mathcal {F}}_{t-1})=\varphi _{i}{\Biggl (}\sum _{j\in I}W_{j\rightarrow i}\sum _{s=L_{t}^{i}}^{t-1}g_{j}(t-s)X_{s}(j),~~~t-L_{t}^{i}{\Biggl )},}
where
W
j
→
i
{\displaystyle W_{j\rightarrow i}}
is a synaptic weight, describing the influence of neuron
j
{\displaystyle j}
on neuron
i
{\displaystyle i}
,
g
j
{\displaystyle g_{j}}
expresses the leak, and
L
t
i
{\displaystyle L_{t}^{i}}
provides the spiking history of neuron
i
{\displaystyle i}
before
t
{\displaystyle t}
, according to
L
t
i
=
sup
{
s
<
t
:
X
s
(
i
)
=
1
}
.
{\displaystyle L_{t}^{i}=\sup\{s<t:X_{s}(i)=1\}.}
Importantly, the spike probability of neuron
i
{\displaystyle i}
depends only on its spike input (filtered with a kernel
g
j
{\displaystyle g_{j}}
and weighted with a factor
W
j
→
i
{\displaystyle W_{j\to i}}
) and the timing of its most recent output spike (summarized by
t
−
L
t
i
{\displaystyle t-L_{t}^{i}}
).
== Didactic toy models of membrane voltage ==
The models in this category are highly simplified toy models that qualitatively describe the membrane voltage as a function of input. They are mainly used for didactic reasons in teaching but are not considered valid neuron models for large-scale simulations or data fitting.
=== FitzHugh–Nagumo ===
Sweeping simplifications to Hodgkin–Huxley were introduced by FitzHugh and Nagumo in 1961 and 1962. Seeking to describe "regenerative self-excitation" by a nonlinear positive-feedback membrane voltage and recovery by a linear negative-feedback gate voltage, they developed the model described by
r
c
l
d
V
d
t
=
V
−
V
3
/
3
−
w
+
I
e
x
t
τ
d
w
d
t
=
V
−
a
−
b
w
{\displaystyle {\begin{aligned}{rcl}{\dfrac {dV}{dt}}&=V-V^{3}/3-w+I_{\mathrm {ext} }\\\tau {\dfrac {dw}{dt}}&=V-a-bw\end{aligned}}}
where we again have a membrane-like voltage and input current with a slower general gate voltage w and experimentally-determined parameters a = -0.7, b = 0.8, τ = 1/0.08. Although not derivable from biology, the model allows for a simplified, immediately available dynamic, without being a trivial simplification. The experimental support is weak, but the model is useful as a didactic tool to introduce dynamics of spike generation through phase plane analysis. See Chapter 7 in the textbook Methods of Neuronal Modeling.
=== Morris–Lecar ===
In 1981, Morris and Lecar combined the Hodgkin–Huxley and FitzHugh–Nagumo models into a voltage-gated calcium channel model with a delayed-rectifier potassium channel represented by
C
d
V
d
t
=
−
I
i
o
n
(
V
,
w
)
+
I
d
w
d
t
=
φ
⋅
w
∞
−
w
τ
w
{\displaystyle {\begin{aligned}C{\frac {dV}{dt}}&=-I_{\mathrm {ion} }(V,w)+I\\{\frac {dw}{dt}}&=\varphi \cdot {\frac {w_{\infty }-w}{\tau _{w}}}\end{aligned}}}
where
I
i
o
n
(
V
,
w
)
=
g
¯
C
a
m
∞
⋅
(
V
−
V
C
a
)
+
g
¯
K
w
⋅
(
V
−
V
K
)
+
g
¯
L
⋅
(
V
−
V
L
)
{\displaystyle I_{\mathrm {ion} }(V,w)={\bar {g}}_{\mathrm {Ca} }m_{\infty }\cdot (V-V_{\mathrm {Ca} })+{\bar {g}}_{\mathrm {K} }w\cdot (V-V_{\mathrm {K} })+{\bar {g}}_{\mathrm {L} }\cdot (V-V_{\mathrm {L} })}
. The experimental support of the model is weak, but the model is useful as a didactic tool to introduce dynamics of spike generation through phase plane analysis. See Chapter 7 in the textbook Methods of Neuronal Modeling.
A two-dimensional neuron model very similar to the Morris-Lecar model can be derived step-by-step starting from the Hodgkin-Huxley model. See Chapter 4.2 in the textbook Neuronal Dynamics.
=== Hindmarsh–Rose ===
Building upon the FitzHugh–Nagumo model, Hindmarsh and Rose proposed in 1984 a model of neuronal activity described by three coupled first-order differential equations:
d
x
d
t
=
y
+
3
x
2
−
x
3
−
z
+
I
d
y
d
t
=
1
−
5
x
2
−
y
d
z
d
t
=
r
⋅
(
4
(
x
+
8
5
)
−
z
)
{\displaystyle {\begin{aligned}{\frac {dx}{dt}}&=y+3x^{2}-x^{3}-z+I\\{\frac {dy}{dt}}&=1-5x^{2}-y\\{\frac {dz}{dt}}&=r\cdot (4(x+{\tfrac {8}{5}})-z)\end{aligned}}}
with r2 = x2 + y2 + z2, and r ≈ 10−2 so that the z variable only changes very slowly. This extra mathematical complexity allows a great variety of dynamic behaviors for the membrane potential, described by the x variable of the model, which includes chaotic dynamics. This makes the Hindmarsh–Rose neuron model very useful, because it is still simple, allows a good qualitative description of the many different firing patterns of the action potential, in particular bursting, observed in experiments. Nevertheless, it remains a toy model and has not been fitted to experimental data. It is widely used as a reference model for bursting dynamics.
=== Theta model and quadratic integrate-and-fire ===
The theta model, or Ermentrout–Kopell canonical Type I model, is mathematically equivalent to the quadratic integrate-and-fire model which in turn is an approximation to the exponential integrate-and-fire model and the Hodgkin-Huxley model. It is called a canonical model because it is one of the generic models for constant input close to the bifurcation point, which means close to the transition from silent to repetitive firing.
The standard formulation of the theta model is
d
θ
(
t
)
d
t
=
(
I
−
I
0
)
[
1
+
cos
(
θ
)
]
+
[
1
−
cos
(
θ
)
]
{\displaystyle {\frac {d\theta (t)}{dt}}=(I-I_{0})[1+\cos(\theta )]+[1-\cos(\theta )]}
The equation for the quadratic integrate-and-fire model is (see Chapter 5.3 in the textbook Neuronal Dynamics )
τ
m
d
V
m
(
t
)
d
t
=
(
I
−
I
0
)
R
+
[
V
m
(
t
)
−
E
m
]
[
V
m
(
t
)
−
V
T
]
{\displaystyle \tau _{\mathrm {m} }{\frac {dV_{\mathrm {m} }(t)}{dt}}=(I-I_{0})R+[V_{\mathrm {m} }(t)-E_{\mathrm {m} }][V_{\mathrm {m} }(t)-V_{\mathrm {T} }]}
The equivalence of theta model and quadratic integrate-and-fire is for example reviewed in Chapter 4.1.2.2 of spiking neuron models.
For input
I
(
t
)
{\displaystyle I(t)}
that changes over time or is far away from the bifurcation point, it is preferable to work with the exponential integrate-and-fire model (if one wants to stay in the class of one-dimensional neuron models), because real neurons exhibit the nonlinearity of the exponential integrate-and-fire model.
== Sensory input-stimulus encoding neuron models ==
The models in this category were derived following experiments involving natural stimulation such as light, sound, touch, or odor. In these experiments, the spike pattern resulting from each stimulus presentation varies from trial to trial, but the averaged response from several trials often converges to a clear pattern. Consequently, the models in this category generate a probabilistic relationship between the input stimulus to spike occurrences. Importantly, the recorded neurons are often located several processing steps after the sensory neurons, so that these models summarize the effects of the sequence of processing steps in a compact form
=== The non-homogeneous Poisson process model (Siebert) ===
Siebert modeled the neuron spike firing pattern using a non-homogeneous Poisson process model, following experiments involving the auditory system. According to Siebert, the probability of a spiking event at the time interval
[
t
,
t
+
Δ
t
]
{\displaystyle [t,t+\Delta _{t}]}
is proportional to a non-negative function
g
[
s
(
t
)
]
{\displaystyle g[s(t)]}
, where
s
(
t
)
{\displaystyle s(t)}
is the raw stimulus.:
P
spike
(
t
∈
[
t
′
,
t
′
+
Δ
t
]
)
=
Δ
t
⋅
g
[
s
(
t
)
]
{\displaystyle P_{\text{spike}}(t\in [t',t'+\Delta _{t}])=\Delta _{t}\cdot g[s(t)]}
Siebert considered several functions as
g
[
s
(
t
)
]
{\displaystyle g[s(t)]}
, including
g
[
s
(
t
)
]
∝
s
2
(
t
)
{\displaystyle g[s(t)]\propto s^{2}(t)}
for low stimulus intensities.
The main advantage of Siebert's model is its simplicity. The shortcomings of the model is its inability to reflect properly the following phenomena:
The transient enhancement of the neuronal firing activity in response to a step stimulus.
The saturation of the firing rate.
The values of inter-spike-interval-histogram at short intervals values (close to zero).
These shortcomings are addressed by the age-dependent point process model and the two-state Markov Model.
=== Refractoriness and age-dependent point process model ===
Berry and Meister studied neuronal refractoriness using a stochastic model that predicts spikes as a product of two terms, a function f(s(t)) that depends on the time-dependent stimulus s(t) and one a recovery function
w
(
t
−
t
^
)
{\displaystyle w(t-{\hat {t}})}
that depends on the time since the last spike
ρ
(
t
)
=
f
(
s
(
t
)
)
w
(
t
−
t
^
)
{\displaystyle \rho (t)=f(s(t))w(t-{\hat {t}})}
The model is also called an inhomogeneous Markov interval (IMI) process. Similar models have been used for many years in auditory neuroscience. Since the model keeps memory of the last spike time it is non-Poisson and falls in the class of time-dependent renewal models. It is closely related to the model SRM0 with exponential escape rate. Importantly, it is possible to fit parameters of the age-dependent point process model so as to describe not just the PSTH response, but also the interspike-interval statistics.
=== Linear-nonlinear Poisson cascade model and GLM ===
The linear-nonlinear-Poisson cascade model is a cascade of a linear filtering process followed by a nonlinear spike generation step. In the case that output spikes feed back, via a linear filtering process, we arrive at a model that is known in the neurosciences as Generalized Linear Model (GLM). The GLM is mathematically equivalent to the spike response model SRM) with escape noise; but whereas in the SRM the internal variables are interpreted as the membrane potential and the firing threshold, in the GLM the internal variables are abstract quantities that summarizes the net effect of input (and recent output spikes) before spikes are generated in the final step.
=== The two-state Markov model (Nossenson & Messer) ===
The spiking neuron model by Nossenson & Messer produces the probability of the neuron firing a spike as a function of either an external or pharmacological stimulus. The model consists of a cascade of a receptor layer model and a spiking neuron model, as shown in Fig 4. The connection between the external stimulus to the spiking probability is made in two steps: First, a receptor cell model translates the raw external stimulus to neurotransmitter concentration, and then, a spiking neuron model connects neurotransmitter concentration to the firing rate (spiking probability). Thus, the spiking neuron model by itself depends on neurotransmitter concentration at the input stage.
An important feature of this model is the prediction for neurons firing rate pattern which captures, using a low number of free parameters, the characteristic edge emphasized response of neurons to a stimulus pulse, as shown in Fig. 5. The firing rate is identified both as a normalized probability for neural spike firing and as a quantity proportional to the current of neurotransmitters released by the cell. The expression for the firing rate takes the following form:
R
fire
(
t
)
=
P
spike
(
t
;
Δ
t
)
Δ
t
=
[
y
(
t
)
+
R
0
]
⋅
P
0
(
t
)
{\displaystyle R_{\text{fire}}(t)={\frac {P_{\text{spike}}(t;\Delta _{t})}{\Delta _{t}}}=[y(t)+R_{0}]\cdot P_{0}(t)}
where,
P0 is the probability of the neuron being "armed" and ready to fire. It is given by the following differential equation:
P
˙
0
=
−
[
y
(
t
)
+
R
0
+
R
1
]
⋅
P
0
(
t
)
+
R
1
{\displaystyle {\dot {P}}_{0}=-[y(t)+R_{0}+R_{1}]\cdot P_{0}(t)+R_{1}}
P0 could be generally calculated recursively using the Euler method, but in the case of a pulse of stimulus, it yields a simple closed-form expression.
y(t) is the input of the model and is interpreted as the neurotransmitter concentration on the cell surrounding (in most cases glutamate). For an external stimulus it can be estimated through the receptor layer model:
y
(
t
)
≃
g
gain
⋅
⟨
s
2
(
t
)
⟩
,
{\displaystyle y(t)\simeq g_{\text{gain}}\cdot \langle s^{2}(t)\rangle ,}
with
⟨
s
2
(
t
)
⟩
{\displaystyle \langle s^{2}(t)\rangle }
being a short temporal average of stimulus power (given in Watt or other energy per time unit).
R0 corresponds to the intrinsic spontaneous firing rate of the neuron.
R1 is the recovery rate of the neuron from the refractory state.
Other predictions by this model include:
1) The averaged evoked response potential (ERP) due to the population of many neurons in unfiltered measurements resembles the firing rate.
2) The voltage variance of activity due to multiple neuron activity resembles the firing rate (also known as Multi-Unit-Activity power or MUA).
3) The inter-spike-interval probability distribution takes the form a gamma-distribution like function.
== Pharmacological input stimulus neuron models ==
The models in this category produce predictions for experiments involving pharmacological stimulation.
=== Synaptic transmission (Koch & Segev) ===
According to the model by Koch and Segev, the response of a neuron to individual neurotransmitters can be modeled as an extension of the classical Hodgkin–Huxley model with both standard and nonstandard kinetic currents. Four neurotransmitters primarily influence the CNS. AMPA/kainate receptors are fast excitatory mediators while NMDA receptors mediate considerably slower currents. Fast inhibitory currents go through GABAA receptors, while GABAB receptors mediate by secondary G-protein-activated potassium channels. This range of mediation produces the following current dynamics:
I
A
M
P
A
(
t
,
V
)
=
g
¯
A
M
P
A
⋅
[
O
]
⋅
(
V
(
t
)
−
E
A
M
P
A
)
{\displaystyle I_{\mathrm {AMPA} }(t,V)={\bar {g}}_{\mathrm {AMPA} }\cdot [O]\cdot (V(t)-E_{\mathrm {AMPA} })}
I
N
M
D
A
(
t
,
V
)
=
g
¯
N
M
D
A
⋅
B
(
V
)
⋅
[
O
]
⋅
(
V
(
t
)
−
E
N
M
D
A
)
{\displaystyle I_{\mathrm {NMDA} }(t,V)={\bar {g}}_{\mathrm {NMDA} }\cdot B(V)\cdot [O]\cdot (V(t)-E_{\mathrm {NMDA} })}
I
G
A
B
A
A
(
t
,
V
)
=
g
¯
G
A
B
A
A
⋅
(
[
O
1
]
+
[
O
2
]
)
⋅
(
V
(
t
)
−
E
C
l
)
{\displaystyle I_{\mathrm {GABA_{A}} }(t,V)={\bar {g}}_{\mathrm {GABA_{A}} }\cdot ([O_{1}]+[O_{2}])\cdot (V(t)-E_{\mathrm {Cl} })}
I
G
A
B
A
B
(
t
,
V
)
=
g
¯
G
A
B
A
B
⋅
[
G
]
n
[
G
]
n
+
K
d
⋅
(
V
(
t
)
−
E
K
)
{\displaystyle I_{\mathrm {GABA_{B}} }(t,V)={\bar {g}}_{\mathrm {GABA_{B}} }\cdot {\tfrac {[G]^{n}}{[G]^{n}+K_{\mathrm {d} }}}\cdot (V(t)-E_{\mathrm {K} })}
where ḡ is the maximal conductance (around 1S) and E is the equilibrium potential of the given ion or transmitter (AMDA, NMDA, Cl, or K), while [O] describes the fraction of open receptors. For NMDA, there is a significant effect of magnesium block that depends sigmoidally on the concentration of intracellular magnesium by B(V). For GABAB, [G] is the concentration of the G-protein, and Kd describes the dissociation of G in binding to the potassium gates.
The dynamics of this more complicated model have been well-studied experimentally and produce important results in terms of very quick synaptic potentiation and depression, that is fast, short-term learning.
The stochastic model by Nossenson and Messer translates neurotransmitter concentration at the input stage to the probability of releasing neurotransmitter at the output stage. For a more detailed description of this model, see the Two state Markov model section above.
== HTM neuron model ==
The HTM neuron model was developed by Jeff Hawkins and researchers at Numenta and is based on a theory called Hierarchical Temporal Memory, originally described in the book On Intelligence. It is based on neuroscience and the physiology and interaction of pyramidal neurons in the neocortex of the human brain.
== Applications ==
Spiking Neuron Models are used in a variety of applications that need encoding into or decoding from neuronal spike trains in the context of neuroprosthesis and brain-computer interfaces such as retinal prosthesis: or artificial limb control and sensation. Applications are not part of this article; for more information on this topic please refer to the main article.
== Relation between artificial and biological neuron models ==
The most basic model of a neuron consists of an input with some synaptic weight vector and an activation function or transfer function inside the neuron determining output. This is the basic structure used for artificial neurons, which in a neural network often looks like
y
i
=
φ
(
∑
j
w
i
j
x
j
)
{\displaystyle y_{i}=\varphi \left(\sum _{j}w_{ij}x_{j}\right)}
where yi is the output of the i th neuron, xj is the jth input neuron signal, wij is the synaptic weight (or strength of connection) between the neurons i and j, and φ is the activation function. While this model has seen success in machine-learning applications, it is a poor model for real (biological) neurons, because it lacks time-dependence in input and output.
When an input is switched on at a time t and kept constant thereafter, biological neurons emit a spike train. Importantly, this spike train is not regular but exhibits a temporal structure characterized by adaptation, bursting, or initial bursting followed by regular spiking. Generalized integrate-and-fire models such as the Adaptive Exponential Integrate-and-Fire model, the spike response model, or the (linear) adaptive integrate-and-fire model can capture these neuronal firing patterns.
Moreover, neuronal input in the brain is time-dependent. Time-dependent input is transformed by complex linear and nonlinear filters into a spike train in the output. Again, the spike response model or the adaptive integrate-and-fire model enables to prediction of the spike train in the output for arbitrary time-dependent input, whereas an artificial neuron or a simple leaky integrate-and-fire does not.
If we take the Hodkgin-Huxley model as a starting point, generalized integrate-and-fire models can be derived systematically in a step-by-step simplification procedure. This has been shown explicitly for the exponential integrate-and-fire model and the spike response model.
In the case of modeling a biological neuron, physical analogs are used in place of abstractions such as "weight" and "transfer function". A neuron is filled and surrounded with water-containing ions, which carry electric charge. The neuron is bound by an insulating cell membrane and can maintain a concentration of charged ions on either side that determines a capacitance Cm. The firing of a neuron involves the movement of ions into the cell, that occurs when neurotransmitters cause ion channels on the cell membrane to open. We describe this by a physical time-dependent current I(t). With this comes a change in voltage, or the electrical potential energy difference between the cell and its surroundings, which is observed to sometimes result in a voltage spike called an action potential which travels the length of the cell and triggers the release of further neurotransmitters. The voltage, then, is the quantity of interest and is given by Vm(t).
If the input current is constant, most neurons emit after some time of adaptation or initial bursting a regular spike train. The frequency of regular firing in response to a constant current I is described by the frequency-current relation, which corresponds to the transfer function
φ
{\displaystyle \varphi }
of artificial neural networks. Similarly, for all spiking neuron models, the transfer function
φ
{\displaystyle \varphi }
can be calculated numerically (or analytically).
== Cable theory and compartmental models ==
All of the above deterministic models are point-neuron models because they do not consider the spatial structure of a neuron. However, the dendrite contributes to transforming input into output. Point neuron models are valid description in three cases. (i) If input current is directly injected into the soma. (ii) If synaptic input arrives predominantly at or close to the soma (closeness is defined by a length scale
λ
{\displaystyle \lambda }
introduced below. (iii) If synapse arrives anywhere on the dendrite, but the dendrite is completely linear. In the last case, the cable acts as a linear filter; these linear filter properties can be included in the formulation of generalized integrate-and-fire models such as the spike response model.
The filter properties can be calculated from a cable equation.
Let us consider a cell membrane in the form of a cylindrical cable. The position on the cable is denoted by x and the voltage across the cell membrane by V. The cable is characterized by a longitudinal resistance
r
l
{\displaystyle r_{l}}
per unit length and a membrane resistance
r
m
{\displaystyle r_{m}}
. If everything is linear, the voltage changes as a function of timeWe introduce a length scale
λ
2
=
r
m
/
r
l
{\displaystyle \lambda ^{2}={r_{m}}/{r_{l}}}
on the left side and time constant
τ
=
c
m
r
m
{\displaystyle \tau =c_{m}r_{m}}
on the right side. The cable equation can now be written in its perhaps best-known form:
The above cable equation is valid for a single cylindrical cable.
Linear cable theory describes the dendritic arbor of a neuron as a cylindrical structure undergoing a regular pattern of bifurcation, like branches in a tree. For a single cylinder or an entire tree, the static input conductance at the base (where the tree meets the cell body or any such boundary) is defined as
G
i
n
=
G
∞
tanh
(
L
)
+
G
L
1
+
(
G
L
/
G
∞
)
tanh
(
L
)
{\displaystyle G_{in}={\frac {G_{\infty }\tanh(L)+G_{L}}{1+(G_{L}/G_{\infty })\tanh(L)}}}
,
where L is the electrotonic length of the cylinder, which depends on its length, diameter, and resistance. A simple recursive algorithm scales linearly with the number of branches and can be used to calculate the effective conductance of the tree. This is given by
G
D
=
G
m
A
D
tanh
(
L
D
)
/
L
D
{\displaystyle \,\!G_{D}=G_{m}A_{D}\tanh(L_{D})/L_{D}}
where AD = πld is the total surface area of the tree of total length l, and LD is its total electrotonic length. For an entire neuron in which the cell body conductance is GS and the membrane conductance per unit area is Gmd = Gm / A, we find the total neuron conductance GN for n dendrite trees by adding up all tree and soma conductances, given by
G
N
=
G
S
+
∑
j
=
1
n
A
D
j
F
d
g
a
j
,
{\displaystyle G_{N}=G_{S}+\sum _{j=1}^{n}A_{D_{j}}F_{dga_{j}},}
where we can find the general correction factor Fdga experimentally by noting GD = GmdADFdga.
The linear cable model makes several simplifications to give closed analytic results, namely that the dendritic arbor must branch in diminishing pairs in a fixed pattern and that dendrites are linear. A compartmental model allows for any desired tree topology with arbitrary branches and lengths, as well as arbitrary nonlinearities. It is essentially a discretized computational implementation of nonlinear dendrites.
