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22509163
|
Targets for a comparative neurobiology of language.
|
One longstanding impediment to progress in understanding the neural basis of language is the development of model systems that retain language-relevant cognitive behaviors yet permit invasive cellular neuroscience methods. Recent experiments in songbirds suggest that this group may be developed into a powerful animal model, particularly for components of grammatical processing. It remains unknown, however, what a neuroscience of language perception may look like when instantiated at the cellular or network level. Here we deconstruct language perception into a minimal set of cognitive processes necessary to support grammatical processing. We then review the current state of our understanding about the neural mechanisms of these requisite cognitive processes in songbirds. We note where current knowledge is lacking, and suggest how these mechanisms may ultimately combine to support an emergent mechanism capable of processing grammatical structures of differing complexity.</AbstractText
|
[
[
"10378865",
"Neurokinin type-1 receptor antagonist inhibits enhancement of T cell functions by substance P in normal and neuromanipulated capsaicin-treated rats.",
"Substance P (SP) plays a major role in the regulation of the interaction between immune and nervous systems. SP administration stimulates Con A-induced proliferation of spleen and peripheral blood lymphocytes from normal and neonatally capsaicin treated rats, which correlated with enhanced IL-2 production and expression of activation antigens such as IL-2 receptor alpha chain (CD25) and RT1B MHC class II molecule. Moreover, SP markedly increased the percentage of CD5+ and CD4+ T lymphocytes in the peripheral blood of capsaicin-treated rats. Concomitant administration of SP with the non-peptide Neurokinin-1 receptor (NK1R) antagonist SR140333 completely inhibited the SP-mediated augmentation of Con A-induced PBL proliferation and IL-2 production as well as of CD4+ CD25+ and CD4+ RT1B+ T cell numbers in normal and capsaicin-treated rats. SR 140333 also blocked the increased percentage of peripheral blood CD4+ T cells induced by SP in capsaicin-treated rats.</AbstractText"
]
] |
[
[
"23264884",
"Neurogenetics and Epigenetics in Impulsive Behaviour: Impact on Reward Circuitry.",
"Adverse, unfavourable life conditions, particularly during early life stages and infancy, can lead to epigenetic regulation of genes involved in stress-response, behavioral disinhibition, and cognitive-emotional systems. Over time, the ultimate final outcome can be expressed through behaviors bedeviled by problems with impulse control, such as eating disorders, alcoholism, and indiscriminate social behavior. While many reward gene polymorphisms are involved in impulsive behaviors, a polymorphism by itself may not translate to the development of a particular behavioral disorder unless it is impacted by epigenetic effects. Brain-derived neurotrophic factor (BDNF) affects the development and integrity of the noradrenergic, dopaminergic, serotonergic, glutamatergic, and cholinergic neurotransmitter systems, and plasma levels of the neurotrophin are associated with both cognitive and aggressive impulsiveness. Epigenetic mechanisms associated with a multitude of environmental factors, including premature birth, low birth weight, prenatal tobacco exposure, non-intact family, young maternal age at birth of the target child, paternal history of antisocial behavior, and maternal depression, alter the developmental trajectories for several neuropsychiatric disorders. These mechanisms affect brain development and integrity at several levels that determine structure and function in resolving the final behavioral expressions.</AbstractText"
]
] |
23195310
|
Model organism databases in behavioral neuroscience.
|
Model Organism Databases (MODs) are an important informatics tool for researchers. They provide comprehensive organism specific genetic, genomic, and phenotype datasets. MODs ensure accurate data identification and integrity and provide official nomenclature for genes, Quantitative Trait Loci, and strains. Most importantly, the MODs provide professionally curated data drawn from the literature for function, phenotype and disease associations, and pathway involvement. These data, along with nomenclature and data identity, are incorporated into larger scale genomic databases and research publications. MODs also offer a number of software tools that allow researchers to access, display, and analyze data from reports to genome browsers.</AbstractText
|
[
[
"19254758",
"Re-exposure to endotoxin induces differential cytokine gene expression in the rat hypothalamus and spleen.",
"This study was designed to investigate whether the pattern of hypothalamic and splenic cytokine expression induced by peripheral administration of a bacterial lipopolysaccharide (LPS) is affected by prior exposure to LPS derived from another bacterial strain. Injection of LPS from Salmonella enteritidis (LPS(2)) alone resulted in increased hypothalamic gene expression of IL-1beta, IL-6, TNFalpha, IL-1ra and IL-10. However, pre-exposure to LPS derived from Escherichia coli (LPS(1)) 3 weeks before, significantly attenuated hypothalamic IL-1ra, IL-6 and IL-10 expression. IL-1beta expression also tended to be lower. This pattern contrasted with the robust cytokine expression in the spleen of LPS(2)-treated rats previously exposed to LPS(1), since pre-treatment with endotoxin resulted in a significantly greater response of IL-1beta and IL-1ra to LPS(2). Expression of TNFalpha and IL-10 also tended to be higher. Pre-treatment with LPS(1) did not significantly affect the marked increase in corticosterone and adrenaline blood levels induced by LPS(2). Thus, while endotoxin pre-exposure seemed not to induce a \"tolerant\" state in the periphery as judged by the immune and endocrine parameters evaluated upon re-stimulation, expression of four of the six cytokines measured was decreased in the hypothalamus. This is the first demonstration that endotoxin priming can differentially affect cytokine expression in the central nervous system and peripheral tissues when a host is confronted with a second, acute, pro-inflammatory stimulus. These results may provide new evidence for the involvement of cytokine pathways in the central nervous system in modulating peripheral inflammation and mediating cognitive and behavioural alterations during inflammatory diseases.</AbstractText"
]
] |
[
[
"23181017",
"Support vector machines for spike pattern classification with a leaky integrate-and-fire neuron.",
"Spike pattern classification is a key topic in machine learning, computational neuroscience, and electronic device design. Here, we offer a new supervised learning rule based on Support Vector Machines (SVM) to determine the synaptic weights of a leaky integrate-and-fire (LIF) neuron model for spike pattern classification. We compare classification performance between this algorithm and other methods sharing the same conceptual framework. We consider the effect of postsynaptic potential (PSP) kernel dynamics on patterns separability, and we propose an extension of the method to decrease computational load. The algorithm performs well in generalization tasks. We show that the peak value of spike patterns separability depends on a relation between PSP dynamics and spike pattern duration, and we propose a particular kernel that is well-suited for fast computations and electronic implementations.</AbstractText"
]
] |
23372986
|
Experience with multimodality telepathology at the University of Pittsburgh Medical Center.
|
Several modes of telepathology exist including static (store-and-forward), dynamic (live video streaming or robotic microscopy), and hybrid technology involving whole slide imaging (WSI). Telepathology has been employed at the University of Pittsburgh Medical Center (UPMC) for over a decade at local, national, and international sites. All modes of telepathology have been successfully utilized to exploit our institutions subspecialty expertise and to compete for pathology services. This article discusses the experience garnered at UPMC with each of these teleconsultation methods. Static and WSI telepathology systems have been utilized for many years in transplant pathology using a private network and client-server architecture. Only minor clinically significant differences of opinion were documented. In hematopathology, the CellaVision(®) system is used to transmit, via email, static images of blood cells in peripheral blood smears for remote interpretation. While live video streaming has remained the mode of choice for providing immediate adequacy assessment of cytology specimens by telecytology, other methods such as robotic microscopy have been validated and shown to be effective. Robotic telepathology has been extensively used to remotely interpret intra-operative neuropathology consultations (frozen sections). Adoption of newer technology and increased pathologist experience has improved accuracy and deferral rates in teleneuropathology. A digital pathology consultation portal (https://pathconsult.upmc.com/) was recently created at our institution to facilitate digital pathology second opinion consults, especially for WSI. The success of this web-based tool is the ability to handle vendor agnostic, large image files of digitized slides, and ongoing user-friendly customization for clients and teleconsultants. It is evident that the practice of telepathology at our institution has evolved in concert with advances in technology and user experience. Early and continued adoption of telepathology has promoted additional digital pathology resources that are now being leveraged for other clinical, educational, and research purposes.</AbstractText
|
[
[
"3974835",
"Bilateral traumatic abducens nerve palsy without skull fracture and with cervical spine fracture: case report and review of the literature.",
"Bilateral traumatic abducens nerve palsy is a rare condition. Here a case without skull fracture and associated with cervical spine fracture is reported. Only two cases like this were found in a review of the literature. The mechanism of the lesion is discussed in light of the two main theories proposed thus far. When the injury is acute, as happens in the majority of cases, the nerve lesion probably is due to contusion and stretch of the nerve trunk against the ridge of the petrous bone and the rigid dural hole of entrance in the extradural space at the basilar process.</AbstractText"
]
] |
[
[
"23193602",
"Arthropod venoms: a vast arsenal of insecticidal neuropeptides.",
"Arthropods are the most diverse animal group on the planet, and occupy almost all ecological niches. Venomous arthropods are a rich source of bioactive compounds evolved for prey capture and defense against predators and/or microorganisms. These highly potent chemical arsenals represent an available source for new insecticidal compounds as they act selectively on their molecular targets. These toxins affect the invertebrate nervous system and, until the moment, several insecticidal compounds belonging to the class of peptides or polyamine-like compounds have been purified and characterized from the venom of arachnids and hymenopterans. This review focuses on invertebrate-specific peptide neurotoxins that have been isolated from the venom ofspiders, scorpions, centipedes, ants, and wasps, discussing their potential in pest control and as invaluable tools in neuropharmacology.</AbstractText"
]
] |
23060761
|
A computational approach to "free will" constrained by the games we play.
|
Human choice is not free-we are bounded by a multitude of biological constraints. Yet, within the various landscapes we face, we do express choice, preference, and varying degrees of so-called willful behavior. Moreover, it appears that the capacity for choice in humans is variable. Empirical studies aimed at investigating the experience of "free will" will benefit from theoretical disciplines that constrain the language used to frame the relevant issues. The combination of game theory and computational reinforcement learning theory with empirical methods is already beginning to provide valuable insight into the biological variables underlying capacity for choice in humans and how things may go awry in individuals with brain disorders. These disciplines operate within abstract quantitative landscapes, but have successfully been applied to investigate strategic and adaptive human choice guided by formal notions of optimal behavior. Psychiatric illness is an extreme, but interesting arena for studying human capacity for choice. The experiences and behaviors of patients suggest these individuals fundamentally suffer from a diminished capacity of willful choice. Herein, I will briefly discuss recent applications of computationally guided approaches to human choice behavior and the underlying neurobiology. These approaches can be integrated into empirical investigation at multiple temporal scales of analysis including the growing body of experiments in human functional magnetic resonance imaging (fMRI), and newly emerging sub-second electrochemical and electrophysiological measurements in the human brain. These cross-disciplinary approaches hold promise for revealing the underlying neurobiological mechanisms for the variety of choice capacity in humans.</AbstractText
|
[
[
"19400719",
"The science of neural interface systems.",
"The ultimate goal of neural interface research is to create links between the nervous system and the outside world either by stimulating or by recording from neural tissue to treat or assist people with sensory, motor, or other disabilities of neural function. Although electrical stimulation systems have already reached widespread clinical application, neural interfaces that record neural signals to decipher movement intentions are only now beginning to develop into clinically viable systems to help paralyzed people. We begin by reviewing state-of-the-art research and early-stage clinical recording systems and focus on systems that record single-unit action potentials. We then address the potential for neural interface research to enhance basic scientific understanding of brain function by offering unique insights in neural coding and representation, plasticity, brain-behavior relations, and the neurobiology of disease. Finally, we discuss technical and scientific challenges faced by these systems before they are widely adopted by severely motor-disabled patients.</AbstractText"
]
] |
[
[
"24294562",
"Dorello's Canal and Gruber's Ligament: Historical Perspective.",
"Wenzel Leopold Gruber and Primo Dorello were great anatomists and researchers during the 19th and 20th centuries. Their contributions to neuroanatomy-namely the Gruber's (petrosphenoidal) ligament and Dorello's canal, respectively-have come to be important structures in various approaches through the middle fossa. These structures have also helped provide us with an understanding of the mechanism of sixth nerve paresis in various pathological conditions, such as raised intracranial pressure and Gradenigo syndrome. Their numerous publications have stood as a reference to anatomical researchers. Gruber's description of internal mesogastric hernia and the Meckel-Gruber anastomosis are also widely known in medical literature. The following article is an attempt to reflect upon the life and works of Gruber and Dorello and the importance of their research.</AbstractText"
]
] |
23035093
|
Optimization of a GCaMP calcium indicator for neural activity imaging.
|
Genetically encoded calcium indicators (GECIs) are powerful tools for systems neuroscience. Recent efforts in protein engineering have significantly increased the performance of GECIs. The state-of-the art single-wavelength GECI, GCaMP3, has been deployed in a number of model organisms and can reliably detect three or more action potentials in short bursts in several systems in vivo. Through protein structure determination, targeted mutagenesis, high-throughput screening, and a battery of in vitro assays, we have increased the dynamic range of GCaMP3 by severalfold, creating a family of "GCaMP5" sensors. We tested GCaMP5s in several systems: cultured neurons and astrocytes, mouse retina, and in vivo in Caenorhabditis chemosensory neurons, Drosophila larval neuromuscular junction and adult antennal lobe, zebrafish retina and tectum, and mouse visual cortex. Signal-to-noise ratio was improved by at least 2- to 3-fold. In the visual cortex, two GCaMP5 variants detected twice as many visual stimulus-responsive cells as GCaMP3. By combining in vivo imaging with electrophysiology we show that GCaMP5 fluorescence provides a more reliable measure of neuronal activity than its predecessor GCaMP3. GCaMP5 allows more sensitive detection of neural activity in vivo and may find widespread applications for cellular imaging in general.</AbstractText
|
[
[
"19064491",
"Retention of high tactile acuity throughout the life span in blindness.",
"Previous studies of tactile acuity on the fingertip, using passive touch, have demonstrated an age-related decline in spatial resolution for both sighted and blind subjects. We have reexamined this age dependence with two newly designed tactile-acuity charts that require active exploration of the test symbols. One chart used dot patterns similar to braille, and the other used embossed Landolt rings. Groups of blind braille readers and sighted subjects ranging from 12 to 85 years old were tested in two experiments. We replicated previous findings for sighted subjects by showing an age-related decrease in tactile acuity by nearly 1% per year. Surprisingly, the blind subjects retained high acuity into old age, showing no age-related decline. For the blind subjects, tactile acuity did not correlate with braille reading speed, the amount of daily reading, or the age at which braille was learned. We conclude that when measured with active touch, blind subjects retain high tactile acuity into old age, unlike their aging sighted peers. We propose that blind people's use of active touch in daily activities, not specifically braille reading, results in preservation of tactile acuity across the life span.</AbstractText"
]
] |
[
[
"23033443",
"Apraxia of speech: concepts and controversies.",
"This article was written as an editorial to a collection of original articles on apraxia of speech (AOS) in which some of the more recent advancements in the understanding of this syndrome are discussed. It covers controversial issues concerning the theoretical foundations of AOS. Our approach was motivated by a change of perspective on motor speech that has taken place in neurobiology, neurolinguistics, phonology, and phonetics during the past few decades.</AbstractText The literature on AOS is reviewed from 3 different but overlapping perspectives-that is, a disconnection, a motor memory, and a fine motor skill perspective. Separate sections are devoted to the delimitations of AOS from oral facial apraxia, dysarthria, and phonological impairment.</AbstractText We conclude that many of the still unresolved conceptual issues about AOS arise from an underspecification of existing models of spoken language production. We suggest that phonological and motor impairments of sound production should be studied by an integrated approach.</AbstractText"
]
] |
23055482
|
Towards a new neurobiology of language.
|
Theoretical advances in language research and the availability of increasingly high-resolution experimental techniques in the cognitive neurosciences are profoundly changing how we investigate and conceive of the neural basis of speech and language processing. Recent work closely aligns language research with issues at the core of systems neuroscience, ranging from neurophysiological and neuroanatomic characterizations to questions about neural coding. Here we highlight, across different aspects of language processing (perception, production, sign language, meaning construction), new insights and approaches to the neurobiology of language, aiming to describe promising new areas of investigation in which the neurosciences intersect with linguistic research more closely than before. This paper summarizes in brief some of the issues that constitute the background for talks presented in a symposium at the Annual Meeting of the Society for Neuroscience. It is not a comprehensive review of any of the issues that are discussed in the symposium.</AbstractText
|
[
[
"21748284",
"A failure to normalize biochemical and metabolic insults during morphine withdrawal disrupts synaptic repair in mice transgenic for HIV-gp120.",
"Drug abuse in HIV-infected individuals accelerates the onset and progression of HIV-associated neurocognitive disorders (HAND). Opiates are a class of commonly abused drugs that have interactive effects with neurotoxic HIV proteins that facilitate glial dysfunction, neuronal damage and death. While the combined effects of neurotoxic HIV proteins and morphine have been extensively studied in the setting of chronic and acute morphine use, very little in known about the effects of HIV proteins during drug withdrawal. Since opiate withdrawal can induce considerable neuronal stress, we determined the effects of opiates (morphine) on brain redox balance, sphingolipid metabolism and synaptic integrity during both chronic and withdrawal conditions in non-transgenic mice (nTg), and in mice transgenic for the HIV-coat protein gp120 (gp120tg). In nTg mice, we found that chronic morphine increased brain oxidative capacity and induced synaptic damage that was largely reversed during drug withdrawal. Gp120tg mice showed a similar response to chronic morphine, but the diminished oxidative capacity and synaptic damage failed to normalize during drug withdrawal. In nTg mice, brain sphingolipid content was not affected by morphine during chronic or withdrawal conditions. In gp120tg mice there was a baseline perturbation in sphingolipid metabolism that manifest as decreased sphingomyelin with accumulations of the bioactive lipid ceramide. Sphingolipid metabolism was highly reactive to morphine in gp120tg mice. Chronic morphine increased sphingomyelin content with a consequent reduction in ceramide. During drug withdrawal, these effects reversed, and sphingomyelin levels were reduced with consequent increases of ceramide. We interpret these findings to suggest that neuronal repair during morphine withdrawal is inhibited in the setting of gp120 by mechanisms that involve sustained oxidative insult and accumulations of the highly reactive intermediate ceramide.</AbstractText"
]
] |
[
[
"23195316",
"Opportunities for bioinformatics in the classification of behavior and psychiatric disorders.",
"A bioinformatics approach to behavioral neuroscience provides both unique opportunities and challenges for research on behavior. A major challenge has been to describe, define, and discriminate among abstract behavioral processes, in large part by distinguishing among the biological mechanisms of unique but not entirely discrete, entities of behavior. Understanding the complexity of neurobiology and behavior requires integration of data across diverse biological systems, types of data, and levels of scale. With the perspective and application of bioinformatics, we can uncover the relationships among these systems and take steps forward in realizing the common and distinct bases of psychiatric disease.</AbstractText"
]
] |
23505339
|
Baby Steps to Superintelligence: Neuroprosthetics and Children.
|
Children surviving neural injuries face challenges not seen by their adult counterparts, namely that they experience neural injury before reaching neurodevelopmental maturity. Neural prostheses offer one possible path to recovery, along with the potential for functional outcomes that could exceed expectations. Although the first cochlear implant was placed more than fifty years ago, the field of neuroprosthetics is still relatively young. Several types of neural prostheses are in development stages ranging from animal models to (adult) human trials. In this paper, I discuss how neural prostheses may assist recovery for children surviving neural injury. I argue that approaching the use of neural prosthetics in children with considerations derived from transhumanism alongside traditional bioethics can provide an opportunity to reframe adult-focused ethics toward a child/family focus and to strip away the prejudicial metaphor of cyborgization.</AbstractText
|
[
[
"12951145",
"Structure and function of the vomeronasal system: an update.",
"Several developments during the past 15 years have profoundly affected our understanding of the vomeronasal system (VNS) of vertebrates. In the mid 1990s, the vomeronasal epithelium of mammals was found to contain two populations of receptor cells, based on their expression of G-proteins. These two populations of neurons were subsequently found to project their axons to different parts of the accessory olfactory bulb (AOB), forming the basis of segregated pathways with possibly heterogeneous functions. A related discovery was the cloning of members of at least two gene families of putative vomeronasal G-protein-coupled receptors (GPRs) in the vomeronasal epithelium. Ligand binding to these receptors was found to activate a phospholipase C (PLC)-dependent signal transduction pathway that primarily involves an increase in intracellular inositol-tris-phosphate and intracellular calcium. In contrast to what was previously believed, neuron replacement in the vomeronasal epithelium appears to occur through a process of vertical migration in most mammals. New anatomical studies of the central pathways of the olfactory and vomeronasal systems indicated that these two systems converge on neurons in the telencephalon, providing an anatomical substrate for functional interactions. Combined anatomical, physiological and behavioral studies in mice provided new information that furthered our understanding of one of the most striking pheromonal phenomena, the Bruce effect. Finally, contrary to prior observations, new anatomical studies indicated that a vomeronasal organ (VNO) was present in human adults and reports were published indicating that this system might be functional. These latter observations are still controversial and require confirmation from independent laboratories.</AbstractText"
]
] |
[
[
"22850833",
"Complex biomedical systems: from basic science to translation.",
"The Department of Biomedical Engineering (BME) of the University of Southern California (BME@USC) has a longstanding tradition of advancing biomedicine through the development and application of novel engineering ideas. More than 80 primary and affiliated faculty members conduct cutting-edge research in a wide variety of areas, such as neuroengineering, biosystems and biosignal analysis, medical devices (including biomicroelectromechanical systems (bioMEMS) and bionanotechnology), biomechanics, bioimaging, and imaging informatics. Currently, the department hosts six internationally recognized research centers: the Biomimetic MicroElectronic Systems Engineering Research Center (funded by the National Science Foundation), the Biomedical Simulations Resource [funded by the National Institutes of Health (NIH)], the Medical Ultrasonic Transducer Center (funded by NIH), the Center for Neural Engineering, the Center for Vision Science and Technology (funded by an NIH Bioengineering Research Partnership Grant), and the Center for Genomic and Phenomic Studies in Autism (funded by NIH). BME@USC ranks in the top tier of all U.S. BME departments in terms of research funding per faculty.</AbstractText"
]
] |
23176028
|
Iranians' contribution to world literature on neuroscience.
|
The purpose of this study is to analyse Iranian scientific publications in the neuroscience subfields by librarians and neuroscientists, using Science Citation Index Expanded (SCIE) via Web of Science data over the period, 2002-2008.</AbstractText Data were retrieved from the SCIE. Data were collected from the 'subject area' of the database and classified by neuroscience experts into 14 subfields. To identify the citation patterns, we applied the 'impact factor' and the 'number of publication'. Data were also analysed using HISTCITE, Excel 2007 and SPSS.</AbstractText Seven hundred and thirty-four papers have been published by Iranian between 2002 and 2008. Findings showed a growing trend of neuroscience papers in the last 3 years with most papers (264) classified in the neuropharmacology subfield. There were fewer papers in neurohistory, psychopharmacology and artificial intelligence. International contributions of authors were mostly in the neurology subfield, and 'Collaboration Coefficient' for the neuroscience subfields in Iran was 0.686 which is acceptable. Most international collaboration between Iranians and developed countries was from USA. Eighty-seven percent of the published papers were in journals with the impact factor between 0 and 4; 25% of papers were published by the researchers affiliated to Tehran University of Medical Sciences.</AbstractText Progress of neuroscience in Iran is mostly seen in the neuropharmacology and the neurology subfields. Other subfields should also be considered as a research priority by health policymakers. As this study was carried out by the collaboration of librarians and neuroscientists, it has been proved valuable for both librarians and policymakers. This study may be encouraging for librarians from other developing countries.</AbstractText
|
[
[
"21312401",
"Functional brain imaging in schizophrenia: selected results and methods.",
"Functional brain imaging studies of patients with schizophrenia may be grouped into those that assume that the signs and symptoms of schizophrenia are due to disordered circuitry within a critical brain region and studies that assume that the signs and symptoms are due to disordered connections among brain regions. Studies have investigated the disordered functional brain anatomy of both the positive and negative symptoms of schizophrenia. Studies of spontaneous hallucinations find that although hallucinations are associated with abnormal brain activity in primary and secondary sensory areas, disordered brain activation associated with hallucinations is not limited to sensory systems. Disordered activation in non-sensory regions appear to contribute to the emotional strength and valence of hallucinations, to be a factor underlying an inability to distinguish ongoing mental processing from memories, and to reflect the brain's attempt to modulate the intensity of hallucinations and resolve conflicts with other processing demands. Brain activation studies support the view that auditory/verbal hallucinations are associated with an impaired ability of internal speech plans to modulate neural activation in sensory language areas. In early studies, negative symptoms of schizophrenia were hypothesized to be associated with impaired function in frontal brain areas. In support of this hypothesis meta-analytical studies have found that resting blood flow or metabolism in frontal cortex is reduced in schizophrenia, though the magnitude of the effect is only small to moderate. Brain activation studies of working memory (WM) functioning are typically associated with large effect sizes in the frontal cortex, whereas studies of functions other than WM generally reveal smaller effects. Findings from some functional connectivity studies have supported the hypothesis that schizophrenia patients experience impaired functional connections between frontal and temporal cortex, although the nature of the disordered connectivity is complex. More recent studies have used functional brain imaging to study neural compensation in schizophrenia, to serve as endophenotypes in genetic studies and to provide biomarkers in drug development studies. These emerging trends in functional brain imaging research are likely to help stimulate the development of a general neurobiological theory of the complex symptoms of schizophrenia.</AbstractText"
]
] |
[
[
"22963524",
"Non-genomic action of beclomethasone dipropionate on bronchoconstriction caused by leukotriene C4 in precision cut lung slices in the horse.",
"Glucocorticoids have been proven to be effective in the therapy of recurrent airway obstruction (RAO) in horses via systemic as well as local (inhalative) administration. Elective analysis of the effects of this drug on bronchoconstriction in viable lung tissue offers an insight into the mechanism of action of the inflammatory cascade occurring during RAO which is still unclear. The mechanism of action of steroids in treatment of RAO is thought to be induced through classical genomic pathways. We aimed at electively studying the effects of the glucocorticoid beclomethasone dipropionate on equine precision-cut lung slices (PCLS).PCLS were used to analyze ex-vivo effects of beclomethasone on inhibiting bronchoconstriction in the horse. The inhibiting effect was measured through instillation of a known mediator of inflammation and bronchoconstriction, leukotriene C4. For this, the accessory lobes of 13 horses subjected to euthanasia for reasons unrelated to the respiratory apparatus were used to obtain viable lung slices.</AbstractText After 30 minutes of PCLS incubation, beclomethasone showed to significantly inhibit the contraction of the bronchioles after instillation with leukotriene C4. The EC50 values of the two contraction curves (LTC4 with and without BDP) differed significantly from each other (p = 0.002). The possibility of a non-genomic rapid mechanism of action seems likely since transcriptional activities require a longer lag period.</AbstractText In human neuroendocrinology, high levels of glucocorticoids have been proven to function via a non-genomic mechanism of membrane receptors. The concentration of beclomethasone used on the lung slices in our study can be considered as high. This allows speculation about similar rapid non-genomic mechanisms of high-dosage inhaled glucocorticoids in the lower airways of horses. However, further assessment on a molecular basis is needed to confirm this.</AbstractText"
]
] |
23174433
|
When do people cooperate? The neuroeconomics of prosocial decision making.