Each piece, or compartment, of a dendrite, is modeled by a straight cylinder of arbitrary length l and diameter d which connects with fixed resistance to any number of branching cylinders. We define the conductance ratio of the ith cylinder as Bi = Gi / G∞, where
G
∞
=
π
d
3
/
2
2
R
i
R
m
{\displaystyle G_{\infty }={\tfrac {\pi d^{3/2}}{2{\sqrt {R_{i}R_{m}}}}}}
and Ri is the resistance between the current compartment and the next. We obtain a series of equations for conductance ratios in and out of a compartment by making corrections to the normal dynamic Bout,i = Bin,i+1, as
B
o
u
t
,
i
=
B
i
n
,
i
+
1
(
d
i
+
1
/
d
i
)
3
/
2
R
m
,
i
+
1
/
R
m
,
i
{\displaystyle B_{\mathrm {out} ,i}={\frac {B_{\mathrm {in} ,i+1}(d_{i+1}/d_{i})^{3/2}}{\sqrt {R_{\mathrm {m} ,i+1}/R_{\mathrm {m} ,i}}}}}
B
i
n
,
i
=
B
o
u
t
,
i
+
tanh
X
i
1
+
B
o
u
t
,
i
tanh
X
i
{\displaystyle B_{\mathrm {in} ,i}={\frac {B_{\mathrm {out} ,i}+\tanh X_{i}}{1+B_{\mathrm {out} ,i}\tanh X_{i}}}}
B
o
u
t
,
p
a
r
=
B
i
n
,
d
a
u
1
(
d
d
a
u
1
/
d
p
a
r
)
3
/
2
R
m
,
d
a
u
1
/
R
m
,
p
a
r
+
B
i
n
,
d
a
u
2
(
d
d
a
u
2
/
d
p
a
r
)
3
/
2
R
m
,
d
a
u
2
/
R
m
,
p
a
r
+
…
{\displaystyle B_{\mathrm {out,par} }={\frac {B_{\mathrm {in,dau1} }(d_{\mathrm {dau1} }/d_{\mathrm {par} })^{3/2}}{\sqrt {R_{\mathrm {m,dau1} }/R_{\mathrm {m,par} }}}}+{\frac {B_{\mathrm {in,dau2} }(d_{\mathrm {dau2} }/d_{\mathrm {par} })^{3/2}}{\sqrt {R_{\mathrm {m,dau2} }/R_{\mathrm {m,par} }}}}+\ldots }
where the last equation deals with parents and daughters at branches, and
X
i
=
l
i
4
R
i
d
i
R
m
{\displaystyle X_{i}={\tfrac {l_{i}{\sqrt {4R_{i}}}}{\sqrt {d_{i}R_{m}}}}}
. We can iterate these equations through the tree until we get the point where the dendrites connect to the cell body (soma), where the conductance ratio is Bin,stem. Then our total neuron conductance for static input is given by
G
N
=
A
s
o
m
a
R
m
,
s
o
m
a
+
∑
j
B
i
n
,
s
t
e
m
,
j
G
∞
,
j
.
{\displaystyle G_{N}={\frac {A_{\mathrm {soma} }}{R_{\mathrm {m,soma} }}}+\sum _{j}B_{\mathrm {in,stem} ,j}G_{\infty ,j}.}
Importantly, static input is a very special case. In biology, inputs are time-dependent. Moreover, dendrites are not always linear.
Compartmental models enable to include nonlinearities via ion channels positioned at arbitrary locations along the dendrites. For static inputs, it is sometimes possible to reduce the number of compartments (increase the computational speed) and yet retain the salient electrical characteristics.
== Conjectures regarding the role of the neuron in the wider context of the brain principle of operation ==
=== The neurotransmitter-based energy detection scheme ===
The neurotransmitter-based energy detection scheme suggests that the neural tissue chemically executes a Radar-like detection procedure.
As shown in Fig. 6, the key idea of the conjecture is to account for neurotransmitter concentration, neurotransmitter generation, and neurotransmitter removal rates as the important quantities in executing the detection task, while referring to the measured electrical potentials as a side effect that only in certain conditions coincide with the functional purpose of each step. The detection scheme is similar to a radar-like "energy detection" because it includes signal squaring, temporal summation, and a threshold switch mechanism, just like the energy detector, but it also includes a unit that emphasizes stimulus edges and a variable memory length (variable memory). According to this conjecture, the physiological equivalent of the energy test statistics is neurotransmitter concentration, and the firing rate corresponds to neurotransmitter current. The advantage of this interpretation is that it leads to a unit-consistent explanation which allows for bridge between electrophysiological measurements, biochemical measurements, and psychophysical results.
The evidence reviewed in suggests the following association between functionality to histological classification:
Stimulus squaring is likely to be performed by receptor cells.
Stimulus edge emphasizing and signal transduction is performed by neurons.
Temporal accumulation of neurotransmitters is performed by glial cells. Short-term neurotransmitter accumulation is likely to occur also in some types of neurons.
Logical switching is executed by glial cells, and it results from exceeding a threshold level of neurotransmitter concentration. This threshold crossing is also accompanied by a change in neurotransmitter leak rate.
Physical all-or-non movement switching is due to muscle cells and results from exceeding a certain neurotransmitter concentration threshold on muscle surroundings.
Note that although the electrophysiological signals in Fig.6 are often similar to the functional signal (signal power/neurotransmitter concentration / muscle force), there are some stages in which the electrical observation differs from the functional purpose of the corresponding step. In particular, Nossenson et al. suggested that glia threshold crossing has a completely different functional operation compared to the radiated electrophysiological signal and that the latter might only be a side effect of glia break.
== General comments regarding the modern perspective of scientific and engineering models ==
The models above are still idealizations. Corrections must be made for the increased membrane surface area given by numerous dendritic spines, temperatures significantly hotter than room-temperature experimental data, and nonuniformity in the cell's internal structure. Certain observed effects do not fit into some of these models. For instance, the temperature cycling (with minimal net temperature increase) of the cell membrane during action potential propagation is not compatible with models that rely on modeling the membrane as a resistance that must dissipate energy when current flows through it. The transient thickening of the cell membrane during action potential propagation is also not predicted by these models, nor is the changing capacitance and voltage spike that results from this thickening incorporated into these models. The action of some anesthetics such as inert gases is problematic for these models as well. New models, such as the soliton model attempt to explain these phenomena, but are less developed than older models and have yet to be widely applied.
Modern views regarding the role of the scientific model suggest that "All models are wrong but some are useful" (Box and Draper, 1987, Gribbin, 2009; Paninski et al., 2009).
Recent conjecture suggests that each neuron might function as a collection of independent threshold units. It is suggested that a neuron could be anisotropically activated following the origin of its arriving signals to the membrane, via its dendritic trees. The spike waveform was also proposed to be dependent on the origin of the stimulus.
== External links ==
Neuronal Dynamics: from single neurons to networks and models of cognition (W. Gerstner, W. Kistler, R. Naud, L. Paninski, Cambridge University Press, 2014). In particular, Chapters 6 - 10, html online version.
Spiking Neuron Models (W. Gerstner and W. Kistler, Cambridge University Press, 2002)
== See also ==
Binding neuron
Bayesian approaches to brain function
Brain-computer interfaces
Free energy principle
Models of neural computation
Neural coding
Neural oscillation
Quantitative models of the action potential
Spiking neural network
== References == | Wikipedia/Integrate_and_fire |
Computational neuroscience (also known as theoretical neuroscience or mathematical neuroscience) is a branch of neuroscience which employs mathematics, computer science, theoretical analysis and abstractions of the brain to understand the principles that govern the development, structure, physiology and cognitive abilities of the nervous system.
Computational neuroscience employs computational simulations to validate and solve mathematical models, and so can be seen as a sub-field of theoretical neuroscience; however, the two fields are often synonymous. The term mathematical neuroscience is also used sometimes, to stress the quantitative nature of the field.
Computational neuroscience focuses on the description of biologically plausible neurons (and neural systems) and their physiology and dynamics, and it is therefore not directly concerned with biologically unrealistic models used in connectionism, control theory, cybernetics, quantitative psychology, machine learning, artificial neural networks, artificial intelligence and computational learning theory;
although mutual inspiration exists and sometimes there is no strict limit between fields, with model abstraction in computational neuroscience depending on research scope and the granularity at which biological entities are analyzed.
Models in theoretical neuroscience are aimed at capturing the essential features of the biological system at multiple spatial-temporal scales, from membrane currents, and chemical coupling via network oscillations, columnar and topographic architecture, nuclei, all the way up to psychological faculties like memory, learning and behavior. These computational models frame hypotheses that can be directly tested by biological or psychological experiments.
== History ==
The term 'computational neuroscience' was introduced by Eric L. Schwartz, who organized a conference, held in 1985 in Carmel, California, at the request of the Systems Development Foundation to provide a summary of the current status of a field which until that point was referred to by a variety of names, such as neural modeling, brain theory and neural networks. The proceedings of this definitional meeting were published in 1990 as the book Computational Neuroscience. The first of the annual open international meetings focused on Computational Neuroscience was organized by James M. Bower and John Miller in San Francisco, California in 1989. The first graduate educational program in computational neuroscience was organized as the Computational and Neural Systems Ph.D. program at the California Institute of Technology in 1985.
The early historical roots of the field can be traced to the work of people including Louis Lapicque, Hodgkin & Huxley, Hubel and Wiesel, and David Marr. Lapicque introduced the integrate and fire model of the neuron in a seminal article published in 1907, a model still popular for artificial neural networks studies because of its simplicity (see a recent review).
About 40 years later, Hodgkin and Huxley developed the voltage clamp and created the first biophysical model of the action potential. Hubel and Wiesel discovered that neurons in the primary visual cortex, the first cortical area to process information coming from the retina, have oriented receptive fields and are organized in columns. David Marr's work focused on the interactions between neurons, suggesting computational approaches to the study of how functional groups of neurons within the hippocampus and neocortex interact, store, process, and transmit information. Computational modeling of biophysically realistic neurons and dendrites began with the work of Wilfrid Rall, with the first multicompartmental model using cable theory.
== Major topics ==
Research in computational neuroscience can be roughly categorized into several lines of inquiry. Most computational neuroscientists collaborate closely with experimentalists in analyzing novel data and synthesizing new models of biological phenomena.
=== Single-neuron modeling ===
Even a single neuron has complex biophysical characteristics and can perform computations (e.g.). Hodgkin and Huxley's original model only employed two voltage-sensitive currents (Voltage sensitive ion channels are glycoprotein molecules which extend through the lipid bilayer, allowing ions to traverse under certain conditions through the axolemma), the fast-acting sodium and the inward-rectifying potassium. Though successful in predicting the timing and qualitative features of the action potential, it nevertheless failed to predict a number of important features such as adaptation and shunting. Scientists now believe that there are a wide variety of voltage-sensitive currents, and the implications of the differing dynamics, modulations, and sensitivity of these currents is an important topic of computational neuroscience.
The computational functions of complex dendrites are also under intense investigation. There is a large body of literature regarding how different currents interact with geometric properties of neurons.
There are many software packages, such as GENESIS and NEURON, that allow rapid and systematic in silico modeling of realistic neurons. Blue Brain, a project founded by Henry Markram from the École Polytechnique Fédérale de Lausanne, aims to construct a biophysically detailed simulation of a cortical column on the Blue Gene supercomputer.
Modeling the richness of biophysical properties on the single-neuron scale can supply mechanisms that serve as the building blocks for network dynamics. However, detailed neuron descriptions are computationally expensive and this computing cost can limit the pursuit of realistic network investigations, where many neurons need to be simulated. As a result, researchers that study large neural circuits typically represent each neuron and synapse with an artificially simple model, ignoring much of the biological detail. Hence there is a drive to produce simplified neuron models that can retain significant biological fidelity at a low computational overhead. Algorithms have been developed to produce faithful, faster running, simplified surrogate neuron models from computationally expensive, detailed neuron models.
=== Modeling Neuron-glia interactions ===
Glial cells participate significantly in the regulation of neuronal activity at both the cellular and the network level. Modeling this interaction allows to clarify the potassium cycle, so important for maintaining homeostasis and to prevent epileptic seizures. Modeling reveals the role of glial protrusions that can penetrate in some cases the synaptic cleft to interfere with the synaptic transmission and thus control synaptic communication.
=== Development, axonal patterning, and guidance ===
Computational neuroscience aims to address a wide array of questions, including: How do axons and dendrites form during development? How do axons know where to target and how to reach these targets? How do neurons migrate to the proper position in the central and peripheral systems? How do synapses form? We know from molecular biology that distinct parts of the nervous system release distinct chemical cues, from growth factors to hormones that modulate and influence the growth and development of functional connections between neurons.
Theoretical investigations into the formation and patterning of synaptic connection and morphology are still nascent. One hypothesis that has recently garnered some attention is the minimal wiring hypothesis, which postulates that the formation of axons and dendrites effectively minimizes resource allocation while maintaining maximal information storage.
=== Sensory processing ===
Early models on sensory processing understood within a theoretical framework are credited to Horace Barlow. Somewhat similar to the minimal wiring hypothesis described in the preceding section, Barlow understood the processing of the early sensory systems to be a form of efficient coding, where the neurons encoded information which minimized the number of spikes. Experimental and computational work have since supported this hypothesis in one form or another. For the example of visual processing, efficient coding is manifested in the
forms of efficient spatial coding, color coding, temporal/motion coding, stereo coding, and combinations of them.
Further along the visual pathway, even the efficiently coded visual information is too much for the capacity of the information bottleneck, the visual attentional bottleneck. A subsequent theory, V1 Saliency Hypothesis (V1SH), has been developed on exogenous attentional selection of a fraction of visual input for further processing, guided by a bottom-up saliency map in the primary visual cortex.
Current research in sensory processing is divided among a biophysical modeling of different subsystems and a more theoretical modeling of perception. Current models of perception have suggested that the brain performs some form of Bayesian inference and integration of different sensory information in generating our perception of the physical world.
=== Motor control ===
Many models of the way the brain controls movement have been developed. This includes models of processing in the brain such as the cerebellum's role for error correction, skill learning in motor cortex and the basal ganglia, or the control of the vestibulo ocular reflex. This also includes many normative models, such as those of the Bayesian or optimal control flavor which are built on the idea that the brain efficiently solves its problems.
=== Memory and synaptic plasticity ===
Earlier models of memory are primarily based on the postulates of Hebbian learning. Biologically relevant models such as Hopfield net have been developed to address the properties of associative (also known as "content-addressable") style of memory that occur in biological systems. These attempts are primarily focusing on the formation of medium- and long-term memory, localizing in the hippocampus.
One of the major problems in neurophysiological memory is how it is maintained and changed through multiple time scales. Unstable synapses are easy to train but also prone to stochastic disruption. Stable synapses forget less easily, but they are also harder to consolidate. It is likely that computational tools will contribute greatly to our understanding of how synapses function and change in relation to external stimulus in the coming decades.
=== Behaviors of networks ===
Biological neurons are connected to each other in a complex, recurrent fashion. These connections are, unlike most artificial neural networks, sparse and usually specific. It is not known how information is transmitted through such sparsely connected networks, although specific areas of the brain, such as the visual cortex, are understood in some detail. It is also unknown what the computational functions of these specific connectivity patterns are, if any.
The interactions of neurons in a small network can be often reduced to simple models such as the Ising model. The statistical mechanics of such simple systems are well-characterized theoretically. Some recent evidence suggests that dynamics of arbitrary neuronal networks can be reduced to pairwise interactions. It is not known, however, whether such descriptive dynamics impart any important computational function. With the emergence of two-photon microscopy and calcium imaging, we now have powerful experimental methods with which to test the new theories regarding neuronal networks.
In some cases the complex interactions between inhibitory and excitatory neurons can be simplified using mean-field theory, which gives rise to the population model of neural networks. While many neurotheorists prefer such models with reduced complexity, others argue that uncovering structural-functional relations depends on including as much neuronal and network structure as possible. Models of this type are typically built in large simulation platforms like GENESIS or NEURON. There have been some attempts to provide unified methods that bridge and integrate these levels of complexity.
=== Visual attention, identification, and categorization ===
Visual attention can be described as a set of mechanisms that limit some processing to a subset of incoming stimuli. Attentional mechanisms shape what we see and what we can act upon. They allow for concurrent selection of some (preferably, relevant) information and inhibition of other information. In order to have a more concrete specification of the mechanism underlying visual attention and the binding of features, a number of computational models have been proposed aiming to explain psychophysical findings. In general, all models postulate the existence of a saliency or priority map for registering the potentially interesting areas of the retinal input, and a gating mechanism for reducing the amount of incoming visual information, so that the limited computational resources of the brain can handle it.
An example theory that is being extensively tested behaviorally and physiologically is the V1 Saliency Hypothesis that a bottom-up saliency map is created in the primary visual cortex to guide attention exogenously. Computational neuroscience provides a mathematical framework for studying the mechanisms involved in brain function and allows complete simulation and prediction of neuropsychological syndromes.
=== Cognition, discrimination, and learning ===
Computational modeling of higher cognitive functions has only recently begun. Experimental data comes primarily from single-unit recording in primates. The frontal lobe and parietal lobe function as integrators of information from multiple sensory modalities. There are some tentative ideas regarding how simple mutually inhibitory functional circuits in these areas may carry out biologically relevant computation.
The brain seems to be able to discriminate and adapt particularly well in certain contexts. For instance, human beings seem to have an enormous capacity for memorizing and recognizing faces. One of the key goals of computational neuroscience is to dissect how biological systems carry out these complex computations efficiently and potentially replicate these processes in building intelligent machines.
The brain's large-scale organizational principles are illuminated by many fields, including biology, psychology, and clinical practice. Integrative neuroscience attempts to consolidate these observations through unified descriptive models and databases of behavioral measures and recordings. These are the bases for some quantitative modeling of large-scale brain activity.
The Computational Representational Understanding of Mind (CRUM) is another attempt at modeling human cognition through simulated processes like acquired rule-based systems in decision making and the manipulation of visual representations in decision making.
=== Consciousness ===
One of the ultimate goals of psychology/neuroscience is to be able to explain the everyday experience of conscious life. Francis Crick, Giulio Tononi and Christof Koch made some attempts to formulate consistent frameworks for future work in neural correlates of consciousness (NCC), though much of the work in this field remains speculative.
=== Computational clinical neuroscience ===
Computational clinical neuroscience is a field that brings together experts in neuroscience, neurology, psychiatry, decision sciences and computational modeling to quantitatively define and investigate problems in neurological and psychiatric diseases, and to train scientists and clinicians that wish to apply these models to diagnosis and treatment.
=== Predictive computational neuroscience ===
Predictive computational neuroscience is a recent field that combines signal processing, neuroscience, clinical data and machine learning to predict the brain during coma or anesthesia. For example, it is possible to anticipate deep brain states using the EEG signal. These states can be used to anticipate hypnotic concentration to administrate to the patient.
=== Computational Psychiatry ===
Computational psychiatry is a new emerging field that brings together experts in machine learning, neuroscience, neurology, psychiatry, psychology to provide an understanding of psychiatric disorders.
== Technology ==
=== Neuromorphic computing ===
A neuromorphic computer/chip is any device that uses physical artificial neurons (made from silicon) to do computations (See: neuromorphic computing, physical neural network). One of the advantages of using a physical model computer such as this is that it takes the computational load of the processor (in the sense that the structural and some of the functional elements don't have to be programmed since they are in hardware). In recent times, neuromorphic technology has been used to build supercomputers which are used in international neuroscience collaborations. Examples include the Human Brain Project SpiNNaker supercomputer and the BrainScaleS computer.
== See also ==
== References ==
== Bibliography ==
Chklovskii DB (2004). "Synaptic connectivity and neuronal morphology: two sides of the same coin". Neuron. 43 (5): 609–17. doi:10.1016/j.neuron.2004.08.012. PMID 15339643. S2CID 16217065.
Sejnowski, Terrence J.; Churchland, Patricia Smith (1992). The computational brain. Cambridge, Mass: MIT Press. ISBN 978-0-262-03188-2.
Gerstner, W.; Kistler, W.; Naud, R.; Paninski, L. (2014). Neuronal Dynamics. Cambridge, UK: Cambridge University Press. ISBN 9781107447615.
Dayan P.; Abbott, L. F. (2001). Theoretical neuroscience: computational and mathematical modeling of neural systems. Cambridge, Mass: MIT Press. ISBN 978-0-262-04199-7.
Eliasmith, Chris; Anderson, Charles H. (2003). Neural engineering: Representation, computation, and dynamics in neurobiological systems. Cambridge, Mass: MIT Press. ISBN 978-0-262-05071-5.
Hodgkin AL, Huxley AF (28 August 1952). "A quantitative description of membrane current and its application to conduction and excitation in nerve". J. Physiol. 117 (4): 500–44. doi:10.1113/jphysiol.1952.sp004764. PMC 1392413. PMID 12991237.
William Bialek; Rieke, Fred; David Warland; Rob de Ruyter van Steveninck (1999). Spikes: exploring the neural code. Cambridge, Mass: MIT. ISBN 978-0-262-68108-7.
Schutter, Erik de (2001). Computational neuroscience: realistic modeling for experimentalists. Boca Raton: CRC. ISBN 978-0-8493-2068-2.
Sejnowski, Terrence J.; Hemmen, J. L. van (2006). 23 problems in systems neuroscience. Oxford [Oxfordshire]: Oxford University Press. ISBN 978-0-19-514822-0.
Michael A. Arbib; Shun-ichi Amari; Prudence H. Arbib (2002). The Handbook of Brain Theory and Neural Networks. Cambridge, Massachusetts: The MIT Press. ISBN 978-0-262-01197-6.
Zhaoping, Li (2014). Understanding vision: theory, models, and data. Oxford, UK: Oxford University Press. ISBN 978-0199564668.
== See also ==
=== Software ===
BRIAN, a Python based simulator
Budapest Reference Connectome, web based 3D visualization tool to browse connections in the human brain
Emergent, neural simulation software.
GENESIS, a general neural simulation system.
NEST is a simulator for spiking neural network models that focuses on the dynamics, size and structure of neural systems rather than on the exact morphology of individual neurons.
== External links ==
=== Journals ===
Journal of Mathematical Neuroscience
Journal of Computational Neuroscience
Neural Computation
Cognitive Neurodynamics
Frontiers in Computational Neuroscience
PLoS Computational Biology
Frontiers in Neuroinformatics
=== Conferences ===
Computational and Systems Neuroscience (COSYNE) – a computational neuroscience meeting with a systems neuroscience focus.
Annual Computational Neuroscience Meeting (CNS) – a yearly computational neuroscience meeting.
Neural Information Processing Systems (NIPS)– a leading annual conference covering mostly machine learning.
Cognitive Computational Neuroscience (CCN) – a computational neuroscience meeting focusing on computational models capable of cognitive tasks.
International Conference on Cognitive Neurodynamics (ICCN) – a yearly conference.
UK Mathematical Neurosciences Meeting– a yearly conference, focused on mathematical aspects.
Bernstein Conference on Computational Neuroscience (BCCN)– a yearly computational neuroscience conference ].
AREADNE Conferences– a biennial meeting that includes theoretical and experimental results.
=== Websites ===
Encyclopedia of Computational Neuroscience, part of Scholarpedia, an online expert curated encyclopedia on computational neuroscience and dynamical systems | Wikipedia/Computational_clinical_neuroscience |
In computational neuroscience, the Wilson–Cowan model describes the dynamics of interactions between populations of very simple excitatory and inhibitory model neurons. It was developed by Hugh R. Wilson and Jack D. Cowan and extensions of the model have been widely used in modeling neuronal populations. The model is important historically because it uses phase plane methods and numerical solutions to describe the responses of neuronal populations to stimuli. Because the model neurons are simple, only elementary limit cycle behavior, i.e. neural oscillations, and stimulus-dependent evoked responses are predicted. The key findings include the existence of multiple stable states, and hysteresis, in the population response.
== Mathematical description ==
The Wilson–Cowan model considers a homogeneous population of interconnected neurons of excitatory and inhibitory subtypes. All cells receive the same number of excitatory and inhibitory afferents, that is, all cells receive the same average excitation, x(t). The target is to analyze the evolution in time of number of excitatory and inhibitory cells firing at time t,
E
(
t
)
{\displaystyle E(t)}
and
I
(
t
)
{\displaystyle I(t)}
respectively.