|
Understanding the roots of prosocial behavior is an interdisciplinary research endeavor that has generated an abundance of empirical data across many disciplines. This review integrates research findings from different fields into a novel theoretical framework that can account for when prosocial behavior is likely to occur. Specifically, we propose that the motivation to cooperate (or not), generated by the reward system in the brain (extending from the striatum to the ventromedial prefrontal cortex), is modulated by two neural networks: a cognitive control system (centered on the lateral prefrontal cortex) that processes extrinsic cooperative incentives, and/or a social cognition system (including the temporo-parietal junction, the medial prefrontal cortex and the amygdala) that processes trust and/or threat signals. The independent modulatory influence of incentives and trust on the decision to cooperate is substantiated by a growing body of neuroimaging data and reconciles the apparent paradox between economic versus social rationality in the literature, suggesting that we are in fact wired for both. Furthermore, the theoretical framework can account for substantial behavioral heterogeneity in prosocial behavior. Based on the existing data, we postulate that self-regarding individuals (who are more likely to adopt an economically rational strategy) are more responsive to extrinsic cooperative incentives and therefore rely relatively more on cognitive control to make (un)cooperative decisions, whereas other-regarding individuals (who are more likely to adopt a socially rational strategy) are more sensitive to trust signals to avoid betrayal and recruit relatively more brain activity in the social cognition system. Several additional hypotheses with respect to the neural roots of social preferences are derived from the model and suggested for future research.</AbstractText
|
[
[
"12716950",
"Hierarchical processing in spoken language comprehension.",
"Understanding spoken language requires a complex series of processing stages to translate speech sounds into meaning. In this study, we use functional magnetic resonance imaging to explore the brain regions that are involved in spoken language comprehension, fractionating this system into sound-based and more abstract higher-level processes. We distorted English sentences in three acoustically different ways, applying each distortion to varying degrees to produce a range of intelligibility (quantified as the number of words that could be reported) and collected whole-brain echo-planar imaging data from 12 listeners using sparse imaging. The blood oxygenation level-dependent signal correlated with intelligibility along the superior and middle temporal gyri in the left hemisphere and in a less-extensive homologous area on the right, the left inferior frontal gyrus (LIFG), and the left hippocampus. Regions surrounding auditory cortex, bilaterally, were sensitive to intelligibility but also showed a differential response to the three forms of distortion, consistent with sound-form-based processes. More distant intelligibility-sensitive regions within the superior and middle temporal gyri, hippocampus, and LIFG were insensitive to the acoustic form of sentences, suggesting more abstract nonacoustic processes. The hierarchical organization suggested by these results is consistent with cognitive models and auditory processing in nonhuman primates. Areas that were particularly active for distorted speech conditions and, thus, might be involved in compensating for distortion, were found exclusively in the left hemisphere and partially overlapped with areas sensitive to intelligibility, perhaps reflecting attentional modulation of auditory and linguistic processes.</AbstractText"
]
] |
[
[
"23001148",
"An observational study of the effectiveness and safety of growth hormone (Humatrope(®)) treatment in Japanese children with growth hormone deficiency or Turner syndrome.",
"This study assessed the effectiveness and safety of growth hormone (GH; Humatrope(®)) therapy in Japanese children with GH deficiency (GHD) or Turner syndrome (TS) enrolled in the Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS). GeNeSIS is an open-label, multinational, multicenter, observational study conducted in 30 countries. In this interim report, there were 1129 GH treatment-naïve children with GHD, with a mean chronological age (± standard deviation) of 8.75 (3.32) years, and 90 girls with TS, with a mean chronological age of 8.93 (3.67) years. The mean height standard deviation score (SDS) increased from -2.73 (0.63) SD and -2.71 (0.63) SD at study entry to -2.22 (0.68) SD and -2.20 (0.60) SD after 1 year of treatment in the GHD and TS groups, respectively. In both groups, mean height SDS increased further with each year of treatment to 4 years; however, the magnitude of change in height SDS declined with time. The mean insulin-like growth factor-I SDS increased from below the mean of the reference population at study entry to a level similar to (GHD group) or higher than (TS group) the mean of the reference population during the 4-year treatment period. The incidence of serious adverse events (AEs), treatment-related AEs, and AEs related to glucose intolerance was low in both groups (0.1% to 3.0%). In conclusion, GH treatment in Japanese children with GHD or TS resulted in increased growth over a 4-year treatment period with a favorable safety profile; however, the improvements in growth declined with time.</AbstractText"
]
] |
22240730
|
Birdsong neurolinguistics: songbird context-free grammar claim is premature.
|
There are remarkable behavioral, neural, and genetic similarities between song learning in songbirds and speech acquisition in human infants. Previously, we have argued that this parallel cannot be extended to the level of sentence syntax. Although birdsong can indeed have a complex structure, it lacks the combinatorial complexity of human language syntax. Recently, this conclusion has been challenged by a report purporting to show that songbirds can learn so-called context-free syntactic rules and then use them to discriminate particular syllable patterns. Here, we demonstrate that the design of this study is inadequate to draw such a conclusion, and offer alternative explanations for the experimental results that do not require the acquisition and use of context-free grammar rules or a grammar of any kind, only the simpler hypothesis of acoustic similarity matching. We conclude that the evolution of vocal learning involves both neural homologies and behavioral convergence, and that human language reflects a unique cognitive capacity.</AbstractText
|
[
[
"19400719",
"The science of neural interface systems.",
"The ultimate goal of neural interface research is to create links between the nervous system and the outside world either by stimulating or by recording from neural tissue to treat or assist people with sensory, motor, or other disabilities of neural function. Although electrical stimulation systems have already reached widespread clinical application, neural interfaces that record neural signals to decipher movement intentions are only now beginning to develop into clinically viable systems to help paralyzed people. We begin by reviewing state-of-the-art research and early-stage clinical recording systems and focus on systems that record single-unit action potentials. We then address the potential for neural interface research to enhance basic scientific understanding of brain function by offering unique insights in neural coding and representation, plasticity, brain-behavior relations, and the neurobiology of disease. Finally, we discuss technical and scientific challenges faced by these systems before they are widely adopted by severely motor-disabled patients.</AbstractText"
]
] |
[
[
"23351052",
"On the neural basis of rule-guided behavior.",
"Human behavior emerges from a complex dynamic interaction between graded and context-sensitive neural processes, the biomechanics of our bodies, and the vicissitudes of our environments. These coupled processes bear little resemblance to the iterated application of simple symbolic rules. Still, there are circumstances under which our behavior appears to be guided by explicit mental rules. A prototypical case is when succinct verbal instructions are communicated and are promptly followed by another. How does the brain support such rule-guided behavior? How are explicit rules represented in the brain? How are rule representations shaped by experience? What neural processes form the foundation of our ability to systematically represent and apply rules from the vast range of possible rules? This article reviews a line of research that has sought a computational cognitive neuroscience account of rule-guided behavior in terms of the functioning of the prefrontal cortex, the basal ganglia, and related brain systems.</AbstractText"
]
] |
21645998
|
Are we studying and treating schizophrenia correctly?
|
New findings are rapidly revealing an increasingly detailed image of neural- and molecular-level dysfunction in schizophrenia, distributed throughout interconnected cortico-striato-pallido-thalamic circuitry. Some disturbances appear to reflect failures of early brain maturation, that become codified into dysfunctional circuit properties, resulting in a substantial loss of, or failure to develop, both cells and/or appropriate connectivity across widely dispersed brain regions. These circuit disturbances are variable across individuals with schizophrenia, perhaps reflecting the interaction of multiple different risk genes and epigenetic events. Given these complex and variable hard-wired circuit disturbances, it is worth considering how new and emerging findings can be integrated into actionable treatment models. This paper suggests that future efforts towards developing more effective therapeutic approaches for the schizophrenias should diverge from prevailing models in genetics and molecular neuroscience, and focus instead on a more practical three-part treatment strategy: 1) systematic rehabilitative psychotherapies designed to engage healthy neural systems to compensate for and replace dysfunctional higher circuit elements, used in concert with 2) medications that specifically target cognitive mechanisms engaged by these rehabilitative psychotherapies, and 3) antipsychotic medications that target nodal or convergent circuit points within the limbic-motor interface, to constrain the scope and severity of psychotic exacerbations and thereby facilitate engagement in cognitive rehabilitation. The use of targeted cognitive rehabilitative psychotherapy plus synergistic medication has both common sense and time-tested efficacy with numerous other neuropsychiatric disorders.</AbstractText
|
[
[
"15996748",
"Correlates of trait impulsiveness in performance measures and neuropsychological tests.",
"Performance measures of impulsiveness offer great promise for assessing this trait in clinical and experimental studies. However, little is known about their relative superiority or inferiority to standard cognitive performance measures as correlates of this trait. In this study, 58 healthy volunteers completed a self-rating of impulsiveness (Barratt Impulsiveness Scale) and a battery of neuropsychological tests. The test battery included measures of reaction time, attention, memory, fluency, and executive function, as well as two performance measures of impulsiveness--Time Estimation and a Go-No Go task. Self-ratings correlated moderately with a number of these test scores, but many correlations became non-significant after adjustment for age and education. Correlations with the Go-No Go task, verbal fluency, executive function measures (Trails B), and tasks requiring decision-making against time (Choice Reaction Time, Reaction Time to Paired Words and Paired Faces Memory Tasks, and response bias on the Continuous Performance Test) remained significant. Performance on the Go-No Go task was the strongest correlate of self-rated impulsiveness. The findings suggest that once general demographic or ability factors are accounted for, specialized performance tasks requiring decision-making and response organization under time pressure provide the most effective means of assessing this behavioral trait.</AbstractText"
]
] |
[
[
"21625624",
"\"Studying injured minds\" - the Vietnam head injury study and 40 years of brain injury research.",
"The study of those who have sustained traumatic brain injuries (TBI) during military conflicts has greatly facilitated research in the fields of neuropsychology, neurosurgery, psychiatry, neurology, and neuroimaging. The Vietnam Head Injury Study (VHIS) is a prospective, long-term follow-up study of a cohort of 1,221 Vietnam veterans with mostly penetrating brain injuries, which has stretched over more than 40 years. The scope of this study, both in terms of the types of injury and fields of examination, has been extremely broad. It has been instrumental in extending the field of TBI research and in exposing pressing medical and social issues that affect those who suffer such injuries. This review summarizes the history of conflict-related TBI research and the VHIS to date, as well as the vast range of important findings the VHIS has established.</AbstractText"
]
] |
23062307
|
Childhood adversity and DNA methylation of genes involved in the hypothalamus-pituitary-adrenal axis and immune system: whole-genome and candidate-gene associations.
|
In recent years, translational research involving humans and animals has uncovered biological and physiological pathways that explain associations between early adverse circumstances and long-term mental and physical health outcomes. In this article, we summarize the human and animal literature demonstrating that epigenetic alterations in key biological systems, the hypothalamus-pituitary-adrenal axis and immune system, may underlie such disparities. We review evidence suggesting that changes in DNA methylation profiles of the genome may be responsible for the alterations in hypothalamus-pituitary-adrenal axis and immune system trajectories. Using some preliminary data, we demonstrate how explorations of genome-wide and candidate-gene DNA methylation profiles may inform hypotheses and guide future research efforts in these areas. We conclude our article by discussing the many important future directions, merging perspectives from developmental psychology, molecular genetics, neuroendocrinology, and immunology, that are essential for furthering our understanding of how early adverse circumstances may shape developmental trajectories, particularly in the areas of stress reactivity and physical or mental health.</AbstractText
|
[
[
"15831717",
"Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo.",
"Microglial cells represent the immune system of the mammalian brain and therefore are critically involved in various injuries and diseases. Little is known about their role in the healthy brain and their immediate reaction to brain damage. By using in vivo two-photon imaging in neocortex, we found that microglial cells are highly active in their presumed resting state, continually surveying their microenvironment with extremely motile processes and protrusions. Furthermore, blood-brain barrier disruption provoked immediate and focal activation of microglia, switching their behavior from patroling to shielding of the injured site. Microglia thus are busy and vigilant housekeepers in the adult brain.</AbstractText"
]
] |
[
[
"23576843",
"Possibilities offered by implantable miniaturized cuff-electrodes for insect neurophysiology.",
"Recent advances in microsystems technology led to a miniaturization of cuff-electrodes, which suggests these electrodes not just for long-term neuronal recordings in mammalians, but also in medium-sized insects. In this study we investigated the possibilities offered by cuff-electrodes for neuroethology using insects as a model organism. The implantation in the neck of a tropical bushcricket resulted in high quality extracellular nerve recordings of different units responding to various acoustic, vibratory, optical and mechanical stimuli. In addition, multi-unit nerve activity related to leg movements was recorded in insects walking on a trackball. A drawback of bi-polar nerve recordings obtained during tethered flight was overlay of nerve activity with large amplitude muscle potentials. Interestingly, cuff-electrode recordings were robust to withstand walking and flight activity so that good quality nerve recordings were possible even three days after electrode implantation. Recording multi-unit nerve activity in intact insects required an elaborate spike sorting algorithm in order to discriminate neuronal units responding to external stimuli from background activity. In future, a combination of miniaturized cuff-electrodes and light-weight amplifiers equipped with a wireless transmitter will allow the investigation of neuronal processes underlying natural behavior in freely moving insects. By this means cuff-electrodes may contribute to the development of realistic neuronal models simulating neuronal processes underlying natural insect behavior, such like mate choice and predator avoidance.</AbstractText"
]
] |
23196557
|
[A new neuroscientific approach using decoded neurofeedback (DecNef)].
|
Neurofeedback is defined as a method to read out information from the brain and feed the information back to the brain. This technology has developed in the past ten years and attracted considerable attention as potential treatments for rehabilitation and psychiatric disease. We recently invented the decoded neurofeedback (DecNef) method, a new neurofeedback technique using functional magnetic resonance imaging. With DecNef, subjects were trained to regulate their brain activation pattern in a specific area and lead the pattern to a target state. We found that the DecNef training for several days leads to perceptual improvement that corresponds to the induced target state. DecNef enables us to test cause-and-effect relationships between neural activation in a target brain area and changes in perception, cognition, and behavior. In this sense, this method can be a powerful tool in cognitive and systems neuroscience. In addition, the concept of DecNef, leading a neural activation pattern to a specific state, can be applied for a variety of fields including engineering and medical treatment.</AbstractText
|
[
[
"15831717",
"Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo.",
"Microglial cells represent the immune system of the mammalian brain and therefore are critically involved in various injuries and diseases. Little is known about their role in the healthy brain and their immediate reaction to brain damage. By using in vivo two-photon imaging in neocortex, we found that microglial cells are highly active in their presumed resting state, continually surveying their microenvironment with extremely motile processes and protrusions. Furthermore, blood-brain barrier disruption provoked immediate and focal activation of microglia, switching their behavior from patroling to shielding of the injured site. Microglia thus are busy and vigilant housekeepers in the adult brain.</AbstractText"
]
] |
[
[
"23176028",
"Iranians' contribution to world literature on neuroscience.",
"The purpose of this study is to analyse Iranian scientific publications in the neuroscience subfields by librarians and neuroscientists, using Science Citation Index Expanded (SCIE) via Web of Science data over the period, 2002-2008.</AbstractText Data were retrieved from the SCIE. Data were collected from the 'subject area' of the database and classified by neuroscience experts into 14 subfields. To identify the citation patterns, we applied the 'impact factor' and the 'number of publication'. Data were also analysed using HISTCITE, Excel 2007 and SPSS.</AbstractText Seven hundred and thirty-four papers have been published by Iranian between 2002 and 2008. Findings showed a growing trend of neuroscience papers in the last 3 years with most papers (264) classified in the neuropharmacology subfield. There were fewer papers in neurohistory, psychopharmacology and artificial intelligence. International contributions of authors were mostly in the neurology subfield, and 'Collaboration Coefficient' for the neuroscience subfields in Iran was 0.686 which is acceptable. Most international collaboration between Iranians and developed countries was from USA. Eighty-seven percent of the published papers were in journals with the impact factor between 0 and 4; 25% of papers were published by the researchers affiliated to Tehran University of Medical Sciences.</AbstractText Progress of neuroscience in Iran is mostly seen in the neuropharmacology and the neurology subfields. Other subfields should also be considered as a research priority by health policymakers. As this study was carried out by the collaboration of librarians and neuroscientists, it has been proved valuable for both librarians and policymakers. This study may be encouraging for librarians from other developing countries.</AbstractText"
]
] |
23428294
|
Neuropsychological assessment and the paradox of ADHD.
|
Attention-deficit hyperactivity disorder (ADHD) is a behaviorally defined diagnosis. Despite the fact that neuropsychological tests have typically been used successfully to investigate the functional neuroanatomy of ADHD in neuroimaging research paradigms, these tests have been of surprisingly limited utility in the clinical diagnosis of the disorder. This article examines this paradox by reviewing the characteristics of the Diagnostic and Statistical Manual of Mental Disorders diagnosis versus neuropsychological nomenclature, by reviewing the assumptions about etiologies for ADHD and by demonstrating how an emerging dimensional approach to diagnostic assessment can be combined with large-scale brain network studies to enhance the role of neuropsychological evaluation within clinical settings. This selective topical review is intended to arm practicing neuropsychologists with knowledge of new ideas, theories, and methods related to the causes of ADHD to prepare them for meaningful advances in understanding and assessing the disorder that are possible during the next decade.</AbstractText
|
[
[
"21325522",
"Origin and determination of inhibitory cell lineages in the vertebrate retina.",
"Multipotent progenitors in the vertebrate retina often generate clonally related mixtures of excitatory and inhibitory neurons. The postmitotically expressed transcription factor, Ptf1a, is essential for all inhibitory fates in the zebrafish retina, including three types of horizontal and 28 types of amacrine cell. Here, we show that specific types of inhibitory neurons arise from the cell-autonomous influence of Ptf1a in the daughters of fate-restricted progenitors, such as Ath5 or Vsx1/2-expressing progenitors, and that in the absence of Ptf1a, cells that would have become these specific inhibitory subtypes revert to the histogenetically appropriate excitatory subtypes of the same lineage. Altered proportions of amacrine subtypes respecified by the misexpression of Ptf1a in the Ath5 lineage suggest that Ath5-expressing progenitors are biased, favoring the generation of some subtypes more than others. Yet the full array of inhibitory cell subtypes in Ath5 mutants implies the existence of Ath5-independent factors involved in inhibitory cell specification. We also show that an extrinsic negative feedback on the expression of Ptf1a provides a control mechanism by which the number of any and all types of inhibitory cells in the retina can be regulated in this lineage-dependent way.</AbstractText"
]
] |
[
[
"23275858",
"Brain state-triggered stimulus delivery: An efficient tool for probing ongoing brain activity.",
"What is the relationship between variability in ongoing brain activity <i"
]
] |
22520647
|
European study of research and development in mobility technology for persons with disabilities.
|
\In the fall of 2010, the National Science Foundation, the National Institutes of Health and the U.S. Veteran's Administration jointly supported a review of mobility technology in Europe. A delegation of American Scientists traveled to Europe to visit a number of research centers and engaged in a demonstration and dialogue related to the global state-of-the-art for mobility impairment rectification and augmentation. From the observations and exchanges between the U.S. delegation and host institutions, the researchers were able to derive a series of papers which are now published in this thematic series of Journal of NeuroEngineering and Rehabilitation. The papers describe the main themes of the European mobility technology research activities showing a healthy picture of research and innovation in the field.</AbstractText
|
[
[
"20427643",
"Emotional automaticity is a matter of timing.",
"There has been a long controversy concerning whether the amygdala's response to emotional stimuli is automatic or dependent on attentional load. Using magnoencephalography and an advanced beamformer source localization technique, we found that amygdala automaticity was a function of time: while early amygdala responding to emotional stimuli (40-140 ms) was unaffected by attentional load, later amygdala response (280-410 ms), subsequent to frontoparietal cortex activity, was modulated by attentional load.</AbstractText"
]
] |
[
[
"22155385",
"Metabotropic glutamate receptor 1 (mGluR1): antibody specificity and receptor expression in cultured primary neurons.",
"The availability of high quality, well-characterized antibodies for molecular and cellular neuroscience studies is important. However, not all available antibodies are rigorously evaluated, nor are limitations of particular antibodies often reported. We have examined a panel of currently available mGluR1 antibodies and have identified which ones are selective for use by western blots and immunocytochemistry. We have also specifically determined whether the antibodies cross-react to recognize mGluR5, by examining (1) tissue from both mGluR1 and mGluR5 knock-out mice and (2) primary cortical cultures, in which mGluR5 is widely expressed but mGluR1 is not. Together, these data provide a baseline characterization of antibodies that can and cannot be reliably used in these types of studies, and will hopefully facilitate and positively impact the research efforts of others studying mGluR1.</AbstractText"
]
] |
22751865
|
Human aquaporin 4281-300 is the immunodominant linear determinant in the context of HLA-DRB1*03:01: relevance for diagnosing and monitoring patients with neuromyelitis optica.
|
OBJECTIVE To identify linear determinants of human aquaporin 4 (hAQP4) in the context of HLA-DRB1*03:01. DESIGN In this controlled study with humanized experimental animals, HLA-DRB1*03:01 transgenic mice were immunized with whole-protein hAQP4 emulsified in complete Freund adjuvant. To test T-cell responses, lymph node cells and splenocytes were cultured in vitro with synthetic peptides 20 amino acids long that overlap by 10 amino acids across the entirety of hAQP4. The frequency of interferon γ, interleukin (IL) 17, granulocyte-macrophage colony-stimulating factor, and IL-5-secreting CD4+ T cells was determined by the enzyme-linked immunosorbent sport assay. Quantitative immunofluorescence microscopy was performed to determine whether hAQP4281-300 inhibits the binding of anti-hAQP4 recombinant antibody to surface full-length hAQP4. SETTING Academic neuroimmunology laboratories. SUBJECTS Humanized HLA-DRB1*03:01+/+ H-2b-/- transgenic mice on a B10 background. RESULTS Peptide hAQP4281-300 generated a significantly (P &lt;.01) greater TH1 and TH17 immune response than any of the other linear peptides screened. This 20mer peptide contains 2 dominant immunogenic 15mer peptides. hAQP4284-298 induced predominantly an IL-17 and granulocyte-macrophage colony-stimulating factor TH cell phenotype, whereas hAQP4285-299 resulted in a higher frequency of TH1 cells. hAQP4281-300 did not interfere with recombinant AQP4 autoantibody binding. CONCLUSIONS hAQP4281-330 is the dominant linear immunogenic determinant of hAQP4 in the context of HLA-DRB1*03:01. Within hAQP4281-330 are 2 dominant immunogenic determinants that induce differential TH phenotypes. hAQP4 determinants identified in this study can serve as diagnostic biomarkers in patients with neuromyelitis optica and may facilitate the monitoring of treatment responses to pharmacotherapies.</AbstractText
|
[
[
"21731699",
"Recognition of 5-hydroxymethylcytosine by the Uhrf1 SRA domain.",
"Recent discovery of 5-hydroxymethylcytosine (5hmC) in genomic DNA raises the question how this sixth base is recognized by cellular proteins. In contrast to the methyl-CpG binding domain (MBD) of MeCP2, we found that the SRA domain of Uhrf1, an essential factor in DNA maintenance methylation, binds 5hmC and 5-methylcytosine containing substrates with similar affinity. Based on the co-crystal structure, we performed molecular dynamics simulations of the SRA:DNA complex with the flipped cytosine base carrying either of these epigenetic modifications. Our data indicate that the SRA binding pocket can accommodate 5hmC and stabilizes the flipped base by hydrogen bond formation with the hydroxyl group.</AbstractText"
]
] |
[
[
"24294562",
"Dorello's Canal and Gruber's Ligament: Historical Perspective.",
"Wenzel Leopold Gruber and Primo Dorello were great anatomists and researchers during the 19th and 20th centuries. Their contributions to neuroanatomy-namely the Gruber's (petrosphenoidal) ligament and Dorello's canal, respectively-have come to be important structures in various approaches through the middle fossa. These structures have also helped provide us with an understanding of the mechanism of sixth nerve paresis in various pathological conditions, such as raised intracranial pressure and Gradenigo syndrome. Their numerous publications have stood as a reference to anatomical researchers. Gruber's description of internal mesogastric hernia and the Meckel-Gruber anastomosis are also widely known in medical literature. The following article is an attempt to reflect upon the life and works of Gruber and Dorello and the importance of their research.</AbstractText"
]
] |
23276394
|
Biological mechanisms associated with increased perseveration and hyperactivity in a genetic mouse model of neurodevelopmental disorder.
|
Chromosomal deletions at Xp22.3 appear to influence vulnerability to the neurodevelopmental disorders attention deficit hyperactivity disorder (ADHD) and autism. 39,X(Y*)O mice, which lack the murine orthologue of the Xp22.3 ADHD candidate gene STS (encoding steroid sulfatase), exhibit behavioural phenotypes relevant to such disorders (e.g. hyperactivity), elevated hippocampal serotonin (5-HT) levels, and reduced serum levels of dehydroepiandrosterone (DHEA). Here we initially show that 39,X(Y*)O mice are also deficient for the recently-characterised murine orthologue of the Xp22.3 autism candidate gene ASMT (encoding acetylserotonin-O-methyltransferase). Subsequently, to specify potential behavioural correlates of elevated hippocampal 5-HT arising due to the genetic lesion, we compared 39,X(Y*)O MF1 mice to 40,XY MF1 mice on behavioural tasks taxing hippocampal and/or 5-HT function (a 'foraging' task, an object-location task, and the 1-choice serial reaction time task of impulsivity). Although Sts/Asmt deficiency did not influence foraging behaviour, reactivity to familiar objects in novel locations, or 'ability to wait', it did result in markedly increased response rates; these rates correlated with hippocampal 5-HT levels and are likely to index behavioural perseveration, a frequent feature of neurodevelopmental disorders. Additionally, we show that whilst there was no systematic relationship between serum DHEA levels and hippocampal 5-HT levels across 39,X(Y*)O and 40,XY mice, there was a significant inverse linear correlation between serum DHEA levels and activity. Our data suggest that deficiency for genes within Xp22.3 could influence core behavioural features of neurodevelopmental disorders via dissociable effects on hippocampal neurochemistry and steroid hormone levels, and that the mediating neurobiological mechanisms may be investigated in the 39,X(Y*)O model.</AbstractText
|
[
[
"18457512",
"Timing, storage, and comparison of stimulus duration engage discrete anatomical components of a perceptual timing network.",
"The temporal discrimination paradigm requires subjects to compare the duration of a probe stimulus to that of a sample previously stored in working or long-term memory, thus providing an index of timing that is independent of a motor response. However, the estimation process itself comprises several component cognitive processes, including timing, storage, retrieval, and comparison of durations. Previous imaging studies have attempted to disentangle these components by simply measuring brain activity during early versus late scanning epochs. We aim to improve the temporal resolution and precision of this approach by using rapid event-related functional magnetic resonance imaging to time-lock the hemodynamic response to presentation of the sample and probe stimuli themselves. Compared to a control (color-estimation) task, which was matched in terms of difficulty, sustained attention, and motor preparation requirements, we found selective activation of the left putamen for the storage (\"encoding\") of stimulus duration into working memory (WM). Moreover, increased putamen activity was linked to enhanced timing performance, suggesting that the level of putamen activity may modulate the depth of temporal encoding. Retrieval and comparison of stimulus duration in WM selectively activated the right superior temporal gyrus. Finally, the supplementary motor area was equally active during both sample and probe stages of the task, suggesting a fundamental role in timing the duration of a stimulus that is currently unfolding in time.</AbstractText"
]
] |
[
[
"23269483",
"Metabolomic analysis of cerebrospinal fluid indicates iron deficiency compromises cerebral energy metabolism in the infant monkey.",
"Iron deficiency anemia affects many pregnant women and young infants worldwide. The health impact is significant, given iron's known role in many body functions, including oxidative and lipid metabolism, protein synthesis and brain neurochemistry. The following research determined if (1)H NMR spectroscopy-based metabolomic analysis of cerebrospinal fluid (CSF) could detect the adverse influence of early life iron deficiency on the central nervous system. Using a controlled dietary model in 43 infant primates, distinct differences were found in spectra acquired at 600 MHz from the CSF of anemic monkeys. Three metabolite ratios, citrate/pyruvate, citrate/lactate and pyruvate/glutamine ratios, differed significantly in the iron deficient infant and then normalized following the consumption of dietary iron and improvement of clinical indices of anemia in the heme compartment. This distinctive metabolomic profile associated with anemia in the young infant indicates that CSF can be employed to track the neurological effects of iron deficiency and benefits of iron supplementation.</AbstractText"
]
] |
23130007
|
When Do We Confuse Self and Other in Action Memory? Reduced False Memories of Self-Performance after Observing Actions by an Out-Group vs. In-Group Actor.
|
Observing another person performing an action can lead to a false memory of having performed the action oneself - the observation-inflation effect. In the experimental paradigm, participants first perform or do not perform simple actions, and then observe another person perform some of these actions. The observation-inflation effect is found when participants later remember performing actions that they have merely observed. In this case, self and other are confused in action memory. We examined social conditions of this self-other confusion when remembering actions, specifically whether the effect depends on the observed actor's group membership. In our experiment, we manipulated group membership based on physical appearance, specifically complexion of the hands. Fair-skinned participants observed either an in-group (i.e., fair-skinned) or an out-group (i.e., dark-skinned) actor. Our results revealed that the observed actor's group membership moderated the observation-inflation effect: False memories were significantly reduced when the actor was from the out-group (vs. in-group). We found no difference to a control condition in which the actor wore black gloves, suggesting that distinctiveness of perceptual or sensory features alone (due to the out-group member's dark skin) is not critical. We discuss these findings in light of social-neuroscience studies demonstrating the impact of an observed person's group membership on motor simulation. Overall, our findings suggest that action memory can be affected by a ubiquitous feature of people's social perception, that is, group-based social categorization of others.</AbstractText
|
[
[
"19298949",
"Perceptual simulation in conceptual combination: evidence from property generation.",
"In three experiments, participants received nouns or noun phrases for objects and verbally generated their properties (\"feature listing\"). Several sources of evidence indicated that participants constructed perceptual simulations to generate properties for the noun phrases during conceptual combination. First, the production of object properties for noun phrases depended on occlusion, with unoccluded properties being generated more often than occluded properties. Because a perceptual variable affected conceptual combination, perceptual simulations appeared central to combining the concepts for modifiers and head nouns. Second, neutral participants produced the same distributions of properties as participants instructed to describe images, suggesting that the conceptual representations used by neutral participants were similar to the mental images used by imagery participants. Furthermore, the property distributions for neutral and imagery participants differed from those for participants instructed to produce word associations. Third, participants produced large amounts of information about background situations associated with the object cues, suggesting that the simulations used to generate properties were situated. The experiments ruled out alternative explanations that simulation effects occur only for familiar noun phrases associated with perceptual memories and that rules associated with modifiers produce occlusion effects. A process model of the property generation task grounded in simulation mechanisms is presented. The possibility of integrating the simulation account of conceptual combination with traditional accounts and well-established findings is explored.</AbstractText"
]
] |
[
[
"23055968",
"Detection of self-paced reaching movement intention from EEG signals.",
"Future neuroprosthetic devices, in particular upper limb, will require decoding and executing not only the user's intended movement type, but also when the user intends to execute the movement. This work investigates the potential use of brain signals recorded non-invasively for detecting the time before a self-paced reaching movement is initiated which could contribute to the design of practical upper limb neuroprosthetics. In particular, we show the detection of self-paced reaching movement intention in single trials using the readiness potential, an electroencephalography (EEG) slow cortical potential (SCP) computed in a narrow frequency range (0.1-1 Hz). Our experiments with 12 human volunteers, two of them stroke subjects, yield high detection rates prior to the movement onset and low detection rates during the non-movement intention period. With the proposed approach, movement intention was detected around 500 ms before actual onset, which clearly matches previous literature on readiness potentials. Interestingly, the result obtained with one of the stroke subjects is coherent with those achieved in healthy subjects, with single-trial performance of up to 92% for the paretic arm. These results suggest that, apart from contributing to our understanding of voluntary motor control for designing more advanced neuroprostheses, our work could also have a direct impact on advancing robot-assisted neurorehabilitation.</AbstractText"
]
] |
23279177
|
Neurochemistry of schizophrenia: the contribution of neuroimaging postmortem pathology and neurochemistry in schizophrenia.
|
The advent of molecular neuroimaging has greatly impacted on understanding the neurochemical changes occurring in the CNS from subjects with psychiatric disorders, especially schizophrenia. This review focuses on the outcomes from studies using positron emission tomography and single photon emission computer tomography that have measure levels of neurotransmitter receptors and transporters in the CNS from subjects with schizophrenia. One outcome from such studies is the confirmation of a number of findings using postmortem tissue, but in the case of neuroimaging, using drug na�ve and drug free subjects. These findings add weight to the argument that findings from postmortem studies are not an artifact of tissue processing or a simple drug effect. However, there are some important unique findings from studies using neuroimaging studies. These include evidence to suggest that in schizophrenia there are alterations in dopamine synthesis and release, which are not accompanied by an appropriate down-regulation of dopamine D2 receptors. There are also data that would support the notion that decreased levels of serotonin 2A receptors may be an early marker of the onset of schizophrenia. Whilst there is a clear need for on-going development of neuroimaging ligands to expand the number of targets that can be studied and to increase cohort sizes in neuroimaging studies to give power to the analyses of the resulting data, current studies show that existing neuroimaging studies have already extended our understanding of the underlying pathophysiology of psychiatric disorders such as schizophrenia.</AbstractText
|
[
[
"11330208",
"Microdialysis perfusion of orexin-A in the basal forebrain increases wakefulness in freely behaving rats.",
"Recent work indicates that the orexin/hypocretin-containing neurons of the lateral hypothalamus are involved in control of REM sleep phenomena, but site-specific actions in control of wakefulness have been less studied. Orexin-containing neurons project to both brainstem and forebrain regions that are known to regulate sleep and wakefulness, including the field of cholinergic neurons in the basal forebrain (BF) that is implicated in regulation of wakefulness, and includes, in the rat, the horizontal limb of the diagonal band, the substantia innominata, and the magnocellular preoptic region. The present study used microdialysis perfusion of orexin-A directly in the cholinergic BF region of rat to test the hypothesis that orexin-A enhances W via a local action in the BF. A significant dose-dependent increase in W was produced by the perfusion of three doses of orexin-A in the BF (0.1, 1.0, and 10.0 microM), with 10.0 microM producing more than a 5-fold increase in wakefulness, which occupied 44% of the light (inactive) phase recording period. Orexin-A perfusion also produced a significant dose-dependent decrease in nonREM sleep, and a trend-level decrease in REM sleep. The results clearly demonstrate a potent capacity of orexin-A to induce wakefulness via a local action in the BF, and are consistent with previous work indicating that the BF cholinergic zone neurons have a critical role in the regulation of EEG activation and W. The data suggest further that orexin-A has a significant role in the regulation of arousal/wakefulness, in addition to the previously described role of orexin in the regulation and expression of REM sleep and REM sleep-related phenomena.</AbstractText"
]
] |
[
[
"22986407",
"How a common variant in the growth factor receptor gene, NTRK1, affects white matter.",
"Growth factors and their receptors are important for cellular migration as well as axonal guidance and myelination in the brain. They also play a key role in programmed cell death, and are implicated in a number of mental illnesses. Recently, we reported that healthy young adults who carry the T allele variant in the growth factor gene, NTRK1 (at location rs6336), had lower white matter integrity than non-carriers on diffusion images of the brain. Diffusion tensor imaging (DTI) revealed how this single nucleotide polymorphism affects white matter microstructure in human populations; DTI is also used to identify characteristic features of brain connectivity in typically developing children and in patients. Newly discovered links between neuroimaging measures and growth factors whose molecular neuroscience is well known offer an important step in understanding mechanisms that contribute to brain connectivity. Altered fiber connectivity may mediate the relationship between some genetic risk factors and a variety of mental illnesses.</AbstractText"
]
] |
23197532
|
A large-scale model of the functioning brain.
|
A central challenge for cognitive and systems neuroscience is to relate the incredibly complex behavior of animals to the equally complex activity of their brains. Recently described, large-scale neural models have not bridged this gap between neural activity and biological function. In this work, we present a 2.5-million-neuron model of the brain (called "Spaun") that bridges this gap by exhibiting many different behaviors. The model is presented only with visual image sequences, and it draws all of its responses with a physically modeled arm. Although simplified, the model captures many aspects of neuroanatomy, neurophysiology, and psychological behavior, which we demonstrate via eight diverse tasks.</AbstractText
|
[
[
"8854339",
"Role of an S4-S5 linker in sodium channel inactivation probed by mutagenesis and a peptide blocker.",
"A pair of conserved methionine residues, located on the cytoplasmic linker between segments S4 and S5 in the fourth domain of human heart Na channels (hH1), plays a role in the kinetics and voltage dependence of inactivation. Substitution of these residues by either glutamine (M1651M1652/QQ) or alanine (MM/AA) increases the inactivation time constant (tau) at depolarized voltages, shifts steady-state inactivation (h infinity) in a depolarized direction, and decreases the time constant for recovery from inactivation. The data indicate that the mutations affect the rate constants for both binding and unbinding of a hypothetical inactivation particle from its binding site. Cytoplasmic application of the pentapeptide KIFMK in Na channels mutated to remove inactivation produces current decays resembling inactivation (Eaholtz, G., T. Scheuer, and W.A. Catterall. 1994. Neuron. 12: 1041-1048.). KIFMK produces a concentration-dependent, voltage-independent increase in the decay rate of MM/QQ and MM/AA currents at positive membrane potentials (Ki approximately 30 microM), while producing only a small increase in the decay rate of wild-type currents at a concentration of 200 microM. Although MM/QQ inactivates approximately 2.5-fold faster than MM/AA in the absence of peptide, the estimated rate constants for peptide block and unblock do not differ in these mutants. External Na+ ions antagonize the block by cytoplasmic KIFMK of MM/AA channels, but not the inactivation kinetics of this mutant in the absence of peptide. The effect of external [Na+] is interpreted as a voltage-dependent knock-off mechanism. The data provide evidence that KIFMK can only block channels when they are open and that peptide block does not mimic the inactivation process.</AbstractText"
]
] |
[
[
"23505339",
"Baby Steps to Superintelligence: Neuroprosthetics and Children.",
"Children surviving neural injuries face challenges not seen by their adult counterparts, namely that they experience neural injury before reaching neurodevelopmental maturity. Neural prostheses offer one possible path to recovery, along with the potential for functional outcomes that could exceed expectations. Although the first cochlear implant was placed more than fifty years ago, the field of neuroprosthetics is still relatively young. Several types of neural prostheses are in development stages ranging from animal models to (adult) human trials. In this paper, I discuss how neural prostheses may assist recovery for children surviving neural injury. I argue that approaching the use of neural prosthetics in children with considerations derived from transhumanism alongside traditional bioethics can provide an opportunity to reframe adult-focused ethics toward a child/family focus and to strip away the prejudicial metaphor of cyborgization.</AbstractText"
]
] |
22143364
|
Postural tachycardia syndrome--current experience and concepts.
|
Postural tachycardia syndrome (PoTS) is a poorly understood but important cause of orthostatic intolerance resulting from cardiovascular autonomic dysfunction. PoTS is distinct from the syndromes of autonomic failure usually associated with orthostatic hypotension, such as pure autonomic failure and multiple system atrophy. Individuals affected by PoTS are mainly young (aged between 15 years and 40 years) and predominantly female. The symptoms--palpitations, dizziness and occasionally syncope--mainly occur when the patient is standing upright, and are often relieved by sitting or lying flat. Common stimuli in daily life, such as modest exertion, food ingestion and heat, are now recognized to be capable of exacerbating the symptoms. Onset of the syndrome can be linked to infection, trauma, surgery or stress. PoTS can be associated with various other disorders; in particular, joint hypermobility syndrome (also known as Ehlers-Danlos syndrome hypermobility type, formerly termed Ehlers-Danlos syndrome type III). This Review describes the characteristics and neuroepidemiology of PoTS, and outlines possible pathophysiological mechanisms of this syndrome, as well as current and investigational treatments.</AbstractText
|
[
[
"21749952",
"Social neuroscience: mirror neurons recorded in humans.",
"New single-cell recordings show that humans do have mirror neurons, and in more brain regions than previously suspected. Some action-execution neurons were seen to be inhibited during observation, possibly preventing imitation and helping self/other discrimination.</AbstractText"
]
] |
[
[
"21960308",
"Open questions in computational motor control.",
"Computational motor control covers all applications of quantitative tools for the study of the biological movement control system. This paper provides a review of this field in the form of a list of open questions. After an introduction in which we define computational motor control, we describe: a Turing-like test for motor intelligence; internal models, inverse model, forward model, feedback error learning and distal teacher; time representation, and adaptation to delay; intermittence control strategies; equilibrium hypotheses and threshold control; the spatiotemporal hierarchy of wide sense adaptation, i.e., feedback, learning, adaptation, and evolution; optimization based models for trajectory formation and optimal feedback control; motor memory, the past and the future; and conclude with the virtue of redundancy. Each section in this paper starts with a review of the relevant literature and a few more specific studies addressing the open question, and ends with speculations about the possible answer and its implications to motor neuroscience. This review is aimed at concisely covering the topic from the author's perspective with emphasis on learning mechanisms and the various structures and limitations of internal models.</AbstractText"
]
] |
22481743
|
Brain enabled by next-generation neurotechnology: using multiscale and multimodal models.
|
As many articles in this issue of IEEE Pulse demonstrate, interfacing directly with the brain presents several fundamental challenges. These challenges reside at multiple levels and span many disciplines, ranging from the need to understand brain states at the level of neural circuits to creating technological innovations to facilitate new therapeutic options. The goal of our multiuniversity research team, composed of researchers from Stanford University, Brown University, the University of California at San Francisco (UCSF), and the University College London (UCL), is to substantially elevate the fundamental understanding of brain information processing and its relationship with sensation, behavior, and injury. Our team was assembled to provide expertise ranging from neuroscience to neuroengineering and to neurological and psychiatric clinical guidance, all of which are critical to the overarching research goal. By employing a suite of innovative experimental, computational, and theoretical approaches, the Defense Advanced Research Projects Agency (DARPA) Reorganization and Plasticity to Accelerate Injury Recovery (REPAIR) team has set its sights on learning how the brain and its microcircuitry react (e.g., to sudden physiological changes) and what can be done to encourage recovery from such (reversible) injury. In this article, we summarize some of the team's technical goals, approaches, and early illustrative results.</AbstractText
|
[
[
"15928068",
"Reward, motivation, and emotion systems associated with early-stage intense romantic love.",
"Early-stage romantic love can induce euphoria, is a cross-cultural phenomenon, and is possibly a developed form of a mammalian drive to pursue preferred mates. It has an important influence on social behaviors that have reproductive and genetic consequences. To determine which reward and motivation systems may be involved, we used functional magnetic resonance imaging and studied 10 women and 7 men who were intensely \"in love\" from 1 to 17 mo. Participants alternately viewed a photograph of their beloved and a photograph of a familiar individual, interspersed with a distraction-attention task. Group activation specific to the beloved under the two control conditions occurred in dopamine-rich areas associated with mammalian reward and motivation, namely the right ventral tegmental area and the right postero-dorsal body and medial caudate nucleus. Activation in the left ventral tegmental area was correlated with facial attractiveness scores. Activation in the right anteromedial caudate was correlated with questionnaire scores that quantified intensity of romantic passion. In the left insula-putamen-globus pallidus, activation correlated with trait affect intensity. The results suggest that romantic love uses subcortical reward and motivation systems to focus on a specific individual, that limbic cortical regions process individual emotion factors, and that there is localization heterogeneity for reward functions in the human brain.</AbstractText"
]
] |
[
[
"22963990",
"Further characterization of repetitive behavior in C58 mice: developmental trajectory and effects of environmental enrichment.",
"Aberrant repetitive behaviors are commonly observed in a variety of neurodevelopmental, neurological, and neuropsychiatric disorders. Little is known about the specific neurobiological mechanisms that underlie such behaviors, however, and effective treatments are lacking. Valid animal models can aid substantially in identifying pathophysiological factors mediating aberrant repetitive behavior and aid in treatment development. The C58 inbred mouse strain is a particularly promising model, and we have further characterized its repetitive behavior phenotype. Compared to C57BL/6 mice, C58 mice exhibit high rates of spontaneous hindlimb jumping and backward somersaulting reaching adult frequencies by 5 weeks post-weaning and adult temporal organization by 2 weeks post-weaning. The development of repetitive behavior in C58 mice was markedly attenuated by rearing these mice in larger, more complex environments. In addition to characterizing repetitive motor behavior, we also assessed related forms of inflexible behavior that reflect restricted and perseverative responding. Contrary to our hypothesis, C58 mice did not exhibit increased marble burying nor did they display reduced exploratory behavior in the holeboard task. The C58 strain appears to be a very useful model for the repetitive motor behavior characteristic of a number of clinical disorders. As an inbred mouse strain, studies using the C58 model can take full advantage of the tool kit of modern genetics and molecular neuroscience. This technical advantage makes the model a compelling choice for use in studies designed to elucidate the etiology and pathophysiology of aberrant repetitive behavior. Such findings should, in turn, translate into effective new treatments.</AbstractText"
]
] |
23493966
|
Exploring sensory neuroscience through experience and experiment.
|
Many phenomena that we take for granted are illusions - color and motion on a TV or computer monitor, for example, or the impression of space in a stereo music recording. Even the stable image that we perceive when looking directly at the real world is illusory. One of the important lessons from sensory neuroscience is that our perception of the world is constructed rather than received. Sensory illusions effectively capture student interest, but how do you then move on to substantive discussion of neuroscience? This article illustrates several illusions, attempts to connect them to neuroscience, and shows how students can explore and experiment with them. Even when (as is often the case) there is no agreed-upon mechanistic explanation for an illusion, students can form hypotheses and test them by manipulating stimuli and measuring their effects. In effect, students can experiment with illusions using themselves as subjects.</AbstractText
|
[
[
"11377409",
"Double-blind naltrexone and placebo comparison study in the treatment of pathological gambling.",
"The authors' goal was to assess the efficacy and tolerability of naltrexone in the treatment of pathologic gambling disorder.</AbstractText Eighty-three subjects who met criteria for DSM-IV pathologic gambling disorder were enrolled in a 1-week single-blind placebo lead-in followed by an 11-week double-blind naltrexone or placebo trial. Naltrexone was started at 25 mg/day and titrated upward until maximum symptom improvement or 250 mg/day was achieved. Gambling symptom change was assessed with the patient-rated Clinical Global Impression (PG-CGI-PT), clinician-rated CGI (PG-CGI-MD), and the Gambling Symptom Rating Scale (G-SAS). Side effects were monitored weekly and liver function tests biweekly.</AbstractText Data from 45 patients were analyzed. Using random regression analysis, significant improvement was noted in all three gambling symptom measures: patient-rated Clinical Global Impression, p <.001; clinician-rated CGI, p <.001; Gambling Symptom Rating Scale, p <.019. At study end, 75% of subjects taking naltrexone were much or very much improved on both the PE-CEI PT and the PG-CGI-MD, compared with only 24% of those on placebo. Elevated liver enzymes occurred in four subjects who were taking analgesics concurrently. Nausea was common during the first week of treatment.</AbstractText Results suggest that naltrexone is effective in reducing the symptoms of pathologic gambling. Until further studies corroborate the present findings, our report should be interpreted cautiously.</AbstractText"
]
] |
[
[
"23140422",
"Comparison of GPU- and CPU-implementations of mean-firing rate neural networks on parallel hardware.",
"Modern parallel hardware such as multi-core processors (CPUs) and graphics processing units (GPUs) have a high computational power which can be greatly beneficial to the simulation of large-scale neural networks. Over the past years, a number of efforts have focused on developing parallel algorithms and simulators best suited for the simulation of spiking neural models. In this article, we aim at investigating the advantages and drawbacks of the CPU and GPU parallelization of mean-firing rate neurons, widely used in systems-level computational neuroscience. By comparing OpenMP, CUDA and OpenCL implementations towards a serial CPU implementation, we show that GPUs are better suited than CPUs for the simulation of very large networks, but that smaller networks would benefit more from an OpenMP implementation. As this performance strongly depends on data organization, we analyze the impact of various factors such as data structure, memory alignment and floating precision. We then discuss the suitability of the different hardware depending on the networks' size and connectivity, as random or sparse connectivities in mean-firing rate networks tend to break parallel performance on GPUs due to the violation of coalescence.</AbstractText"
]
] |
23177656
|
Synthetic event-related potentials: a computational bridge between neurolinguistic models and experiments.