The equations that describes this evolution are the Wilson-Cowan model:
E
(
t
+
τ
)
=
[
1
−
∫
t
−
r
t
E
(
t
′
)
d
t
′
]
S
e
(
∫
−
∞
t
α
(
t
−
t
′
)
[
c
1
E
(
t
′
)
−
c
2
I
(
t
′
)
+
P
(
t
′
)
]
d
t
′
)
{\displaystyle E(t+\tau )=\left[1-\int _{t-r}^{t}E(t')dt'\right]\;S_{e}\left(\int _{-\infty }^{t}\alpha (t-t')[c_{1}E(t')-c_{2}I(t')+P(t')]dt'\right)}
I
(
t
+
τ
)
=
[
1
−
∫
t
−
r
t
I
(
t
′
)
d
t
′
]
S
i
(
∫
−
∞
t
α
(
t
−
t
′
)
[
c
3
E
(
t
′
)
−
c
4
I
(
t
′
)
+
Q
(
t
′
)
]
d
t
′
)
{\displaystyle I(t+\tau )=\left[1-\int _{t-r}^{t}I(t')dt'\right]\;S_{i}\left(\int _{-\infty }^{t}\alpha (t-t')[c_{3}E(t')-c_{4}I(t')+Q(t')]dt'\right)}
where:
S
e
{
}
{\displaystyle S_{e}\{\}}
and
S
i
{
}
{\displaystyle S_{i}\{\}}
are functions of sigmoid form that depends on the distribution of the trigger thresholds (see below)
α
(
t
)
{\displaystyle \alpha (t)}
is the stimulus decay function
c
1
{\displaystyle c_{1}}
and
c
2
{\displaystyle c_{2}}
are respectively the connectivity coefficient giving the average number of excitatory and inhibitory synapses per excitatory cell;
c
3
{\displaystyle c_{3}}
and
c
4
{\displaystyle c_{4}}
its counterparts for inhibitory cells
P
(
t
)
{\displaystyle P(t)}
and
Q
(
t
)
{\displaystyle Q(t)}
are the external input to the excitatory/inhibitory populations.
If
θ
{\displaystyle \theta }
denotes a cell's threshold potential and
D
(
θ
)
{\displaystyle D(\theta )}
is the distribution of thresholds in all cells, then the expected proportion of neurons receiving an excitation at or above threshold level per unit time is:
S
(
x
)
=
∫
0
x
D
(
θ
)
d
θ
{\displaystyle S(x)=\int _{0}^{x}D(\theta )d\theta }
,
that is a function of sigmoid form if
D
(
)
{\displaystyle D()}
is unimodal.
If, instead of all cells receiving same excitatory inputs and different threshold, we consider that all cells have same threshold but different number of afferent synapses per cell, being
C
(
w
)
{\displaystyle C(w)}
the distribution of the number of afferent synapses, a variant of function
S
(
)
{\displaystyle S()}
must be used:
S
(
x
)
=
∫
θ
x
∞
C
(
w
)
d
w
{\displaystyle S(x)=\int _{\frac {\theta }{x}}^{\infty }C(w)dw}
=== Derivation of the model ===
If we denote by
τ
{\displaystyle \tau }
the refractory period after a trigger, the proportion of cells in refractory period is
∫
t
−
r
t
E
(
t
′
)
d
t
′
{\displaystyle \int _{t-r}^{t}E(t')dt'}
and the proportion of sensitive (able to trigger) cells is
1
−
∫
t
−
r
t
E
(
t
′
)
d
t
′
{\displaystyle 1-\int _{t-r}^{t}E(t')dt'}
.
The average excitation level of an excitatory cell at time
t
{\displaystyle t}
is:
x
(
t
)
=
∫
−
∞
t
α
(
t
−
t
′
)
[
c
1
E
(
t
′
)
−
c
2
I
(
t
′
)
+
P
(
t
′
)
]
d
t
′
{\displaystyle x(t)=\int _{-\infty }^{t}\alpha (t-t')[c_{1}E(t')-c_{2}I(t')+P(t')]dt'}
Thus, the number of cells that triggers at some time
E
(
t
+
τ
)
{\displaystyle E(t+\tau )}
is the number of cells not in refractory interval,
1
−
∫
t
−
r
t
E
(
t
′
)
d
t
′
{\displaystyle 1-\int _{t-r}^{t}E(t')dt'}
AND that have reached the excitatory level,
S
e
(
x
(
t
)
)
{\displaystyle S_{e}(x(t))}
, obtaining in this way the product at right side of the first equation of the model (with the assumption of uncorrelated terms). Same rationale can be done for inhibitory cells, obtaining second equation.
=== Simplification of the model assuming time coarse graining ===
When time coarse-grained modeling is assumed the model simplifies, being the new equations of the model:
τ
d
E
¯
d
t
=
−
E
¯
+
(
1
−
r
E
¯
)
S
e
[
k
c
1
E
¯
(
t
)
−
k
c
2
I
¯
(
t
)
+
k
P
(
t
)
]
{\displaystyle \tau {\frac {d{\bar {E}}}{dt}}=-{\bar {E}}+(1-r{\bar {E}})S_{e}[kc_{1}{\bar {E}}(t)-kc_{2}{\bar {I}}(t)+kP(t)]}
τ
′
d
I
¯
d
t
=
−
I
¯
+
(
1
−
r
′
I
¯
)
S
i
[
k
′
c
3
E
¯
(
t
)
−
k
′
c
4
I
¯
(
t
)
+
k
′
Q
(
t
)
]
{\displaystyle \tau '{\frac {d{\bar {I}}}{dt}}=-{\bar {I}}+(1-r'{\bar {I}})S_{i}[k'c_{3}{\bar {E}}(t)-k'c_{4}{\bar {I}}(t)+k'Q(t)]}
where bar terms are the time coarse-grained versions of original ones.
== Application to epilepsy ==
The determination of three concepts is fundamental to an understanding of hypersynchronization of neurophysiological activity at the global (system) level:
The mechanism by which normal (baseline) neurophysiological activity evolves into hypersynchronization of large regions of the brain during epileptic seizures
The key factors that govern the rate of expansion of hypersynchronized regions
The electrophysiological activity pattern dynamics on a large-scale
A canonical analysis of these issues, developed in 2008 by Shusterman and Troy using the Wilson–Cowan model, predicts qualitative and quantitative features of epileptiform activity. In particular, it accurately predicts the propagation speed of epileptic seizures (which is approximately 4–7 times slower than normal brain wave activity) in a human subject with chronically implanted electroencephalographic electrodes.
=== Transition into hypersynchronization ===
The transition from normal state of brain activity to epileptic seizures was not formulated theoretically until 2008, when a theoretical path from a baseline state to large-scale self-sustained oscillations, which spread out uniformly from the point of stimulus, has been mapped for the first time.
A realistic state of baseline physiological activity has been defined, using the following two-component definition:
(1) A time-independent component represented by subthreshold excitatory activity E and superthreshold inhibitory activity I.
(2) A time-varying component which may include singlepulse waves, multipulse waves, or periodic waves caused by spontaneous neuronal activity.
This baseline state represents activity of the brain in the state of relaxation, in which neurons receive some level of spontaneous, weak stimulation by small, naturally present concentrations of neurohormonal substances. In waking adults this state is commonly associated with alpha rhythm, whereas slower (theta and delta) rhythms are usually observed during deeper relaxation and sleep. To describe this general setting, a 3-variable
(
u
,
I
,
v
)
{\displaystyle (u,I,v)}
spatially dependent extension of the classical Wilson–Cowan model can be utilized. Under appropriate initial conditions, the excitatory component, u, dominates over the inhibitory component, I, and the three-variable system reduces to the two-variable Pinto-Ermentrout type model
∂
u
∂
t
=
u
−
v
+
∫
R
2
ω
(
x
−
x
′
,
y
−
y
′
)
f
(
u
−
θ
)
d
x
d
y
+
ζ
(
x
,
y
,
t
)
,
{\displaystyle {\partial u \over \partial t}=u-v+\int _{R^{2}}\omega (x-x',y-y')f(u-\theta )\,dxdy+\zeta (x,y,t),}
∂
v
∂
t
=
ϵ
(
β
u
−
v
)
.
{\displaystyle {\partial v \over \partial t}=\epsilon (\beta u-v).}
The variable v governs the recovery of excitation u;
ϵ
>
0
{\displaystyle \epsilon >0}
and
β
>
0
{\displaystyle \beta >0}
determine the rate of change of recovery. The connection function
ω
(
x
,
y
)
{\displaystyle \omega (x,y)}
is positive, continuous, symmetric, and has the typical form
ω
=
A
e
−
λ
−
(
x
2
+
y
2
)
{\displaystyle \omega =Ae^{-\lambda {\sqrt {-(x^{2}+y^{2})}}}}
. In Ref.
(
A
,
λ
)
=
(
2.1
,
1
)
.
{\displaystyle (A,\lambda )=(2.1,1).}
The firing rate function, which is generally accepted to have a sharply increasing sigmoidal shape, is approximated by
f
(
u
−
θ
)
=
H
(
u
−
θ
)
{\displaystyle f(u-\theta )=H(u-\theta )}
, where H denotes the Heaviside function;
ζ
(
x
,
y
,
t
)
{\displaystyle \zeta (x,y,t)}
is a short-time stimulus. This
(
u
,
v
)
{\displaystyle (u,v)}
system has been successfully used in a wide variety of neuroscience research studies. In particular, it predicted the existence of spiral waves, which can occur during seizures; this theoretical prediction was subsequently confirmed experimentally using optical imaging of slices from the rat cortex.
=== Rate of expansion ===
The expansion of hypersynchronized regions exhibiting large-amplitude stable bulk oscillations occurs when the oscillations coexist with the stable rest state
(
u
,
v
)
=
(
0
,
0
)
{\displaystyle (u,v)=(0,0)}
. To understand the mechanism responsible for the expansion, it is necessary to linearize the
(
u
,
v
)
{\displaystyle (u,v)}
system around
(
0
,
0
)
{\displaystyle (0,0)}
when
ϵ
>
0
{\displaystyle \epsilon >0}
is held fixed. The linearized system exhibits subthreshold decaying oscillations whose frequency increases as
β
{\displaystyle \beta }
increases. At a critical value
β
∗
{\displaystyle \beta ^{*}}
where the oscillation frequency is high enough, bistability occurs in the
(
u
,
v
)
{\displaystyle (u,v)}
system: a stable, spatially independent, periodic solution (bulk oscillation) and a stable rest state coexist over a continuous range of parameters. When
β
≥
β
∗
{\displaystyle \beta \geq \beta ^{*}}
where bulk oscillations occur, "The rate of expansion of the hypersynchronization region is determined by an interplay between two key features: (i) the speed c of waves that form and propagate outward from the edge of the region, and (ii) the concave shape of the graph of the activation variable u as it rises, during each bulk oscillation cycle, from the rest state u=0 to the activation threshold. Numerical experiments show that during the rise of
u towards threshold, as the rate of vertical increase slows down, over time interval
Δ
t
,
{\displaystyle \Delta t,}
due to the concave component, the stable solitary wave emanating from the region causes the region to expand spatially at a Rate proportional to the wave speed. From this initial observation it is natural to expect that the proportionality constant should be the fraction of the time that the solution is concave during one cycle." Therefore, when
β
≥
β
∗
{\displaystyle \beta \geq \beta ^{*}}
, the rate of expansion of the region is estimated by
R
a
t
e
=
(
Δ
t
/
T
)
∗
c
(
1
)
{\displaystyle Rate=(\Delta t/T)*c~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~(1)}
where
Δ
t
{\displaystyle \Delta t}
is the length of subthreshold time interval, T is period of the periodic solution; c is the speed of waves emanating from the hypersynchronization region. A realistic value of c, derived by Wilson et al., is c=22.4 mm/s.
How to evaluate the ratio
Δ
t
/
T
?
{\displaystyle \Delta t/T?}
To determine values for
Δ
t
/
T
{\displaystyle \Delta t/T}
it is necessary to analyze the underlying bulk oscillation which satisfies the spatially independent system
d
u
d
t
=
u
−
v
+
H
(
u
−
θ
)
,
{\displaystyle {{du} \over {dt}}=u-v+H(u-\theta ),}
d
v
d
t
=
ϵ
(
β
u
−
v
)
.
{\displaystyle {{dv} \over {dt}}=\epsilon (\beta u-v).}
This system is derived using standard functions and parameter values
ω
=
2.1
e
−
λ
−
(
x
2
+
y
2
)
{\displaystyle \omega =2.1e^{-\lambda {\sqrt {-(x^{2}+y^{2})}}}}
,
ϵ
=
0.1
{\displaystyle \epsilon =0.1}
and
θ
=
0.1
{\displaystyle \theta =0.1}
Bulk oscillations occur when
β
≥
β
∗
=
12.61
{\displaystyle \beta \geq \beta ^{*}=12.61}
. When
12.61
≤
β
≤
17
{\displaystyle 12.61\leq \beta \leq 17}
, Shusterman and Troy analyzed the bulk oscillations and found
0.136
≤
Δ
t
/
T
≤
0.238
{\displaystyle 0.136\leq \Delta t/T\leq 0.238}
. This gives the range
3.046
m
m
/
s
≤
R
a
t
e
≤
5.331
m
m
/
s
(
2
)
{\displaystyle 3.046mm/s\leq Rate\leq 5.331mm/s~~~~~~~~~~~~(2)}
Since
0.136
≤
Δ
t
/
T
≤
0.238
{\displaystyle 0.136\leq \Delta t/T\leq 0.238}
, Eq. (1) shows that the migration Rate is a fraction of the traveling wave speed, which is consistent with experimental and clinical observations regarding the slow spread of epileptic activity. This migration mechanism also provides a plausible explanation for spread and sustenance of epileptiform activity without a driving source that, despite a number of experimental studies, has never been observed.
=== Comparing theoretical and experimental migration rates ===
The rate of migration of hypersynchronous activity that was experimentally recorded during seizures in a human subject, using chronically implanted subdural electrodes on the surface of the left temporal lobe, has been estimated as
R
a
t
e
≈
4
m
m
/
s
{\displaystyle Rate\approx 4mm/s}
,
which is consistent with the theoretically predicted range given above in (2). The ratio
R
a
t
e
/
c
{\displaystyle Rate/c}
in formula (1) shows that the leading edge of the region of synchronous seizure activity migrates approximately 4–7 times more slowly than normal brain wave activity, which is in agreement with the experimental data described above.
To summarize, mathematical modeling and theoretical analysis of large-scale electrophysiological activity provide tools for predicting the spread and migration of hypersynchronous brain activity, which can be useful for diagnostic evaluation and management of patients with epilepsy. It might be also useful for predicting migration and spread of electrical activity over large regions of the brain that occur during deep sleep (Delta wave), cognitive activity and in other functional settings.
== References == | Wikipedia/Wilson–Cowan_model |
On the Sacred Disease is a work of the Hippocratic Corpus, written about 400 B.C. Its authorship cannot be confirmed, so is regarded as dubious. The treatise is thought to contain one of the first recorded observations of epilepsy in humans. The author explains these phenomena by the flux of the phlegm flowing from the brain into the veins rather than assigning them a divine origin. This turn from a supernatural to a naturalistic explanation is considered a major breakthrough in the history of medicine.
== Summary ==
The author, putatively Hippocrates, comments on the "sacred" disease, declaring that it is no more sacred than other diseases. He stresses the importance of the disease having no relation with the divine whatsoever, but instead being purely of human origin. The author of On the Sacred Disease argues that even the most mysterious of diseases was still of natural cause and not of divine origin:
Men regard its nature and cause as divine from ignorance and wonder because it is not at all like to other diseases…Men being in want of the means of life, invent many and various things, and devise many contrivances for all other things and for this disease, in every phase of the disease, assigning the cause to a god... Neither truly do I count it a worth opinion to hold that the body of man is polluted by god, the most impure by the most holy,
Symptoms of this disease are described as men becoming mad either by crying out, suffocating on saliva, frothing at the mouth, or by shaking uncontrollably. Such symptoms were thought to be a punishment from the gods on an individual. Hippocrates continues his argument by noting that such phenomena are not of divine origin because previous treatments to the affected involved incantations and prayer patterns that were unsuccessful.
The text continues with the known anatomy of the brain at the time. The brain of a human is similar to other animals in that it is double and divided by a thin membrane through the middle. Hippocrates attributes this fact as the reason that a patient's pain is not always located in the same spot on his or her head. Veins from the body's major organs connect to the brain and vary in size. The veins that run along the right region of the body through the heart and lungs are continued to be described to the best of Hippocrates' knowledge:
The other runs upward by the right veins in the lungs and divides into branches for the heart and the right arm. The remaining part of it rises across the clavicle to the right side of the neck, and is superficial so as to be seen; near the ear it is concealed, and there it divides; its thickest, largest, and most hollow part ends in the brain; another small vein goes to the right ear, another to the right eye, and another to the nostril. Such are the distributions of the hepatic vein.
Hippocrates argues that the start of this sacred disease begins with the accumulation of phlegm (one of the "four humors") in the veins of the head. The author points to dissection of epileptic cattle as evidence that phlegm builds up in the brain. This build-up begins to be formed in utero. If this disease continues to grow after birth and into adulthood, the affected person will have a "melted" brain which results in mental illness. Once the disease is stuck within the head, the patient loses his speech and chokes, causing foam to fall from his or her mouth.
Young children who obtain the disease mostly die; Hippocrates argues that due to their small veins, they are not able to accommodate the increased amount of phlegm. When the phlegm gathers, the child quickly "cools" and the blood congeals, causing death.
The elderly for the most part survive the disease due to the Hippocratic theory that their veins are larger and filled with hot, flowing blood that is safe from the coldness of the phlegm.
Summary of symptoms
Shivering
Loss of speech
Trouble breathing
Contraction of the brain
Blood stops circulating
Excretion of the phlegm
Many of those affected seem to know when they are about to have another episode. When this happens, they become ashamed and flee from the surrounding crowd to hide. Hippocrates mentions that this is due to their shame around the disease, rather than fear of the divine as was the common opinion.
Hippocrates concludes that the sacred disease is proof that the brain has the greatest power over man. Through this part of the body, air from breathing first enters. When the disease dilutes the mind to the point where phlegm in the veins increases sufficiently, causing air blockage, is when the patient begins to suffer and possibly die.
== References ==
== Further reading ==
Lindberg, David C. (2007). The Beginnings of Western Science. Chicago: The University of Chicago Press.
Lloyd, G.E.R.. (1979). "The Criticism of Magic and the Inquiry Concerning Nature," in Magic, Reason, and Experience, Cambridge: Cambridge University Press, pages 1-58.
== External links ==
English translation by Francis Adams: with parallel Greek text (Perseus Project), HTML (MIT)
English translation by W.H.S. Jones (Loeb Classical Library, with facing Greek text): archive.org | Wikipedia/On_the_Sacred_Disease |
Hippocrates is a lunar impact crater on the far side of the Moon. It is located in the northern region of the lunar surface, to the north of the crater Stebbins. To the southwest of Hippocrates are Kirkwood and the large Sommerfeld.
This is a relatively old formation that has become worn and eroded due to subsequent impacts. The general outline of the outer rim is still visible, but it is overlaid along the eastern edge by a smaller crater. There is also a small craterlet along the western edge. The inner wall is marked by a number of tiny craterlets, and is slightly wider at the southern edge with a ridge-like projection. The interior floor is level and almost featureless, with only a few tiny craterlets to mark the surface.
This crater was named after Hippocrates, the ancient Greek physician.
== Satellite craters ==
By convention these features are identified on lunar maps by placing the letter on the side of the crater midpoint that is closest to Hippocrates.
== References == | Wikipedia/Hippocrates_(lunar_crater) |
Hippocrates was an ancient Greek physician of the Age of Pericles, considered one of the most outstanding figures in the history of medicine.
Hippocrates may also refer to:
Hippocrates (physician), the name of several other physicians related to Hippocrates
Hippocrates of Chios (c. 470 – c. 410 BC), ancient Greek geometer who wrote the first known work systematizing the fundamentals of geometry
Hippocrates of Athens (died 424 BC), ancient Greek general who was slain at the battle of Delium
Hippocrates, father of Peisistratos
Hippocrates (lunar crater)
Hippocrates of Gela, ancient Greek tyrant who dominated Sicilian politics during his rule between 498 BC and 491 BC
Pseudo-Hippocrates, an anonymous writer, dubbed with the name because his works had been included in Hippocratic Corpus
Hippocrates Prize for Poetry and Medicine
Hippocrates Otthen, French physician
"Hypocrates", song from 2012 album Electra Heart by Welsh singer Marina and the Diamonds
Hippocrate, a 2014 French film directed by Thomas Lilti
== See also ==
Harpocrates, Greek god of silence
Hippocras, drink of spiced wine
Hypocrite (disambiguation), similar sounding word | Wikipedia/Hippocrates_(disambiguation) |
Hippocrates (Greek: Ἱπποκράτης) was the name of several physicians in the time of Ancient Greece, some of whom were in the same family as the celebrated Hippocrates of Kos (Hippocrates II).
Hippocrates I. The grandfather of Hippocrates II. He was the eldest son of Gnosidicus, the brother of Podaleirius and Aeneius, and the father of Heraclides, the father of Hippocrates. He lived in the 6th and 5th centuries BC. Some ancient writers attributed to him the two works De Fracturis and De Articulis, while others contended that he wrote nothing at all.
Hippocrates II of Kos, usually known simply as Hippocrates. Grandson of Hippocrates I, and the most celebrated physician of ancient Greece.
Hippocrates III. The son of Thessalus, the brother of Draco II, and the grandson of Hippocrates II. He lived in the 4th century BC. He is said by the Suda to have written some medical works.
Hippocrates IV. According to Galen (Latin: Galenus), he was the son of Draco I, and the grandson of Hippocrates II; he lived in the 4th century BC, and is said to have written some medical works. The Suda, which may be confused, makes him the son of Draco II, (and therefore, the great-grandson of Hippocrates II), and the father of Draco III. He is said to have been one of the physicians to Roxana, the wife of Alexander the Great, and to have died at the hands of Cassander, the son of Antipater.
Hippocrates V and VI. According to the Suda, Thymbraeus of Kos had two sons named Hippocrates, each of whom wrote some medical works. Their date is unknown.
Hippocrates VII. The son of Praxianax of Kos. He wrote some medical works.
== See also ==
Hippocrates Otthen, French physician
== References ==
== Sources ==
This article incorporates text from a publication now in the public domain: Smith, William, ed. (1870). "Hippocrates". Dictionary of Greek and Roman Biography and Mythology. | Wikipedia/Hippocrates_(physician) |
Hippocrates (Greek: Ἱπποκράτης) was the name of several physicians in the time of Ancient Greece, some of whom were in the same family as the celebrated Hippocrates of Kos (Hippocrates II).
Hippocrates I. The grandfather of Hippocrates II. He was the eldest son of Gnosidicus, the brother of Podaleirius and Aeneius, and the father of Heraclides, the father of Hippocrates. He lived in the 6th and 5th centuries BC. Some ancient writers attributed to him the two works De Fracturis and De Articulis, while others contended that he wrote nothing at all.
Hippocrates II of Kos, usually known simply as Hippocrates. Grandson of Hippocrates I, and the most celebrated physician of ancient Greece.
Hippocrates III. The son of Thessalus, the brother of Draco II, and the grandson of Hippocrates II. He lived in the 4th century BC. He is said by the Suda to have written some medical works.
Hippocrates IV. According to Galen (Latin: Galenus), he was the son of Draco I, and the grandson of Hippocrates II; he lived in the 4th century BC, and is said to have written some medical works. The Suda, which may be confused, makes him the son of Draco II, (and therefore, the great-grandson of Hippocrates II), and the father of Draco III. He is said to have been one of the physicians to Roxana, the wife of Alexander the Great, and to have died at the hands of Cassander, the son of Antipater.
Hippocrates V and VI. According to the Suda, Thymbraeus of Kos had two sons named Hippocrates, each of whom wrote some medical works. Their date is unknown.
Hippocrates VII. The son of Praxianax of Kos. He wrote some medical works.
== See also ==
Hippocrates Otthen, French physician
== References ==
== Sources ==
This article incorporates text from a publication now in the public domain: Smith, William, ed. (1870). "Hippocrates". Dictionary of Greek and Roman Biography and Mythology. | Wikipedia/Hippocrates_(physicians) |
The Hippocrates Project is a program of the New York University Medical Center which works with modern technologies to "enhance the learning process". It was established in 1987, presumably named after the ancient Greek physician Hippocrates.
== History ==
The Hippocrates Project began in 1987 in an unused microbiology laboratory by six medical students (Alan Simon, M.D.; Howard M. Karpoff, MD and others) and one member of the faculty, Martin Nachbar, MD (1937-2015). It was one of the early adopters of the use of computers and multimedia in education. Courseware was created, such as a computerized atlas of Histology in HyperCard and a multidimensional Neuroanatomy Atlas using SuperCard. Software expanded to include other courseware, digitized video, and 3-D simulations of surgery, such as Laparoscopic Cholecystectomy. The Hippocrates Project also created early versions of the electronic medical record. As of 1997, the Hippocrates Project is officially an Educational Computing Division (ECD).
== Accomplishments ==
Hippocrates has produced over 100 "medical education modules", most of which are used in NYU curricula as exercises or as educational resources. These "modules" may be "expository presentations, laboratory simulations, self-assessment and testing programs, three-dimensional anatomic reconstructions, animations, virtual reality environments, case studies, and databases". The Hippocrates Project also provides email services, hosts websites, grades examinations by computer, and automates course surveys.
== References ==
== External links ==
Home page | Wikipedia/The_Hippocrates_Project |
Cardiothoracic surgery is the field of medicine involved in surgical treatment of organs inside the thoracic cavity — generally treatment of conditions of the heart (heart disease), lungs (lung disease), and other pleural or mediastinal structures.
In most countries, cardiothoracic surgery is further subspecialized into cardiac surgery (involving the heart and the great vessels) and thoracic surgery (involving the lungs, esophagus, thymus, etc.); the exceptions are the United States, Australia, New Zealand, the United Kingdom, India and some European Union countries such as Portugal.
== Training ==
A cardiac surgery residency typically comprises anywhere from four to six years (or longer) of training to become a fully qualified surgeon. Cardiac surgery training may be combined with thoracic surgery and/or vascular surgery and called cardiovascular (CV) / cardiothoracic (CT) / cardiovascular thoracic (CVT) surgery. Cardiac surgeons may enter a cardiac surgery residency directly from medical school, or first complete a general surgery residency followed by a fellowship. Cardiac surgeons may further sub-specialize cardiac surgery by doing a fellowship in a variety of topics including pediatric cardiac surgery, cardiac transplantation, adult-acquired heart disease, weak heart issues, and many more problems in the heart.
=== Australia and New Zealand ===
The highly competitive Surgical Education and Training (SET) program in Cardiothoracic Surgery is six years in duration, usually commencing several years after completing medical school. Training is administered and supervised via a bi-national (Australia and New Zealand) training program. Multiple examinations take place throughout the course of training, culminating in a final fellowship exam in the final year of training. Upon completion of training, surgeons are awarded a Fellowship of the Royal Australasian College of Surgeons (FRACS), denoting that they are qualified specialists. Trainees having completed a training program in General Surgery and have obtained their FRACS will have the option to complete fellowship training in Cardiothoracic Surgery of four years in duration, subject to college approval. It takes around eight to ten years minimum of post-graduate (post-medical school) training to qualify as a cardiothoracic surgeon. Competition for training places and for public (teaching) hospital places is very high currently, leading to concerns regarding workforce planning in Australia.
=== Canada ===
Historically, cardiac surgeons in Canada completed general surgery followed by a fellowship in CV / CT / CVT. During the 1990s, the Canadian cardiac surgery training programs changed to six-year "direct-entry" programs following medical school. The direct-entry format provides residents with experience related to cardiac surgery they would not receive in a general surgery program (e.g. echocardiography, coronary care unit, cardiac catheterization etc.). Residents in this program will also spend time training in thoracic and vascular surgery. Typically, this is followed by a fellowship in either Adult Cardiac Surgery, Heart Failure/Transplant, Minimally Invasive Cardiac Surgery, Aortic Surgery, Thoracic Surgery, Pediatric Cardiac Surgery or Cardiac ICU. Contemporary Canadian candidates completing general surgery and wishing to pursue cardiac surgery often complete a cardiothoracic surgery fellowship in the United States. The Royal College of Physicians and Surgeons of Canada also provides a three-year cardiac surgery fellowship for qualified general surgeons that is offered at several training sites including the University of Alberta, the University of British Columbia and the University of Toronto.
Thoracic surgery is its own separate 2–3 year fellowship of general or cardiac surgery in Canada.
Cardiac surgery programs in Canada:
University of Alberta – 1 position
University of British Columbia – 1 position
University of Calgary – 1 position
Dalhousie University – 1 position every other year
Université Laval – 1 position every three years
University of Manitoba – 1 position
McGill University – 1 position every three years
McMaster University – 1 position every other year
Université de Montréal – 1 position every three years
University of Ottawa – 1 position
University of Toronto – 1 position
Western University – 1 position
=== United States ===
Cardiac surgery training in the United States is combined with general thoracic surgery and called cardiothoracic surgery or thoracic surgery. A cardiothoracic surgeon in the U.S. is a physician who first completes a general surgery residency (typically 5–7 years), followed by a cardiothoracic surgery fellowship (typically 2–3 years). The cardiothoracic surgery fellowship typically spans two or three years, but certification is based on the number of surgeries performed as the operating surgeon, not the time spent in the program, in addition to passing rigorous board certification tests. Two other pathways to shorten the duration of training have been developed: (1) a combined general-thoracic surgery residency consisting of four years of general surgery training and three years of cardiothoracic training at the same institution and (2) an integrated six-year cardiothoracic residency (in place of the general surgery residency plus cardiothoracic residency), which have each been established at many programs (over 20). Applicants match into the integrated six-year (I-6) programs directly out of medical school, and the application process has been extremely competitive for these positions as there were approximately 160 applicants for 10 spots in the U.S. in 2010. As of May 2013, there are 20 approved programs, which include the following:
Integrated six-year Cardiothoracic Surgery programs in the United States:
Medical College of Wisconsin
Stanford University – two positions
University of North Carolina at Chapel Hill
University of Virginia
Columbia University – two positions
University of Pennsylvania
University of Pittsburgh – two positions
University of Washington
Northwestern University
Mount Sinai Hospital, New York
University of Maryland
University of California, Los Angeles UCLA – two resident positions, one Transplant Fellowship; one Congenital resident position
University of Texas Health Science Center at San Antonio
Medical University of South Carolina
University of Southern California – two positions
University of Rochester
University of California, Davis
Indiana University
University of Kentucky
Emory University
University of Michigan
Yale University
The American Board of Thoracic Surgery offers a special pathway certificate in congenital cardiac surgery which typically requires an additional year of fellowship. This formal certificate is unique because congenital cardiac surgeons in other countries do not have formal evaluation and recognition of pediatric training by a licensing body.
== Cardiac surgery ==
The earliest operations on the pericardium (the sac that surrounds the heart) took place in the 19th century and were performed by Francisco Romero (1801) Dominique Jean Larrey, Henry Dalton, and Daniel Hale Williams. The first surgery on the heart itself was performed by Norwegian surgeon Axel Cappelen on 4 September 1895 at Rikshospitalet in Kristiania, now Oslo. He ligated a bleeding coronary artery in a 24-year-old man who had been stabbed in the left axilla and was in deep shock upon arrival. Access was through a left thoracotomy. The patient awoke and seemed fine for 24 hours, but became ill with increasing temperature and he ultimately died from what the post mortem proved to be mediastinitis on the third postoperative day. The first successful surgery of the heart, performed without any complications, was by Ludwig Rehn of Frankfurt, Germany, who repaired a stab wound to the right ventricle on September 7, 1896.
Surgery in great vessels (aortic coarctation repair, Blalock-Taussig shunt creation, closure of patent ductus arteriosus) became common after the turn of the century and falls in the domain of cardiac surgery, but technically cannot be considered heart surgery. One of the more commonly known cardiac surgery procedures is the coronary artery bypass graft (CABG), also known as "bypass surgery."
=== Early approaches to heart malformations ===
In 1925 operations on the heart valves were unknown. Henry Souttar operated successfully on a young woman with mitral stenosis. He made an opening in the appendage of the left atrium and inserted a finger into this chamber in order to palpate and explore the damaged mitral valve. The patient survived for several years but Souttar's physician colleagues at that time decided the procedure was not justified and he could not continue.
Cardiac surgery changed significantly after World War II. In 1948 four surgeons carried out successful operations for mitral stenosis resulting from rheumatic fever. Horace Smithy (1914–1948) revived an operation due to Dr Dwight Harken of the Peter Bent Brigham Hospital using a punch to remove a portion of the mitral valve. Charles Bailey (1910–1993) at the Hahnemann Hospital, Philadelphia, Dwight Harken in Boston and Russell Brock at Guy's Hospital all adopted Souttar's method. All these men started work independently of each other, within a few months. This time Souttar's technique was widely adopted although there were modifications.
In 1947 Thomas Holmes Sellors (1902–1987) of the Middlesex Hospital operated on a Fallot's Tetralogy patient with pulmonary stenosis and successfully divided the stenosed pulmonary valve. In 1948, Russell Brock, probably unaware of Sellor's work, used a specially designed dilator in three cases of pulmonary stenosis. Later in 1948 he designed a punch to resect the infundibular muscle stenosis which is often associated with Fallot's Tetralogy. Many thousands of these "blind" operations were performed until the introduction of heart bypass made direct surgery on valves possible.
=== Open heart surgery ===
Open heart surgery is a procedure in which the patient's heart is opened and surgery is performed on the internal structures of the heart. It was discovered by Wilfred G. Bigelow of the University of Toronto that the repair of intracardiac pathologies was better done with a bloodless and motionless environment, which means that the heart should be stopped and drained of blood. The first successful intracardiac correction of a congenital heart defect using hypothermia was performed by C. Walton Lillehei and F. John Lewis at the University of Minnesota on September 2, 1952. The following year, Soviet surgeon Aleksandr Aleksandrovich Vishnevskiy conducted the first cardiac surgery under local anesthesia.
Surgeons realized the limitations of hypothermia – complex intracardiac repairs take more time and the patient needs blood flow to the body, particularly to the brain. The patient needs the function of the heart and lungs provided by an artificial method, hence the term cardiopulmonary bypass. John Heysham Gibbon at Jefferson Medical School in Philadelphia reported in 1953 the first successful use of extracorporeal circulation by means of an oxygenator, but he abandoned the method, disappointed by subsequent failures. In 1954 Lillehei realized a successful series of operations with the controlled cross-circulation technique in which the patient's mother or father was used as a 'heart-lung machine'. John W. Kirklin at the Mayo Clinic in Rochester, Minnesota started using a Gibbon type pump-oxygenator in a series of successful operations, and was soon followed by surgeons in various parts of the world.
Nazih Zuhdi performed the first total intentional hemodilution open heart surgery on Terry Gene Nix, age 7, on February 25, 1960, at Mercy Hospital, Oklahoma City, OK. The operation was a success; however, Nix died three years later in 1963. In March, 1961, Zuhdi, Carey, and Greer, performed open heart surgery on a child, age 3+1⁄2, using the total intentional hemodilution machine. In 1985 Zuhdi performed Oklahoma's first successful heart transplant on Nancy Rogers at Baptist Hospital. The transplant was successful, but Rogers, who had cancer, died from an infection 54 days after surgery.
=== Modern beating-heart surgery ===
Since the 1990s, surgeons have begun to perform "off-pump bypass surgery" – coronary artery bypass surgery without the aforementioned cardiopulmonary bypass. In these operations, the heart is beating during surgery, but is stabilized to provide an almost still work area in which to connect the conduit vessel that bypasses the blockage; in the U.S., most conduit vessels are harvested endoscopically, using a technique known as endoscopic vessel harvesting (EVH).
Some researchers believe that the off-pump approach results in fewer post-operative complications, such as postperfusion syndrome, and better overall results. Study results are controversial as of 2007, the surgeon's preference and hospital results still play a major role.
=== Minimally invasive surgery ===
A new form of heart surgery that has grown in popularity is robot-assisted heart surgery. This is where a machine is used to perform surgery while being controlled by the heart surgeon. The main advantage to this is the size of the incision made in the patient. Instead of an incision being at least big enough for the surgeon to put his hands inside, it does not have to be bigger than "pencil-sized" holes for the robot's much smaller "hands" to enter a surgical patient's body.
In September 2024, the first successful fully robotic heart transplant took place at King Faisal Specialist Hospital and Research Centre in Riyadh, led by surgeon Feras Khaliel, head of the hospital's cardiac surgery and director of its Robotics and Minimally Invasive Surgery Program. In December 2024, the first robotic surgery for a combined robotic aortic valve replacement (AVR) and coronary artery bypass grafting (CABG) was successfully performed through one small incision at West Virginia University, led by surgeon Vinay Badhwar, who is the executive chair of the WVU Heart and Vascular Institute and a vice president of the Society of Thoracic Surgeons.
=== Pediatric cardiovascular surgery ===
Pediatric cardiovascular surgery is surgery of the heart of children. The first operations to repair cardio-vascular defects in children were performed by Clarence Crafoord in Sweden when he repaired coarctation of the aorta in a 12-year-old boy. The first attempts to palliate congenital heart disease were performed by Alfred Blalock with the assistance of William Longmire, Denton Cooley, and Blalock's experienced technician, Vivien Thomas in 1944 at Johns Hopkins Hospital. Techniques for repair of congenital heart defects without the use of a bypass machine were developed in the late 1940s and early 1950s. Among them was an open repair of an atrial septal defect using hypothermia, inflow occlusion and direct vision in a 5-year-old child performed in 1952 by Lewis and Lillihei. Lillihei used cross-circulation between a boy and his father to maintain perfusion while performing a direct repair of a ventricular septal defect in a 4-year-old child in 1954. He continued to use cross-circulation and performed the first corrections of tetralogy of Fallot and presented those results in 1955 at the American Surgical Association. In the long-run, pediatric cardiovascular surgery would rely on the cardiopulmonary bypass machine developed by Gibbon and Lillehei as noted above.
=== Risks of cardiac surgery ===
The development of cardiac surgery and cardiopulmonary bypass techniques has reduced the mortality rates of these surgeries to relatively low ranks. For instance, repairs of congenital heart defects are currently estimated to have 4–6% mortality rates. A major concern with cardiac surgery is the incidence of neurological damage. Stroke occurs in 5% of all people undergoing cardiac surgery, and is higher in patients at risk for stroke. A more subtle constellation of neurocognitive deficits attributed to cardiopulmonary bypass is known as postperfusion syndrome, sometimes called "pumphead". The symptoms of postperfusion syndrome were initially felt to be permanent, but were shown to be transient with no permanent neurological impairment.
To assess the performance of surgical units and individual surgeons, a popular risk model has been created called the EuroSCORE. This takes a number of health factors from a patient and using precalculated logistic regression coefficients attempts to give a percentage chance of survival to discharge. Within the UK this EuroSCORE was used to give a breakdown of all the centres for cardiothoracic surgery and to give some indication of whether the units and their individual surgeons performed within an acceptable range. The results are available on the CQC website. The precise methodology used has however not been published to date nor has the raw data on which the results are based.
Infection represents the primary non-cardiac complication from cardiothoracic surgery. Infections include mediastinitis, infectious myo- or pericarditis, endocarditis, cardiac device infection, pneumonia, empyema, and bloodstream infections. Clostridioides difficile colitis can develop when prophylactic or post-operative antibiotics are used.
Post-operative patients of cardiothoracic surgery are at risk of nausea, vomiting, dysphagia, and aspiration pneumonia.
== Thoracic surgery ==
A pleurectomy is a surgical procedure in which part of the pleura is removed. It is sometimes used in the treatment of pneumothorax and mesothelioma. In case of pneumothorax, only the apical and the diaphragmatic portions of the parietal pleura are removed.
=== Lung volume reduction surgery ===
Lung volume reduction surgery, or LVRS, can improve the quality of life for certain patients with COPD of emphysematous type, when other treatment options are not enough. Parts of the lung that are particularly damaged by emphysema are removed, allowing the remaining, relatively good lung to expand and work more efficiently. The beneficial effects are correlated with the achieved reduction in residual volume. Conventional LVRS involves resection of the most severely affected areas of emphysematous, non-bullous lung (aim is for 20–30%). This is a surgical option involving a mini-thoracotomy for patients in end stage COPD due to underlying emphysema, and can improve lung elastic recoil as well as diaphragmatic function.
The National Emphysema Treatment Trial (NETT) was a large multicentre study (N = 1218) comparing LVRS with non-surgical treatment. Results suggested that there was no overall survival advantage in the LVRS group, except for mainly upper-lobe emphysema + poor exercise capacity, and significant improvements were seen in exercise capacity in the LVRS group. Later studies have shown a wider scope of treatment with better outcomes.
Possible complications of LVRS include prolonged air leak (mean duration post surgery until all chest tubes removed is 10.9 ± 8.0 days.
In people who have a predominantly upper lobe emphysema, lung volume reduction surgery could result in better health status and lung function, though it also increases the risk of early mortality and adverse events.
LVRS is used widely in Europe, though its application in the United States is mostly experimental.
A less invasive treatment is available as a bronchoscopic lung volume reduction procedure.
=== Lung cancer surgery ===
Not all lung cancers are suitable for surgery. The stage, location and cell type are important limiting factors. In addition, people who are very ill with a poor performance status or who have inadequate pulmonary reserve would be unlikely to survive. Even with careful selection, the overall operative death rate is about 4.4%.
In non-small cell lung cancer staging, stages IA, IB, IIA, and IIB are suitable for surgical resection.
Pulmonary reserve is measured by spirometry. If there is no evidence of undue shortness of breath or diffuse parenchymal lung disease, and the FEV1 exceeds 2 litres or 80% of predicted, the person is fit for pneumonectomy. If the FEV1 exceeds 1.5 litres, the patient is fit for lobectomy.
There is weak evidence to indicate that participation in exercise programs before lung cancer surgery may reduce the risk of complications after surgery.
==== Complications ====
A prolonged air leak (PAL) can occur in 8–25% of people following lung cancer surgery. This complication delays chest tube removal and is associated with an increased length of hospital stay following a lung resection (lung cancer surgery). The use of surgical sealants may reduce the incidence of prolonged air leaks, however, this intervention alone has not been shown to results in a decreased length of hospital stay following lung cancer surgery.
There is no strong evidence to support using non-invasive positive pressure ventilation following lung cancer surgery to reduce pulmonary complications.
==== Types ====
Lobectomy (removal of a lobe of the lung)
Sublobar resection (removal of part of lobe of the lung)
Segmentectomy (removal of an anatomic division of a particular lobe of the lung)
Pneumonectomy (removal of an entire lung)
Wedge resection
Sleeve/bronchoplastic resection (removal of an associated tubular section of the associated main bronchial passage during lobectomy with subsequent reconstruction of the bronchial passage)
VATS lobectomy (minimally invasive approach to lobectomy that may allow for diminished pain, quicker return to full activity, and diminished hospital costs)
esophagectomy (removal of the esophagus)
== See also ==
Annals of Thoracic Surgery
European Journal of Cardio-Thoracic Surgery
Journal of Thoracic and Cardiovascular Surgery
== References ==
== External links ==
The Cardiothoracic Surgery Network
The Society of Thoracic Surgeons
American Association for Thoracic Surgery
International Society for Minimally Invasive Cardiothoracic Surgery | Wikipedia/Cardiothoracic_Surgery |
Medicine is the science and practice of caring for patients, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness. Contemporary medicine applies biomedical sciences, biomedical research, genetics, and medical technology to diagnose, treat, and prevent injury and disease, typically through pharmaceuticals or surgery, but also through therapies as diverse as psychotherapy, external splints and traction, medical devices, biologics, and ionizing radiation, amongst others.
Medicine has been practiced since prehistoric times, and for most of this time it was an art (an area of creativity and skill), frequently having connections to the religious and philosophical beliefs of local culture. For example, a medicine man would apply herbs and say prayers for healing, or an ancient philosopher and physician would apply bloodletting according to the theories of humorism. In recent centuries, since the advent of modern science, most medicine has become a combination of art and science (both basic and applied, under the umbrella of medical science). For example, while stitching technique for sutures is an art learned through practice, knowledge of what happens at the cellular and molecular level in the tissues being stitched arises through science.
Prescientific forms of medicine, now known as traditional medicine or folk medicine, remain commonly used in the absence of scientific medicine and are thus called alternative medicine. Alternative treatments outside of scientific medicine with ethical, safety and efficacy concerns are termed quackery.
== Etymology ==
Medicine (UK: , US: ) is the science and practice of the diagnosis, prognosis, treatment, and prevention of disease. The word "medicine" is derived from Latin medicus, meaning "a physician". The word "physic" itself, from which "physician" derives, was the old word for what is now called a medicine, and also the field of medicine.
== Clinical practice ==
Medical availability and clinical practice vary across the world due to regional differences in culture and technology. Modern scientific medicine is highly developed in the Western world, while in developing countries such as parts of Africa or Asia, the population may rely more heavily on traditional medicine with limited evidence and efficacy and no required formal training for practitioners.
In the developed world, evidence-based medicine is not universally used in clinical practice; for example, a 2007 survey of literature reviews found that about 49% of the interventions lacked sufficient evidence to support either benefit or harm.
In modern clinical practice, physicians and physician assistants personally assess patients to diagnose, prognose, treat, and prevent disease using clinical judgment. The doctor-patient relationship typically begins with an interaction with an examination of the patient's medical history and medical record, followed by a medical interview and a physical examination. Basic diagnostic medical devices (e.g., stethoscope, tongue depressor) are typically used. After examining for signs and interviewing for symptoms, the doctor may order medical tests (e.g., blood tests), take a biopsy, or prescribe pharmaceutical drugs or other therapies. Differential diagnosis methods help to rule out conditions based on the information provided. During the encounter, properly informing the patient of all relevant facts is an important part of the relationship and the development of trust. The medical encounter is then documented in the medical record, which is a legal document in many jurisdictions. Follow-ups may be shorter but follow the same general procedure, and specialists follow a similar process. The diagnosis and treatment may take only a few minutes or a few weeks, depending on the complexity of the issue.
The components of the medical interview and encounter are:
Chief complaint (CC): the reason for the current medical visit. These are the symptoms. They are in the patient's own words and are recorded along with the duration of each one. Also called chief concern or presenting complaint.
Current activity: occupation, hobbies, what the patient actually does.
Family history (FH): listing of diseases in the family that may impact the patient. A family tree is sometimes used.
History of present illness (HPI): the chronological order of events of symptoms and further clarification of each symptom. Distinguishable from history of previous illness, often called past medical history (PMH). Medical history comprises HPI and PMH.
Medications (Rx): what drugs the patient takes including prescribed, over-the-counter, and home remedies, as well as alternative and herbal medicines or remedies. Allergies are also recorded.
Past medical history (PMH/PMHx): concurrent medical problems, past hospitalizations and operations, injuries, past infectious diseases or vaccinations, history of known allergies.
Review of systems (ROS) or systems inquiry: a set of additional questions to ask, which may be missed on HPI: a general enquiry (have you noticed any weight loss, change in sleep quality, fevers, lumps and bumps? etc.), followed by questions on the body's main organ systems (heart, lungs, digestive tract, urinary tract, etc.).
Social history (SH): birthplace, residences, marital history, social and economic status, habits (including diet, medications, tobacco, alcohol).
The physical examination is the examination of the patient for medical signs of disease that are objective and observable, in contrast to symptoms that are volunteered by the patient and are not necessarily objectively observable. The healthcare provider uses sight, hearing, touch, and sometimes smell (e.g., in infection, uremia, diabetic ketoacidosis). Four actions are the basis of physical examination: inspection, palpation (feel), percussion (tap to determine resonance characteristics), and auscultation (listen), generally in that order, although auscultation occurs prior to percussion and palpation for abdominal assessments.
The clinical examination involves the study of:
Abdomen and rectum
Cardiovascular (heart and blood vessels)
General appearance of the patient and specific indicators of disease (nutritional status, presence of jaundice, pallor or clubbing)
Genitalia (and pregnancy if the patient is or could be pregnant)
Head, eye, ear, nose, and throat (HEENT)
Musculoskeletal (including spine and extremities)
Neurological (consciousness, awareness, brain, vision, cranial nerves, spinal cord and peripheral nerves)
Psychiatric (orientation, mental state, mood, evidence of abnormal perception or thought).
Respiratory (large airways and lungs)
Skin
Vital signs including height, weight, body temperature, blood pressure, pulse, respiration rate, and hemoglobin oxygen saturation
It is to likely focus on areas of interest highlighted in the medical history and may not include everything listed above.
The treatment plan may include ordering additional medical laboratory tests and medical imaging studies, starting therapy, referral to a specialist, or watchful observation. A follow-up may be advised. Depending upon the health insurance plan and the managed care system, various forms of "utilization review", such as prior authorization of tests, may place barriers on accessing expensive services.