|
Our previous work developed Synthetic Brain Imaging to link neural and schema network models of cognition and behavior to PET and fMRI studies of brain function. We here extend this approach to Synthetic Event-Related Potentials (Synthetic ERP). Although the method is of general applicability, we focus on ERP correlates of language processing in the human brain. The method has two components: Phase 1: To generate cortical electro-magnetic source activity from neural or schema network models; and Phase 2: To generate known neurolinguistic ERP data (ERP scalp voltage topographies and waveforms) from putative cortical source distributions and activities within a realistic anatomical model of the human brain and head. To illustrate the challenges of Phase 2 of the methodology, spatiotemporal information from Friederici's 2002 model of auditory language comprehension was used to define cortical regions and time courses of activation for implementation within a forward model of ERP data. The cortical regions from the 2002 model were modeled using atlas-based masks overlaid on the MNI high definition single subject cortical mesh. The electromagnetic contribution of each region was modeled using current dipoles whose position and orientation were constrained by the cortical geometry. In linking neural network computation via EEG forward modeling to empirical results in neurolinguistics, we emphasize the need for neural network models to link their architecture to geometrically sound models of the cortical surface, and the need for conceptual models to refine and adopt brain-atlas based approaches to allow precise brain anchoring of their modules. The detailed analysis of Phase 2 sets the stage for a brief introduction to Phase 1 of the program, including the case for a schema-theoretic approach to language production and perception presented in detail elsewhere. Unlike Dynamic Causal Modeling (DCM) and Bojak's mean field model, Synthetic ERP builds on models of networks that mediate the relation between the brain's inputs, outputs, and internal states in executing a specific task. The neural networks used for Synthetic ERP must include neuroanatomically realistic placement and orientation of the cortical pyramidal neurons. These constraints pose exciting challenges for future work in neural network modeling that is applicable to systems and cognitive neuroscience.</AbstractText
|
[
[
"17691351",
"An introduction to operative neuromodulation and functional neuroprosthetics, the new frontiers of clinical neuroscience and biotechnology.",
"Operative neuromodulation is the field of altering electrically or chemically the signal transmission in the nervous system by implanted devices in order to excite, inhibit or tune the activities of neurons or neural networks and produce therapeutic effects. It is a rapidly evolving biomedical and high-technology field on the cutting-edge of developments across a wide range of scientific disciplines. The authors review relevant literature on the neuromodulation procedures that are performed in the spinal cord or peripheral nerves in order to treat a considerable number of conditions such as (a) chronic pain (craniofacial, somatic, pelvic, limb, or due to failed back surgery), (b) spasticity (due to spinal trauma, multiple sclerosis, upper motor neuron disease, dystonia, cerebral palsy, cerebrovascular disease or head trauma), (c) respiratory disorders, (d) cardiovascular ischemia, (e) neuropathic bladder, and (f) bowel dysfunction of neural cause. Functional neuroprosthetics, a field of operative neuromodulation, encompasses the design, construction and implantation of artificial devices capable of generating electrical stimuli, thereby, replacing the function of damaged parts of the nervous system. The present article also reviews important literature on functional neuroprostheses, functional electrical stimulation (FES), and various emerging applications based on microsystems devices, neural engineering, neuroaugmentation, neurostimulation, and assistive technologies. The authors highlight promising lines of research such as endoneural prostheses for peripheral nerve stimulation, closed-loop systems for responsive neurostimulation or implanted microwires for microstimulation of the spinal cord to enable movements of paralyzed limbs. The above growing scientific fields, in combination with biological regenerative methods, are certainly going to enhance the practice of neuromodulation. The range of neuromodulatory procedures in the spine and peripheral nerves and the dynamics of the biomedical and technological domains which are reviewed in this article indicate that new breakthroughs are likely to improve substantially the quality of life of patients who are severely disabled by neurological disorders.</AbstractText"
]
] |
[
[
"23269439",
"The p.Ala510Val mutation in the SPG7 (paraplegin) gene is the most common mutation causing adult onset neurogenetic disease in patients of British ancestry.",
"The c.1529C >T change in the SPG7 gene, encoding the mutant p.Ala510Val paraplegin protein, was first described as a polymorphism in 1998. This was based on its frequency of 3 % and 4 % in two separate surveys of controls in the United Kingdom (UK) population. Subsequently, it has been found to co-segregate with disease in a number of different populations. Yeast expression studies support its having a deleterious effect. In this paper a consanguineous sibship is described in which four members who are homozygous for the p.Ala510Val variant present with a spectrum of disease. This spectrum encompasses moderately severe hereditary spastic paraparesis (HSP) with more minor ataxia in two siblings, moderately severe ataxia without spasticity in the third, and a very mild gait ataxia in the fourth. Two of the siblings also manifest vestibular failure. The remaining eight unaffected siblings are either heterozygous for the p.Ala510Val variant, or do not carry it at all. Homozygosity mapping using a high-density SNP array across the whole genome found just 11 genes (on two regions of chromosome 3) outside the SPG7 region on chromosome 16, which were homozygously shared by the affected siblings, but not shared by the unaffected siblings; none of them are likely to be causative. The weight of evidence is strongly in favour of the p.Ala510Val variant being a disease-causing mutation. We present additional data from the Auckland City Hospital neurogenetics clinic to show that the p.Ala510Val mutation is prevalent amongst HSP patients of UK extraction belying any suggestion that European p.Ala510Val haplotypes harbour a disease-causing mutation which the UK p.Ala510Val haplotypes do not. Taken together with previous findings of a carrier frequency of 3-4 % in the UK population (giving a homozygosity rate of 20-40/100,000), the data imply that the p.Ala510Val is the most common mutation causing neurogenetic disease in adults of UK ancestry, albeit the penetrance may be low or the disease caused may be mild.</AbstractText"
]
] |
22814704
|
Inflammation in anxiety.
|
The idea of the existence of an interaction between the immune system and the central nervous system (CNS) has prompted extensive research interest into the subject of "Psychoneuroimmunology" taking the field to an interesting level where new hypotheses are being increasingly tested. Specifically, exactly how the cross talk of pathways and mechanisms enable immune system to influence our brain and behavior is a question of immense significance. Of particular relevance to this topic is the role of cytokines in regulating functions within the CNS that ultimately modulate behavior. Interestingly, psychological stress is reported to modulate cytokine production, suggesting potential relevance of this mediator to mental health. In fact, cytokine signaling in the brain is known to regulate important brain functions including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, as well as the neural circuitry of mood. It is rather obvious to expect an aberrant behavioral outcome as a result of a dysregulation in cytokine signaling which might lead to occurrence of depression, anxiety, and cognitive dysfunction. Thus, understanding the mechanisms by which the immune system influences behavior would reveal targets for potential therapeutic development as well as strategies for the prevention of neuropsychiatric diseases. To date, the presence of inflammatory responses and the crucial role of cytokines in depression have received most attention. However, considering a big socioeconomic impact due to an alarming increase in anxiety disorder patients, there is an urgent research need for a better understanding of the role of cytokines in anxiety. In this review, we discuss recent research on the role of neuroimmunology in anxiety. At the end, we offer an "oxidative stress theory," which we propose works perhaps as a "sensor of distress," the imbalance of which leads to neuroinflammation and causes anxiety disorders. Much research is needed to extensively test this theory keeping an open mind!</AbstractText
|
[
[
"17670965",
"Cell type-specific tuning of hippocampal interneuron firing during gamma oscillations in vivo.",
"Cortical gamma oscillations contribute to cognitive processing and are thought to be supported by perisomatic-innervating GABAergic interneurons. We performed extracellular recordings of identified interneurons in the hippocampal CA1 area of anesthetized rats, revealing that the firing patterns of five distinct interneuron types are differentially correlated to spontaneous gamma oscillations. The firing of bistratified cells, which target dendrites of pyramidal cells coaligned with the glutamatergic input from hippocampal area CA3, is strongly phase locked to field gamma oscillations. Parvalbumin-expressing basket, axo-axonic, and cholecystokinin-expressing interneurons exhibit moderate gamma modulation, whereas the spike timing of distal dendrite-innervating oriens-lacunosum moleculare interneurons is not correlated to field gamma oscillations. Cholecystokinin-expressing interneurons fire earliest in the gamma cycle, a finding that is consistent with their suggested function of thresholding individual pyramidal cells. Furthermore, we show that field gamma amplitude correlates with interneuronal spike-timing precision and firing rate. Overall, our recordings suggest that gamma synchronization in vivo is assisted by temporal- and domain-specific GABAergic inputs to pyramidal cells and is initiated in pyramidal cell dendrites in addition to somata and axon initial segments.</AbstractText"
]
] |
[
[
"22986407",
"How a common variant in the growth factor receptor gene, NTRK1, affects white matter.",
"Growth factors and their receptors are important for cellular migration as well as axonal guidance and myelination in the brain. They also play a key role in programmed cell death, and are implicated in a number of mental illnesses. Recently, we reported that healthy young adults who carry the T allele variant in the growth factor gene, NTRK1 (at location rs6336), had lower white matter integrity than non-carriers on diffusion images of the brain. Diffusion tensor imaging (DTI) revealed how this single nucleotide polymorphism affects white matter microstructure in human populations; DTI is also used to identify characteristic features of brain connectivity in typically developing children and in patients. Newly discovered links between neuroimaging measures and growth factors whose molecular neuroscience is well known offer an important step in understanding mechanisms that contribute to brain connectivity. Altered fiber connectivity may mediate the relationship between some genetic risk factors and a variety of mental illnesses.</AbstractText"
]
] |
23226198
|
Formal comparison of dual-parameter temporal discounting models in controls and pathological gamblers.
|
Temporal or delay discounting refers to the phenomenon that the value of a reward is discounted as a function of time to delivery. A range of models have been proposed that approximate the shape of the discount curve describing the relationship between subjective value and time. Recent evidence suggests that more than one free parameter may be required to accurately model human temporal discounting data. Nonetheless, many temporal discounting studies in psychiatry, psychology and neuroeconomics still apply single-parameter models, despite their oftentimes poor fit to single-subject data. Previous comparisons of temporal discounting models have either not taken model complexity into account, or have overlooked particular models. Here we apply model comparison techniques in a large sample of temporal discounting datasets using several discounting models employed in the past. Among the models examined, an exponential-power model from behavioural economics (CS model, Ebert & Prelec 2007) provided the best fit to human laboratory discounting data. Inter-parameter correlations for the winning model were moderate, whereas they were substantial for other dual-parameter models examined. Analyses of previous group and context effects on temporal discounting with the winning model provided additional theoretical insights. The CS model may be a useful tool in future psychiatry, psychology and neuroscience work on inter-temporal choice.</AbstractText
|
[
[
"12951145",
"Structure and function of the vomeronasal system: an update.",
"Several developments during the past 15 years have profoundly affected our understanding of the vomeronasal system (VNS) of vertebrates. In the mid 1990s, the vomeronasal epithelium of mammals was found to contain two populations of receptor cells, based on their expression of G-proteins. These two populations of neurons were subsequently found to project their axons to different parts of the accessory olfactory bulb (AOB), forming the basis of segregated pathways with possibly heterogeneous functions. A related discovery was the cloning of members of at least two gene families of putative vomeronasal G-protein-coupled receptors (GPRs) in the vomeronasal epithelium. Ligand binding to these receptors was found to activate a phospholipase C (PLC)-dependent signal transduction pathway that primarily involves an increase in intracellular inositol-tris-phosphate and intracellular calcium. In contrast to what was previously believed, neuron replacement in the vomeronasal epithelium appears to occur through a process of vertical migration in most mammals. New anatomical studies of the central pathways of the olfactory and vomeronasal systems indicated that these two systems converge on neurons in the telencephalon, providing an anatomical substrate for functional interactions. Combined anatomical, physiological and behavioral studies in mice provided new information that furthered our understanding of one of the most striking pheromonal phenomena, the Bruce effect. Finally, contrary to prior observations, new anatomical studies indicated that a vomeronasal organ (VNO) was present in human adults and reports were published indicating that this system might be functional. These latter observations are still controversial and require confirmation from independent laboratories.</AbstractText"
]
] |
[
[
"23195123",
"Text-mining and neuroscience.",
"The wealth and diversity of neuroscience research are inherent characteristics of the discipline that can give rise to some complications. As the field continues to expand, we generate a great deal of data about all aspects, and from multiple perspectives, of the brain, its chemistry, biology, and how these affect behavior. The vast majority of research scientists cannot afford to spend their time combing the literature to find every article related to their research, nor do they wish to spend time adjusting their neuroanatomical vocabulary to communicate with other subdomains in the neurosciences. As such, there has been a recent increase in the amount of informatics research devoted to developing digital resources for neuroscience research. Neuroinformatics is concerned with the development of computational tools to further our understanding of the brain and to make sense of the vast amount of information that neuroscientists generate (French & Pavlidis, 2007). Many of these tools are related to the use of textual data. Here, we review some of the recent developments for better using the vast amount of textual information generated in neuroscience research and publication and suggest several use cases that will demonstrate how bench neuroscientists can take advantage of the resources that are available.</AbstractText"
]
] |
22960226
|
Empiricists are from Venus, modelers are from Mars: Reconciling experimental and computational approaches in cognitive neuroscience.
|
We describe how computational models can be useful to cognitive and behavioral neuroscience, and discuss some guidelines for deciding whether a model is useful. We emphasize that because instantiating a cognitive theory as a computational model requires specification of an explicit mechanism for the function in question, it often produces clear and novel behavioral predictions to guide empirical research. However, computational modeling in cognitive and behavioral neuroscience remains somewhat rare, perhaps because of misconceptions concerning the use of computational models (in particular, connectionist models) in these fields. We highlight some common misconceptions, each of which relates to an aspect of computational models: the problem space of the model, the level of biological organization at which the model is formulated, and the importance (or not) of biological plausibility, parsimony, and model parameters. Careful consideration of these aspects of a model by empiricists, along with careful delineation of them by modelers, may facilitate communication between the two disciplines and promote the use of computational models for guiding cognitive and behavioral experiments.</AbstractText
|
[
[
"19120115",
"Chronic stress, combined with a high-fat/high-sugar diet, shifts sympathetic signaling toward neuropeptide Y and leads to obesity and the metabolic syndrome.",
"In response to stress, some people lose while others gain weight. This is believed to be due to either increased beta-adrenergic activation, the body's main fat-burning mechanism, or increased intake of sugar- and fat-rich \"comfort foods.\" A high-fat, high-sugar (HFS) diet alone, however, cannot account for the epidemic of obesity, and chronic stress alone tends to lower adiposity in mice. Here we discuss how chronic stress, when combined with an HFS diet, leads to abdominal obesity by releasing a sympathetic neurotransmitter, neuropeptide Y (NPY), directly into the adipose tissue. In vitro, when \"stressed\" with dexamethasone, sympathetic neurons shift toward expressing more NPY, which stimulates endothelial cell (angiogenesis) and preadipocyte proliferation, differentiation, and lipid-filling (adipogenesis) by activating the same NPY-Y2 receptors (Y2Rs). In vivo, chronic stress, consisting of cold water or aggression in HFS-fed mice, stimulates the release of NPY and the expression of Y2Rs in visceral fat, increasing its growth by 50% in 2 weeks. After 3 months, this results in metabolic syndrome-like symptoms with abdominal obesity, inflammation, hyperlipidemia, hyperinsulinemia, glucose intolerance, hepatic steatosis, and hypertension. Remarkably, local intra-fat Y2R inhibition pharmacologically or via adenoviral Y2R knock-down reverses or prevents fat accumulation and metabolic complications. These studies demonstrated for the first time that chronic stress, via the NPY-Y2R pathway, amplifies and accelerates diet-induced obesity and the metabolic syndrome. Our findings also suggest the use of local administration of Y2R antagonists for treatment of obesity and NPY-Y2 agonists for fat augmentation in other clinical applications.</AbstractText"
]
] |
[
[
"23476081",
"Framing Nicotine Addiction as a \"Disease of the Brain\": Social and Ethical Consequences.",
"In this article, we seek to better understand how a genomic vision of addiction may influence drug prevention and treatment. Though <i We explore the emerging view of addiction as a \"disease of the brain\" in open-ended interviews with 86 stakeholders from the fields of nicotine research and tobacco control. Interview data were analyzed using standard qualitative techniques.</AbstractText Most stakeholders hold a medicalized view of addiction. Though environmental variables are understood to be a primary cause of smoking initiation, the speed and strength with which addiction occurs is understood to be a largely biological process. Though stakeholders believe that an increased focus on addiction as a disease of the brain is not likely to lead to widespread unrealistic expectations for cessation therapies, they remain concerned that it may reinforce teenagers' expectations that quitting is not difficult. Finally, stakeholder responses indicate that genetic and neuroscientific research is unlikely to increase or decrease stigmatization, but will be used by interest groups to buttress their existing views of the stigma associated with smoking.</AbstractText We argue that the main potential harms of focusing on biological etiology stem from a concept of addiction that is disassociated from social context. Focusing on genetic testing and brain scans may lead one to overemphasize pharmaceutical \"magic bullet cures\" and underemphasize, and underfund, more traditional therapies and public health prevention strategies that have proven to be effective. Genetic research on addiction may fundamentally change our conception of deviance and our identities, and may thus transform our susceptibility to substance use into something isolated in our biology, not embedded in a biosocial context.</AbstractText"
]
] |
23267340
|
Social working memory: neurocognitive networks and directions for future research.
|
Navigating the social world requires the ability to maintain and manipulate information about people's beliefs, traits, and mental states. We characterize this capacity as social working memory (SWM). To date, very little research has explored this phenomenon, in part because of the assumption that general working memory systems would support working memory for social information. Various lines of research, however, suggest that social cognitive processing relies on a neurocognitive network (i.e., the "mentalizing network") that is functionally distinct from, and considered antagonistic with, the canonical working memory network. Here, we review evidence suggesting that demanding social cognition requires SWM and that both the mentalizing and canonical working memory neurocognitive networks support SWM. The neural data run counter to the common finding of parametric decreases in mentalizing regions as a function of working memory demand and suggest that the mentalizing network can support demanding cognition, when it is demanding social cognition. Implications for individual differences in social cognition and pathologies of social cognition are discussed.</AbstractText
|
[
[
"16482083",
"Antipsychotic effects on prepulse inhibition in normal 'low gating' humans and rats.",
"Development of new antipsychotics and their novel applications may be facilitated through the use of physiological markers in clinically normal individuals. Both genetic and neurochemical evidence suggests that reduced prepulse inhibition of startle (PPI) may be a physiological marker for individuals at-risk for schizophrenia, and the ability of antipsychotics to normalize PPI may reflect properties linked to their clinical efficacy. We assessed the effects of the atypical antipsychotic quetiapine (12.5 mg p.o.) on PPI in 20 normal men with a 'low PPI' trait, based on PPI levels in the lowest 25% of a normal PPI distribution. The effects of quetiapine (7.5 mg/kg s.c.) on PPI were then assessed in rats with phenotypes of high PPI (Sprague Dawley (SD)) and low PPI (Brown Norway (BN)); effects of clozapine (7.5 mg/kg i.p.) and haloperidol (0.1 mg/kg s.c.) on PPI were also tested in SD rats. At a time of maximal psychoactivity, quetiapine significantly enhanced PPI to short prepulse intervals (20-30 ms) in 'low gating' human subjects. Quetiapine increased PPI in low gating BN rats for prepulse intervals <120 ms; this effect of quetiapine was limited to 20 ms prepulse intervals in SD rats, who also exhibited this pattern in response to clozapine but not haloperidol. In both humans and rats, normal 'low gating' appears to be an atypical antipsychotic-sensitive phenotype. PPI at short intervals may be most sensitive to pro-gating effects of these drugs.</AbstractText"
]
] |
[
[
"22922354",
"Selective interactions of spinophilin with the C-terminal domains of the δ- and μ-opioid receptors and G proteins differentially modulate opioid receptor signaling.",
"Previous studies have shown that the intracellular domains of opioid receptors serve as platforms for the formation of a multi-component signaling complex consisting of various interacting partners (Leontiadis et al., 2009, Cell Signal. 21, 1218-1228; Georganta et al., 2010, Neuropharmacology, 59(3), 139-148). In the present study we demonstrate that spinophilin a dendritic-spine enriched scaffold protein associates with δ- and μ-opioid receptors (δ-ΟR, μ-OR) constitutively in HEK293 an interaction that is altered upon agonist administration and enhanced upon forskolin treatment for both μ-OR and δ-ΟR. Spinophilin association with the opioid receptors is mediated via the third intracellular loop and a conserved region of the C-terminal tails. The portion of spinophilin responsible for interaction with the δ-OR and μ-OR is narrowed to a region encompassing amino acids 151-444. Spinophilin, RGS4, Gα and Gβγ subunits of G proteins form a multi-protein complex using specific regions of spinophilin and a conserved amino acid stretch of the C-terminal tails of both δ-μ-ORs. Expression of spinophilin in HEK293 cells potentiated DPDPE-mediated adenylyl-cyclase inhibition of δ-OR leaving unaffected the levels of cAMP accumulation mediated by the μ-OR. Moreover, measurements of extracellular signal regulated kinase (ERK1,2) phosphorylation indicated that the presence of spinophilin attenuated agonist-driven ERK1,2 phosphorylation mediated upon activation of the δ-OR but not the μ-OR. Collectively, these findings suggest that spinophilin associates with both δ- and μ-ΟR and G protein subunits in HEK293 cells participating in a multimeric signaling complex that displays a differential regulatory role in opioid receptor signaling.</AbstractText"
]
] |
19654141
|
Neuroanthropology: a humanistic science for the study of the culture-brain nexus.
|
In this article, we argue that a combined anthropology/neuroscience field of enquiry can make a significant and distinctive contribution to the study of the relationship between culture and the brain. This field, which can appropriately be termed as neuroanthropology, is conceived of as being complementary to and mutually informative with social and cultural neuroscience. We start by providing an introduction to the culture concept in anthropology. We then present a detailed characterization of neuroanthropology and its methods and how they relate to the anthropological understanding of culture. The field is described as a humanistic science, that is, a field of enquiry founded on the perceived epistemological and methodological interdependence of science and the humanities. We also provide examples that illustrate the proposed methodological model for neuroanthropology. We conclude with a discussion about specific contributions the field can make to the study of the culture-brain nexus.</AbstractText
|
[
[
"19400719",
"The science of neural interface systems.",
"The ultimate goal of neural interface research is to create links between the nervous system and the outside world either by stimulating or by recording from neural tissue to treat or assist people with sensory, motor, or other disabilities of neural function. Although electrical stimulation systems have already reached widespread clinical application, neural interfaces that record neural signals to decipher movement intentions are only now beginning to develop into clinically viable systems to help paralyzed people. We begin by reviewing state-of-the-art research and early-stage clinical recording systems and focus on systems that record single-unit action potentials. We then address the potential for neural interface research to enhance basic scientific understanding of brain function by offering unique insights in neural coding and representation, plasticity, brain-behavior relations, and the neurobiology of disease. Finally, we discuss technical and scientific challenges faced by these systems before they are widely adopted by severely motor-disabled patients.</AbstractText"
]
] |
[
[
"25205899",
"Neuroepidemiology of epilepsy in northwest India.",
"Epilepsy has a complex etiology characterised by recurring seizures.</AbstractText To study clinical profile of epilepsy patients with reference to type of epilepsy in northwest India. No previous Indian study has reported relative incidence of various types of seizures with reference to type of epilepsy.</AbstractText Data of 400 epilepsy patients (200 idiopathic and 200 symptomatic) was collected for their clinical characteristics. The classification of epilepsy into idiopathic and symptomatic types was done on the basis of findings of EEG, CT scan and MRI tests.</AbstractText The age of onset of seizures was less than 15 years in only one third of the total patients. The number of non-vegetarians was higher in SE (68.5%) than IE (58%). The male to female ratio was significantly higher (1.33:1 in IE and 1.47:1 in SE). No difference was seen for place of residence (urban vs rural) patients with epilepsy (PWE). The majority of patients (58.5% of symptomatic and 52.8% idiopathic) though reported no triggering factors, yet many of them, when questioned, had held supernatural powers to be the cause of the disease. Sleep deprivation was reported as a major triggering factor by 28.5% of idiopathic epilepsy (IE) and 25% of symptomatic epilepsy (SE) patients. The incidence of mental retardation (1.25%) and behavioral disorders (7%) was found to be relatively low. Loss of memory was reported in 46% of IE and 43.5% of SE and poor scholastic performance in 23% of IE and 16.5% of SE. A positive history was recorded in 11% first-degree relatives and 4% second-degree relatives. Generalized seizures were more common in IE patients (67.5%), while partial seizures with and without secondary generalization (50.5%), and generalized seizures (49.5%) were equally common in SE.</AbstractText The study demonstrates differences in the type of seizures between idiopathic and symptomatic epilepsies and not other demographic, clinical and psycho-social traits. The males were found to have higher risk of epilepsy than females. The epidemiological characteristics of epileptics show variations across populations and also within population.</AbstractText Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a disorder of the urea cycle and ornithine degradation pathway. Clinical manifestations and age of onset vary among individuals even in the same family. <i The biochemical diagnosis of HHH syndrome is established in a proband with the classic metabolic triad of episodic or postprandial hyperammonemia, persistent hyperornithinemia, and urinary excretion of homocitrulline. The molecular diagnosis of HHH syndrome is established in a symptomatic individual with or without suggestive metabolic/biochemical findings by identification of biallelic pathogenic variants in <i <i HHH syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the <i"
]
] |
19943188
|
Fast Kalman filtering on quasilinear dendritic trees.
|
Optimal filtering of noisy voltage signals on dendritic trees is a key problem in computational cellular neuroscience. However, the state variable in this problem-the vector of voltages at every compartment-is very high-dimensional: realistic multicompartmental models often have on the order of N = 10(4) compartments. Standard implementations of the Kalman filter require O(N (3)) time and O(N (2)) space, and are therefore impractical. Here we take advantage of three special features of the dendritic filtering problem to construct an efficient filter: (1) dendritic dynamics are governed by a cable equation on a tree, which may be solved using sparse matrix methods in O(N) time; and current methods for observing dendritic voltage (2) provide low SNR observations and (3) only image a relatively small number of compartments at a time. The idea is to approximate the Kalman equations in terms of a low-rank perturbation of the steady-state (zero-SNR) solution, which may be obtained in O(N) time using methods that exploit the sparse tree structure of dendritic dynamics. The resulting methods give a very good approximation to the exact Kalman solution, but only require O(N) time and space. We illustrate the method with applications to real and simulated dendritic branching structures, and describe how to extend the techniques to incorporate spatially subsampled, temporally filtered, and nonlinearly transformed observations.</AbstractText
|
[
[
"11222789",
"Paraplegin gene analysis in hereditary spastic paraparesis (HSP) pedigrees in northeast England.",
"To identify the frequency and characterize the phenotype of paraplegin mutations in the hereditary spastic paraparesis (HSP) population in the northeast of England.</AbstractText HSP is a disorder that shows both clinical and genetic heterogeneity. To date, 13 loci have been associated with an HSP phenotype, with the causative gene having been identified in four of these. Two autosomal genes have been identified, paraplegin and spastin, and two X-linked genes have been identified, L1CAM (cell adhesion molecule) and proteolipid protein.</AbstractText Thirty HSP pedigrees from the northeast of England were analyzed for mutation in each of the 17 exons of the paraplegin gene.</AbstractText A single family with a paraplegin mutation was identified in which the paraplegin mutation co-segregates with an HSP phenotype in an apparent dominant manner. The authors also describe frequent polymorphism in the paraplegin gene in both the HSP and control populations.</AbstractText Mutations in the paraplegin gene are not a common cause of HSP in the northeast of England. The phenotype of the paraplegin-related HSP family described had several striking features including amyotrophy, raised creatine kinase, sensorimotor peripheral neuropathy, and oxidative phosphorylation defect on muscle biopsy.</AbstractText"
]
] |
[
[
"20826300",
"Neuroscience and education: an ideal partnership for producing evidence-based solutions to Guide 21(st) Century Learning.",
"Neuro-Education is a nascent discipline that seeks to blend the collective fields of neuroscience, psychology, cognitive science, and education to create a better understanding of how we learn and how this information can be used to create more effective teaching methods, curricula, and educational policy. Though still in its infancy as a research discipline, this initiative is already opening critical new dialog between teachers, administrators, parents, and brain scientists.</AbstractText"
]
] |
23365838
|
Simultaneous ODF estimation and tractography in HARDI.