The medical decision-making (MDM) process includes the analysis and synthesis of all the above data to come up with a list of possible diagnoses (the differential diagnoses), along with an idea of what needs to be done to obtain a definitive diagnosis that would explain the patient's problem.
On subsequent visits, the process may be repeated in an abbreviated manner to obtain any new history, symptoms, physical findings, lab or imaging results, or specialist consultations.
== Institutions ==
Contemporary medicine is, in general, conducted within health care systems. Legal, credentialing, and financing frameworks are established by individual governments, augmented on occasion by international organizations, such as churches. The characteristics of any given health care system have a significant impact on the way medical care is provided.
From ancient times, Christian emphasis on practical charity gave rise to the development of systematic nursing and hospitals, and the Catholic Church today remains the largest non-government provider of medical services in the world. Advanced industrial countries (with the exception of the United States) and many developing countries provide medical services through a system of universal health care that aims to guarantee care for all through a single-payer health care system or compulsory private or cooperative health insurance. This is intended to ensure that the entire population has access to medical care on the basis of need rather than ability to pay. Delivery may be via private medical practices, state-owned hospitals and clinics, or charities, most commonly a combination of all three.
Most tribal societies provide no guarantee of healthcare for the population as a whole. In such societies, healthcare is available to those who can afford to pay for it, have self-insured it (either directly or as part of an employment contract), or may be covered by care financed directly by the government or tribe.
Transparency of information is another factor defining a delivery system. Access to information on conditions, treatments, quality, and pricing greatly affects the choice of patients/consumers and, therefore, the incentives of medical professionals. While the US healthcare system has come under fire for its lack of openness, new legislation may encourage greater openness. There is a perceived tension between the need for transparency on the one hand and such issues as patient confidentiality and the possible exploitation of information for commercial gain on the other.
The health professionals who provide care in medicine comprise multiple professions, such as medics, nurses, physiotherapists, and psychologists. These professions will have their own ethical standards, professional education, and bodies. The medical profession has been conceptualized from a sociological perspective.
=== Delivery ===
Provision of medical care is classified into primary, secondary, and tertiary care categories.
Primary care medical services are provided by physicians, physician assistants, nurse practitioners, or other health professionals who have first contact with a patient seeking medical treatment or care. These occur in physician offices, clinics, nursing homes, schools, home visits, and other places close to patients. About 90% of medical visits can be treated by the primary care provider. These include treatment of acute and chronic illnesses, preventive care and health education for all ages and both sexes.
Secondary care medical services are provided by medical specialists in their offices or clinics or at local community hospitals for a patient referred by a primary care provider who first diagnosed or treated the patient. Referrals are made for those patients who required the expertise or procedures performed by specialists. These include both ambulatory care and inpatient services, emergency departments, intensive care medicine, surgery services, physical therapy, labor and delivery, endoscopy units, diagnostic laboratory and medical imaging services, hospice centers, etc. Some primary care providers may also take care of hospitalized patients and deliver babies in a secondary care setting.
Tertiary care medical services are provided by specialist hospitals or regional centers equipped with diagnostic and treatment facilities not generally available at local hospitals. These include trauma centers, burn treatment centers, advanced neonatology unit services, organ transplants, high-risk pregnancy, radiation oncology, etc.
Modern medical care also depends on information – still delivered in many health care settings on paper records, but increasingly nowadays by electronic means.
In low-income countries, modern healthcare is often too expensive for the average person. International healthcare policy researchers have advocated that "user fees" be removed in these areas to ensure access, although even after removal, significant costs and barriers remain.
Separation of prescribing and dispensing is a practice in medicine and pharmacy in which the physician who provides a medical prescription is independent from the pharmacist who provides the prescription drug. In the Western world there are centuries of tradition for separating pharmacists from physicians. In Asian countries, it is traditional for physicians to also provide drugs.
== Branches ==
Working together as an interdisciplinary team, many highly trained health professionals besides medical practitioners are involved in the delivery of modern health care. Examples include: nurses, emergency medical technicians and paramedics, laboratory scientists, pharmacists, podiatrists, physiotherapists, respiratory therapists, speech therapists, occupational therapists, radiographers, dietitians, and bioengineers, medical physicists, surgeons, surgeon's assistant, surgical technologist.
The scope and sciences underpinning human medicine overlap many other fields. A patient admitted to the hospital is usually under the care of a specific team based on their main presenting problem, e.g., the cardiology team, who then may interact with other specialties, e.g., surgical, radiology, to help diagnose or treat the main problem or any subsequent complications/developments.
Physicians have many specializations and subspecializations into certain branches of medicine, which are listed below. There are variations from country to country regarding which specialties certain subspecialties are in.
The main branches of medicine are:
Basic sciences of medicine; this is what every physician is educated in, and some return to in biomedical research.
Interdisciplinary fields, where different medical specialties are mixed to function in certain occasions.
Medical specialties
=== Basic sciences ===
Anatomy is the study of the physical structure of organisms. In contrast to macroscopic or gross anatomy, cytology and histology are concerned with microscopic structures.
Biochemistry is the study of the chemistry taking place in living organisms, especially the structure and function of their chemical components.
Biomechanics is the study of the structure and function of biological systems by means of the methods of Mechanics.
Biophysics is an interdisciplinary science that uses the methods of physics and physical chemistry to study biological systems.
Biostatistics is the application of statistics to biological fields in the broadest sense. A knowledge of biostatistics is essential in the planning, evaluation, and interpretation of medical research. It is also fundamental to epidemiology and evidence-based medicine.
Cytology is the microscopic study of individual cells.
Embryology is the study of the early development of organisms.
Endocrinology is the study of hormones and their effect throughout the body of animals.
Epidemiology is the study of the demographics of disease processes, and includes, but is not limited to, the study of epidemics.
Genetics is the study of genes, and their role in biological inheritance.
Gynecology is the study of female reproductive system.
Histology is the study of the structures of biological tissues by light microscopy, electron microscopy and immunohistochemistry.
Immunology is the study of the immune system, which includes the innate and adaptive immune system in humans, for example.
Lifestyle medicine is the study of the chronic conditions, and how to prevent, treat and reverse them.
Medical physics is the study of the applications of physics principles in medicine.
Microbiology is the study of microorganisms, including protozoa, bacteria, fungi, and viruses.
Molecular biology is the study of molecular underpinnings of the process of replication, transcription and translation of the genetic material.
Neuroscience includes those disciplines of science that are related to the study of the nervous system. A main focus of neuroscience is the biology and physiology of the human brain and spinal cord. Some related clinical specialties include neurology, neurosurgery and psychiatry.
Nutrition science (theoretical focus) and dietetics (practical focus) is the study of the relationship of food and drink to health and disease, especially in determining an optimal diet. Medical nutrition therapy is done by dietitians and is prescribed for diabetes, cardiovascular diseases, weight and eating disorders, allergies, malnutrition, and neoplastic diseases.
Pathology as a science is the study of disease – the causes, course, progression and resolution thereof.
Pharmacology is the study of drugs and their actions.
Photobiology is the study of the interactions between non-ionizing radiation and living organisms.
Physiology is the study of the normal functioning of the body and the underlying regulatory mechanisms.
Radiobiology is the study of the interactions between ionizing radiation and living organisms.
Toxicology is the study of hazardous effects of drugs and poisons.
=== Specialties ===
In the broadest meaning of "medicine", there are many different specialties. In the UK, most specialities have their own body or college, which has its own entrance examination. These are collectively known as the Royal Colleges, although not all currently use the term "Royal". The development of a speciality is often driven by new technology (such as the development of effective anaesthetics) or ways of working (such as emergency departments); the new specialty leads to the formation of a unifying body of doctors and the prestige of administering their own examination.
Within medical circles, specialities usually fit into one of two broad categories: "Medicine" and "Surgery". "Medicine" refers to the practice of non-operative medicine, and most of its subspecialties require preliminary training in Internal Medicine. In the UK, this was traditionally evidenced by passing the examination for the Membership of the Royal College of Physicians (MRCP) or the equivalent college in Scotland or Ireland. "Surgery" refers to the practice of operative medicine, and most subspecialties in this area require preliminary training in General Surgery, which in the UK leads to membership of the Royal College of Surgeons of England (MRCS). At present, some specialties of medicine do not fit easily into either of these categories, such as radiology, pathology, or anesthesia. Most of these have branched from one or other of the two camps above; for example anaesthesia developed first as a faculty of the Royal College of Surgeons (for which MRCS/FRCS would have been required) before becoming the Royal College of Anaesthetists and membership of the college is attained by sitting for the examination of the Fellowship of the Royal College of Anesthetists (FRCA).
==== Surgical specialty ====
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate or treat a pathological condition such as disease or injury, to help improve bodily function or appearance or to repair unwanted ruptured areas (for example, a perforated ear drum). Surgeons must also manage pre-operative, post-operative, and potential surgical candidates on the hospital wards. In some centers, anesthesiology is part of the division of surgery (for historical and logistical reasons), although it is not a surgical discipline. Other medical specialties may employ surgical procedures, such as ophthalmology and dermatology, but are not considered surgical sub-specialties per se.
Surgical training in the U.S. requires a minimum of five years of residency after medical school. Sub-specialties of surgery often require seven or more years. In addition, fellowships can last an additional one to three years. Because post-residency fellowships can be competitive, many trainees devote two additional years to research. Thus in some cases surgical training will not finish until more than a decade after medical school. Furthermore, surgical training can be very difficult and time-consuming.
Surgical subspecialties include those a physician may specialize in after undergoing general surgery residency training as well as several surgical fields with separate residency training. Surgical subspecialties that one may pursue following general surgery residency training:
Bariatric surgery
Cardiovascular surgery – may also be pursued through a separate cardiovascular surgery residency track
Colorectal surgery
Endocrine surgery
General surgery
Hand surgery
Hepatico-Pancreatico-Biliary Surgery
Minimally invasive surgery
Pediatric surgery
Plastic surgery – may also be pursued through a separate plastic surgery residency track
Surgical critical care
Surgical oncology
Transplant surgery
Trauma surgery
Vascular surgery – may also be pursued through a separate vascular surgery residency track
Other surgical specialties within medicine with their own individual residency training:
Dermatology
Neurosurgery
Ophthalmology
Oral and maxillofacial surgery
Orthopedic surgery
Otorhinolaryngology
Podiatric surgery – do not undergo medical school training, but rather separate training in podiatry school
Urology
==== Internal medicine specialty ====
Internal medicine is the medical specialty dealing with the prevention, diagnosis, and treatment of adult diseases. According to some sources, an emphasis on internal structures is implied. In North America, specialists in internal medicine are commonly called "internists". Elsewhere, especially in Commonwealth nations, such specialists are often called physicians. These terms, internist or physician (in the narrow sense, common outside North America), generally exclude practitioners of gynecology and obstetrics, pathology, psychiatry, and especially surgery and its subspecialities.
Because their patients are often seriously ill or require complex investigations, internists do much of their work in hospitals. Formerly, many internists were not subspecialized; such general physicians would see any complex nonsurgical problem; this style of practice has become much less common. In modern urban practice, most internists are subspecialists: that is, they generally limit their medical practice to problems of one organ system or to one particular area of medical knowledge. For example, gastroenterologists and nephrologists specialize respectively in diseases of the gut and the kidneys.
In the Commonwealth of Nations and some other countries, specialist pediatricians and geriatricians are also described as specialist physicians (or internists) who have subspecialized by age of patient rather than by organ system. Elsewhere, especially in North America, general pediatrics is often a form of primary care.
There are many subspecialities (or subdisciplines) of internal medicine:
Training in internal medicine (as opposed to surgical training), varies considerably across the world: see the articles on medical education for more details. In North America, it requires at least three years of residency training after medical school, which can then be followed by a one- to three-year fellowship in the subspecialties listed above. In general, resident work hours in medicine are less than those in surgery, averaging about 60 hours per week in the US. This difference does not apply in the UK where all doctors are now required by law to work less than 48 hours per week on average.
==== Diagnostic specialties ====
Clinical laboratory sciences are the clinical diagnostic services that apply laboratory techniques to diagnosis and management of patients. In the United States, these services are supervised by a pathologist. The personnel that work in these medical laboratory departments are technically trained staff who do not hold medical degrees, but who usually hold an undergraduate medical technology degree, who actually perform the tests, assays, and procedures needed for providing the specific services. Subspecialties include transfusion medicine, cellular pathology, clinical chemistry, hematology, clinical microbiology and clinical immunology.
Clinical neurophysiology is concerned with testing the physiology or function of the central and peripheral aspects of the nervous system. These kinds of tests can be divided into recordings of: (1) spontaneous or continuously running electrical activity, or (2) stimulus evoked responses. Subspecialties include electroencephalography, electromyography, evoked potential, nerve conduction study and polysomnography. Sometimes these tests are performed by techs without a medical degree, but the interpretation of these tests is done by a medical professional.
Diagnostic radiology is concerned with imaging of the body, e.g. by x-rays, x-ray computed tomography, ultrasonography, and nuclear magnetic resonance tomography. Interventional radiologists can access areas in the body under imaging for an intervention or diagnostic sampling.
Nuclear medicine is concerned with studying human organ systems by administering radiolabelled substances (radiopharmaceuticals) to the body, which can then be imaged outside the body by a gamma camera or a PET scanner. Each radiopharmaceutical consists of two parts: a tracer that is specific for the function under study (e.g., neurotransmitter pathway, metabolic pathway, blood flow, or other), and a radionuclide (usually either a gamma-emitter or a positron emitter). There is a degree of overlap between nuclear medicine and radiology, as evidenced by the emergence of combined devices such as the PET/CT scanner.
Pathology as a medical specialty is the branch of medicine that deals with the study of diseases and the morphologic, physiologic changes produced by them. As a diagnostic specialty, pathology can be considered the basis of modern scientific medical knowledge and plays a large role in evidence-based medicine. Many modern molecular tests such as flow cytometry, polymerase chain reaction (PCR), immunohistochemistry, cytogenetics, gene rearrangements studies and fluorescent in situ hybridization (FISH) fall within the territory of pathology.
==== Other major specialties ====
The following are some major medical specialties that do not directly fit into any of the above-mentioned groups:
Anesthesiology (also known as anaesthetics): concerned with the perioperative management of the surgical patient. The anesthesiologist's role during surgery is to prevent derangement in the vital organs' (i.e. brain, heart, kidneys) functions and postoperative pain. Outside of the operating room, the anesthesiology physician also serves the same function in the labor and delivery ward, and some are specialized in critical medicine.
Emergency medicine is concerned with the diagnosis and treatment of acute or life-threatening conditions, including trauma, surgical, medical, pediatric, and psychiatric emergencies.
Family medicine, family practice, general practice or primary care is, in many countries, the first port-of-call for patients with non-emergency medical problems. Family physicians often provide services across a broad range of settings including office based practices, emergency department coverage, inpatient care, and nursing home care.
Medical genetics is concerned with the diagnosis and management of hereditary disorders.
Neurology is concerned with diseases of the nervous system. In the UK, neurology is a subspecialty of general medicine.
Obstetrics and gynecology (often abbreviated as OB/GYN (American English) or Obs & Gynae (British English)) are concerned respectively with childbirth and the female reproductive and associated organs. Reproductive medicine and fertility medicine are generally practiced by gynecological specialists.
Pediatrics (AE) or paediatrics (BE) is devoted to the care of infants, children, and adolescents. Like internal medicine, there are many pediatric subspecialties for specific age ranges, organ systems, disease classes, and sites of care delivery.
Pharmaceutical medicine is the medical scientific discipline concerned with the discovery, development, evaluation, registration, monitoring and medical aspects of marketing of medicines for the benefit of patients and public health.
Physical medicine and rehabilitation (or physiatry) is concerned with functional improvement after injury, illness, or congenital disorders.
Podiatric medicine is the study of, diagnosis, and medical and surgical treatment of disorders of the foot, ankle, lower limb, hip and lower back.
Preventive medicine is the branch of medicine concerned with preventing disease.
Community health or public health is an aspect of health services concerned with threats to the overall health of a community based on population health analysis.
Psychiatry is the branch of medicine concerned with the bio-psycho-social study of the etiology, diagnosis, treatment and prevention of cognitive, perceptual, emotional and behavioral disorders. Related fields include psychotherapy and clinical psychology.
=== Interdisciplinary fields ===
Some interdisciplinary sub-specialties of medicine include:
Addiction medicine deals with the treatment of addiction.
Aerospace medicine deals with medical problems related to flying and space travel.
Biomedical Engineering is a field dealing with the application of engineering principles to medical practice.
Clinical pharmacology is concerned with how systems of therapeutics interact with patients.
Conservation medicine studies the relationship between human and non-human animal health, and environmental conditions. Also known as ecological medicine, environmental medicine, or medical geology.
Disaster medicine deals with medical aspects of emergency preparedness, disaster mitigation and management.
Diving medicine (or hyperbaric medicine) is the prevention and treatment of diving-related problems.
Evolutionary medicine is a perspective on medicine derived through applying evolutionary theory.
Forensic medicine deals with medical questions in legal context, such as determination of the time and cause of death, type of weapon used to inflict trauma, reconstruction of the facial features using remains of deceased (skull) thus aiding identification.
Gender-based medicine studies the biological and physiological differences between the human sexes and how that affects differences in disease.
Health informatics is a relatively recent field that deal with the application of computers and information technology to medicine.
Hospice and Palliative Medicine is a relatively modern branch of clinical medicine that deals with pain and symptom relief and emotional support in patients with terminal illnesses including cancer and heart failure.
Hospital medicine is the general medical care of hospitalized patients. Physicians whose primary professional focus is hospital medicine are called hospitalists in the United States and Canada. The term Most Responsible Physician (MRP) or attending physician is also used interchangeably to describe this role.
Laser medicine involves the use of lasers in the diagnostics or treatment of various conditions.
Many other health science fields, e.g. dietetics
Medical ethics deals with ethical and moral principles that apply values and judgments to the practice of medicine.
Medical humanities includes the humanities (literature, philosophy, ethics, history and religion), social science (anthropology, cultural studies, psychology, sociology), and the arts (literature, theater, film, and visual arts) and their application to medical education and practice.
Nosokinetics is the science/subject of measuring and modelling the process of care in health and social care systems.
Nosology is the classification of diseases for various purposes.
Occupational medicine is the provision of health advice to organizations and individuals to ensure that the highest standards of health and safety at work can be achieved and maintained.
Pain management (also called pain medicine, or algiatry) is the medical discipline concerned with the relief of pain.
Pharmacogenomics is a form of individualized medicine.
Podiatric medicine is the study of, diagnosis, and medical treatment of disorders of the foot, ankle, lower limb, hip and lower back.
Sexual medicine is concerned with diagnosing, assessing and treating all disorders related to sexuality.
Sports medicine deals with the treatment and prevention and rehabilitation of sports/exercise injuries such as muscle spasms, muscle tears, injuries to ligaments (ligament tears or ruptures) and their repair in athletes, amateur and professional.
Therapeutics is the field, more commonly referenced in earlier periods of history, of the various remedies that can be used to treat disease and promote health.
Travel medicine or emporiatrics deals with health problems of international travelers or travelers across highly different environments.
Tropical medicine deals with the prevention and treatment of tropical diseases. It is studied separately in temperate climates where those diseases are quite unfamiliar to medical practitioners and their local clinical needs.
Urgent care focuses on delivery of unscheduled, walk-in care outside of the hospital emergency department for injuries and illnesses that are not severe enough to require care in an emergency department. In some jurisdictions this function is combined with the emergency department.
Veterinary medicine; veterinarians apply similar techniques as physicians to the care of non-human animals.
Wilderness medicine entails the practice of medicine in the wild, where conventional medical facilities may not be available.
== Education and legal controls ==
Medical education and training varies around the world. It typically involves entry level education at a university medical school, followed by a period of supervised practice or internship, or residency. This can be followed by postgraduate vocational training. A variety of teaching methods have been employed in medical education, still itself a focus of active research. In Canada and the United States of America, a Doctor of Medicine degree, often abbreviated M.D., or a Doctor of Osteopathic Medicine degree, often abbreviated as D.O. and unique to the United States, must be completed in and delivered from a recognized university.
Since knowledge, techniques, and medical technology continue to evolve at a rapid rate, many regulatory authorities require continuing medical education. Medical practitioners upgrade their knowledge in various ways, including medical journals, seminars, conferences, and online programs. A database of objectives covering medical knowledge, as suggested by national societies across the United States, can be searched at http://data.medobjectives.marian.edu/ Archived 4 October 2018 at the Wayback Machine.
In most countries, it is a legal requirement for a medical doctor to be licensed or registered. In general, this entails a medical degree from a university and accreditation by a medical board or an equivalent national organization, which may ask the applicant to pass exams. This restricts the considerable legal authority of the medical profession to physicians that are trained and qualified by national standards. It is also intended as an assurance to patients and as a safeguard against charlatans that practice inadequate medicine for personal gain. While the laws generally require medical doctors to be trained in "evidence based", Western, or Hippocratic Medicine, they are not intended to discourage different paradigms of health.
In the European Union, the profession of doctor of medicine is regulated. A profession is said to be regulated when access and exercise is subject to the possession of a specific professional qualification. The regulated professions database contains a list of regulated professions for doctor of medicine in the EU member states, EEA countries and Switzerland. This list is covered by the Directive 2005/36/EC.
Doctors who are negligent or intentionally harmful in their care of patients can face charges of medical malpractice and be subject to civil, criminal, or professional sanctions.
== Medical ethics ==
Medical ethics is a system of moral principles that apply values and judgments to the practice of medicine. As a scholarly discipline, medical ethics encompasses its practical application in clinical settings as well as work on its history, philosophy, theology, and sociology. Six of the values that commonly apply to medical ethics discussions are:
autonomy – the patient has the right to refuse or choose their treatment. (Latin: Voluntas aegroti suprema lex.)
beneficence – a practitioner should act in the best interest of the patient. (Latin: Salus aegroti suprema lex.)
justice – concerns the distribution of scarce health resources, and the decision of who gets what treatment (fairness and equality).
non-maleficence – "first, do no harm" (Latin: primum non-nocere).
respect for persons – the patient (and the person treating the patient) have the right to be treated with dignity.
truthfulness and honesty – the concept of informed consent has increased in importance since the historical events of the Doctors' Trial of the Nuremberg trials, Tuskegee syphilis experiment, and others.
Values such as these do not give answers as to how to handle a particular situation, but provide a useful framework for understanding conflicts. When moral values are in conflict, the result may be an ethical dilemma or crisis. Sometimes, no good solution to a dilemma in medical ethics exists, and occasionally, the values of the medical community (i.e., the hospital and its staff) conflict with the values of the individual patient, family, or larger non-medical community. Conflicts can also arise between health care providers, or among family members. For example, some argue that the principles of autonomy and beneficence clash when patients refuse blood transfusions, considering them life-saving; and truth-telling was not emphasized to a large extent before the HIV era.
== History ==
=== Ancient world ===
Prehistoric medicine incorporated plants (herbalism), animal parts, and minerals. In many cases these materials were used ritually as magical substances by priests, shamans, or medicine men. Well-known spiritual systems include animism (the notion of inanimate objects having spirits), spiritualism (an appeal to gods or communion with ancestor spirits); shamanism (the vesting of an individual with mystic powers); and divination (magically obtaining the truth). The field of medical anthropology examines the ways in which culture and society are organized around or impacted by issues of health, health care and related issues.
The earliest known medical texts in the world were found in the ancient Syrian city of Ebla and date back to 2500 BCE. Other early records on medicine have been discovered from ancient Egyptian medicine, Babylonian Medicine, Ayurvedic medicine (in the Indian subcontinent), classical Chinese medicine (Alternative medicine) predecessor to the modern traditional Chinese medicine), and ancient Greek medicine and Roman medicine.
In Egypt, Imhotep (3rd millennium BCE) is the first physician in history known by name. The oldest Egyptian medical text is the Kahun Gynaecological Papyrus from around 2000 BCE, which describes gynaecological diseases. The Edwin Smith Papyrus dating back to 1600 BCE is an early work on surgery, while the Ebers Papyrus dating back to 1500 BCE is akin to a textbook on medicine.
In China, archaeological evidence of medicine in Chinese dates back to the Bronze Age Shang dynasty, based on seeds for herbalism and tools presumed to have been used for surgery. The Huangdi Neijing, the progenitor of Chinese medicine, is a medical text written beginning in the 2nd century BCE and compiled in the 3rd century.
In India, the surgeon Sushruta described numerous surgical operations, including the earliest forms of plastic surgery.Earliest records of dedicated hospitals come from Mihintale in Sri Lanka where evidence of dedicated medicinal treatment facilities for patients are found.
In Greece, the ancient Greek physician Hippocrates, the "father of modern medicine", laid the foundation for a rational approach to medicine. Hippocrates introduced the Hippocratic Oath for physicians, which is still relevant and in use today, and was the first to categorize illnesses as acute, chronic, endemic and epidemic, and use terms such as, "exacerbation, relapse, resolution, crisis, paroxysm, peak, and convalescence". The Greek physician Galen was also one of the greatest surgeons of the ancient world and performed many audacious operations, including brain and eye surgeries. After the fall of the Western Roman Empire and the onset of the Early Middle Ages, the Greek tradition of medicine went into decline in Western Europe, although it continued uninterrupted in the Eastern Roman (Byzantine) Empire.
Most of our knowledge of ancient Hebrew medicine during the 1st millennium BC comes from the Torah, i.e. the Five Books of Moses, which contain various health related laws and rituals. The Hebrew contribution to the development of modern medicine started in the Byzantine Era, with the physician Asaph the Jew.
=== Middle Ages ===
The concept of hospital as institution to offer medical care and possibility of a cure for the patients due to the ideals of Christian charity, rather than just merely a place to die, appeared in the Byzantine Empire.
Although the concept of uroscopy was known to Galen, he did not see the importance of using it to localize the disease. It was under the Byzantines with physicians such of Theophilus Protospatharius that they realized the potential in uroscopy to determine disease in a time when no microscope or stethoscope existed. That practice eventually spread to the rest of Europe.
After 750 CE, the Muslim world had the works of Hippocrates, Galen and Sushruta translated into Arabic, and Islamic physicians engaged in some significant medical research. Notable Islamic medical pioneers include the Persian polymath, Avicenna, who, along with Imhotep and Hippocrates, has also been called the "father of medicine". He wrote The Canon of Medicine which became a standard medical text at many medieval European universities, considered one of the most famous books in the history of medicine. Others include Abulcasis, Avenzoar, Ibn al-Nafis, and Averroes. Persian physician Rhazes was one of the first to question the Greek theory of humorism, which nevertheless remained influential in both medieval Western and medieval Islamic medicine. Some volumes of Rhazes's work Al-Mansuri, namely "On Surgery" and "A General Book on Therapy", became part of the medical curriculum in European universities. Additionally, he has been described as a doctor's doctor, the father of pediatrics, and a pioneer of ophthalmology. For example, he was the first to recognize the reaction of the eye's pupil to light. The Persian Bimaristan hospitals were an early example of public hospitals.
In Europe, Charlemagne decreed that a hospital should be attached to each cathedral and monastery and the historian Geoffrey Blainey likened the activities of the Catholic Church in health care during the Middle Ages to an early version of a welfare state: "It conducted hospitals for the old and orphanages for the young; hospices for the sick of all ages; places for the lepers; and hostels or inns where pilgrims could buy a cheap bed and meal". It supplied food to the population during famine and distributed food to the poor. This welfare system the church funded through collecting taxes on a large scale and possessing large farmlands and estates. The Benedictine order was noted for setting up hospitals and infirmaries in their monasteries, growing medical herbs and becoming the chief medical care givers of their districts, as at the great Abbey of Cluny. The Church also established a network of cathedral schools and universities where medicine was studied. The Schola Medica Salernitana in Salerno, looking to the learning of Greek and Arab physicians, grew to be the finest medical school in medieval Europe.
However, the fourteenth and fifteenth century Black Death devastated both the Middle East and Europe, and it has even been argued that Western Europe was generally more effective in recovering from the pandemic than the Middle East. In the early modern period, important early figures in medicine and anatomy emerged in Europe, including Gabriele Falloppio and William Harvey.
The major shift in medical thinking was the gradual rejection, especially during the Black Death in the 14th and 15th centuries, of what may be called the "traditional authority" approach to science and medicine. This was the notion that because some prominent person in the past said something must be so, then that was the way it was, and anything one observed to the contrary was an anomaly (which was paralleled by a similar shift in European society in general – see Copernicus's rejection of Ptolemy's theories on astronomy). Physicians like Vesalius improved upon or disproved some of the theories from the past. The main tomes used both by medicine students and expert physicians were Materia Medica and Pharmacopoeia.
Andreas Vesalius was the author of De humani corporis fabrica, an important book on human anatomy. Bacteria and microorganisms were first observed with a microscope by Antonie van Leeuwenhoek in 1676, initiating the scientific field microbiology. Independently from Ibn al-Nafis, Michael Servetus rediscovered the pulmonary circulation, but this discovery did not reach the public because it was written down for the first time in the "Manuscript of Paris" in 1546, and later published in the theological work for which he paid with his life in 1553. Later this was described by Renaldus Columbus and Andrea Cesalpino. Herman Boerhaave is sometimes referred to as a "father of physiology" due to his exemplary teaching in Leiden and textbook 'Institutiones medicae' (1708). Pierre Fauchard has been called "the father of modern dentistry".
=== Modern ===
Veterinary medicine was, for the first time, truly separated from human medicine in 1761, when the French veterinarian Claude Bourgelat founded the world's first veterinary school in Lyon, France. Before this, medical doctors treated both humans and other animals.
Modern scientific biomedical research (where results are testable and reproducible) began to replace early Western traditions based on herbalism, the Greek "four humours" and other such pre-modern notions. The modern era really began with Edward Jenner's discovery of the smallpox vaccine at the end of the 18th century (inspired by the method of variolation originated in ancient China), Robert Koch's discoveries around 1880 of the transmission of disease by bacteria, and then the discovery of antibiotics around 1900.
The post-18th century modernity period brought more groundbreaking researchers from Europe. From Germany and Austria, doctors Rudolf Virchow, Wilhelm Conrad Röntgen, Karl Landsteiner and Otto Loewi made notable contributions. In the United Kingdom, Alexander Fleming, Joseph Lister, Francis Crick and Florence Nightingale are considered important. Spanish doctor Santiago Ramón y Cajal is considered the father of modern neuroscience.
From New Zealand and Australia came Maurice Wilkins, Howard Florey, and Frank Macfarlane Burnet.
Others that did significant work include William Williams Keen, William Coley, James D. Watson (United States); Salvador Luria (Italy); Alexandre Yersin (Switzerland); Kitasato Shibasaburō (Japan); Jean-Martin Charcot, Claude Bernard, Paul Broca (France); Adolfo Lutz (Brazil); Nikolai Korotkov (Russia); Sir William Osler (Canada); and Harvey Cushing (United States).
As science and technology developed, medicine became more reliant upon medications. Throughout history and in Europe right until the late 18th century, not only plant products were used as medicine, but also animal (including human) body parts and fluids. Pharmacology developed in part from herbalism and some drugs are still derived from plants (atropine, ephedrine, warfarin, aspirin, digoxin, vinca alkaloids, taxol, hyoscine, etc.). Vaccines were discovered by Edward Jenner and Louis Pasteur.
The first antibiotic was arsphenamine (Salvarsan) discovered by Paul Ehrlich in 1908 after he observed that bacteria took up toxic dyes that human cells did not. The first major class of antibiotics was the sulfa drugs, derived by German chemists originally from azo dyes.
Pharmacology has become increasingly sophisticated; modern biotechnology allows drugs targeted towards specific physiological processes to be developed, sometimes designed for compatibility with the body to reduce side-effects. Genomics and knowledge of human genetics and human evolution is having increasingly significant influence on medicine, as the causative genes of most monogenic genetic disorders have now been identified, and the development of techniques in molecular biology, evolution, and genetics are influencing medical technology, practice and decision-making.
Evidence-based medicine is a contemporary movement to establish the most effective algorithms of practice (ways of doing things) through the use of systematic reviews and meta-analysis. The movement is facilitated by modern global information science, which allows as much of the available evidence as possible to be collected and analyzed according to standard protocols that are then disseminated to healthcare providers. The Cochrane Collaboration leads this movement. A 2001 review of 160 Cochrane systematic reviews revealed that, according to two readers, 21.3% of the reviews concluded insufficient evidence, 20% concluded evidence of no effect, and 22.5% concluded positive effect.
== Quality, efficiency, and access ==
Evidence-based medicine, prevention of medical error (and other "iatrogenesis"), and avoidance of unnecessary health care are a priority in modern medical systems. These topics generate significant political and public policy attention, particularly in the United States where healthcare is regarded as excessively costly but population health metrics lag similar nations.
Globally, many developing countries lack access to care and access to medicines. As of 2015, most wealthy developed countries provide health care to all citizens, with a few exceptions such as the United States where lack of health insurance coverage may limit access.
== See also ==
== Notes ==
== References == | Wikipedia/Clinical_medicine |
The emotional thought method (Spanish: Pensamiento emocional) is a technique for increasing emotional intelligence using a group of activities that can be used in a personal or group-oriented way.
== Origins ==
The emotional thought method was created by Carlos Hué, a Spanish psychologist who is a teacher at the University of Zaragoza. It is explained in the book Pensamiento emocional. Un método para el desarrollo de la autoestima y el liderazgo (Hué, 2007). This book has not yet been translated into English. Carlos Hué gathers a lot of exercises in this method in order to develop emotional skills.
== Emotional intelligence ==
Emotional intelligence is based on several competencies intended to enhance success in their personal, professional, and social lives. These kinds of competencies develop throughout life, but they are not explicitly taught.
Training actions are offered by companies, public administrations, entities, institutions, and social agents to develop such competencies. However, these methods are not complete.
== Competencies ==
The emotional though method proposes seven competencies. Four pertain to the self: self-knowledge, self-evaluation, emotional control, and personal motivation; and three pertain to others: knowledge of others, appreciation of others, and control of them.
Self-knowledge includes knowledge of personal capacities, skills, personality, interests, goals, etc. It involves introspection, knowledge of skills, personal emotions, ability to apply self-criticism, and self-awareness.
Self-evaluation requires knowledge of self and some degree of self-esteem. Self-esteem is advanced as the driving force of behaviour. This competence is the result of developing sensibility, sensuality, sexuality, optimism, happiness and self-esteem.
Emotional control involves managing stress, fear and anxiety by developing three emotional skills: motor inhibition, self-control, and mental control.
Personal motivation involves learning activation, productivity, quality, instrumental tools, globality, planning, culture, innovation, interests' wideness, determination and evaluation.
Three competences in this emotional method are oriented to how to make relationships. Knowledge of others involves knowing their personality, interests, aptitudes, empathy, communication ability, social analysis, and appreciation of diversity.
Appreciation of others involves ten abilities. They are structured in four groups:
Necessary capacities for a relationship: approximation, affability, and tolerance.
Capacities for creating a link: confidence, comprehension and sociability.
Three levels of proximity: companionship, friendship and love.
Responsibility, as the sum of the others.
The last competence is control of others. This competence has been criticized as not respectful of others, even to persuade others to pursue their interests. This involves the capacity to have relations, the capacity to organize groups, the capacity to solve conflicts, and leadership.
These seven competencies are developed through exercises, as much as in Hué's book, as in the TREIN project.
== References ==
Goleman, Daniel, 1995. Emotional intelligence. New York: Bantam Books.
Goleman, Daniel, 2006. Social intelligence: the new science of human relationships. New York: Bantam Books.
Hué, Carlos, 2007. Pensamiento emocional. Un método para el desarrollo de la autoestima y el liderazgo. Zaragoza: Mira. | Wikipedia/Emotional_thought_method |
Somatic theory is a theory of human social behavior based on the somatic marker hypothesis of António Damásio. The theory proposes a mechanism by which emotional processes can guide (or bias) behavior: in particular, decision-making, the attachment theory of John Bowlby, and the self-psychology of Heinz Kohut (especially as consolidated by Allan Schore).
It draws on various philosophical models: On the Genealogy of Morals of Friedrich Nietzsche, Martin Heidegger on das Man, Maurice Merleau-Ponty practiced on the lived body as a center of experience, Ludwig Wittgenstein on social practices, Michel Foucault on discipline, as well as theories of performativity emerging out of the speech act theory by J. L. Austin, in point of fact was developed by Judith Butler and Shoshana Felman. Some somatic theorists have also put into somatic theory to performance in the schools of acting, the training was developed by Konstantin Stanislavski and Bertolt Brecht.
== Theorists ==
=== Barbara Sellers-Young ===
Barbara Sellers-Young applies Damasio’s somatic-marker hypothesis to critical thinking as an embodied performance and provides a review of the theoretical literature in performance studies that supports something like Damasio’s approach:
Howard Gardner’s theory of multiple intelligences, especially bodily-kinesthetic intelligence
Thomas Hanna’s believe that “we cannot sense without acting and we cannot act without sensing”
Bonnie Bainbridge Cohen's movement-pedagogy
Konstantin Stanislavski’s acting theory that “in every physical action, unless it is purely mechanical, there is concealed some inner action, some feelings. This is how the two levels of life in a part are created, the inner and the outer. They are intertwined. A common purpose brings them together and reinforces the unbreakable bond.”
=== Edward Slingerland ===
Edward Slingerland applies Damasio's somatic-marker hypothesis to the cognitive linguistics by Gilles Fauconnier and Mark Turner, as well as George Lakoff and Mark Johnson. In particular, Slingerland combines Fauconnier and Turner's theory of conceptual blending and Lakoff and Johnson's embodied mind theory of metaphor in his hypothesis. His goal to apply somatic theory into cognitive linguistics is to show that:
the primary purpose of achieving human scale is not to help us apprehend a situation but rather to help us to know how to feel about it. Especially in political and religious discourse--situations where speakers are attempting to influence their listeners' values and decision-making processes--, I would like to argue that the achievement of human scale is intended primarily to import normativity to the blend, which is accomplished through the recruitment of human-scale emotional-somatic reactions. This argument is essentially an attempt to connect conceptual blending theorists with those neuroscientists who argue for the importance of somatic states and emotional reactions in human value creation and decision-making.
=== Douglas Robinson ===
Douglas Robinson first began developing a somatic theory of language for a keynote presentation at the 9th American Imagery Conference in Los Angeles, in October 1985. It was based on Ahkter Ahsen's theory of somatic response to images as the basis for therapeutic transformations. In contradistinction to Ahsan's model, which rejected Freud's "talking cure" on the grounds that words do not awaken somatic responses, Robinson argued that there is a very powerful somatics of language. He later incorporated this notion into The Translator's Turn (1991), drawing on the (passing) somatic theories of William James, Ludwig Wittgenstein, and Kenneth Burke in order to argue that somatic response may be "idiosomatic" (somatically idiosyncratic), but is typically "ideosomatic" (somatically ideological, or shaped and guided by society). Furthermore, the ideosomatics of language explain how language remains stable enough for communication to be possible. This work preceded the Damasio group's first scientific publication on the somatic-marker hypothesis in 1991, and Robinson did not begin to incorporate Damasio's somatic-marker hypothesis into his somatic theory until later in the 1990s.
In Translation and Taboo (1996), Robinson drew on the proto-somatic theories of Sigmund Freud, Jacques Lacan, and Gregory Bateson to explore the ways in which the ideosomatics of taboo structure (and partly sanction and conceal) the translation of sacred texts. His first book to draw on Damasio's somatic-marker hypothesis is Performative Linguistics (2003); there he draws on J. L. Austin's theory of speech acts, Jacques Derrida's theory of iterability, and Mikhail Bakhtin's theory of dialogism, to argue that performativity as an activity of the speaking body is grounded in somatic theory. He also draws on Daniel Simeoni's application of Pierre Bourdieu's theory of habitus in order to argue that his somatics of translation as developed in The Translator's Turn actually explains translation norms more fully than Gideon Toury's account in Descriptive Translation Studies and beyond (1995).
In 2005, Robinson began writing a series of books exploring somatic theory in different communicative contexts: modernist/formalist theories of estrangement (Robinson 2008), translation as ideological pressure (Robinson 2011), first-year writing (Robinson 2012), and the refugee experience, (de)colonization, and the intergenerational transmission of trauma (Robinson 2013).
In Robinson's articulation, the somatic theory has four main planks:
The stabilization of social constructions through somatic markers.
The interpersonal sharing of such stabilization through the mimetic somatic transfer.
The regulatory (ideosomatic) circulation or reticulation of such somatomimeses through an entire group in the somatic exchange.
The "klugey" nature of social regulation through the somatic exchange, leading to various idiosomatic failures and refusals to be fully regulated.
In addition, he has tied additional concepts to somatic theory along the way: the proprioception of the body politic as a homeostatic balancing between too much familiarity and too much strangeness (Robinson 2008); tensions between loconormativity and xenonormativity, the exosomatization of places, objects, and skin color, and paleosomaticity (Robinson 2013); ecosis and icosis (unpublished work).
=== Stephanie Fetta ===
Stephanie Fetta’s approach to somatic theory weaves together an extensive array of disciplinary discourses, ranging from cognitive science and neuroscience to sociology and Sophiology. As a literary and cultural critic, Fetta draws attention to and investigates the role of the soma in her study of US Latin@/x creative texts. Her scholarly work broadens the scope of somatic theory and literary scholarship by drawing support from the natural and social sciences to position the soma as a “psychobiological agent” and social actor, and thus an overlooked (albeit indispensable) lens in the study of social power (2018, 37). Building on both biblical and contemporary uses of the term, Fetta reconceptualizes the soma as ‘the emotional, intelligent and communicative body’ and explains that it refers to the gestures of the physical body in internal response to external social pressures. Hence, she is one of the first somatic theorists to employ the term soma along these lines—despite the current spate of studies in neurology, cognitive literary studies, behavioral science, body studies, affect theory, theories of mind (ToM) and philosophy of mind (PoM), which piece together the connections among cognitive processes, bodily feeling reactions, and evaluative perceptions.
In 2018, she published Shaming into Brown: Somatic Transactions of Race in Latina/o Literature—a detailed and analytic transdisciplinary study that renders the soma as “a pervasive yet unexpected site of subjectivity.” She employs this conception of soma as a primary tool to investigate intersectional racialization and the transactions of race in her case studies of Latin@/x literature (xiii). This book develops somatic analysis as a line of investigation, which reviewers maintain has applications in fields such as the humanities, critical race theory, neurology, behavioral studies, and so on. Somatic analysis has inspired, and been cited in, a growing number of academic, personal, and artistic works.
Fetta’s key applications of somatic analysis are as follows:
Racial Shaming: a social technology that uses the somatic body to materialize Brown into social fact. Her thesis is anchored in two psychoanalytic theories: bioenergetic analysis, developed by Alexander Lowen, and affect theory, put forth by Silvan Tomkins.
Scenes of Racialization: a social practice in which “bodies impose social asymmetries through the somatic expression” (2018, xv). Fetta identifies four steps, or somatic sequences, through which the notion of race conditions personal and intersubjective interactions. The racializer begins by (1) identifying phenotypic and somatic cues as a reason to stymie somatic mirroring and withdraw interpersonal rapport with the racialized interlocutor, blocking any empathy toward her or him. This leads, in turn, to (2) social rejection and somatic dissonance, which functions as a source of shame. In line with Damasio’s somatic marker hypothesis, she argues (3) socially and culturally crafted sensory scripts are applied, (4) completing the process of racialization with a somatic expression of disgust, as registered through the senses (vision, audition, and olfaction).
Internal Soma: Fetta examines racialization from the perspective of the somatic interior body. In her case study of Oscar ‘Zeta’ Acosta’s Autobiography of a Brown Buffalo (1972), she takes heed of the parallels between Oscar’s struggle with internalized self-loathing and his nonconforming somatic stomach.
Somatic Portrayal: a process relied on by successful Method actors, in which actors must override their own somatic expression by inhabiting and portraying the soma of their character. Fetta further complicates the performance goal of Method acting’s the purportedly real somatic portrayal and contends that such portrayal may “rub up against another style of acting [she] refers to as body image management […] which lacks the naturalness of lived somatic expression” (2018, 95). Extended to the concept of magico nanny, somatic performance is exacted on social inferiors, whose true somatic expression could betray vulnerability to shaming or even violence.
The Soma and Sophia: Fetta also (re)introduces Sophia, the second figure in certain Christian trinities, to literary analysis and somatic theory. She explains that Andres Montoya’s poetry collection, The Ice Worker Sings and Other Poems (1999), provides another vision of the soma—a spiritual or divine soma, one that transforms pain, suffering, and sin through the sacred figure of Sophia. Thereby, she claims that Sophia is not only a biblical figure but also a powerful analysis of the divine soma.
== References ==
== Further reading ==
Damasio, Antonio R. (1994). Descartes’ Error: Emotion, Reason, and the Human Brain. New York: Putnam.
Damasio, Antonio R. (1999). The Feeling of What Happens: Body and Emotion in the Making of Consciousness. New York: Harcourt.
Damasio, Antonio R. (2003). Looking for Spinoza: Joy, Sorrow, and the Feeling Brain. New York: Harcourt.
Felman, Shoshana. (1980/2003). The Scandal of the Speaking Body: Don Juan With J. L. Austin, or Seduction in Two Languages. Translated by Catherine Porter. Stanford: Stanford University Press.
Fetta, Stephanie. (2016). "A Bad Attitude and A Bad Stomach: The Soma in Oscar 'Zeta' Acosta’s The Autobiography of a Brown Buffalo." Transmodernity: Journal of Peripheral Cultural Production of the Luso-Hispanic World, 6.1: 89-109.
Fetta, Stephanie. (2018). Shaming into Brown: Somatic Transactions of Race in Latina/o Literature. Columbus: Ohio State University Press.
Hanna, Thomas. (1995). "What is Somatics?" In Don Hanlon Johnson, ed., Bone, Breath and Gesture, 341-53. Berkeley: North Atlantic.
Robinson, Douglas. (1991). The Translator’s Turn. Baltimore and London: Johns Hopkins University Press.
Robinson, Douglas. (1996). Translation and Taboo. DeKalb: Northern Illinois University Press.
Robinson, Douglas. (2003). Performative Linguistics: Speaking and Translating as Doing Things With Words. London and New York: Routledge.
Robinson, Douglas. (2008). Estrangement and the Somatics of Literature: Tolstoy, Shklovsky, Brecht. Baltimore: Johns Hopkins University Press.
Robinson, Douglas. (2011). Translation and the Problem of Sway. Amsterdam and Philadelphia: John Benjamins.
Robinson, Douglas. (2012). First-Year Writing and the Somatic Exchange. New York: Hampton.
Robinson, Douglas. (2013). Displacement and the Somatics of Postcolonial Culture. Columbus: Ohio State University Press, forthcoming.
Sellers-Young, Barbara. (2002). "Breath, Perception, and Action: The Body and Critical Thinking." Consciousness, Literature and the Arts 3.2 (August).
Sellers-Young, Barbara (1998) "Somatic Processes: Convergence of Theory and Practice," Theatre Topics 8/2 (September 1998) 173-187.
Sellers-Young, Barbara (1999) "Technique and the Embodied Actor," Theatre Research International 24/1 (Spring 199) 89-102.
Sellers-Young, Barbara (2008) “Consciousness, Contemplation and the Academy,” Consciousness, Literature, and the Arts, 9/1 (April) 1-15.
Sellers-Young, Barbara (2013) “Stillness in Motion – Motion in Stillness: Contemplative Practice and the Performing Arts”, Embodied Consciousness – Performance Technologies, New York: Palgrave.
Slingerland, Edward G. (2005). "Conceptual Blending, Somatic Marking, and Normativity: A Case Example from Ancient China." Cognitive Linguistics 16.3: 557-584.
Slingerland, Edward G., Eric Blanchard, and Lyn Boyd-Judson. (2007). "Collision with China: Conceptual Metaphor Analysis, Somatic Marking, and the EP3 Incident." International Studies Quarterly 51: 53-77.