|
We consider the problem of tracking white matter fibers in high angular resolution diffusion imaging (HARDI) data while simultaneously estimating the local fiber orientation profile. Prior work showed that an unscented Kalman filter (UKF) can be used for this problem, yet existing algorithms employ parametric mixture models to represent water diffusion and to define the state space. To address this restrictive model dependency, we propose to extend the UKF to HARDI data modeled by orientation distribution functions (ODFs), a more generic diffusion model. We consider the spherical harmonic representation of the HARDI signal as the state, enforce nonnegativity of the ODFs, and perform tractography using the directions at which the ODFs attain their peaks. In simulations, our method outperforms filtered two-tensor tractography at different levels of noise by achieving a reduction in mean Chamfer error of 0.05 to 0.27 voxels; it also produced in vivo fiber tracking that is consistent with the neuroanatomy.</AbstractText
|
[
[
"15831717",
"Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo.",
"Microglial cells represent the immune system of the mammalian brain and therefore are critically involved in various injuries and diseases. Little is known about their role in the healthy brain and their immediate reaction to brain damage. By using in vivo two-photon imaging in neocortex, we found that microglial cells are highly active in their presumed resting state, continually surveying their microenvironment with extremely motile processes and protrusions. Furthermore, blood-brain barrier disruption provoked immediate and focal activation of microglia, switching their behavior from patroling to shielding of the injured site. Microglia thus are busy and vigilant housekeepers in the adult brain.</AbstractText"
]
] |
[
[
"23542825",
"Neuroanatomy of Cornudescoides kulkarnii n. sp., a gill parasite of Mystus vittatus in Meerut (UP), India.",
"Chemical named 5-bromo indoxyl acetate has been used to describe the nervous system of a viviparous monogenean Cornudescoides Kulkarni (1969), a gill parasite of Mystus vittatus. Central nervous system consists of paired cerebral ganglia from which anterior and posterior neuronal pathways arise. These neuronal pathways are interlinked by cross connectives and commissures. Paired dorsal, ventral and lateral nerve cords emanate from the cerebral ganglia, connected at intervals by transverse connectives. Huge arrangement of dorsal, ventral and lateral nerve cords and their innervations have been examined. Peripheral nervous system (PNS) includes innervations of the alimentary tract, reproductive organs and attachment organs (anterior adhesive areas and haptor). Both the CNS and PNS are bilaterally symmetrical, and better developed ventrally than laterally and dorsally.</AbstractText"
]
] |
23926462
|
Neurogenetics and Nutrigenomics of Neuro-Nutrient Therapy for Reward Deficiency Syndrome (RDS): Clinical Ramifications as a Function of Molecular Neurobiological Mechanisms.
|
In accord with the new definition of addiction published by American Society of Addiction Medicine (ASAM) it is well-known that individuals who present to a treatment center involved in chemical dependency or other documented reward dependence behaviors have impaired brain reward circuitry. They have hypodopaminergic function due to genetic and/or environmental negative pressures upon the reward neuro-circuitry. This impairment leads to aberrant craving behavior and other behaviors such as Substance Use Disorder (SUD). Neurogenetic research in both animal and humans revealed that there is a well-defined cascade in the reward site of the brain that leads to normal dopamine release. This cascade has been termed the "Brain Reward Cascade" (BRC). Any impairment due to either genetics or environmental influences on this cascade will result in a reduced amount of dopamine release in the brain reward site. Manipulation of the BRC has been successfully achieved with neuro-nutrient therapy utilizing nutrigenomic principles. After over four decades of development, neuro-nutrient therapy has provided important clinical benefits when appropriately utilized. This is a review, with some illustrative case histories from a number of addiction professionals, of certain molecular neurobiological mechanisms which if ignored may lead to clinical complications.</AbstractText
|
[
[
"15663891",
"Orexin A promotes histamine, but not norepinephrine or serotonin, release in frontal cortex of mice.",
"To investigate the effects of orexin A on release of histamine, norepinephrine, and serotonin in the frontal cortex of mice.</AbstractText Samples for measuring histamine, norepinephrine, and serotonin contents were collected by in vivo microdialysis of the frontal cortex of anesthetized mice. The histamine, noradrenaline, and serotonin content in dialysates were measured by HPLC techniques.</AbstractText Intracrebroventricular injection of orexin A at doses of 12.5, 50, and 200 pmol per mouse promoted histamine release from the frontal cortex in a dose-dependent manner. At the highest dose given, 200 pmol, orexin A significantly induced histamine release, with the maximal magnitude being 230% over the mean basal release. The enhanced histamine release was sustained for 140 min, and then gradually returned to the basal level. However, no change in norepinephrine or serotonin release was observed under application of the same dose of orexin A.</AbstractText These results suggest that the arousal effect of orexin A is mainly mediated by histamine, not by norepinephrine or serotonin.</AbstractText"
]
] |
[
[
"23060781",
"Using \"smart stimulators\" to treat Parkinson's disease: re-engineering neurostimulation devices.",
"Let's imagine the cruise control of your car locked at 120 km/h on any road in any condition (city, country, highway, sunny or rainy weather), or your car air conditioner set on maximum cold in any temperature condition (even during a snowy winter): would you find it efficient? That would probably not be the most optimal strategy for a proper and comfortable driving experience. As surprising as this may seem, this is a pretty accurate illustration of how deep brain stimulation is used today to treat Parkinson's disease motor symptoms and other neurological disorders such as essential tremor, obsessive-compulsive disorder, or epilepsy.</AbstractText"
]
] |
22639700
|
Mitochondrial DNA: A Blind Spot in Neuroepigenetics.
|
Neuroepigenetics, which includes nuclear DNA modifications such as 5-methylcytosine and 5-hydoxymethylcytosine and modifications of nuclear proteins such as histones, is emerging as the leading field in molecular neuroscience. Historically, a functional role for epigenetic mechanisms, including in neuroepigenetics, has been sought in the area of the regulation of nuclear transcription. However, one important compartment of mammalian cell DNA, different from nuclear but equally important for physiological and pathological processes (including in the brain), mitochondrial DNA has for the most part not had a systematic epigenetic characterization. The importance of mitochondria and mitochondrial DNA (particularly its mutations) in central nervous system physiology and pathology has long been recognized. Only recently have mechanisms of mitochondrial DNA methylation and hydroxymethylation, including the discovery of mitochondrial DNA-methyltransferases and the presence and the functionality of 5-methylcytosine and 5-hydroxymethylcytosine in mitochondrial DNA (e.g., in modifying the transcription of mitochondrial genome), been unequivocally recognized as a part of mammalian mitochondrial physiology. Here we summarize for the first time evidence supporting the existence of these mechanisms and we propose the term "mitochondrial epigenetics" to be used when referring to them. Currently, neuroepigenetics does not include mitochondrial epigenetics - a gap that we expect to close in the near future.</AbstractText
|
[
[
"8490989",
"Epidemiology of epilepsy in developing countries.",
"Epilepsy is an important health problem in developing countries, where its prevalence can be up to 57 per 1000 population. This article reviews the epidemiology of epilepsy in developing countries in terms of its incidence, prevalence, seizure type, mortality data, and etiological factors. The prevalence of epilepsy is particularly high in Latin America and in several African countries, notably Liberia, Nigeria, and the United Republic of Tanzania. Parasitic infections, particularly neurocysticercosis, are important etiological factors for epilepsy in many of these countries. Other reasons for the high prevalence include intracranial infections of bacterial or viral origin, perinatal brain damage, head injuries, toxic agents, and hereditary factors. Many of these factors are, however, preventable or modifiable, and the introduction of appropriate measures to achieve this could lead to a substantial decrease in the incidence of epilepsy in developing countries.</AbstractText"
]
] |
[
[
"23366028",
"Transcranial direct current stimulation in pediatric brain: a computational modeling study.",
"Transcranial direct current stimulation (tDCS) is a method of non-invasive brain stimulation which uses weak electric currents applied on the scalp to modulate activity of underlying brain tissue. In addition to being used as a tool for cognitive neuroscience investigations, tDCS has generated considerable interest for use as a therapeutic modality for neurologic disorders. Though the safety and tolerability of tDCS in adults is well-established, there is little information on the safety of tDCS in children. Because there are differences between children and adults in several key parameters (such as skull thickness and cerebrospinal fluid volume) which affect current flow through the brain, special consideration should be given to the stimulation parameters which are used in a pediatric study population. In this study we present cortical electrical field maps at different stimulation intensities and electrode configurations using a high-resolution-MRI derived finite element model of a typically developing, anatomically normal 12 year old child. The peak electrical fields for a given stimulus intensity in the adolescent brain were twice as high as in the adult brain for conventional tDCS and nearly four times as high for a 4X1 High-Definition tDCS electrode configuration. These data suggest that acceptable tDCS stimulation parameters may be different in children compared to adults, and that further modeling studies are needed to help guide decisions about applied current intensity.</AbstractText"
]
] |
23366028
|
Transcranial direct current stimulation in pediatric brain: a computational modeling study.
|
Transcranial direct current stimulation (tDCS) is a method of non-invasive brain stimulation which uses weak electric currents applied on the scalp to modulate activity of underlying brain tissue. In addition to being used as a tool for cognitive neuroscience investigations, tDCS has generated considerable interest for use as a therapeutic modality for neurologic disorders. Though the safety and tolerability of tDCS in adults is well-established, there is little information on the safety of tDCS in children. Because there are differences between children and adults in several key parameters (such as skull thickness and cerebrospinal fluid volume) which affect current flow through the brain, special consideration should be given to the stimulation parameters which are used in a pediatric study population. In this study we present cortical electrical field maps at different stimulation intensities and electrode configurations using a high-resolution-MRI derived finite element model of a typically developing, anatomically normal 12 year old child. The peak electrical fields for a given stimulus intensity in the adolescent brain were twice as high as in the adult brain for conventional tDCS and nearly four times as high for a 4X1 High-Definition tDCS electrode configuration. These data suggest that acceptable tDCS stimulation parameters may be different in children compared to adults, and that further modeling studies are needed to help guide decisions about applied current intensity.</AbstractText
|
[
[
"12721816",
"Dopamine D3 receptor gene polymorphism and violent behavior: relation to impulsiveness and ADHD-related psychopathology.",
"Several lines of evidence indicate that dopaminergic neurotransmission is involved in the regulation of impulsive aggression and violence and that genetically determined variability in dopaminergic gene expression modifies complex traits including that of impulsivity and aggression. In this study we report an association of the dopamine D3 receptor (DRD3) polymorphism with impulsiveness according to Eysenck's EIQ and scores on the German short version of the Wender Utah Rating Scale (WURS-k), which we used for the assessment of a history of ADHD-related symptoms. This association was detected in a group of violent offenders, but not in non-violent individuals. Highest scores of EIQ impulsiveness and of the WURS-k were found in heterozygous violent individuals, while homozygotes showed significant lower rating scores, suggesting an heterosis effect. The results of our study suggest that variations of the DRD3 gene are likely involved in the regulation of impulsivity and some psychopathological aspects of ADHD related to violent behavior.</AbstractText"
]
] |
[
[
"23202064",
"Three-dimensional multiwaveguide probe array for light delivery to distributed brain circuits.",
"To deliver light to the brain for neuroscientific and neuroengineering applications like optogenetics, in which light is used to activate or silence neurons expressing specific photosensitive proteins, optical fibers are commonly used. However, an optical fiber is limited to delivering light to a single target within the 3D structure of the brain. Here, we describe the design and fabrication of an array of thin microwaveguides, which terminates at a three-dimensionally distributed set of points, appropriate for delivering light to targets distributed in a 3D pattern throughout the brain.</AbstractText"
]
] |
23504543
|
Bio-amplifier with Driven Shield Inputs to Reduce Electrical Noise and its Application to Laboratory Teaching of Electrophysiology.
|
We describe a custom-designed bio-amplifier and its use in teaching neurophysiology to undergraduate students. The amplifier has the following features: 1) differential amplification with driven shield inputs, which makes it workable even in electrically unshielded environments, 2) high input impedance to allow recordings of small signals through high signal source impedance, 3) dual fixed frequency bandpass filters (1-340Hz for surface EMG, EEG, local field potential etc and 320Hz - 3.4kHz for neuronal action potential recording) and independent gain controllers (up to x107,000) to allow the recording of different signals from the same source (e.g., local field potential and spiking activity of neurons), and 4) printed circuit board technology for easy replication with consistent quality. We compared its performance with a commercial amplifier in an electrically noisy environment. Even without any electrostatic shield, it recorded clear electromyographic activity with little interference from other electric appliances. In contrast, the commercial amplifier's performance severely deteriorated under the same condition. We used this amplifier to build a computer-controlled stimulation and measurement system for electroencephalographic recordings by undergraduate students. The students successfully recorded various sensory evoked potentials with clarity that otherwise would have required costly instruments. This amplifier is a low-cost yet reliable instrument for electro-physiological recording both in education and research.</AbstractText
|
[
[
"21386006",
"Optogenetics in the teaching laboratory: using channelrhodopsin-2 to study the neural basis of behavior and synaptic physiology in Drosophila.",
"Here we incorporate recent advances in Drosophila neurogenetics and \"optogenetics\" into neuroscience laboratory exercises. We used the light-activated ion channel channelrhodopsin-2 (ChR2) and tissue-specific genetic expression techniques to study the neural basis of behavior in Drosophila larvae. We designed and implemented exercises using inexpensive, easy-to-use systems for delivering blue light pulses with fine temporal control. Students first examined the behavioral effects of activating glutamatergic neurons in Drosophila larvae and then recorded excitatory junctional potentials (EJPs) mediated by ChR2 activation at the larval neuromuscular junction (NMJ). Comparison of electrically and light-evoked EJPs demonstrates that the amplitudes and time courses of light-evoked EJPs are not significantly different from those generated by electrical nerve stimulation. These exercises introduce students to new genetic technology for remotely manipulating neural activity, and they simplify the process of recording EJPs at the Drosophila larval NMJ. Relatively little research work has been done using ChR2 in Drosophila, so students have opportunities to test novel hypotheses and make tangible contributions to the scientific record. Qualitative and quantitative assessment of student experiences suggest that these exercises help convey principles of synaptic transmission while also promoting integrative and inquiry-based studies of genetics, cellular physiology, and animal behavior.</AbstractText"
]
] |
[
[
"22958820",
"How variable clones build an invariant retina.",
"A fundamental question in developmental neuroscience is how a collection of progenitor cells proliferates and differentiates to create a brain of the appropriate size and cellular composition. To address this issue, we devised lineage-tracing assays in developing zebrafish embryos to reconstruct entire retinal lineage progressions in vivo and thereby provide a complete quantitative map of the generation of a vertebrate CNS tissue from individual progenitors. These lineage data are consistent with a simple model in which the retina is derived from a set of equipotent retinal progenitor cells (RPCs) that are subject to stochastic factors controlling lineage progression. Clone formation in mutant embryos reveals that the transcription factor Ath5 acts as a molecular link between fate choice and mode of cell division, giving insight into the elusive molecular mechanisms of histogenesis, the conserved temporal order by which neurons of different types exit the cell cycle.</AbstractText"
]
] |
22557965
|
An ontological approach to describing neurons and their relationships.
|
The advancement of neuroscience, perhaps one of the most information rich disciplines of all the life sciences, requires basic frameworks for organizing the vast amounts of data generated by the research community to promote novel insights and integrated understanding. Since Cajal, the neuron remains a fundamental unit of the nervous system, yet even with the explosion of information technology, we still have few comprehensive or systematic strategies for aggregating cell-level knowledge. Progress toward this goal is hampered by the multiplicity of names for cells and by lack of a consensus on the criteria for defining neuron types. However, through umbrella projects like the Neuroscience Information Framework (NIF) and the International Neuroinformatics Coordinating Facility (INCF), we have the opportunity to propose and implement an informatics infrastructure for establishing common tools and approaches to describe neurons through a standard terminology for nerve cells and a database (a Neuron Registry) where these descriptions can be deposited and compared. This article provides an overview of the problem and outlines a solution approach utilizing ontological characterizations. Based on illustrative implementation examples, we also discuss the need for consensus criteria to be adopted by the research community, and considerations on future developments. A scalable repository of neuron types will provide researchers with a resource that materially contributes to the advancement of neuroscience.</AbstractText
|
[
[
"17049754",
"Behavioral impulsivity predicts treatment outcome in a smoking cessation program for adolescent smokers.",
"To examine the relationship between impulsivity and smoking cessation treatment response among adolescents.</AbstractText Thirty adolescent smokers participated in a high school based smoking cessation program combining contingency management and cognitive behavioral therapy. Self-report (Barratt impulsiveness scale (BIS-II); Kirby delay discounting measure (DDM)) and behavioral (experiential discounting task (EDT); continuous performance task (CPT)) measures of impulsivity were assessed at treatment onset.</AbstractText Sixteen participants (53%) were abstinent from smoking at completion of the four-week study. Compared to abstinent adolescents, those not achieving abstinence discounted monetary rewards more on the EDT and committed more commission errors on the CPT. Group differences were not observed on the BIS-II or DDM.</AbstractText These preliminary results suggest that specific behavioral measures of impulsivity may be associated with the ability to initiate and/or maintain abstinence from smoking among adolescent smokers.</AbstractText"
]
] |
[
[
"23130007",
"When Do We Confuse Self and Other in Action Memory? Reduced False Memories of Self-Performance after Observing Actions by an Out-Group vs. In-Group Actor.",
"Observing another person performing an action can lead to a false memory of having performed the action oneself - the observation-inflation effect. In the experimental paradigm, participants first perform or do not perform simple actions, and then observe another person perform some of these actions. The observation-inflation effect is found when participants later remember performing actions that they have merely observed. In this case, self and other are confused in action memory. We examined social conditions of this self-other confusion when remembering actions, specifically whether the effect depends on the observed actor's group membership. In our experiment, we manipulated group membership based on physical appearance, specifically complexion of the hands. Fair-skinned participants observed either an in-group (i.e., fair-skinned) or an out-group (i.e., dark-skinned) actor. Our results revealed that the observed actor's group membership moderated the observation-inflation effect: False memories were significantly reduced when the actor was from the out-group (vs. in-group). We found no difference to a control condition in which the actor wore black gloves, suggesting that distinctiveness of perceptual or sensory features alone (due to the out-group member's dark skin) is not critical. We discuss these findings in light of social-neuroscience studies demonstrating the impact of an observed person's group membership on motor simulation. Overall, our findings suggest that action memory can be affected by a ubiquitous feature of people's social perception, that is, group-based social categorization of others.</AbstractText"
]
] |
23504612
|
An undergraduate laboratory exercise examining the psychomotor stimulant effects of caffeine in laboratory rats.
|
This paper describes an exercise in a Systems and Behavioral Neuroscience with Laboratory class, an introductory laboratory class taken by Barnard College students majoring in a wide range of academic topics. The study took place over three weeks, allowing students to assess the effects of caffeine on motor stimulation in laboratory rats. The within-subject design involved injecting rats with three different caffeine doses and measuring five different motor outputs in a standard open field. Students completed four different assignments related to this study, demonstrating acquisition of the stated learning goals. This lab exercise allowed students to learn about basal ganglia neural circuitry and stimulant pharmacology, to work directly with an animal model, and to generate enough data to perform statistical analyses. Course evaluations suggest that students liked learning about caffeine, a stimulant many of them have personal experience consuming. They also expressed appreciation for working with rats and for learning how to analyze data. This study can easily be implemented at most undergraduate institutions under minimal cost. The wide-ranging effects of caffeine also permit for flexibility in experimental design, allowing instructors and students options for different avenues of investigation.</AbstractText
|
[
[
"17940025",
"Short-term meditation training improves attention and self-regulation.",
"Recent studies suggest that months to years of intensive and systematic meditation training can improve attention. However, the lengthy training required has made it difficult to use random assignment of participants to conditions to confirm these findings. This article shows that a group randomly assigned to 5 days of meditation practice with the integrative body-mind training method shows significantly better attention and control of stress than a similarly chosen control group given relaxation training. The training method comes from traditional Chinese medicine and incorporates aspects of other meditation and mindfulness training. Compared with the control group, the experimental group of 40 undergraduate Chinese students given 5 days of 20-min integrative training showed greater improvement in conflict scores on the Attention Network Test, lower anxiety, depression, anger, and fatigue, and higher vigor on the Profile of Mood States scale, a significant decrease in stress-related cortisol, and an increase in immunoreactivity. These results provide a convenient method for studying the influence of meditation training by using experimental and control methods similar to those used to test drugs or other interventions.</AbstractText"
]
] |
[
[
"22925211",
"Developmental neurotoxicity testing: scientific approaches towards the next generation to protect the developing nervous system of children. An overview of the Developmental Neurotoxicity Symposium in 2011.",
"The Developmental Neurotoxicology (DNT) Committee has been working to promote developmental neurotoxicology and related scientific areas of interest to integrate academic and regulatory sciences in this field since the Behavioral Teratology Meeting was established by the Japanese Teratology Society in 1982. The committee has led several large-scale collaborative studies to standardize existing methodologies and held symposiums and workshops periodically at the society's annual meetings. This overview provides a history of the DNT Committee, as well as a brief summary of the DNT Symposium in 2011.</AbstractText"
]
] |
22977368
|
Coping with Brain Disorders using Neurotechnology.
|
Brain disorders account for more than 34% of the global burden of disease, crippling nations by decreasing their "mental capital"-with greater effect in developing countries. Early detection is the key to their management, but establishing such programmes seems nearly impossible due to the high prevalence of the dysfunctions as compared with the high cost of neuroimaging devices. Thus, at first sight, the research of the Decade of the Brain and the international Human Brain Mapping Project might seem to be condemned to benefit only a small elite. Cuba has shown that is not so by using neurotechnology for the last 3 decades to implement stratified active screening programmes for brain disorders at the population level. This experience has shown that, by the transformation of health indicators, an appropriate use of technology can be integrated with attention to the population at the primary levels of both health care and education. An essential component of neurotechnology is neuroinformatics, which-like its counterpart bioinformatics-combines databases, analysis tools, and theoretical models to craft tools for early disease diagnosis and management. Much work remains to be done and will depend critically on south-south cooperation to solve problems for countries with similar situations.</AbstractText
|
[
[
"12716950",
"Hierarchical processing in spoken language comprehension.",
"Understanding spoken language requires a complex series of processing stages to translate speech sounds into meaning. In this study, we use functional magnetic resonance imaging to explore the brain regions that are involved in spoken language comprehension, fractionating this system into sound-based and more abstract higher-level processes. We distorted English sentences in three acoustically different ways, applying each distortion to varying degrees to produce a range of intelligibility (quantified as the number of words that could be reported) and collected whole-brain echo-planar imaging data from 12 listeners using sparse imaging. The blood oxygenation level-dependent signal correlated with intelligibility along the superior and middle temporal gyri in the left hemisphere and in a less-extensive homologous area on the right, the left inferior frontal gyrus (LIFG), and the left hippocampus. Regions surrounding auditory cortex, bilaterally, were sensitive to intelligibility but also showed a differential response to the three forms of distortion, consistent with sound-form-based processes. More distant intelligibility-sensitive regions within the superior and middle temporal gyri, hippocampus, and LIFG were insensitive to the acoustic form of sentences, suggesting more abstract nonacoustic processes. The hierarchical organization suggested by these results is consistent with cognitive models and auditory processing in nonhuman primates. Areas that were particularly active for distorted speech conditions and, thus, might be involved in compensating for distortion, were found exclusively in the left hemisphere and partially overlapped with areas sensitive to intelligibility, perhaps reflecting attentional modulation of auditory and linguistic processes.</AbstractText"
]
] |
[
[
"23110153",
"Prediction of muscle activities from electrocorticograms in primary motor cortex of primates.",
"Electrocorticography (ECoG) has drawn attention as an effective recording approach for brain-machine interfaces (BMI). Previous studies have succeeded in classifying movement intention and predicting hand trajectories from ECoG. Despite such successes, however, there still remains considerable work for the realization of ECoG-based BMIs as neuroprosthetics. We developed a method to predict multiple muscle activities from ECoG measurements. We also verified that ECoG signals are effective for predicting muscle activities in time varying series when performing sequential movements. ECoG signals were band-pass filtered into separate sensorimotor rhythm bands, z-score normalized, and smoothed with a Gaussian filter. We used sparse linear regression to find the best fit between frequency bands of ECoG and electromyographic activity. The best average correlation coefficient and the normalized root-mean-square error were 0.92±0.06 and 0.06±0.10, respectively, in the flexor digitorum profundus finger muscle. The δ (1.5∼4Hz) and γ2 (50∼90Hz) bands contributed significantly more strongly than other frequency bands (P<0.001). These results demonstrate the feasibility of predicting muscle activity from ECoG signals in an online fashion.</AbstractText"
]
] |
23420996
|
The fundamental role of morphology in experimental neurotoxicology: the example of chemotherapy-induced peripheral neurotoxicity.