Stanislavski, Konstantin. (1961/1989). Creating a Role. Translated by Elizabeth Reynolds Hapgood. London and New York: Routledge. | Wikipedia/Somatic_theory |
Discrete emotion theory is the claim that there is a small number of core emotions. For example, Silvan Tomkins (1962, 1963) concluded that there are nine basic affects which correspond with what we come to know as emotions: interest, enjoyment, surprise, distress, fear, anger, shame, dissmell (reaction to bad smell) and disgust. More recently, Carroll Izard at the University of Delaware factor analytically delineated 12 discrete emotions labeled: Interest, Joy, Surprise, Sadness, Anger, Disgust, Contempt, Self-Hostility, Fear, Shame, Shyness, and Guilt (as measured via his Differential Emotions Scale or DES-IV).
Discrete emotion theory states that these specific core emotions are biologically determined emotional responses whose expression and recognition is fundamentally the same for all individuals regardless of ethnic or cultural differences.
== History ==
The biological and physiological underpinnings of emotions were discussed by Aristotle in De Anima, by Charles Darwin in The Expression of the Emotions in Man and Animals (1872), by William James (1884), and by John Dewey (1895).
Tomkins' (1962, 1963) idea was influenced by Darwin's concept. He proposed that there is a limited number of inborn basic "affect programs": surprise, interest-excitement, enjoyment-joy, anger-rage, fear-terror, shame-humiliation, distress-anguish, disgust, dissmell. These affects are not necessarily recognizable consciously, but they become recognizable as emotions when they combine meaningfully with personal and cultural experience.
John Watson believed that emotions could be described in physical states.
Edwin Newman and colleagues believed emotions were a combination of one's experiences, physiology, and behaviour.
Ross Buck came up with the facial feedback hypothesis, "that skeletal muscle feedback from facial expressions plays a causal role in regulating emotional experience and behaviour".
After performing a series of cross-cultural studies, Paul Ekman and Carroll Izard reported that there are various similarities in the way people across the world produce and recognize the facial expressions of at least six emotions.
== Evidence for the theory ==
A study investigated whether the emotions behind specific facial expressions could be identified by people from a group in New Guinea who had had little to no exposure to Westerners and who had never seen a movie. The researchers showed the people pictures of people portraying six different emotions that are known as core emotions: happiness, anger, sadness, disgust, surprise and fear. Researchers found that the people of New Guinea could in fact point out the different emotions and distinguish between them.
Various parts in the brain can trigger different emotions. For example, the amygdala is the locus of fear. The amygdala senses fear and it orchestrates physical actions and emotions. From this experiment, researchers concluded that these specific emotions are innate. They also looked at pictures of people ranging in age from infants to elders, and saw that the core emotions look the same, further supporting the discrete emotion hypothesis. Additionally, deaf and blind children show typical facial expressions for these same core emotions.
== Criticism ==
James Russell and Lisa Barrett have criticized discrete emotion theory on several points. Those include problems in finding correspondences between discrete emotions and brain activity, variability in facial expressions and behavior, and gradations in emotional responses.
== See also ==
Affect theory
Developmental psychology
Emotions and culture
Emotion classification
== Bibliography ==
Tomkins, Silvan S. (1962), Affect Imagery Consciousness: Volume I, The Positive Affects. London: Tavistock.
Tomkins, Silvan S. (1963), Affect Imagery Consciousness: Volume II, The Negative Affects.
== References == | Wikipedia/Discrete_emotion_theory |
In science fiction, wireheading is a term associated with fictional or futuristic applications of brain stimulation reward, the act of directly triggering the brain's reward center by electrical stimulation of an inserted wire, for the purpose of 'short-circuiting' the brain's normal reward process and artificially inducing pleasure. Scientists have successfully performed brain stimulation reward on rats (1950s) and humans (1960s). This stimulation does not appear to lead to tolerance or satiation in the way that sex or drugs do. The term is sometimes associated with science fiction writer Larry Niven, who used the term in his Known Space series. In the philosophy of artificial intelligence, the term is used to refer to AI systems that hack their own reward channel.
More broadly, the term can also refer to various kinds of interaction between human beings and technology.
== In fiction ==
=== Literature ===
Wireheading, like other forms of brain alteration, is often treated as dystopian in science fiction literature.
In Larry Niven's Known Space stories, a "wirehead" is someone who has been fitted with an electronic brain implant known as a "droud" in order to stimulate the pleasure centers of their brain. Wireheading is the most addictive habit known (Louis Wu is the only given example of a recovered addict), and wireheads usually die from neglecting their basic needs in favour of the ceaseless pleasure. Wireheading is so powerful and easy that it becomes an evolutionary pressure, selecting against that portion of humanity without self-control. A wirehead's death is central to Niven's story "Death by Ecstasy", published in 1969 under the title The Organleggers, and a main character in the book Ringworld Engineers is a former wirehead trying to quit.
Also in the Known Space universe, a device called a "tasp" which does not need a surgical implant (similar to transcranial magnetic stimulation) can be used to achieve similar goals: the pleasure center of a person's brain is found and remotely stimulated (considered a violation without seeking the person's consent beforehand). It is an important device in Niven's Ringworld novels.
Niven's stories explain wireheads by mentioning a study in which experimental rats had electrodes implanted at strategic locations in their brains, so that an applied current would induce a pleasant feeling. If the current could be obtained any time the rats pushed the lever, they would use it over and over, ignoring food and physical necessities until they died. Such experiments were actually conducted by James Olds and Peter Milner in the 1950s, first discovering the locations of such areas, and later showing the extremes to which rats would go to obtain the stimulus again.
In the novel Mindkiller (1982) by Spider Robinson, the antagonist "Jacques" has the ability to wirehead his targets by inducing an enslaving brain-ecstasy from a distance.
The Shaper/Mechanist stories by Bruce Sterling use the term "wirehead" in the broader sense of people or cyborgs who can link their minds to computers or other technology.
In The Terminal Man (1972) by Michael Crichton, forty electrodes are implanted into the brain of the character Harold Franklin "Harry" Benson to control his seizures. However, his pleasure center is also stimulated, and his body begins producing more seizures in order to receive the pleasurable sensation.
== See also ==
Wireheading
Brain–computer interface
David Pearce (philosopher)
Experience machine
Hedonic treadmill
Pain and pleasure § Deep brain stimulation
Borg (Star Trek)
Metaverse
Spatial computing
Soma (Brave New World)
== References == | Wikipedia/Wirehead_(science_fiction) |
Appraisal theory is the theory in psychology that emotions are extracted from our evaluations (appraisals or estimates) of events that cause specific reactions in different people. Essentially, our appraisal of a situation causes an emotional, or affective, response that is going to be based on that appraisal. An example of this is going on a first date. If the date is perceived as positive, one might feel happiness, joy, giddiness, excitement, and/or anticipation, because they have appraised this event as one that could have positive long-term effects, i.e. starting a new relationship, engagement, or even marriage. On the other hand, if the date is perceived negatively, then our emotions, as a result, might include dejection, sadness, emptiness, or fear. (Scherer et al., 2001) Reasoning and understanding of one's emotional reaction becomes important for future appraisals as well. The important aspect of the appraisal theory is that it accounts for individual variability in emotional reactions to the same event.
Appraisal theories of emotion are theories that state that emotions result from people's interpretations and explanations of their circumstances even in the absence of physiological arousal (Aronson, 2005). There are two basic approaches; the structural approach and process model. These models both provide an explanation for the appraisal of emotions and explain in different ways how emotions can develop. In the absence of physiological arousal we decide how to feel about a situation after we have interpreted and explained the phenomena. Thus the sequence of events is as follows: event, thinking, and simultaneous events of arousal and emotion. Social psychologists have used this theory to explain and predict coping mechanisms and people's patterns of emotionality. By contrast, for example, personality psychology studies emotions as a function of a person's personality, and thus does not take into account the person's appraisal, or cognitive response, to a situation. Personality psychology relates to analyzing factors that influence how people are similar to one another and their unique differences.
The main controversy surrounding these theories argues that emotions cannot happen without physiological arousal.
== History ==
For the past several decades, appraisal theory has developed and evolved as a prominent theory in the field of communication and psychology by testing affect and emotion. In history, the most basic ideology dates back to some of the most notable philosophers such as Aristotle, Plato, the Stoics, Spinoza and Hume, and even early German psychologist Stumpf (Reisenzein & Schonpflug, 1992). However, in the past fifty years, this theory has expanded exponentially with the dedication of two prominent researchers: Magda Arnold and Richard Lazarus, amongst others who have contributed appraisal theories.
The question studied under appraisal theories is why people react to things differently. Even when presented with the same, or a similar situation all people will react in slightly different ways based on their perception of the situation. These perceptions elicit various emotions that are specific to each person. About 30 years ago, psychologists and researchers began to categorize these emotions into different groups. This is where cognitive appraisal theory stems from. They decided to categorize these emotional reaction behaviors as appraisals. The two main theories of appraisal are the structural model and the process model. These models are broken down into subtypes as well (Smith & Kirby, 2009). Researchers have attempted to specify particular appraisals of events that elicit emotions (Roseman et al., 1996).
=== Magda Arnold ===
Dating back to the 1940s and 1950s, Magda Arnold took an interest in researching the appraisal of emotions accompanying general arousal. Specifically, Arnold wanted to "introduce the idea of emotion differentiation by postulating that emotions such as fear, anger, and excitement could be distinguished by different excitatory phenomena" (Arnold, 1950). With these new ideas, she developed her "cognitive theory" in the 1960s, which specified that the first step in emotion is an appraisal of the situation. According to Arnold, the initial appraisals start the emotional sequence and arouse both the appropriate actions and the emotional experience itself, so that the physiological changes, recognized as important, accompany, but do not initiate, the actions and experiences (Arnold, 1960a). A notable advancement was Arnold's idea of intuitive appraisal in which she describes emotions that are good or bad for the person lead to an action. For example, if a student studies hard in a difficult class and passes the tough mid-term exam with an "A", the felt emotion of happiness will motivate the student to keep studying hard for that class.
Emotion is a difficult concept to define as emotions are constantly changing for each individual, but Arnold's continued advancements and changing theory led her to keep researching her work within appraisal theory. The 1970s were difficult as fellow researchers challenged her theory with questions concerning the involvement of psycho-physiological factors and the psychological experiences at the Loyola Symposium on Feelings and Emotions. Despite this and re-evaluating the theory, Arnold's discoveries paved the way for other researchers to learn about variances of emotion, affect, and their relation to each other.
=== Richard Lazarus ===
Following close to Magda Arnold in terms of appraisal theory examination was Richard Lazarus who continued to research emotions through appraisal theory before his death in 2002. Since he began researching in the 1950s, this concept evolves and expands to include new research, methods, and procedures. Although Arnold had a difficult time with questions, Lazarus and other researchers discussed the biopsychological components of the theory at the Loyola Symposium ("Towards a Cognitive Theory of Emotion").
Specifically, he identified two essential factors in an essay in which he discusses the cognitive aspects of emotion: "first, what is the nature of the cognitions (or appraisals) which underlie separate emotional reactions (e.g. fear, guilt, grief, joy, etc.). Second, what are the determining antecedent conditions of these cognitions." (Lazarus, Averill, & Opton (1970, p. 219) These two aspects are absolutely crucial in defining the reactions that stem from the initial emotions that underlie the reactions. Moreover, Lazarus specified two major types of appraisal methods which sit at the crux of the appraisal method: 1) primary appraisal, directed at the establishment of the significance or meaning of the event to the organism, and 2) secondary appraisal, directed at the assessment of the ability of the organism to cope with the consequences of the event. These two types go hand in hand as one establishes the importance of the event while the following assesses the coping mechanisms which Lazarus divided up into two parts: direct actions and cognitive reappraisal processes.
To simplify Lazarus's theory and emphasize his stress on cognition, as you are experiencing an event, your thought must precede the arousal and emotion (which happen simultaneously). For example: You are about to give a speech in front of 50 of your peers. First, you think: "I've never spoken in front of such a big crowd. I'm going to make a fool of myself." Then, Your mouth goes dry, your heart beat quickens, your palms sweat, and your legs begin to shake and at the same time you experience fear.
== Varieties ==
=== Structural model ===
The structural model of appraisal helps to explain the relation between appraisals and the emotions they elicit. This model involves examination of the appraisal process as well as examination of how different appraisals influence which emotions are experienced.
According to Lazarus (1991), theories of emotion involve a relational aspect, a motivational aspect, and a cognitive aspect (Lazarus, 1991). The relational aspect involves the relationship between a person and the environment and suggests that emotions always involve an interaction between the two (Lazarus, 1991). The motivational aspect involves an assessment of the status of one's goals and is the aspect of the evaluation of a situation in which a person determines how relevant the situation is to his or her goals (Lazarus, 1991). Finally, the cognitive component involves one's appraisal of the situation, or an evaluation of how relevant and significant a situation is to one's life (Lazarus, 1991). Lazarus suggests that different emotions are elicited when situations are evaluated differently according to these three categories. In order to evaluate each emotion individually, however, a structural model of appraisal is necessary (Lazarus, 1991). This model allows for the individual components of the appraisal process to be determined for each emotion. In addition, this model allows for the evaluation of how and where the appraisal processes differ for different emotions (Lazarus, 1991).
==== Primary appraisal ====
The appraisal process is broken up into two different categories, primary appraisal and secondary appraisal (Lazarus, 1991). In a person's primary appraisal, he or she evaluates two aspects of a situation: the motivational relevance and the motivational congruence (Smith & Kirby, 2009). When evaluating motivational relevance, an individual answers the question, "How relevant is this situation to my needs?" Thus, the individual evaluates how important the situation is to his or her well-being. The motivational relevance aspect of the appraisal of the process has been shown to influence the intensity of the experienced emotions so that when a situation is highly relevant to one's well-being, the situation elicits a more intense emotional response (Smith & Kirby, 2009). The second aspect of an individual's primary appraisal of a situation is the evaluation of motivational congruence. When evaluating the motivational congruence of a situation, an individual answers the question, "Is this situation congruent or incongruent (consistent or inconsistent) with my goals?" (Smith & Kirby, 2009). Individuals experience different emotions when they view a situation as consistent with their goals than when they view it as inconsistent.
==== Secondary appraisal ====
People's emotions are also influenced by their secondary appraisal of situations. Secondary appraisal involves people's evaluation of their resources and options for coping (Lazarus, 1991). One aspect of secondary appraisal is a person's evaluation of who should be held accountable. A person can hold herself, another, or a group of other people accountable for the situation at hand. Blame may be given for a harmful event and credit may be given for a beneficial event (Lazarus, 1991). In addition, an individual might also see the situation as due to chance. The way in which people view who or what should be held accountable directs and guides their efforts to cope with the emotions they experience. Another aspect of secondary appraisal is a person's coping potential. Coping potential is potential to use either problem-focused coping or emotion-focused coping strategies to handle an emotional experience. (Smith & Kirby, 2009). Problem-focused coping refers to one's ability to take action and to change a situation to make it more congruent with one's goals (Smith & Kirby, 2009). Thus, a person's belief about their ability to perform problem-focused coping influences the emotions they experience in the situation. On the other hand, emotion-focused coping refers to one's ability to handle or adjust to the situation should the circumstances remain inconsistent with one's goals (Smith & Kirby, 2009). Again, the emotions people experience are influenced by how they perceive their ability to perform emotion-focused coping. The fourth component of secondary appraisal is one's future expectancy (Lazarus, 1991). Future expectancy refers to one's expectations of change in the motivational congruence of a situation (for any reason). Thus, an individual may believe the situation will change favorably or unfavorably (Lazarus, 1991). One's future expectancy influences the emotions elicited during a situation as well as the coping strategies used.
The structural model of appraisal suggests that the answers to the different component questions of the primary and secondary categories allow researchers to predict which emotions will be elicited from a certain set of circumstances. In other words, the theory suggests that researchers are able to examine an individual's appraisal of a situation and then predict the emotional experiences of that individual based upon his or her views of the situation. An example of a particular emotion and its underlying appraisal components can be seen when examining the emotion of anger. If a person appraises a situation as motivationally relevant, motivationally incongruent, and also holds a person other than himself accountable, the individual would most likely experience anger in response to the situation (Smith & Haynes, 1993). Another example of the appraisal components of an emotion can be given in regards to anxiety. Like anger, anxiety comes from the evaluation of a situation as motivationally relevant and motivationally incongruent (Lazarus, 1991). However, where anxiety differs from anger is in who is held accountable. For anger, another person or group of people is held accountable or blamed for a wrongdoing. However, in regards to anxiety, there is no obvious person or group to hold accountable or to blame. The structural model of appraisal allows for researchers to assess different appraisal components that lead to different emotions.
=== Process model ===
Appraisal theory, however, has often been critiqued for failing to capture the dynamic nature of emotion. To better analyze the complexities of emotional appraisal, social psychologists have sought to further complement the structural model. One suggested approach was a cyclical process, which moves from appraisal to coping, and then reappraisal, attempting to capture a more long-term theory of emotional responses (Smith & Lazarus 1990). This model, however, failed to hold up under scholarly and scientific critique, largely due to the fact that it fails to account for the often rapid or automatic nature of emotional responses (Marsella & Gratch 2009). Further addressing the concerns raised with structural and cyclical models of appraisal, two different theories emerged that advocated a process model of appraisal.
==== Two-process model of appraisal ====
Smith and Kirby (2000) argue for a two-process model of appraisal, which expands on the function of the structural model of appraisal. While the structural model of appraisal focuses on what one is evaluating, the process model of appraisal focuses on how one evaluates emotional stimuli. There are three main components to the process model of appraisal: perceptual stimuli, associative processing, and reasoning. Perceptual stimuli are what the individual picks up from his or her surroundings, such as sensations of pain or pleasure, perception of facial expression (Smith & Kirby 2000). In addition to these stimuli, the process model is composed to two main appraisal processes. Associative processing is a memory-based process that makes quick connections and provides appraisal information based on activated memories that are quickly associated with the given stimulus (Marsella & Gratch 2009). Reasoning is a slower, more deliberate, and thorough process that involves logical, critical thinking about the stimulus and/or situation (Marsella & Gratch 2009). In the two-process model of appraisal theory, associative processing and reasoning work in parallel in reaction to perceptual stimuli, thus providing a more complex and cognitively based appraisal of the emotional encounter (Smith & Kirby 2000).
==== Scherer's multi-level sequential check model ====
An alternative process model of appraisal, Scherer's multi-level sequential check model is made up of three levels of appraisal process, with sequential constraints at each level of processing that create a specifically ordered processing construct (Scherer 2001). The three levels of processing are: innate (sensory-motor), learned (schema-based), and deliberate (conceptual) (Marsella & Gratch 2009). Further, Scherer constructs a strict, ordered progression by which these appraisal processes are carried out. There are various evaluation checks throughout the processes, which allow for observation of stimuli at different points in the process sequence, thus creating a sort of step-by-step appraisal process (Scherer 2001). Such checks include: a relevance (novelty and relevance to goals) check, followed by an implication check (cause, goal conduciveness, and urgency), then coping potential check (control and power), and finally the check for normative significance (compatibility with one's standards) (Marsella & Gratch 2009). While the two-process model involves processes occurring at the same time, parallel to one another, Scherer's multi-level sequential check model is composed of processes that take place in a specific sequence.
=== Roseman's theory of appraisal ===
Roseman's theory of appraisal holds that there are certain appraisal components that interact to elicit different emotions (Roseman, 1996). One appraisal component that influences which emotion is expressed is motive consistency. When one evaluates a situation as inconsistent with one's goals, the situation is considered motivationally inconsistent and often elicits a negative emotion, such as anger or regret (Roseman, 1996). A second component of appraisal that influences the emotional response of an individual is the evaluation of responsibility or accountability (Roseman, 1996). A person can hold oneself or another person or group accountable. An individual might also believe the situation was due to chance. An individual's evaluation of accountability influences which emotion is experienced. For example, if one feels responsible for a desirable situation, pride may be an emotion that is experienced.
In addition to the two appraisal components, the different intensities of each component also influence which emotion or emotions are elicited. Specifically, the certainty and the strength of the evaluation of accountability influences which emotions are experienced (Roseman, 1996). In addition, the appetitive or aversive nature of motive consistency also influences the emotions that are elicited (Roseman, 1996).
Roseman's theory of appraisal suggests that motive consistency and accountability are the two most important components of the appraisal process (1996). In addition, the different levels of intensity of each component are important and greatly influence the emotions that are experienced due to a particular situation.
=== Structural v. process oriented models ===
Most models currently advanced are more concerned with structure or contents of appraisals than with process oriented appraisal. "These Gendy models attempt to specify the evaluations that initiate specific emotional reactions. Examination of these models indicates that although there is significant overlap [between the two types of structural models], there also differences: in which appraisals are included; how particular appraisals are operationalized; which emotions are encompassed by a model; and which particular combinations of appraisals are proposed to elicit a particular emotional response." (Scherer et al., 2001). Ultimately, structurally based appraisals rely on the idea that our appraisals cultivate the emotional responses. Process-oriented models of appraisal theory are rooted in the idea that it is important to specify the cognitive principles and operations underlying these appraisal modes. Using this orientation for evaluating appraisals, we find fewer issues with repression, a "mental process by which distressing thoughts, memories, or impulses that may give rise to anxiety are excluded from consciousness and left to operate in the unconscious" (Merriam-Webster, 2007).
=== Continuous v. categorical nature of appraisal and emotion ===
Within the continuous versus categorical nature of appraisal and emotion, there are many standpoints of the flow of this appraisal process. To begin, Roseman's (1996) model shows that appraisal information "can vary continuously but categorical boundaries determine which emotion will occur". Motive consistency and inconsistency make up an example of this categorical framework. A positive or negative emotional response in conjunction with the affect has much to do with the appraisal and the amount of motivational consistency. To accurately understand this concept, an example of Roseman's model could come from a motive-consistent goal as it is caused by the self and someone else to reach one's objective in which a positive emotion is created from the specific appraisal event. In addition, Scherer's (1984) model shows that most appraisal falls in a continuous spectrum in which points along the way represent distinct emotional points made possible from the appraisal. Between appraisal space and number of emotions experienced, these two components are both positively correlated. "According to Scherer (1984a), the major categorical labels we used to describe our emotional experiences reflect a somewhat crude attempt to highlight and describe the major or most important ways these emotional experiences vary". With so much variation and levels within one's emotions, it can be seen as injustice to the emotional experience and the appraisal process to limit oneself to such categories. To solve the problem between categorical and continuous appraisal order, it may be a good idea to place discrete emotional categories (i.e. happiness, sadness, etc.) while continuous models represent the varieties, styles, and levels of these already defined distinct emotions.
== Empirical findings and real world applications ==
Stanley Schachter's contributions should also be noted as his studies supported the relevance of emotion induced in appraisal. In 1962, Schachter and Jerome E. Singer devised an experiment to explain the physiological and psychological factors in emotional appraising behaviors. By inducing an experimental group with epinephrine while maintaining a control group, they were able to test two emotions: euphoria and anger. Using a stooge to elicit a response, the research proved three major findings relevant to appraisal:
Both cognitive and physiological factors contribute to emotion;
Under certain circumstances cognition follows physiological arousal; and
People assess their emotional state, in part, by observing how physiologically stirred up they are (Schachter & Singer, 1962)
By taking into account heightened emotion, reaction to the stooge, as well as prompted questions, all these elicited factors provide a negative or positive affect. Although the study took place in 1962, it is still studied in both psychology and communication fields today as an example of appraisal theory in relation to affect and emotion.
Through these findings, Schachter and Singer assess that an event happens which in turn elicits as physiological arousal. From the reasoning of the arousal, you are then able to have an emotion. For example: You are about to give a speech. You approach the podium and look out into the audience as your mouth goes dry, your heart beat quickens, your palms sweat, and your legs begin to shake. From this arousal, you understand you feel this way because you are about to give a speech in front of 50 of your peers. This feeling causes anxiety and you experience the emotion of fear.
In a study aimed at defining stress and the role of coping, conducted by Dewe (1991), significant relationships between primary appraisal, coping, and emotional discomfort were recorded. It was proven that primary appraisal was the main contributor of predicting how someone will cope. This finding enables psychologists to be able to begin to predict the emotion that will be elicited by a certain event and may give rise to an easier way to predict how well someone will cope with their emotion.