|
The peripheral nervous system is a frequent target of toxic agents. The accurate identification of the sites of neurotoxic action through the morphological characterization of reliable in vivo models or in vitro systems can give fundamental clues when investigating the pathogenesis and interpreting the clinical features of drug-induced neuropathy. The morphological approach has been used to investigate almost all the anticancer drugs able to induce chemotherapy-induced peripheral neurotoxicity, i.e. platinum drugs, antitubulins and proteasome inhibitors. No models have ever been described for thalidomide. This review demonstrates that any pathogenetic study on chemotherapy-induced peripheral neurotoxicity must be based on solid morphological observations obtained in reliable animal and in vitro models. This is particularly true in this setting, since the availability of tissues of human origin is extremely limited. In fact, peripheral (generally sural) nerve biopsies are never required for diagnostic purposes in chemotherapy-treated cancer patients, and their use for a purely scientific aim, although potentially very informative, is not ethical. Moreover, several neurotoxic drugs target the dorsal root ganglia neurons, and it is very difficult to obtain high-quality specimens even from early autopsies. It is, therefore, our opinion that an extensive morphological assessment of the in vitro and in vivo effect of any potentially neurotoxic antineoplastic drugs, as well as of neuroprotectant agents, should be taken into consideration right from the earliest stages of their development.</AbstractText
|
[
[
"22430310",
"Cloning and expression of tachykinins and their association with kisspeptins in the brains of zebrafish.",
"The tachykinins are a family of neuropeptides, including substance P (SP), neurokinin A (NKA), and neurokinin B (NKB), that are encoded by the tac1 (SP and NKA) or tac2/3 (NKB) genes. Tachykinins are widely distributed in the central nervous system and have roles as neurotransmitters and/or neuromodulators. Recent studies in mammals have demonstrated the coexpression of NKB and kisspeptin and their comodulatory roles over the control of reproduction. We have recently identified two kisspeptin-encoding genes, kiss1 and kiss2, in teleosts. However, such relationship between tachykinins and kisspeptins has not been demonstrated in non-mammalian species. To determine the involvement of tachykinins in the reproduction in teleosts, we identified tac1 and two tac2 (tac2a and tac2b) sequences in the zebrafish genome using in silico data mining. Zebrafish tac1 encodes SP and NKA, whereas the tac2 sequences encode NKB and an additional peptide homologous to NKB (NKB-related peptide). Digoxigenin in situ hybridization in the brain of zebrafish showed tac1 mRNA-containing cells in the olfactory bulb, telencephalon, preoptic region, hypothalamus, mesencephalon, and rhombencephalon. The zebrafish tac2a mRNA-containing cells were observed in the preoptic region, habenula, and hypothalamus, whereas the tac2b mRNA-containing cells were predominantly observed in the dorsal telencephalic area. Furthermore, we examined the coexpression of tachykinins and two kisspeptin genes in the brain of zebrafish. Dual fluorescent in situ hybridization showed no coexpression of tachykinins mRNA with kisspeptins mRNA in hypothalamic nuclei or the habenula. These results suggest the presence of independent pathways for kisspeptins and NKB neurons in the brain of zebrafish.</AbstractText"
]
] |
[
[
"23010511",
"Transcriptome analysis of Drosophila CNS midline cells reveals diverse peptidergic properties and a role for castor in neuronal differentiation.",
"One of the key aspects of neuronal differentiation is the array of neurotransmitters and neurotransmitter receptors that each neuron possesses. One important goal of developmental neuroscience is to understand how these differentiated properties are established during development. In this paper, we use fluorescence activated cell sorting and RNA-seq to determine the transcriptome of the Drosophila CNS midline cells, which consist of a small number of well-characterized neurons and glia. These data revealed that midline cells express 9 neuropeptide precursor genes, 13 neuropeptide receptor genes, and 31 small-molecule neurotransmitter receptor genes. In situ hybridization and high-resolution confocal analyses were carried-out to determine the midline cell identity for these neuropeptides and the neuropeptide receptors. The results revealed a surprising level of diversity. Neuropeptide genes are expressed in a variety of midline cell types, including motoneurons, GABAergic interneurons, and midline glia. These data revealed previously unknown functional differences among the highly-related iVUM neurons. There also exist segmental differences in expression for the same neuronal sub-type. Similar experiments on midline-expressed neuropeptide receptor genes reveal considerable diversity in synaptic inputs. Multiple receptor types were expressed in midline interneurons and motoneurons, and, in one case, link feeding behavior to gut peristalsis and locomotion. There were also segmental differences, variations between the 3 iVUMs, and three hormone receptor genes were broadly expressed in most midline cells. The Drosophila Castor transcription factor is present at high levels in iVUM5, which is both GABAergic and expresses the short neuropeptide F precursor gene. Genetic and misexpression experiments indicated that castor specifically controls expression of the short neuropeptide F precursor gene, but does not affect iVUM cell fate or expression of Gad1. This indicates a novel function for castor in regulating neuropeptide gene expression.</AbstractText"
]
] |
23142960
|
Current concept of neuromyelitis optica (NMO) and NMO spectrum disorders.
|
Neuromyelitis optica (NMO) has been described as a disease clinically characterised by severe optic neuritis (ON) and transverse myelitis (TM). Other features of NMO include female preponderance, longitudinally extensive spinal cord lesions (>3 vertebral segments), and absence of oligoclonal IgG bands . In spite of these differences from multiple sclerosis (MS), the relationship between NMO and MS has long been controversial. However, since the discovery of NMO-IgG or aquaporin-4 (AQP4) antibody (AQP4-antibody), an NMO-specific autoantibody to AQP4, the dominant water channel in the central nervous system densely expressed on end-feet of astrocytes, unique clinical features, MRI and other laboratory findings in NMO have been clarified further. AQP4-antibody is now the most important laboratory finding for the diagnosis of NMO. Apart from NMO, some patients with recurrent ON or recurrent longitudinally extensive myelitis alone are also often positive for AQP4-antibody. Moreover, studies of AQP4-antibody-positive patients have revealed that brain lesions are not uncommon in NMO, and some patterns appear to be unique to NMO. Thus, the spectrum of NMO is wider than mere ON and TM. Pathological analyses of autopsied cases strongly suggest that unlike MS, astrocytic damage is the primary pathology in NMO, and experimental studies confirm the pathogenicity of AQP4-antibody. Importantly, therapeutic outcomes of some immunological treatments are different between NMO and MS, making early differential diagnosis of these two disorders crucial. We provide an overview of the epidemiology, clinical and neuroimaging features, immunopathology and therapy of NMO and NMO spectrum disorders.</AbstractText
|
[
[
"22304908",
"Immune cells exploit a neural circuit to enter the CNS.",
"Multiple sclerosis (MS) is associated with the appearance of autoreactive T cells in the central nervous system. Using a mouse model of MS, Arima et al. now show that this attack begins at a specific spinal cord location. T cell entry into the CNS is regulated by a reflex neural circuit originating from leg muscle contractions.</AbstractText"
]
] |
[
[
"23010509",
"Using mouse models of autism spectrum disorders to study the neurotoxicology of gene-environment interactions.",
"To better study the role of genetics in autism, mouse models have been developed which mimic the genetics of specific autism spectrum and related disorders. These models have facilitated research on the role genetic susceptibility factors in the pathogenesis of autism in the absence of environmental factors. Inbred mouse strains have been similarly studied to assess the role of environmental agents on neurodevelopment, typically without the complications of genetic heterogeneity of the human population. What has not been as actively pursued, however, is the methodical study of the interaction between these factors (e.g., gene and environmental interactions in neurodevelopment). This review suggests that a genetic predisposition paired with exposure to environmental toxicants plays an important role in the etiology of neurodevelopmental disorders including autism, and may contribute to the largely unexplained rise in the number of children diagnosed with autism worldwide. Specifically, descriptions of the major mouse models of autism and toxic mechanisms of prevalent environmental chemicals are provided followed by a discussion of current and future research strategies to evaluate the role of gene and environment interactions in neurodevelopmental disorders.</AbstractText"
]
] |
20797539
|
Spatiotemporal response properties of optic-flow processing neurons.
|
A central goal in sensory neuroscience is to fully characterize a neuron's input-output relation. However, strong nonlinearities in the responses of sensory neurons have made it difficult to develop models that generalize to arbitrary stimuli. Typically, the standard linear-nonlinear models break down when neurons exhibit stimulus-dependent modulations of their gain or selectivity. We studied these issues in optic-flow processing neurons in the fly. We found that the neurons' receptive fields are fully described by a time-varying vector field that is space-time separable. Increasing the stimulus strength, however, strongly reduces the neurons' gain and selectivity. To capture these changes in response behavior, we extended the linear-nonlinear model by a biophysically motivated gain and selectivity mechanism. We fit all model parameters directly to the data and show that the model now characterizes the neurons' input-output relation well over the full range of motion stimuli.</AbstractText
|
[
[
"11253062",
"Association study designs for complex diseases.",
"Assessing the association between DNA variants and disease has been used widely to identify regions of the genome and candidate genes that contribute to disease. However, there are numerous examples of associations that cannot be replicated, which has led to skepticism about the utility of the approach for common conditions. With the discovery of massive numbers of genetic markers and the development of better tools for genotyping, association studies will inevitably proliferate. Now is the time to consider critically the design of such studies, to avoid the mistakes of the past and to maximize their potential to identify new components of disease.</AbstractText"
]
] |
[
[
"22958820",
"How variable clones build an invariant retina.",
"A fundamental question in developmental neuroscience is how a collection of progenitor cells proliferates and differentiates to create a brain of the appropriate size and cellular composition. To address this issue, we devised lineage-tracing assays in developing zebrafish embryos to reconstruct entire retinal lineage progressions in vivo and thereby provide a complete quantitative map of the generation of a vertebrate CNS tissue from individual progenitors. These lineage data are consistent with a simple model in which the retina is derived from a set of equipotent retinal progenitor cells (RPCs) that are subject to stochastic factors controlling lineage progression. Clone formation in mutant embryos reveals that the transcription factor Ath5 acts as a molecular link between fate choice and mode of cell division, giving insight into the elusive molecular mechanisms of histogenesis, the conserved temporal order by which neurons of different types exit the cell cycle.</AbstractText"
]
] |
22958820
|
How variable clones build an invariant retina.
|
A fundamental question in developmental neuroscience is how a collection of progenitor cells proliferates and differentiates to create a brain of the appropriate size and cellular composition. To address this issue, we devised lineage-tracing assays in developing zebrafish embryos to reconstruct entire retinal lineage progressions in vivo and thereby provide a complete quantitative map of the generation of a vertebrate CNS tissue from individual progenitors. These lineage data are consistent with a simple model in which the retina is derived from a set of equipotent retinal progenitor cells (RPCs) that are subject to stochastic factors controlling lineage progression. Clone formation in mutant embryos reveals that the transcription factor Ath5 acts as a molecular link between fate choice and mode of cell division, giving insight into the elusive molecular mechanisms of histogenesis, the conserved temporal order by which neurons of different types exit the cell cycle.</AbstractText
|
[
[
"9222381",
"Molecular mimicry between HIV-1 gp41 and an astrocyte isoform of alpha-actinin.",
"A 100-kDa astrocyte antigen previously shown to cross-react with a monoclonal antibody (MAb) generated against amino acids (aa) 598 to 609 of the transmembrane protein gp41 of human immunodeficiency virus type 1 [HIV-1] has now been molecularly characterized and found to be an alpha-actinin (alpha-actinin) related protein. Western blot analyses of human astrocytoma cells fractionated by differential centrifugation and detergent phase separation showed that the antigen was membrane associated. The astrocyte protein was purified to apparent homogeneity by immunoaffinity chromatography. Amino acid analysis of three peptide fragments obtained by cleavage of the purified 100-kDa protein revealed sequence identities of 77, 83 and 100% to a non-muscle isoform of human alpha-actinin. In addition, the aa 598-609 sequence of gp41 recognized by MAb 781.4, and the aa 581-597 sequence recognized by another cross-reactive MAb 781.3, were 73% and 53% similar to regions of alpha-actinin. This molecular mimicry between gp41 and alpha-actinin was supported by antibody cross-reactivity in Western immunoblot and ELISA analyses. Both anti-gp41 and anti-alpha-actinin MAbs bind to the surface of the human astrocytoma cells as detected by a cell surface binding assay and immunofluorescence. Antibodies made against this immunodominant region of gp41 in the serum and CSF of HIV-infected individuals have access to astrocytes within the CNS. The identification of the astrocyte antigen as an alpha-actinin related protein will allow further work to determine how this immunological cross-reactivity could perturb astrocyte function and contribute to HIV neuropathology.</AbstractText"
]
] |
[
[
"23227112",
"A Social Neuroscience Perspective on Stress and Health.",
"Psychological stress is a major risk factor for the development and progression of a number of diseases, including cardiovascular disease, cancer, arthritis, and major depression. A growing body of research suggests that long-term, stress-induced activation of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis may lead to increases in inflammation, which is known to play a key role in the pathophysiology of a variety of diseases. Furthermore, the burgeoning fields of social neuroscience and health neuroscience have begun to identify the neurocognitive mechanisms by which stress may lead to these physiological changes. Here we review the literature examining the neurocognitive correlates of stress-induced SNS, HPA, and inflammatory responses. Specifically, we summarize the results of neuroimaging studies that have examined the neural correlates of stress-related increases in SNS, HPA, and inflammatory activity. A set of neural systems involved in threat processing, safety processing, and social cognition are suggested as key contributors to stress-related changes in physiology. We conclude by offering suggestions for future research in the exciting new field of health neuroscience.</AbstractText"
]
] |
21345429
|
Challenging the supremacy of the frontal lobe: early views (1906-1909) of Christfried Jakob on the human cerebral cortex.
|
This article focuses on a series of six studies that address functional localization in the frontal lobe; they were published in Argentina between 1906 and 1909 by Christfried Jakob (1866-1956), one of the great thinkers in early 20th century neuropathology and neurophilosophy. At that time, the localization-holism controversy was at a peak, having been triggered by the historic Marie-Déjerine aphasiology debate. Jakob held the view that constitutive physiological elements of cognition are localized. Nonetheless, he cast doubt on phrenological approaches that considered the frontal lobe as 'superior' to the other cortical regions. Jakob studied the human frontal lobe from fetal life through senility, in normality and pathology, including tumors, injuries, softening, general paralysis and dementia. Based on those finds, he considered strict localization theories a dead-end. Taking a critical look at Flechsig's ideas on the parallel ontogenies of frontal association centers and intellect, Jakob argued that the frontal lobe does not carry any selective advantage over the remaining human cerebral lobes or even over the frontal lobe in non-human primates. Regarding lesion experiments in laboratory animals, he pointed to methodological caveats, such as insufficient recovery time, that may lead to disorientating conclusions, and rejected élite brain research, calling it superficial and inexact. Jakob was convinced that the verification of the anatomical connections of the frontal lobe would elucidate its functions. Thus, he viewed the frontal lobe as a central station receiving input via olfactory pathways and thalamic radiations, pertinent to muscular and cutaneous senses, and attributed a perceptive character to a brain region traditionally associated with productive functions. Modern neuroscience seems to support Jakob's rejection of distinguishable motor and sensory regions and to adopt a cautious stance concerning oversimplified localization views.</AbstractText
|
[
[
"21896369",
"The size and burden of mental disorders and other disorders of the brain in Europe 2010.",
"To provide 12-month prevalence and disability burden estimates of a broad range of mental and neurological disorders in the European Union (EU) and to compare these findings to previous estimates. Referring to our previous 2005 review, improved up-to-date data for the enlarged EU on a broader range of disorders than previously covered are needed for basic, clinical and public health research and policy decisions and to inform about the estimated number of persons affected in the EU.</AbstractText Stepwise multi-method approach, consisting of systematic literature reviews, reanalyses of existing data sets, national surveys and expert consultations. Studies and data from all member states of the European Union (EU-27) plus Switzerland, Iceland and Norway were included. Supplementary information about neurological disorders is provided, although methodological constraints prohibited the derivation of overall prevalence estimates for mental and neurological disorders. Disease burden was measured by disability adjusted life years (DALY).</AbstractText Prevalence: It is estimated that each year 38.2% of the EU population suffers from a mental disorder. Adjusted for age and comorbidity, this corresponds to 164.8million persons affected. Compared to 2005 (27.4%) this higher estimate is entirely due to the inclusion of 14 new disorders also covering childhood/adolescence as well as the elderly. The estimated higher number of persons affected (2011: 165m vs. 2005: 82m) is due to coverage of childhood and old age populations, new disorders and of new EU membership states. The most frequent disorders are anxiety disorders (14.0%), insomnia (7.0%), major depression (6.9%), somatoform (6.3%), alcohol and drug dependence (>4%), ADHD (5%) in the young, and dementia (1-30%, depending on age). Except for substance use disorders and mental retardation, there were no substantial cultural or country variations. Although many sources, including national health insurance programs, reveal increases in sick leave, early retirement and treatment rates due to mental disorders, rates in the community have not increased with a few exceptions (i.e. dementia). There were also no consistent indications of improvements with regard to low treatment rates, delayed treatment provision and grossly inadequate treatment. Disability: Disorders of the brain and mental disorders in particular, contribute 26.6% of the total all cause burden, thus a greater proportion as compared to other regions of the world. The rank order of the most disabling diseases differs markedly by gender and age group; overall, the four most disabling single conditions were: depression, dementias, alcohol use disorders and stroke.</AbstractText In every year over a third of the total EU population suffers from mental disorders. The true size of \"disorders of the brain\" including neurological disorders is even considerably larger. Disorders of the brain are the largest contributor to the all cause morbidity burden as measured by DALY in the EU. No indications for increasing overall rates of mental disorders were found nor of improved care and treatment since 2005; less than one third of all cases receive any treatment, suggesting a considerable level of unmet needs. We conclude that the true size and burden of disorders of the brain in the EU was significantly underestimated in the past. Concerted priority action is needed at all levels, including substantially increased funding for basic, clinical and public health research in order to identify better strategies for improved prevention and treatment for disorders of the brain as the core health challenge of the 21st century.</AbstractText"
]
] |
[
[
"23110153",
"Prediction of muscle activities from electrocorticograms in primary motor cortex of primates.",
"Electrocorticography (ECoG) has drawn attention as an effective recording approach for brain-machine interfaces (BMI). Previous studies have succeeded in classifying movement intention and predicting hand trajectories from ECoG. Despite such successes, however, there still remains considerable work for the realization of ECoG-based BMIs as neuroprosthetics. We developed a method to predict multiple muscle activities from ECoG measurements. We also verified that ECoG signals are effective for predicting muscle activities in time varying series when performing sequential movements. ECoG signals were band-pass filtered into separate sensorimotor rhythm bands, z-score normalized, and smoothed with a Gaussian filter. We used sparse linear regression to find the best fit between frequency bands of ECoG and electromyographic activity. The best average correlation coefficient and the normalized root-mean-square error were 0.92±0.06 and 0.06±0.10, respectively, in the flexor digitorum profundus finger muscle. The δ (1.5∼4Hz) and γ2 (50∼90Hz) bands contributed significantly more strongly than other frequency bands (P<0.001). These results demonstrate the feasibility of predicting muscle activity from ECoG signals in an online fashion.</AbstractText"
]
] |
23428079
|
Capturing specific abilities as a window into human individuality: the example of face recognition.
|
Proper characterization of each individual's unique pattern of strengths and weaknesses requires good measures of diverse abilities. Here, we advocate combining our growing understanding of neural and cognitive mechanisms with modern psychometric methods in a renewed effort to capture human individuality through a consideration of specific abilities. We articulate five criteria for the isolation and measurement of specific abilities, then apply these criteria to face recognition. We cleanly dissociate face recognition from more general visual and verbal recognition. This dissociation stretches across ability as well as disability, suggesting that specific developmental face recognition deficits are a special case of a broader specificity that spans the entire spectrum of human face recognition performance. Item-by-item results from 1,471 web-tested participants, included as supplementary information, fuel item analyses, validation, norming, and item response theory (IRT) analyses of our three tests: (a) the widely used Cambridge Face Memory Test (CFMT); (b) an Abstract Art Memory Test (AAMT), and (c) a Verbal Paired-Associates Memory Test (VPMT). The availability of this data set provides a solid foundation for interpreting future scores on these tests. We argue that the allied fields of experimental psychology, cognitive neuroscience, and vision science could fuel the discovery of additional specific abilities to add to face recognition, thereby providing new perspectives on human individuality.</AbstractText
|
[
[
"15831717",
"Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo.",
"Microglial cells represent the immune system of the mammalian brain and therefore are critically involved in various injuries and diseases. Little is known about their role in the healthy brain and their immediate reaction to brain damage. By using in vivo two-photon imaging in neocortex, we found that microglial cells are highly active in their presumed resting state, continually surveying their microenvironment with extremely motile processes and protrusions. Furthermore, blood-brain barrier disruption provoked immediate and focal activation of microglia, switching their behavior from patroling to shielding of the injured site. Microglia thus are busy and vigilant housekeepers in the adult brain.</AbstractText"
]
] |
[
[
"22946114",
"Giuseppe Ferrario and the epidemiology of apoplexy during the 19th century.",
"To analyze the pioneering research of Giuseppe Ferrario (1802-1870) on the epidemiology of apoplexy. To our knowledge, his work might have been the first to systematically investigate the epidemiology of cerebrovascular accidents, with the aim of shedding light on the underlying causes.</AbstractText A detailed analysis of the essay \"Statistics of sudden deaths, more particularly of deaths from apoplexy, in the city and neighborhood of Milan, from 1750 to 1834,\" published by Ferrario in 1834.</AbstractText Ferrario conducted a large retrospective study on 13,360 people who died from apoplexy during an 84-year observational period. Analyzed data showed that these events were more frequent among men and during winter. Apoplexy was reported as mainly occurring at the age of 60; an increase in mortality was observed in young women aged between 21 and 30 years, probably due to an abuse of bloodletting. Ferrario introduced the term \"hereditary apoplexy,\" being one of the first to hypothesize hereditary components in cerebrovascular diseases. He also tried to investigate the role of social conditions in the etiopathogenesis of these events, analyzing marital and employment status and suggesting to his colleagues that cultural and economic factors should be further examined.</AbstractText Giuseppe Ferrario may be considered as a pioneer of modern science and epidemiology and his work deserves consideration within the history of neurology and of neuroepidemiology.</AbstractText"
]
] |
22483076
|
Isolating N400 as neural marker of vocal anger processing in 6-11-year old children.
|
Vocal anger is a salient social signal serving adaptive functions in typical child development. Despite recent advances in the developmental neuroscience of emotion processing with regard to visual stimuli, little remains known about the neural correlates of vocal anger processing in childhood. This study represents the first attempt to isolate a neural marker of vocal anger processing in children using electrophysiological methods.</AbstractText We compared ERP wave forms during the processing of non-word emotional vocal stimuli in a population sample of 55 6-11-year-old typically developing children. Children listened to three types of stimuli expressing angry, happy, and neutral prosody and completed an emotion identification task with three response options (angry, happy and neutral/'ok').</AbstractText A distinctive N400 component which was modulated by emotional content of vocal stimulus was observed in children over parietal and occipital scalp regions-amplitudes were significantly attenuated to angry compared to happy and neutral voices.</AbstractText Findings of the present study regarding the N400 are compatible with adult studies showing reduced N400 amplitudes to negative compared to neutral emotional stimuli. Implications for studies of the neural basis of vocal anger processing in children are discussed.</AbstractText
|
[
[
"2687720",
"Two-stage model of memory trace formation: a role for \"noisy\" brain states.",
"Review of the normally occurring neuronal patterns of the hippocampus suggests that the two principal cell types of the hippocampus, the pyramidal neurons and granule cells, are maximally active during different behaviors. Granule cells reach their highest discharge rates during theta-concurrent exploratory activities, while population synchrony of pyramidal cells is maximum during immobility, consummatory behaviors, and slow wave sleep associated with field sharp waves. Sharp waves reflect the summed postsynaptic depolarization of large numbers of pyramidal cells in the CA1 and subiculum as a consequence of synchronous discharge of bursting CA3 pyramidal neurons. The trigger for the population burst in the CA3 region is the temporary release from subcortical tonic inhibition. An overview of the experimentally explored criteria of synaptic enhancement (intensity, frequency, and pattern of postsynaptic depolarization, calcium influx, cooperativity, threshold) suggests that these requirements may be present during sharp wave-concurrent population bursts of pyramidal cells. Experimental evidence is cited showing that (a) population bursts in CA3 may lead to long-term potentiation in their postsynaptic CA1 targets, (b) tetanizing stimuli are capable of increasing the synchrony of the sharp wave-burst, and (c) activity patterns of the neocortical input to the hippocampus determine which subgroup of CA3 neurons will trigger subsequently occurring population bursts (initiator cells). Based on the experimental evidence reviewed a formal model of memory trace formation is outlined. During exploratory (theta) behaviors the neocortical information is transmitted to the hippocampus via the fast-firing granule cells which may induce a weak and transient heterosynaptic potentiation in a subgroup of CA3 pyramidal cells. The weakly potentiated CA3 neurons will then initiate population bursts upon the termination of exploratory activity (sharp wave state). It is assumed that recurrent excitation during the population burst is strongest on those cells which initiated the population event. It is suggested that the strong excitatory drive brought about by the sharp wave-concurrent population bursts during consummatory behaviors, immobility, and slow wave sleep may be sufficient for the induction of long-term synaptic modification in the initiator neurons of the CA3 region and in their targets in CA1. In this two-stage model both exploratory (theta) and sharp wave states of the hippocampus are essential and any interference that might modify the structure of the population bursts (e.g. epileptic spikes) is detrimental to memory trace formation.</AbstractText"
]
] |
[
[
"23493834",
"Teaching neuroinformatics with an emphasis on quantitative locus analysis.",
"Although powerful bioinformatics tools are available for free on the web and are used by neuroscience professionals on a daily basis, neuroscience students are largely ignorant of them. This Neuroinformatics module weaves together several bioinformatics tools to make a comprehensive unit. This unit encompasses quantifying a phenotype through a Quantitative Trait Locus (QTL) analysis, which links phenotype to loci on chromosomes that likely had an impact on the phenotype. Students then are able to sift through a list of genes in the region(s) of the chromosome identified by the QTL analysis and find a candidate gene that has relatively high expression in the brain region of interest. Once such a candidate gene is identified, students can find out more information about the gene, including the cells/layers in which it is expressed, the sequence of the gene, and an article about the gene. All of the resources employed are available at no cost via the internet. Didactic elements of this instructional module include genetics, neuroanatomy, Quantitative Trait Locus analysis, molecular techniques in neuroscience, and statistics-including multiple regression, ANOVA, and a bootstrap technique. This module was presented at the Faculty for Undergraduate Neuroscience (FUN) 2011 Workshop at Pomona College and can be accessed at http://mdcune.psych.ucla.edu/modules/bioinformatics.</AbstractText"
]
] |
23671950
|
Effect of head circumference on parameters of pattern reversal visual evoked potential in healthy adults of central India.