A study by Rogers & Holmbeck (1997) explores a previous finding that "the psychological impact of interparental conflict on children is influenced by children's cognitive appraisals." The researchers hypothesized that cognitive appraisal and coping would help moderate variables for the children, and therefore the emotional impact of parent conflict would vary based on the nature of the child's "appraisals and coping strategies" (Rogers & Holmbeck 1997). The researchers tested coping strategies and measured child adjustment based on the children's self-reported emotional and behavioral adjustment, determined from levels of self-worth and depression (Rogers & Holmbeck 1997). The results demonstrated a significant negative main effect of problematic cognitive appraisal on self-worth and a significant positive main effect of problematic cognitive appraisal on depression, thus showing the impact of cognitive appraisal on children's emotional well being and ability to deal with interparental conflict (Rogers & Holmbeck 1997). This study demonstrates the significance of cognitive appraisal in coping with emotionally difficult circumstances and their own behavioral adjustment and self-esteem. An understanding of the role of cognitive appraisal and cognitive appraisal theories can assist psychologists in understanding and facilitating coping strategies, which could contribute to work in the field that acts to facilitate healthy behavioral adjustment and coping strategies in individuals.
In another study conducted by Jacobucci (2000), findings suggested that individual differences and primary appraisals had a very strong correlation. This shows that primary appraisal is a function of personality and may be stable over time. This in fact is a very strong finding for social psychologists because it proves that if we can predict the primary appraisal strategy and thinking pattern of an individual, then coping patterns and emotional tendencies of an individual may be able to be predicted in any situation and social setting.
A study by Verduyn, Mechelen, & Tuerlinckx (2011) explores the factors that affect the duration of an emotional experience. One aspect of the research focuses on the difference between rumination versus reappraisal of an emotional event, exploring how they affect the duration of an emotional experience, and in which direction (shortening or lengthening) (Verduyn et al. 2011). The researchers argue that cognition is very significant to the duration and experience of emotion, claiming that "thoughts appear to act as fuel that stirs up the emotional fire and leads to a prolongation of the episode" (Verduyn et al. 2011). Further, the researchers reference the significance of emotions "lining up with" initial appraisals of the emotion-eliciting experience, which then strengthens the emotion and may lead to prolongation of the experience (Verduyn et al. 2011). This concept alludes to the significance of congruence among emotions, appraisal, and cognitions. This particular article discusses the coping effect of appraisal and reappraisal, claiming reappraisal can act as an "adaptive strategy," while rumination is not (Verduyn et al. 2011). Both reappraisal (or initial cognitive appraisal) and rumination, however, can affect the duration of an emotional experience. This study demonstrates the significance of cognitive appraisal by indicating its role in the duration of an emotional experience. Because the duration of an emotional experience can have significant effects on how an individual reacts to given stimuli, and thus have relevant real-world application in how individuals deal with emotional experiences. This study also presents reappraisal—appraising the emotional situation in a new way—can act as an adaptive strategy to deal with difficult circumstances, thus further highlighting the necessity of cognitive appraisal to coping with emotional stressors.
One study completed by Folkman et al. (1986) focuses on the relationship between appraisal and coping processes that are used across stressful events, and indicators of long-term adaptation. They define primary appraisal as "the stakes a person has in a stressful encounter," and secondary appraisal as "options for coping." Eighty-five California married couples with at least one child were the participants of the study, and they were interviewed in their homes once a month for 6 months. In each interview the subject was asked what their most stressful event was in the previous week, and then interviewer asked them structured questions about how they dealt with that stressor. There was a significant gender difference in primary appraisal. They also concluded that coping strategies were dependent upon psychological and somatic problems as well (Folkman, Lazarus, Gruen & DeLongis, 1986).
In another study by Folkman, the goal was to look at the relationship between cognitive appraisal and coping processes and their short-term outcomes within stressful situations. Subjects were interviewed once a month for six months. Primary and secondary appraisals were assessed using different subscales. This study found that there is a functional relationship among appraisal and coping and the outcomes of stressful situations. There were significant positive correlations between primary appraisal and coping. There were also significant correlations between secondary appraisal and coping, and they were very specific about the type of stressful situation and with which each would help the most. For example, they found that appraisals of changeability and having to hold back from acting were related to the encounter outcomes (Folkman, Lazarus, Dunkel-Schetter, DeLongis & Gruen, 1986).
In another experiment that was based on this concept of appraisal theory (Lazarus 1991, 1990), a study completed by Amy M. Bippus and Stacy L. Young (2012) looked to closely examine the role of primary as well as secondary appraisals of those receiving hurtful messages, such as cyber bullying, and how this played an effect into how much hurt those people felt upon receiving these messages and also affected how they chose to cope with their pain. The experiment itself aimed to change the role that being emotionally hurt was perceived as in the appraisal process, because in this study, hurt was to be viewed as outcome of appraisal as opposed to other studies that have normally observed the aspect of hurt to be a precedent to the appraisal process. For this study, the researchers gathered a sum of 217 willing participants, which composed of 64 males as well as 153 females, all of whom were collegiate communications studies students who were receiving extra credit in a class for their time. These participants were then given a questionnaire to complete that involved being instructed to explain, in Bippus and Young's words, "the most recent situation in which your feelings were hurt," including aspects such as hurt that was caused by romantic partners, family members, close friends, etc. After this was done, both of the participants' primary and secondary appraisals were measured. The results of this study went on to show that the primary and secondary appraisals of the participants were only meekly able to predict the coping mechanisms that the participants took part in, but, on the other hand, were rather strong predictors as to what emotion they ended up feeling, as those receiving the messages were more likely to be hurt when they viewed the messages as rather intended or out of spite instead of a misunderstood form of humor in bad taste. These findings were able to continue to be in support of this concept of appraisal theory, as the primary and secondary appraisals of the participants were able to predict the emotion that was felt by the individuals more-so than the coping mechanisms they would involve themselves in.
== More appraisal theories of emotion ==
Many current theories of emotion now place the appraisal component of emotion at the forefront in defining and studying emotional experience. However, most contemporary psychologists who study emotion accept a working definition acknowledging that emotion is not just appraisal but a complex multifaceted experience with the following components:
Subjective feelings. The appraisal is accompanied by feelings that are good or bad, pleasant or unpleasant, calm or aroused.
Physiological arousal. Emotions are accompanied by autonomic nervous system activity. Arousal is defined as "to rouse or stimulate to action or to physiological readiness for activity" (Merriam-Webster, 2007). According to Schachter and Singer (1962) we can have arousal without emotion, but we cannot have an emotion without arousal. Essentially, humans injected with epinephrine without knowing the actual content of the injection, feel an increase in heart rate, sweating, and nervousness, but that does not elicit an affective response. When the same physiological responses are paired with a contextual pretext, winning the lottery, for example, the state of arousal is appraised to mean extreme excitement, joy, and happiness. Without a context, we feel aroused, but cannot label it as an emotional response to a stimulus. If a context is present, we can evaluate our arousal in terms of that context, and thus an emotional response is present.
Expressive behaviors. Emotion is communicated through facial and bodily expressions, postural and voice changes.
Action tendencies. Emotions carry behavioral intentions, and the readiness to act in certain ways.
== See also ==
Affect display
Attitude change
Emotions and culture
Emotional expression
Emotional intelligence
Empathy
Information processing (psychology)
Magda B. Arnold
Reversal theory
Richard Lazarus
Stoicism
== References == | Wikipedia/Appraisal_theory |
The theory of constructed emotion (formerly the conceptual act model of emotion) is a theory in affective science proposed by Lisa Feldman Barrett to explain the experience and perception of emotion. The theory posits that instances of emotion are constructed predictively by the brain in the moment as needed. It draws from social construction, psychological construction, and neuroconstruction.
== Motivation ==
Barrett proposed the theory to resolve what she calls the "emotion paradox," which she claims has perplexed emotion researchers for decades, and describes as follows: People have vivid and intense experiences of emotion in day-to-day life: they report seeing emotions like "anger", "sadness", and "happiness" in others, and they report experiencing "anger", "sadness" and so on themselves. Nevertheless, psychophysiological and neuroscientific evidence has failed to yield consistent support for the existence of such discrete categories of experience. Instead, the empirical evidence suggests that what exists in the brain and body is affect, and emotions are constructed by multiple brain networks working in tandem.
Most other theories of emotion assume that emotions are genetically endowed, not learned. Other scientists believe there are circuits in the brain: an anger circuit, a fear circuit, and so on. Charles Darwin, in The Expression of the Emotions in Man and Animals, used examples to support the idea that emotions and their "expressions are a universal part of human nature", and that people can recognize and express emotions without any training.
The theory of constructed emotion calls this assumption into question. It suggests that these emotions (often called "basic emotions") are not biologically hardwired, but instead are phenomena that emerge in consciousness "in the moment" from more fundamental ingredients.
== Statement of the theory ==
The theory is given in simplified form as:
"In every waking moment, your brain uses past experience, organized as concepts, to guide your actions and give your sensations meaning. When the concepts involved are emotion concepts, your brain constructs instances of emotion."
In greater detail, instances of emotion are constructed throughout the entire brain by multiple brain networks in collaboration. Ingredients going into this construction include interoception, concepts, and social reality. Interoceptive predictions provide information about the state of the body and ultimately produce basic, affective feelings of pleasure, displeasure, arousal, and calmness. Concepts are culturally embodied knowledge, including "emotion concepts". Social reality provides the collective agreement and language that make the perception of emotion possible among people who share a culture.
As an analogy, consider the experience of color. People experience colors as discrete categories: blue, red, yellow, and so on, and these categories vary in different cultures. The physics of color, however, is actually continuous, with wavelengths measured in nanometers along a scale from ultraviolet to infrared. When a person experiences an object as "blue", she is (unconsciously) using her color concepts to categorize this wavelength. And in fact, people experience a whole range of wavelengths as "blue."
Likewise, emotions are commonly thought of as discrete and distinct — fear, anger, happiness — while affect (produced by interoception) is continuous. The theory of constructed emotion suggests that at a given moment, the brain predicts and categorizes the present moment (of continuous affect) via interoceptive predictions and the "emotion concepts" from one's culture, to construct an instance of emotion, just as one perceives discrete colors. This process instantiates the experience of "having an emotion".
For example, if someone's brain predicts the presence of a snake as well as the unpleasant affect that would result upon encountering a snake ("interoceptive prediction"), that brain might categorize and construct an experience of "fear." This process takes place before any actual sensory input of a snake reaches conscious awareness. In contrast, a "basic emotions" researcher would say that the person first sees the snake, and this sensory input triggers a dedicated "fear circuit" in the brain.
=== Earlier incarnations of the theory ===
Early incarnations of the theory were phrased in terms of core affect rather than interoception. Core affect is a neurophysiological state characterized along two dimensions:
Pleasure vs. displeasure, measured along a continuous scale from positive to negative.
High arousal vs. low arousal, measured along a continuous scale between these endpoints.
According to the original conceptual act model, emotion is generated when a person categorizes his/her core affective state using knowledge about emotion. This theory combines elements of linguistic relativity and affective neuroscience.
The term "core affect" was first used in print by Russell and Barrett in 1999 in Journal of Personality and Social Psychology where it is used to refer to the affective feelings that are part of every conscious state (as discussed by Wundt in his 1889 System der Philosophie). The term "core affect" also appears to have been used as a phrase that relates to neuropsychological understanding of behavior as a morbid affect at the roots of any type of human behavior.
== Other researchers ==
Joseph LeDoux has reached similar views.
The theory denies "essentialism" of brain areas exclusively dedicated to emotion, such as the seven primary affective systems proposed by the affective neuroscientist Jaak Panksepp. (Note that Barrett and Panksepp use the word "affect" to mean different things. Barrett defines affect as a basic feature of consciousness, akin to light and dark or loudness and softness, consisting of a combination of valence and arousal, consistent with the original definition of affect by Wilhelm Wundt. Panksepp uses the term in the plural, "affects," to refer to his proposed seven systems.) Panksepp characterized the theory of constructed emotion as an "attributional–dimensional constructivist view of human emotions [which] postulates that positive and negative core affects are the basic feelings—the primary processes—from which emotional concepts are cognitively and socially constructed". (Since the theory of constructed emotion is not about core affect, this statement likely refers to Barrett's older conceptual act theory.)
== References == | Wikipedia/Theory_of_constructed_emotion |
The James–Lange theory (1884) is a hypothesis on the origin and nature of emotions and is one of the earliest theories of emotion within modern psychology. It was developed by philosopher John Dewey and named for two 19th-century scholars, William James and Carl Lange (see modern criticism for more on the theory's origin). The basic premise of the theory is that physiological arousal instigates the experience of emotion. Previously people considered emotions as reactions to some significant events or their features, i.e. events come first, and then there is an emotional response. James-Lange theory proposed that the state of the body can induce emotions or emotional dispositions. In other words, this theory suggests that when we feel teary, it generates a disposition for sad emotions; when our heartbeat is out of normality, it makes us feel anxiety. Instead of feeling an emotion and subsequent physiological (bodily) response, the theory proposes that the physiological change is primary, and emotion is then experienced when the brain reacts to the information received via the body's nervous system. It proposes that each specific category of emotion is attached to a unique and different pattern of physiological arousal and emotional behaviour in reaction due to an exciting stimulus.
The theory has been criticized and modified over the course of time, as one of several competing theories of emotion. Modern theorists have built on its ideas by proposing that the experience of emotion is modulated by both physiological feedback and other information, rather than consisting solely of bodily changes, as James suggested. Psychologist Tim Dalgleish states that most modern affective neuroscientists would support such a viewpoint. In 2002, a research paper on the autonomic nervous system stated that the theory has been "hard to disprove". Despite important critical appraisals, the theory finds support even today: famed consciousness researcher Anil Seth is known for supporting a form of this theory.
== Theory ==
Emotions are often assumed to be judgments about a situation that causes feelings and physiological changes. In 1884, psychologist and philosopher William James proposed that physiological changes actually precede emotions, which are equivalent to our subjective experience of physiological changes, and are experienced as feelings. In his words, "our feeling of the same changes as they occur is the emotion." James argued:
If we fancy some strong emotion, and then try to abstract from our consciousness of it all the feelings of its characteristic bodily symptoms, we find we have nothing left behind, no "mind-stuff" out of which the emotion can be constituted, and that a cold and neutral state of intellectual perception is all that remains. … What kind of an emotion of fear would be left, if the feelings neither of quickened heart-beats nor of shallow breathing, neither of trembling lips nor of weakened limbs, neither of goose-flesh nor of visceral stirrings, were present, it is quite impossible to think. Can one fancy the state of rage and picture no ebullition of it in the chest, no flushing of the face, no dilatation of the nostrils, no clenching of the teeth, no impulse to vigorous action, but in their stead limp muscles, calm breathing, and a placid face? The present writer, for one, certainly cannot. The rage is as completely evaporated as the sensation of its so-called manifestations.
Physician Carl Lange developed similar ideas independently in 1885. Both theorists defined emotion as a feeling of physiological changes due to a stimulus, but the theorists focused on different aspects of emotion. Although James did talk about the physiology associated with an emotion, he was more focused on conscious emotion and the conscious experience of emotion. For example, a person who is crying reasons that he must be sad. Lange reinterpreted James's theory by operationalizing it. He made James's theory more testable and applicable to real life examples. However, both agreed that if physiological sensations could be removed, there would be no emotional experience. In other words, physiological arousal causes emotion.
According to James, when an individual is aware of their body's physiological arousal and emotional behavior their emotions are shown. He did not think the idea of common sense reactions were real but that each emotion triggered a specific physiological response. For instance, when someone hears breaking glass and they think someone is breaking in, if their heart starts pounding and they begin trembling, James would argue that they are experiencing this physiological reaction because they feel fear of a would-be burglar. Or, if the person heard glass breaking and thought it was their roommate being careless and clumsy, they would have a pounding heart and raised blood pressure due to their subject anger, according to James.
James argues that the sequence of events in experiencing emotion is:
Emotion stimulus → Physiological Response Pattern → Affective Experience.
The theory itself emphasizes how physiological arousal, with the exclusion of emotional behavior, is the determiner of emotional feelings. It also emphasizes that each emotional feeling has a distinct, unique pattern of physiological responses associated with it. It must meet two criteria which include (a) at least two emotions should be induced and (b) the presence of any emotion should be verified using other measures such as facial expressions or verbal reports. An example would be conducting an experiment to measure happiness and anger. One study is measuring happiness by giving rewards sporadically throughout the experiment while the other study is measuring anger by giving the participants a very difficult cross word puzzle to solve. Their physiological responses will be measured - which are blood pressure and electrodermal responses. Verbal and facial expressions will also be examined to determine either happiness or anger. According to James, the results will show that the physiological patterns, the blood pressure and electrodermal responses, will show different patterns for the different emotions.
Further researchers have also found that there are a few specific physiological differences among discrete emotions. For example, research has shown that heart rate is always higher in people experiencing anger and fear rather than those who are experiencing happiness or even sadness. It also shows that blood pressure is also higher in those experiencing anger than those experiencing fear, sadness and happiness. It also showed that electrodermal responses were higher in people experiencing fear rather than during sadness. But there were also times when the physiological patterns wouldn't differentiate which concludes that this theory is not 100% accurate and that there was not a unique pattern for each basic and distinct emotion. Which led them to blame the autonomic nervous system because the autonomic nervous system responds in a global fashion rather than showing those distinct reactions in an emotion-inducing situation and people also generally only notice changes in their autonomic nervous system rather than any specific physiological change. Which in the end concludes that our own perceptions of our body's physiological reactions doesn't give enough evidence and proof to determine the subject nature of an emotional experience.
The specific pathway involved in the experience of emotion was also described by James. He stated that an object has an effect on a sense organ, which relays the information it is receiving to the cortex. The brain then sends this information to the muscles and viscera, which causes them to respond. Finally, impulses from the muscles and viscera are sent back to the cortex, transforming the object from an "object-simply apprehended" to an "object-emotionally felt."
James explained that his theory went against common sense. For example, while most would think the order of emotional experience would be that a person sees a bear, becomes afraid, and runs away, James thought that first the person has a physiological response to the bear, such as trembling, and then becomes afraid and runs. According to James, the physiological response comes first, and it is perceived as an emotion and followed by a reaction.
== Reception ==
In Mortimer J. Adler's first attempt to earn a PhD in Experimental Psychology, he conducted a research study aligned with the postulates of James-Lange Theory of Emotions along with George Schoonhoven. Adler and Schoonhoven hypothesized that emotions could be grouped into two separate classes: pleasant and unpleasant. In order to demonstrate this hypothesis, they submitted their Psychology graduate students to some laboratory tensions that they could distinguish said emotions based on their physiological reactions.
On unpleasant emotions, they tested anger, shock and fear. Each of these emotions were tested by the following methods. In order to instill anger, Schoonhoven would kick the subject's sheen; shock, by firing a revolver far from the subject's vision field; fear, by involving the subject's head with a boa constrictor from the zoology lab of the Columbia University.
According to Adler, however, the pleasant emotions tests, hunger and sexual desire, were not well envisaged. On the hunger side, the researchers instructed their subjects not to eat for 24 straight hours, and would go to the lab. There, they would be submitted to smelling and seeing a bacon sandwich with a cup of coffee, but would not be permitted to eat it, so the downfall of that was that they would experience the sensations of anger afore-mentioned, such as dilated pupils, and so on. On the sexual desire side, the participants were enclosed with women with which they had already had sexual encounters before, girls which were instructed to engage in mild forms of fondling, accompanied by affectionate speech, which only caused the subject to feel embarrassment.
Unfortunately, the research could not attain to an end, nor would be published, because Schoonhover was diagnosed with cancer, and died thereafter.
== Criticism ==
=== Early criticism ===
Since the theory's inception, scientists have found evidence that not all aspects of the theory are relevant or true. The theory was challenged in the 1920s by psychologists such as Walter Cannon and Philip Bard, who developed an alternative theory of emotion known as Cannon–Bard theory, in which physiological changes arise independently from emotions. A third theory of emotion is Schachter and Singer's two factor theory of emotion. This theory states that cognitions are used to interpret the meaning of physiological reactions to outside events. This theory is different in that emotion is developed from not only cognition, but that combined with a physical reaction.
Cannon emphasized that the viscera had been separated from the central nervous system with no impact on emotional behavior in experiments on animals. He said this contradicted the James–Lange theory because James believed that the viscera were the center of emotion. Cannon examined research on dogs performed by Sherrington, who separated the spinal cord and vagus nerves from all connections in the rest of the body, and found that the expression of emotion did not change, suggesting that the viscera do not have an observable impact on certain emotional behavior in dogs.
Cannon also emphasized that visceral responses occur when experiencing many different emotions, and in the absence of emotion. For example, the same visceral responses such as increased heart rate, sweating, widening of the pupils, and the discharge of adrenaline can be associated with the experience of fear or anger. However, they are also connected to conditions such as fever, feeling cold, and having difficulty breathing. Therefore, the physical emotional responses that had so far been documented are too general to be linked to a specific emotion.
Cannon argued that visceral responses are slow and not sensitive enough to elicit emotional responses. J.N. Langley had shown that there was a period of two to four seconds between when the chorda tympani nerve was stimulated and when the salivary gland associated with this nerve responded. Thus, Cannon argued that there was too much of a delay between the stimulation of the viscera and the physiological response for it to precede the emotion.
Stimulating the viscera to produce a specific emotion was found to be ineffective by physician Gregorio Marañón. In one of his studies, participants had adrenalin injected into their veins, which produced physiological changes expected to be linked with an emotion. However, the emotion was never produced. The only noticeable changes in the participants were physical, such as activation of the sympathetic nerve impulse, which creates constriction of the blood vessels and dilation of the bronchioles. Cannon stated that this study disproved the idea that physiological responses are the sole reason for the experience of emotion.
The James–Lange theory was much discussed amongst the intelligentsia in America and Britain at the end of the nineteenth century. In ‘The Little White Bird’ (1902) J. M. Barrie discusses the psychological abilities of fairies with his young companion, David. He comments, "David tells me that fairies never say, ‘We feel happy’: what they say is, ‘We feel dancey’. " This, and related texts, suggest that J. M. Barrie was familiar with the James-Lange theory. Barrie, who wrote the Peter Pan stories, was a good friend of Henry James, William’s brother and had met William James.
=== Modern criticism ===
In 2017, Lisa Feldman Barrett reported that the James-Lange theory was created by neither William James nor Carl Lange. It was indeed named by the philosopher John Dewey, who misrepresented James' ideas on emotion. James never wrote that each category of emotion (fear, anger, etc.) has a distinct biological state. He wrote that each instance of emotion may have a distinct biological state. Dewey's assumed error "represents a 180-degree inversion of [James'] meaning, as if [James] were claiming the existence of emotion essences, when ironically he was arguing against them." Barrett notes that "Dewey's role in this [error] is forgotten."
Barrett also points out that when testing this theory with electrical stimulation, there is not a one-to-one response between a behavior and emotion category. In other words, "stimulation of the same site produces different mental states across instances, depending on the prior state of the individual and also the immediate context." She concludes that this means there is more going on when a person feels an emotion than just a physiological response: some kind of processing must happen between the physiological response and the perception of the emotion.
Further, Barrett says that the experience of emotion is subjective: there is no way to decipher whether a person is feeling sad, angry, or otherwise without relying on the person's perception of emotion. Also, humans do not always exhibit emotions using the same behaviors; humans may withdraw when angry, or fight out of fear. She says that emotion is more complex than a mere physical sensation. According to Barrett's theory of constructed emotion, a person must make meaning of the physical response based on context, prior experience, and social cues, before they know what emotion is attached to the situation. Barrett and James Gross have reviewed a variety of alternative models to the so-called James–Lange theory.
A study in 2009 found that patients who had lesions to the ventromedial prefrontal cortex had impaired emotional experiences, but unaffected autonomic responses while patients with lesions to the right somatosensory cortex had impaired autonomic responses without affected emotional experiences. This argued that autonomic responses were dissociated with emotional experiences.
The researchers argued that this dissociation between autonomic responses and emotional experiences clashed with James's assertion that physiological responses are required to experience emotions.
== See also ==
Facial feedback hypothesis
Somatic marker hypothesis
Power posing
== References == | Wikipedia/James-Lange_theory |
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