|
Visual evoked response testing has been one of the most exciting clinical tools to be developed from neurophysiologic research in recent years and has provided us with an objective method of identifying abnormalities of the afferent visual pathways. Investigation were carried out to see whether the head circumference influence the pattern reversal visual evoked potential (PRVEP) parameters. The study comprised of pattern reversal visual evoked potential (PRVEP) recordings in 400 eyes of 200 normal subjects. Two hundred fourty eight eyes were males and 152 eyes were from 76 female subjects recruited from the Central Indian population in the age range of 40-79 years. Visual evoked potential (VEP) recordings were performed in accordance to the standardized methodology of International Federation of Clinical Neurophysiology (IFCN) Committee Recommendations and International Society for Clinical Electrophysiology of Vision (ISCEV) Guidelines and montages were kept as per 10-20 International System of EEG Electrode placements. The stimulus configuration in this study consisted of the transient pattern reversal method in which a black and white checker board was generated (full field) and displayed on a VEP Monitor by an electronic pattern regenerator inbuilt in an Evoked Potential Recorder (RMS EMG EP MARK II). VEP latencies, duration and amplitude were measured in all subjects and the data were analyzed. The correlation of all the electrophysiological parameters with head circumference was evaluated by Pearson's correlation co-efficient (r) and its statistical significance was evaluated. The prediction equations for all the VEP parameters with respect to head circumference were derived. We found a positive correlation of P 100 latency and N 155 latency with mean head circumference, while a highly significant negative correlation were noted of P 100 amplitude with head circumference. N 70 latency was significantly correlated with head circumference. P 100 duration showed in negative correlation with head circumference. These findings suggest that VEP latencies, duration and amplitude are influenced by the head circumference of the individual in a sample of healthy subjects and head circumference can be a useful predictor of VEP peak latencies, amplitude and duration.</AbstractText
|
[
[
"15371227",
"Specific non-coplanar PCB-mediated modulation of bottlenose dolphin and beluga whale phagocytosis upon in vitro exposure.",
"Contaminant-induced immunosuppression by organochlorines (OC), particularly polychlorinated biphenyls (PCBs), has been suspected as a cofactor in the deaths of thousands of marine mammals. One important innate defense mechanism is phagocytosis, the ability of cells to ingest extracellular macromolecules. The present study was aimed at characterizing the immunomodulatory potential of representative OCs on phagocytosis in bottlenose dolphins and beluga whales. The ability of peripheral blood leukocytes to engulf fluorescent microspheres was evaluated using flow cytometry. The immunomodulatory effects of three non-coplanar PCB congeners, 138, 153, and 180, one coplanar PCB, 169, and 2,3,7,8-TCDD and all possible mixtures (26) were tested upon in vitro exposure. In both species, all mixtures containing at least two non-coplanar PCBs significantly reduced both neutrophil and monocyte phagocytosis, with effects more marked in dolphins than in belugas. Coplanar OCs, on their own or when added to non-coplanar congeners, did not further modulate phagocytosis, suggesting an Ah receptor-independent mechanism. Concentration-response experiments with individual congeners further demonstrated a non-coplanar PCB-induced suppression of phagocytosis, while coplanar congeners produced no consistent effects. Our results suggest simple additive interactions of chemicals in a mixture. However, calculation of toxic equivalency (TEQs) failed to predict the experimentally induced immunomodulatory effects of OCs on dolphin and beluga phagocytosis, confirming the Ah receptor-independent nature of the effects on phagocytosis. Overall, our results suggest that non-AhR mechanisms may explain one facet of immunotoxicity (phagocytosis), something that is not captured using the TEQ approach. This is the first report demonstrating the immunomodulatory effects of OCs on dolphin and beluga phagocytosis, and the first overall demonstration of immunomodulatory effects on phagocytosis mediated specifically by non-coplanar PCBs.</AbstractText"
]
] |
[
[
"22307590",
"Functional profiling of neurons through cellular neuropharmacology.",
"We describe a functional profiling strategy to identify and characterize subtypes of neurons present in a peripheral ganglion, which should be extendable to neurons in the CNS. In this study, dissociated dorsal-root ganglion neurons from mice were exposed to various pharmacological agents (challenge compounds), while at the same time the individual responses of >100 neurons were simultaneously monitored by calcium imaging. Each challenge compound elicited responses in only a subset of dorsal-root ganglion neurons. Two general types of challenge compounds were used: agonists of receptors (ionotropic and metabotropic) that alter cytoplasmic calcium concentration (receptor-agonist challenges) and compounds that affect voltage-gated ion channels (membrane-potential challenges). Notably, among the latter are K-channel antagonists, which elicited unexpectedly diverse types of calcium responses in different cells (i.e., phenotypes). We used various challenge compounds to identify several putative neuronal subtypes on the basis of their shared and/or divergent functional, phenotypic profiles. Our results indicate that multiple receptor-agonist and membrane-potential challenges may be applied to a neuronal population to identify, characterize, and discriminate among neuronal subtypes. This experimental approach can uncover constellations of plasma membrane macromolecules that are functionally coupled to confer a specific phenotypic profile on each neuronal subtype. This experimental platform has the potential to bridge a gap between systems and molecular neuroscience with a cellular-focused neuropharmacology, ultimately leading to the identification and functional characterization of all neuronal subtypes at a given locus in the nervous system.</AbstractText"
]
] |
23218585
|
Myasthenia gravis in the elderly.
|
The objective of the study is to examine clinical, therapeutic and prognostic factors of myasthenia gravis (MG) in the elderly.</AbstractText We reviewed all MG files of patients who attended the neuro-immunology clinic at Rabin Medical Center, Petah Tikva, Israel from January 1995 until September 2011 for demographic data, MG presentation, and course and response to treatment. Patients were classified as elderly if disease onset was above 69years.</AbstractText Out of 137 patients with MG, 29 developed MG after age 69. The 108 young onset patients had a male:female ratio of 0.9:1 whereas the eighth and ninth decade onset had a significant male predominance with ratios of 2.6:1 and 4.5:1 respectively. There was no difference in the presenting symptomatology and the rate of sero-negativity in the elderly patients when compared to the early onset patients was similar. The older patients had much less thymic pathology and their acetylcholine receptor (AChR) antibody titer was lower. This was associated with better response to therapy and a good prognosis.</AbstractText MG onset in the elderly is not uncommon, is more prevalent in males, is associated with lower titer of AChR antibodies, is readily responsive to therapy and carries a good prognosis.</AbstractText
|
[
[
"20012068",
"Astrocytes: biology and pathology.",
"Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.</AbstractText"
]
] |
[
[
"22367250",
"A 3-dimensional digital atlas of the ascending sensory and the descending motor systems in the pigeon brain.",
"Pigeons are classic animal models for learning, memory, and cognition. The majority of the current understanding about avian neurobiology outside of the domain of the song system has been established using pigeons. Since MRI represents an increasingly relevant tool for comparative neuroscience, a 3-dimensional MRI-based atlas of the pigeon brain becomes essential. Using multiple imaging protocols, we delineated diverse ascending sensory and descending motor systems as well as the hippocampal formation. This pigeon brain atlas can easily be used to determine the stereotactic location of identified neural structures at any angle of the head. In addition, the atlas is useful to find the optimal angle of sectioning for slice experiments, stereotactic injections and electrophysiological recordings. This pigeon brain atlas is freely available for the scientific community.</AbstractText"
]
] |
23262400
|
Low-dose adolescent nicotine and methylphenidate have additive effects on adult behavior and neurochemistry.
|
Adolescents with Attention Deficit Hyperactivity Disorder (ADHD) have higher rates of smoking than adolescents without ADHD. Since methylphenidate is the primary drug used to treat ADHD, it is likely that many adolescents are exposed to both methylphenidate and nicotine. Recent studies have established that adolescent nicotine induces long-term changes in several neurobehavioral variables. Limited data also suggest that adolescent methylphenidate may affect neural development. Nicotine tolerance is a well-established behavioral phenomenon in rodents, yet the underlying mechanism remains elusive. Recent theories suggest that changes in ventral striatal dopamine indices may relate to nicotine tolerance. As an initial determination of whether nicotine and methylphenidate have additive effects on neurobehavioral development, the present study investigated the combined effects of adolescent nicotine [2mg/kg/d] alone or in conjunction with methylphenidate [1.5mg/kg, 2× daily] following a one-month drug free period on adult behavioral tolerance to nicotine [0.5mg/kg s.c.] and its relation to dopamine receptor mRNA expression in the ventral striatum. Animals with chronic combined (nicotine+methylphenidate) adolescent exposure displayed stronger tolerance as adults to the nicotine-induced locomotor effects in comparison to animals with adolescent exposure to nicotine alone, methylphenidate alone, or controls. Combined chronic adolescent exposure significantly elevated adult D3nf mRNA expression levels in the nucleus accumbens, however a single nicotine injection in adults increased D3nf mRNA levels in naïve animals and decreased D3nf mRNA levels in those that had been previously exposed to combined stimulants during adolescence. Conversely, a single adult nicotine injection increased D1 mRNA levels in the adult nucleus accumbens, particularly in the shell, but only in rats previously exposed to nicotine or methylphenidate as adolescents. To our knowledge this is the first study that has shown long-term behavioral and neurochemical changes stemming from low chronic exposure of these two commonly co-consumed stimulants during adolescence.</AbstractText
|
[
[
"12584340",
"Tat-neutralizing antibodies in vaccinated macaques.",
"The human immunodeficiency virus Tat protein is essential for virus replication and is a candidate vaccine antigen. Macaques immunized with Tat or chemically modified Tat toxoid having the same clade B sequence developed strong antibody responses. We compared these antisera for their abilities to recognize diverse Tat sequences. An overlapping peptide array covering three clade B and two clade C Tat sequences was constructed to help identify reactive linear epitopes. Sera from Tat-immunized macaques were broadly cross-reactive with clade B and clade C sequences but recognized a clade B-specific epitope in the basic domain. Sera from Tat toxoid-immunized macaques had a more restricted pattern of recognition, reacting mainly with clade B and with only one clade B basic domain sequence, which included the rare amino acids RPPQ at positions 57 to 60. Monoclonal antibodies against the amino terminus or the domain RPPQ sequence blocked Tat uptake into T cells and neutralized Tat in a cell-based transactivation assay. Macaques immunized with Tat or Tat toxoid proteins varied in their responses to minor epitopes, but all developed a strong response to the amino terminus, and antisera were capable of neutralizing Tat in a transactivation assay.</AbstractText"
]
] |
[
[
"23092761",
"Dreaming of mathematical neuroscience for half a century.",
"Theoreticians have been enchanted by the secrets of the brain for many years: how and why does it work so well? There has been a long history of searching for its mechanisms. Theoretical or even mathematical scientists have proposed various models of neural networks which has led to the birth of a new field of research. We can think of the 'pre-historic' period of Rashevski and Wiener, and then the period of perceptrons which is the beginning of learning machines, neurodynamics approaches, and further connectionist approaches. Now is currently the period of computational neuroscience. I have been working in this field for nearly half a century, and have experienced its repeated rise and fall. Now having reached very old age, I would like to state my own endeavors on establishing mathematical neuroscience for half a century, from a personal, even biased, point of view. It would be my pleasure if my experiences could encourage young researchers to participate in mathematical neuroscience.</AbstractText"
]
] |
23730254
|
Neuronal-glial Interactions Define the Role of Nitric Oxide in Neural Functional Processes.
|
Nitric oxide (NO) is a versatile cellular messenger performing a variety of physiologic and pathologic actions in most tissues. It is particularly important in the nervous system, where it is involved in multiple functions, as well as in neuropathology, when produced in excess. Several of these functions are based on interactions between NO produced by neurons and NO produced by glial cells, mainly astrocytes and microglia. The present paper briefly reviews some of these interactions, in particular those involved in metabolic regulation, control of cerebral blood flow, axonogenesis, synaptic function and neurogenesis. Aim of the paper is mainly to underline the physiologic aspects of these interactions rather than the pathologic ones.</AbstractText
|
[
[
"10210626",
"P300 and response time from a manual Stroop task.",
"Manual response time (RT) and P300 event-related potential (ERP) measures were recorded in a Stroop color naming task to determine if previous results with vocal responses would be obtained using an arbitrary stimulus-response (S-R) mapping.</AbstractText Subjects (n = 32) were instructed to respond to the display color of a word but to ignore its meaning. Display color was congruent, neutral, or incongruent with word meaning.</AbstractText Stroop facilitation and interference effects were observed, as RT was shortest in the congruent condition, intermediate in the neutral condition, and longest in the incongruent condition. In contrast, P300 latency did not vary across color/word congruence conditions, suggesting that the RT difference between congruence conditions originated after stimulus evaluation.</AbstractText These manual RT/P300 findings support the view that Stroop interference and facilitation originate from response competition between the relevant and irrelevant stimulus attributes. By employing an arbitrary mapping of color words onto buttons, the present results indicate that the disparate effects of Stroop stimuli on RT and P300 latency do not depend on the nature of the S-R translation.</AbstractText"
]
] |
[
[
"23493834",
"Teaching neuroinformatics with an emphasis on quantitative locus analysis.",
"Although powerful bioinformatics tools are available for free on the web and are used by neuroscience professionals on a daily basis, neuroscience students are largely ignorant of them. This Neuroinformatics module weaves together several bioinformatics tools to make a comprehensive unit. This unit encompasses quantifying a phenotype through a Quantitative Trait Locus (QTL) analysis, which links phenotype to loci on chromosomes that likely had an impact on the phenotype. Students then are able to sift through a list of genes in the region(s) of the chromosome identified by the QTL analysis and find a candidate gene that has relatively high expression in the brain region of interest. Once such a candidate gene is identified, students can find out more information about the gene, including the cells/layers in which it is expressed, the sequence of the gene, and an article about the gene. All of the resources employed are available at no cost via the internet. Didactic elements of this instructional module include genetics, neuroanatomy, Quantitative Trait Locus analysis, molecular techniques in neuroscience, and statistics-including multiple regression, ANOVA, and a bootstrap technique. This module was presented at the Faculty for Undergraduate Neuroscience (FUN) 2011 Workshop at Pomona College and can be accessed at http://mdcune.psych.ucla.edu/modules/bioinformatics.</AbstractText"
]
] |
22373615
|
Perspective: Upcoming paradigm shifts for psychiatry in clinical care, research, and education.
|
Psychiatry is facing a crisis fueled by a fragmented and inefficient system of care delivery and a disconnection between the state of research and the state of psychiatry education and practice. Many factors contribute to the current state of psychiatric care. Psychiatry is a shortage specialty, and this will become worse in the near future. In addition, financial pressures have led to decreases in psychiatric inpatient and outpatient services and to shorter lengths of hospitalization for even the sickest patients. This has resulted in fragmented care and an overreliance on polypharmacy. To reach the large number of patients needing psychiatric services, health care systems must change and take advantage of collaborative and integrative care models and new technologies. Psychiatrists must learn to partner more effectively with primary care providers to extend their expertise to the greatest number of patients. Currently, psychiatric diagnosis is based on a criteria-based system that was developed in the 1970s. Advances in systems and molecular neuroscience are beginning to elucidate specific brain systems that are dysfunctional in psychiatric illness. This has the potential to revolutionize psychiatric diagnosis and treatment in the future. However, psychiatry has not yet been successful in incorporating the language of this research into clinically meaningful terminology. If neuroscientific progress is to be translated into clinical advances, this must change. Residency programs must better prepare their graduates to keep up with a psychiatry literature that will increasingly use the language of neural circuits to describe psychiatric symptomatology and treatments.</AbstractText
|
[
[
"11330208",
"Microdialysis perfusion of orexin-A in the basal forebrain increases wakefulness in freely behaving rats.",
"Recent work indicates that the orexin/hypocretin-containing neurons of the lateral hypothalamus are involved in control of REM sleep phenomena, but site-specific actions in control of wakefulness have been less studied. Orexin-containing neurons project to both brainstem and forebrain regions that are known to regulate sleep and wakefulness, including the field of cholinergic neurons in the basal forebrain (BF) that is implicated in regulation of wakefulness, and includes, in the rat, the horizontal limb of the diagonal band, the substantia innominata, and the magnocellular preoptic region. The present study used microdialysis perfusion of orexin-A directly in the cholinergic BF region of rat to test the hypothesis that orexin-A enhances W via a local action in the BF. A significant dose-dependent increase in W was produced by the perfusion of three doses of orexin-A in the BF (0.1, 1.0, and 10.0 microM), with 10.0 microM producing more than a 5-fold increase in wakefulness, which occupied 44% of the light (inactive) phase recording period. Orexin-A perfusion also produced a significant dose-dependent decrease in nonREM sleep, and a trend-level decrease in REM sleep. The results clearly demonstrate a potent capacity of orexin-A to induce wakefulness via a local action in the BF, and are consistent with previous work indicating that the BF cholinergic zone neurons have a critical role in the regulation of EEG activation and W. The data suggest further that orexin-A has a significant role in the regulation of arousal/wakefulness, in addition to the previously described role of orexin in the regulation and expression of REM sleep and REM sleep-related phenomena.</AbstractText"
]
] |
[
[
"22305544",
"[Methodology of neuroepidemiological studies in tropical countries: a challenge?].",
"The purpose of this paper is to highlight the difficulties of applying neuroepidemiological methods in low income countries or developing countries, which are mostly tropical countries, taking advantage of the experience of the Institute of Neuroepidemiology and Tropical Neurology, which was created in Limoges in 1982. These difficulties could be related to several aspects: methodological, logistical, political or economical, linked to ethical issues, even difficulties to publish the studies. However, concept and neuroepidemiological methods should stay the same worldwide, even if their translation into practice could sometimes raise some problems in developing countries. Study protocol should be more detailed. Some specific epidemiological methods could be useful. Collection of data should be standardized. True cooperation at every level is needed for these researches to be valid.</AbstractText"
]
] |
22155385
|
Metabotropic glutamate receptor 1 (mGluR1): antibody specificity and receptor expression in cultured primary neurons.
|
The availability of high quality, well-characterized antibodies for molecular and cellular neuroscience studies is important. However, not all available antibodies are rigorously evaluated, nor are limitations of particular antibodies often reported. We have examined a panel of currently available mGluR1 antibodies and have identified which ones are selective for use by western blots and immunocytochemistry. We have also specifically determined whether the antibodies cross-react to recognize mGluR5, by examining (1) tissue from both mGluR1 and mGluR5 knock-out mice and (2) primary cortical cultures, in which mGluR5 is widely expressed but mGluR1 is not. Together, these data provide a baseline characterization of antibodies that can and cannot be reliably used in these types of studies, and will hopefully facilitate and positively impact the research efforts of others studying mGluR1.</AbstractText
|
[
[
"15996748",
"Correlates of trait impulsiveness in performance measures and neuropsychological tests.",
"Performance measures of impulsiveness offer great promise for assessing this trait in clinical and experimental studies. However, little is known about their relative superiority or inferiority to standard cognitive performance measures as correlates of this trait. In this study, 58 healthy volunteers completed a self-rating of impulsiveness (Barratt Impulsiveness Scale) and a battery of neuropsychological tests. The test battery included measures of reaction time, attention, memory, fluency, and executive function, as well as two performance measures of impulsiveness--Time Estimation and a Go-No Go task. Self-ratings correlated moderately with a number of these test scores, but many correlations became non-significant after adjustment for age and education. Correlations with the Go-No Go task, verbal fluency, executive function measures (Trails B), and tasks requiring decision-making against time (Choice Reaction Time, Reaction Time to Paired Words and Paired Faces Memory Tasks, and response bias on the Continuous Performance Test) remained significant. Performance on the Go-No Go task was the strongest correlate of self-rated impulsiveness. The findings suggest that once general demographic or ability factors are accounted for, specialized performance tasks requiring decision-making and response organization under time pressure provide the most effective means of assessing this behavioral trait.</AbstractText"
]
] |
[
[
"22431838",
"The brighter side of music in dystonia.",
"To report a patient with genetically proven DYT1 dystonia who shows dramatic improvement in symptoms while playing the piano.</AbstractText Case study.</AbstractText Sobell Department for Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, England.</AbstractText A 49-year-old right-handed male civil servant.</AbstractText The patient was videotaped, and electromyographic activity was recorded from the splenius capitis, sternocleidomastoid, and orbicularis oculi muscles, while he was (1) at rest, (2) playing an electric piano with auditory feedback, and (3) playing an electric piano without auditory feedback (ie, when the sound of the piano is turned off).</AbstractText At baseline, the patient had generalized dystonia with prominent upper limb, neck, and facial involvement. While he was playing the piano, there was an instant and almost complete improvement in dystonia symptoms. The improvement was also noticeable when he played the piano without auditory feedback. There was a significant reduction in electromyographic activity for all recorded muscles when he played the piano, compared with his baseline electromyographic activity.</AbstractText This is a unique case of “paradoxical” improvement in dystonia symptoms with activity (ie, playing a piano), in contrast to the typical worsening of dystonia symptoms with activity. We discuss the possible mechanisms underlying this phenomenon. One of the most intriguing features of primary dystonia is the variability of abnormal muscle activity relative to the context in which movement is attempted (eg, the exquisite task specificity of focal hand dystonia or the phenomenon of the geste antagoniste). We present a unique case of an amateur pianist with genetically proven DYT1 dystonia who shows dramatic improvement in generalized dystonia symptoms while playing piano.</AbstractText"
]
] |
23053864
|
Estimating summary statistics in the spike-train space.
|
Estimating sample averages and sample variability is important in analyzing neural spike trains data in computational neuroscience. Current approaches have focused on advancing the use of parametric or semiparametric probability models of the underlying stochastic process, where the probabilistic distribution is characterized at each time point with basic statistics such as mean and variance. To directly capture and analyze the average and variability in the observation space of the spike trains, we focus on a data-driven approach where statistics are defined and computed in a function space in which the spike trains are viewed as individual points. Based on the definition of a "Euclidean" metric, a recent paper introduced the notion of the mean of a set of spike trains and developed an efficient algorithm to compute it under some restrictive conditions. Here we extend this study by: (1) developing a novel algorithm for mean computation that is quite general, and (2) introducing a notion of covariance of a set of spike trains. Specifically, we estimate the covariance matrix using the geometry of the warping functions that map the mean spike train to each of the spike trains in the dataset. Results from simulations as well as a neural recording in primate motor cortex indicate that the proposed mean and covariance successfully capture the observed variability in spike trains. In addition, a "Gaussian-type" probability model (defined using the estimated mean and covariance) reasonably characterizes the distribution of the spike trains and achieves a desirable performance in the classification of the spike trains.</AbstractText
|
[
[
"21391760",
"The default network distinguishes construals of proximal versus distal events.",
"Humans enjoy a singular capacity to imagine events that differ from the \"here-and-now.\" Recent cognitive neuroscience research has linked such simulation processes to the brain's \"default network.\" However, extant cognitive theories suggest that perceivers reliably simulate only relatively proximal experiences-those that seem nearby, soon, likely to happen, or relevant to a close other. Here, we test these claims by examining spontaneous engagement of the default network while perceivers consider experiencing events from proximal and distal perspectives. Across manipulations of perspective in four dimensions, two regions of the default network-medial prefrontal cortex and retrosplenial cortex-were more active for proximal than distal events, supporting cognitive accounts that perceivers only richly simulate experiences that seem immediate and that perceivers represent different dimensions of distance similarly. Moreover, stable individual differences in default activity when thinking about distal events correlated with individual variability in an implicit measure of psychological distance, suggesting that perceivers naturally vary in their tendency to simulate far-off or unlikely experiences.</AbstractText"
]
] |
[
[
"23218585",
"Myasthenia gravis in the elderly.",
"The objective of the study is to examine clinical, therapeutic and prognostic factors of myasthenia gravis (MG) in the elderly.</AbstractText We reviewed all MG files of patients who attended the neuro-immunology clinic at Rabin Medical Center, Petah Tikva, Israel from January 1995 until September 2011 for demographic data, MG presentation, and course and response to treatment. Patients were classified as elderly if disease onset was above 69years.</AbstractText Out of 137 patients with MG, 29 developed MG after age 69. The 108 young onset patients had a male:female ratio of 0.9:1 whereas the eighth and ninth decade onset had a significant male predominance with ratios of 2.6:1 and 4.5:1 respectively. There was no difference in the presenting symptomatology and the rate of sero-negativity in the elderly patients when compared to the early onset patients was similar. The older patients had much less thymic pathology and their acetylcholine receptor (AChR) antibody titer was lower. This was associated with better response to therapy and a good prognosis.</AbstractText MG onset in the elderly is not uncommon, is more prevalent in males, is associated with lower titer of AChR antibodies, is readily responsive to therapy and carries a good prognosis.</AbstractText"
]
] |
23316177
|
Affective neuronal selection: the nature of the primordial emotion systems.
|
Based on studies in affective neuroscience and evolutionary psychiatry, a tentative new proposal is made here as to the nature and identification of primordial emotional systems. Our model stresses phylogenetic origins of emotional systems, which we believe is necessary for a full understanding of the functions of emotions and additionally suggests that emotional organizing systems play a role in sculpting the brain during ontogeny. Nascent emotional systems thus affect cognitive development. A second proposal concerns two additions to the affective systems identified by Panksepp. We suggest there is substantial evidence for a primary emotional organizing program dealing with power, rank, dominance, and subordination which instantiates competitive and territorial behavior and is an evolutionary contributor to self-esteem in humans. A program underlying disgust reactions which originally functioned in ancient vertebrates to protect against infection and toxins is also suggested.</AbstractText
|
[
[
"11144366",
"Ensemble patterns of hippocampal CA3-CA1 neurons during sharp wave-associated population events.",
"Transfer of neuronal patterns from the CA3 to CA1 region was studied by simultaneous recording of neuronal ensembles in the behaving rat. A nonlinear interaction among pyramidal neurons was observed during sharp wave (SPW)-related population bursts, with stronger synchrony associated with more widespread spatial coherence. SPW bursts emerged in the CA3a-b subregions and spread to CA3c before invading the CA1 area. Synchronous discharge of >10% of the CA3 within a 100 ms window was required to exert a detectable influence on CA1 pyramidal cells. Activity of some CA3 pyramidal neurons differentially predicted the ripple-related discharge of circumscribed groups of CA1 pyramidal cells. We suggest that, in SPW behavioral state, the coherent discharge of a small group of CA3 cells is the primary cause of spiking activity in CA1 pyramidal neurons.</AbstractText"
]
] |
[
[
"22328183",
"Towards a closed-loop cochlear implant system: application of embedded monitoring of peripheral and central neural activity.",
"Although the cochlear implant (CI) is widely considered the most successful neural prosthesis, it is essentially an open-loop system that requires extensive initial fitting and frequent tuning to maintain a high, but not necessarily optimal, level of performance. Two developments in neuroscience and neuroengineering now make it feasible to design a closed-loop CI. One development is the recording and interpretation of evoked potentials (EPs) from the peripheral to the central nervous system. The other is the embedded hardware and software of a modern CI that allows recording of EPs. We review EPs that are pertinent to behavioral functions from simple signal detection and loudness growth to speech discrimination and recognition. We also describe signal processing algorithms used for electric artifact reduction and cancellation, critical to the recording of electric EPs. We then present a conceptual design for a closed-loop CI that utilizes in an innovative way the embedded implant receiver and stimulators to record short latency compound action potentials ( ~1 ms), auditory brainstem responses (1-10 ms) and mid-to-late cortical potentials (20-300 ms). We compare EPs recorded using the CI to EPs obtained using standard scalp electrodes recording techniques. Future applications and capabilities are discussed in terms of the development of a new generation of closed-loop CIs and other neural prostheses.</AbstractText"
]
] |
30123682
|
Neurotoxicology: Five new things.
|
Neurotoxic disease can mimic many common neurologic disease states, including parkinsonism, myelopathy, neuropathy, and encephalopathy. Accurate diagnosis and appropriate treatment may result in a favorable outcome. This review highlights 5 areas of neurotoxicology for which there is an emerging understanding of disease processes or patterns of exposure, including 3 specific metal toxicities (manganism, zinc-induced copper deficiency, and cobalt-chromium neuropathy). Toxin-induced posterior reversible encephalopathy syndrome is more widely recognized and reported in association with an ever-growing list of drugs. Two new categories of street drugs, synthetic cathinones and cannabinoids, have been identified as public health threats due to their popularity, availability, and severity of toxicity.</AbstractText
|
[
[
"15050709",
"Tactile discrimination activates the visual cortex of the recently blind naive to Braille: a functional magnetic resonance imaging study in humans.",
"The occipital cortex of blind subjects is known to be activated during tactile discrimination tasks such as Braille reading. To investigate whether this is due to long-term learning of Braille or to sensory deafferentation, we used fMRI to study tactile discrimination tasks in subjects who had recently lost their sight and never learned Braille. The occipital cortex of the blind subjects without Braille training was activated during the tactile discrimination task, whereas that of control sighted subjects was not. This finding suggests that the activation of the visual cortex of the blind during performance of a tactile discrimination task may be due to sensory deafferentation, wherein a competitive imbalance favors the tactile over the visual modality.</AbstractText"
]
] |
[
[
"22963990",
"Further characterization of repetitive behavior in C58 mice: developmental trajectory and effects of environmental enrichment.",
"Aberrant repetitive behaviors are commonly observed in a variety of neurodevelopmental, neurological, and neuropsychiatric disorders. Little is known about the specific neurobiological mechanisms that underlie such behaviors, however, and effective treatments are lacking. Valid animal models can aid substantially in identifying pathophysiological factors mediating aberrant repetitive behavior and aid in treatment development. The C58 inbred mouse strain is a particularly promising model, and we have further characterized its repetitive behavior phenotype. Compared to C57BL/6 mice, C58 mice exhibit high rates of spontaneous hindlimb jumping and backward somersaulting reaching adult frequencies by 5 weeks post-weaning and adult temporal organization by 2 weeks post-weaning. The development of repetitive behavior in C58 mice was markedly attenuated by rearing these mice in larger, more complex environments. In addition to characterizing repetitive motor behavior, we also assessed related forms of inflexible behavior that reflect restricted and perseverative responding. Contrary to our hypothesis, C58 mice did not exhibit increased marble burying nor did they display reduced exploratory behavior in the holeboard task. The C58 strain appears to be a very useful model for the repetitive motor behavior characteristic of a number of clinical disorders. As an inbred mouse strain, studies using the C58 model can take full advantage of the tool kit of modern genetics and molecular neuroscience. This technical advantage makes the model a compelling choice for use in studies designed to elucidate the etiology and pathophysiology of aberrant repetitive behavior. Such findings should, in turn, translate into effective new treatments.</AbstractText"
]
] |
23206683
|
Optogenetic neuromodulation.
|
The recent development of optogenetics, a revolutionary research tool in neuroscience, portends an evolution of current clinical neuromodulation tools. A form of gene therapy, optogenetics makes possible highly precise spatial and temporal control of specific neuronal populations. This technique has already provided several new insights relevant to clinical neuroscience, from the physiological substrate of functional magnetic resonance imaging to the mechanism of deep brain stimulation in Parkinson's disease. The increased precision of optogenetic techniques also raises the possibility of eventual human use. Translational efforts have begun in primates, with success reported from multiple labs in rhesus macaques. These developments will remain of ongoing interest to neurologists and neurosurgeons.</AbstractText
|
[
[
"20800054",
"Kisspeptins: bridging energy homeostasis and reproduction.",
"Body energy reserves and metabolic state are relevant modifiers of puberty onset and fertility; forms of metabolic stress ranging from persistent energy insufficiency to morbid obesity are frequently linked to reproductive disorders. The mechanisms for such a close connection between energy balance and reproduction have been the subject of considerable attention; however, our understanding of the neurobiological basis for this phenomenon is still incomplete. In mid 1990s, the adipose-hormone, leptin, was proven as an essential signal for transmitting metabolic information onto the centers governing puberty and reproduction; yet, the ultimate mode of action of leptin on GnRH neurons has remained contentious for years. More recently, kisspeptins, a family of neuropeptides encoded by the Kiss1 gene, have emerged as conduits for the metabolic regulation of reproduction and putative effectors of leptin actions on GnRH neurons. This review recapitulates the experimental evidence obtained to date, mostly in laboratory rodents, supporting the function of kisspeptins in bridging energy balance and reproduction, with special emphasis on recent developments in this field, such as the recognition of mTOR (mammalian target of rapamycin) and Crtc1 (Creb1-regulated transcription coactivator-1) as putative mediators for leptin regulation of Kiss1 expression, as well as the identification of other potential metabolic modulators of kisspeptin signaling, such as ghrelin, neuropeptide Y (NPY) and melanin-concentrating hormone (MCH).</AbstractText"
]
] |
[
[
"23029114",
"Monitoring performance degradation of cerebellar functions using computational neuroscience methods: implications on neurological diseases.",
"Neurodegeneration is a major cause of human disease. Within the cerebellum, neuronal degeneration and/or dysfunction has been associated with many diseases, including several forms of cerebellar ataxia, since normal cerebellar function is paramount for proper motor coordination, balance, and motor learning. The cerebellum represents a well-established neural circuit. Determining the effects of neuronal loss is of great importance for understanding the fundamental workings of the cerebellum and disease-associated dysfunctions. This paper presents computational modeling of cerebellar function in relation to neurodegeneration either affecting a specific cerebellar cell type, such as granule cells or Purkinje cells, or more generally affecting cerebellar cells and the implications on effects in relation to performance degradation throughout the progression of cell death. The results of the models show that the overall number of cells, as a percentage of the total cell number in the model, of a particular type and, primarily, their proximity to the circuit output, and not the neuronal convergence due to the relative number of cells of a particular type, is the main indicator of the gravity of the functional deficit caused by the degradation of that cell type. Specifically, the greater the percentage loss of neurons of a specific type and the closer proximity of those cells to the deep cerebellar neurons, the greater the deficit caused by the neuronal cell loss. These findings contribute to the understanding of the functional consequences of neurodegeneration and the functional importance of specific connectivity within a neuronal circuit.</AbstractText"
]
] |
22431838
|
The brighter side of music in dystonia.
|
To report a patient with genetically proven DYT1 dystonia who shows dramatic improvement in symptoms while playing the piano.</AbstractText Case study.</AbstractText Sobell Department for Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, England.</AbstractText A 49-year-old right-handed male civil servant.</AbstractText The patient was videotaped, and electromyographic activity was recorded from the splenius capitis, sternocleidomastoid, and orbicularis oculi muscles, while he was (1) at rest, (2) playing an electric piano with auditory feedback, and (3) playing an electric piano without auditory feedback (ie, when the sound of the piano is turned off).</AbstractText At baseline, the patient had generalized dystonia with prominent upper limb, neck, and facial involvement. While he was playing the piano, there was an instant and almost complete improvement in dystonia symptoms. The improvement was also noticeable when he played the piano without auditory feedback. There was a significant reduction in electromyographic activity for all recorded muscles when he played the piano, compared with his baseline electromyographic activity.</AbstractText This is a unique case of “paradoxical” improvement in dystonia symptoms with activity (ie, playing a piano), in contrast to the typical worsening of dystonia symptoms with activity. We discuss the possible mechanisms underlying this phenomenon. One of the most intriguing features of primary dystonia is the variability of abnormal muscle activity relative to the context in which movement is attempted (eg, the exquisite task specificity of focal hand dystonia or the phenomenon of the geste antagoniste). We present a unique case of an amateur pianist with genetically proven DYT1 dystonia who shows dramatic improvement in generalized dystonia symptoms while playing piano.</AbstractText
|
[
[
"21723668",
"Steroid sulfatase-deficient mice exhibit endophenotypes relevant to attention deficit hyperactivity disorder.",
"Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental condition characterised by inattention, impulsivity and hyperactivity; it is frequently co-morbid with anxiety and conduct disorders, sleep perturbation and abnormal consummatory behaviours. Recent studies have implicated the neurosteroid-modulating enzyme steroid sulfatase (STS) as a modulator of ADHD-related endophenotypes. The effects of steroid sulfatase deficiency on homecage activity, feeding/drinking behaviours, anxiety-related behaviours (assayed in light-dark box and open field paradigms), social dominance and serum steroid hormone levels were determined by comparing 40,XY and 39,X(Y*)O mice. Subsequently, mice administered the steroid sulfatase inhibitor COUMATE acutely were compared to vehicle-treated mice on behavioural tasks sensitive to enzyme deficiency to dissociate between its developmental and ongoing effects. 39,X(Y*)O mice exhibited heightened reactivity to a novel environment, hyperactivity in the active phase, and increased water (but not food) consumption relative to 40,XY mice during a 24h period; the former group also demonstrated evidence for heightened emotional reactivity. There was no difference in social dominance between the 40,XY and 39,X(Y*)O mice. COUMATE administration had no effect on homecage activity, water consumption or anxiety measures in the open field. 39,X(Y*)O mice exhibited significantly lower dehydroepiandrosterone (DHEA) serum levels than 40,XY mice, but equivalent corticosterone levels. Together with previous data, the present results suggest that steroid sulfatase may influence core and associated ADHD behavioural endophenotypes via both developmental and ongoing mechanisms, and that the 39,X(Y*)O model may represent a useful tool for elucidating the neurobiological basis of these endophenotypes.</AbstractText"
]
] |
[
[
"21861199",
"Optimal experimental design for sampling voltage on dendritic trees in the low-SNR regime.",
"Due to the limitations of current voltage sensing techniques, optimal filtering of noisy, undersampled voltage signals on dendritic trees is a key problem in computational cellular neuroscience. These limitations lead to voltage data that is incomplete (in the sense of only capturing a small portion of the full spatiotemporal signal) and often highly noisy. In this paper we use a Kalman filtering framework to develop optimal experimental design methods for voltage sampling. Our approach is to use a simple greedy algorithm with lazy evaluation to minimize the expected square error of the estimated spatiotemporal voltage signal. We take advantage of some particular features of the dendritic filtering problem to efficiently calculate the Kalman estimator's covariance. We test our framework with simulations of real dendritic branching structures and compare the quality of both time-invariant and time-varying sampling schemes. While the benefit of using the experimental design methods was modest in the time-invariant case, improvements of 25-100% over more naïve methods were found when the observation locations were allowed to change with time. We also present a heuristic approximation to the greedy algorithm that is an order of magnitude faster while still providing comparable results.</AbstractText"
]
] |
20425240
|
Advances in pediatric neurovirology.
|
Viral infections of the pediatric central nervous system (CNS) encompass a broad spectrum of both perinatally and postnatally acquired diseases with potentially devastating effects on the developing brain. In children, viral infections have been associated with chronic encephalopathy, encephalitis, demyelinating disease, tumors, and epilepsy. Older diagnostic techniques of biopsy, viral culture, electron microscopy, gel-based polymerase chain reaction (PCR), and viral titer quantification are being replaced with more rapid, sensitive, and specific real-time and microarray-based PCR technologies. Advances in neuroimaging technologies have provided for earlier recognition of CNS injury without elucidation of specific viral etiology. Although the mainstay therapy of many pediatric neurovirologic diseases, aside from HIV, includes intravenous acyclovir, much work is being done to develop novel antiviral immunotherapies aimed at both treating and preventing pediatric CNS viral disease.</AbstractText
|
[
[
"21325527",
"Emergence of learned categorical representations within an auditory forebrain circuit.",
"Many learned behaviors are thought to require the activity of high-level neurons that represent categories of complex signals, such as familiar faces or native speech sounds. How these complex, experience-dependent neural responses emerge within the brain's circuitry is not well understood. The caudomedial mesopallium (CMM), a secondary auditory region in the songbird brain, contains neurons that respond to specific combinations of song components and respond preferentially to the songs that birds have learned to recognize. Here, we examine the transformation of these learned responses across a broader forebrain circuit that includes the caudolateral mesopallium (CLM), an auditory region that provides input to CMM. We recorded extracellular single-unit activity in CLM and CMM in European starlings trained to recognize sets of conspecific songs and compared multiple encoding properties of neurons between these regions. We find that the responses of CMM neurons are more selective between song components, convey more information about song components, and are more variable over repeated components than the responses of CLM neurons. While learning enhances neural encoding of song components in both regions, CMM neurons encode more information about the learned categories associated with songs than do CLM neurons. Collectively, these data suggest that CLM and CMM are part of a functional sensory hierarchy that is modified by learning to yield representations of natural vocal signals that are increasingly informative with respect to behavior.</AbstractText"
]
] |
[
[
"20797539",
"Spatiotemporal response properties of optic-flow processing neurons.",
"A central goal in sensory neuroscience is to fully characterize a neuron's input-output relation. However, strong nonlinearities in the responses of sensory neurons have made it difficult to develop models that generalize to arbitrary stimuli. Typically, the standard linear-nonlinear models break down when neurons exhibit stimulus-dependent modulations of their gain or selectivity. We studied these issues in optic-flow processing neurons in the fly. We found that the neurons' receptive fields are fully described by a time-varying vector field that is space-time separable. Increasing the stimulus strength, however, strongly reduces the neurons' gain and selectivity. To capture these changes in response behavior, we extended the linear-nonlinear model by a biophysically motivated gain and selectivity mechanism. We fit all model parameters directly to the data and show that the model now characterizes the neurons' input-output relation well over the full range of motion stimuli.</AbstractText"
]
] |
23231650
|
Dissociable brain signatures of choice conflict and immediate reward preferences in alcohol use disorders.
|
Impulsive delayed reward discounting (DRD) is an important behavioral process in alcohol use disorders (AUDs), reflecting incapacity to delay gratification. Recent work in neuroeconomics has begun to unravel the neural mechanisms supporting DRD, but applications of neuroeconomics in relation to AUDs have been limited. This study examined the neural mechanisms of DRD preferences in AUDs, with emphasis on dissociating activation patterns based on DRD choice type and level of cognitive conflict. Heavy drinking adult men with (n = 13) and without (n = 12) a diagnosis of an AUD completed a monetary DRD task during a functional magnetic resonance imaging scan. Participant responses were coded based on choice type (impulsive versus restrained) and level of cognitive conflict (easy versus hard). AUD+ participants exhibited significantly more impulsive DRD decision-making. Significant activation during DRD was found in several decision-making regions, including dorsolateral prefrontal cortex (DLPFC), insula, posterior parietal cortex (PPC), and posterior cingulate. An axis of cognitive conflict was also observed, with hard choices associated with anterior cingulate cortex and easy choices associated with activation in supplementary motor area. AUD+ individuals exhibited significant hyperactivity in regions associated with cognitive control (DLPFC) and prospective thought (PPC) and exhibited less task-related deactivation of areas associated with the brain's default network during DRD decisions. This study provides further clarification of the brain systems supporting DRD in general and in relation to AUDs.</AbstractText
|
[
[
"19005051",
"Light-induced rescue of breathing after spinal cord injury.",
"Paralysis is a major consequence of spinal cord injury (SCI). After cervical SCI, respiratory deficits can result through interruption of descending presynaptic inputs to respiratory motor neurons in the spinal cord. Expression of channelrhodopsin-2 (ChR2) and photostimulation in neurons affects neuronal excitability and produces action potentials without any kind of presynaptic inputs. We hypothesized that after transducing spinal neurons in and around the phrenic motor pool to express ChR2, photostimulation would restore respiratory motor function in cervical SCI adult animals. Here we show that light activation of ChR2-expressing animals was sufficient to bring about recovery of respiratory diaphragmatic motor activity. Furthermore, robust rhythmic activity persisted long after photostimulation had ceased. This recovery was accomplished through a form of respiratory plasticity and spinal adaptation which is NMDA receptor dependent. These data suggest a novel, minimally invasive therapeutic avenue to exercise denervated circuitry and/or restore motor function after SCI.</AbstractText"
]
] |
[
[
"25103077",
"Clinical and electrophysiologic features of childhood Guillain-Barré syndrome in Northeast China.",
"Since little has been reported in previous studies, we aimed to find the clinical and electrophysiologic characteristics associated with childhood Guillain-Barré Syndrome (GBS) in Northeast China.</AbstractText The clinical and electrophysiologic data were collected and reviewed retrospectively in 33 children and 105 adults with GBS during the period between 2006 and 2010 from the First Hospital of Jilin University.</AbstractText Most of the children with GBS were older than 8 years of age and symptoms were severe at GBS onset. Simultaneous involvement of four limbs was the most common clinical feature, and cranial nerve involvement was common; however, previous infection, sensory nerve involvement and elevated proteins in cerebrospinal fluid occurred much less in the children with GBS than those in adult patients. Recruited children were classified as having acute inflammatory demyelinating polyneuropathy (AIDP; 41%), acute motor axonal neuropathy (AMAN; 38%), and were unclassified (21%). Electrophysiologic features and prognosis in these children were not different from those in adults. For children with AMAN, the efficacy of intravenous immunoglobulin (IVIg) was not different from that in adults; however, IVIg was not significantly effective for AIDP in these children.</AbstractText Childhood GBS in Northeast China exhibits characteristics of clinical and electrophysiologic alternations; early diagnosis and appropriate treatments should be provided accordingly.</AbstractText"
]
] |
20530254
|
Sensitivity and selectivity of neurons in auditory cortex to the pitch, timbre, and location of sounds.
|
We are able to rapidly recognize and localize the many sounds in our environment. We can describe any of these sounds in terms of various independent "features" such as their loudness, pitch, or position in space. However, we still know surprisingly little about how neurons in the auditory brain, specifically the auditory cortex, might form representations of these perceptual characteristics from the information that the ear provides about sound acoustics. In this article, the authors examine evidence that the auditory cortex is necessary for processing the pitch, timbre, and location of sounds, and document how neurons across multiple auditory cortical fields might represent these as trains of action potentials. They conclude by asking whether neurons in different regions of the auditory cortex might not be simply sensitive to each of these three sound features but whether they might be selective for one of them. The few studies that have examined neural sensitivity to multiple sound attributes provide only limited support for neural selectivity within auditory cortex. Providing an explanation of the neural basis of feature invariance is thus one of the major challenges to sensory neuroscience obtaining the ultimate goal of understanding how neural firing patterns in the brain give rise to perception.</AbstractText
|
[
[
"3316677",
"Psychoneuroimmunology: interactions between central nervous system and immune system.",
"Psychoneuroimmunology, a rapidly developing field, has to do with the complex bidirectional interactions between the central nervous system and the immune system. Neuroendocrine influences modulate immune function, and there is feedback from the immune system to the brain. CNS-immune interaction appears to play a role in psychosocial influences on immunologically resisted and mediated diseases. With the growing evidence now at hand, over 30 \"postulates\" can be proposed for specific implications of CNS-immune interaction.</AbstractText"
]
] |
[
[
"20953339",
"Sign Languages: Contribution to Neurolinguistics from Cross-Modal Research.",
"Using sign language research as an example, we argue that both the cross-linguistic descriptive approach to data, advocated by Evans and Levinson (2009), as well as abstract ('formal') analyses are necessary steps towards the development of \"neurolinguistic primitives\" for investigating how human languages are instantiated in the brain.</AbstractText"
]
] |
23210812
|
Researchers and the translational reality. Interview with Karen Aboody.
|
Karen Aboody has first-hand experience of taking a potential therapy from the laboratory into clinical trials. Here, she shares with us the challenges and rewards of going from bench to bedside, and why all biomedical researchers need to know what it takes to make the transition if they want the best chance of seeing their discoveries used to help patients. Karen Aboody received her MD at Mount Sinai School of Medicine, and completed her post-doctoral training in Molecular Neurogenetics at Massachusetts General Hospital, Harvard Medical School. After gaining experience in pathology, gene therapy and biotechnology, she joined City of Hope (COH) in 2003 to head a translational research laboratory focused on therapeutic stem cell applications for invasive and metastatic solid tumors. In 2010, she received US FDA approval for a first-in-human clinical trial for neural stem cell-mediated therapy for high-grade glioma patients. This Phase I study is ongoing at COH, supported by NCI/NIH funding. In 2010, she received an US$18 million California Institute of Regenerative Medicine Disease Team Award to develop a second-generation enzyme/prodrug stem cell-mediated brain tumor therapy for clinical trials that may also have applications for other metastatic cancers. Honors include the 2000 AANS Young Investigator Award, and 2008 ASGCT Outstanding New Investigator Award. She recently founded a clinical-stage biopharmaceutical company, TheraBiologics Inc., to support clinical development of neural stem cell-mediated cancer therapies.</AbstractText
|
[
[
"3272153",
"Cellular determination in the Xenopus retina is independent of lineage and birth date.",
"Xenopus embryos injected with tritiated thymidine throughout the stages of embryonic retinal neurogenesis showed that more than 95% of the embryonic retinal cells are born within a 25 hr period. While there are shallow central to peripheral, dorsal to ventral, and interlaminar gradients of neurogenesis in these eyes, throughout most of this 25 hr period, postmitotic cells are being added to all sectors and layers. Small clones of differentiated retinal neurons and glia derived from single neuroepithelial cells injected with HRP. These clones were elongated radially. They were also composed of many different combinations of cell types, suggesting a mechanism whereby determination is arbitrarily and independently assigned to postmitotic cells. Such a model, when tested statistically, fits our data very well. We present a scheme for cellular determination in the Xenopus retina in which a coherent group of clonally related cells stretch out radially as lamination begins. This brings different cells into different microenvironments. Local interactions in these microenvironments then lead the cells toward specific fates.</AbstractText"
]
] |
[
[
"22936912",
"Decoding semantics across fMRI sessions with different stimulus modalities: a practical MVPA study.",
"Both embodied and symbolic accounts of conceptual organization would predict partial sharing and partial differentiation between the neural activations seen for concepts activated via different stimulus modalities. But cross-participant and cross-session variability in BOLD activity patterns makes analyses of such patterns with MVPA methods challenging. Here, we examine the effect of cross-modal and individual variation on the machine learning analysis of fMRI data recorded during a word property generation task. We present the same set of living and non-living concepts (land-mammals, or work tools) to a cohort of Japanese participants in two sessions: the first using auditory presentation of spoken words; the second using visual presentation of words written in Japanese characters. Classification accuracies confirmed that these semantic categories could be detected in single trials, with within-session predictive accuracies of 80-90%. However cross-session prediction (learning from auditory-task data to classify data from the written-word-task, or vice versa) suffered from a performance penalty, achieving 65-75% (still individually significant at p « 0.05). We carried out several follow-on analyses to investigate the reason for this shortfall, concluding that distributional differences in neither time nor space alone could account for it. Rather, combined spatio-temporal patterns of activity need to be identified for successful cross-session learning, and this suggests that feature selection strategies could be modified to take advantage of this.</AbstractText"
]
] |
23269439
|
The p.Ala510Val mutation in the SPG7 (paraplegin) gene is the most common mutation causing adult onset neurogenetic disease in patients of British ancestry.
|
The c.1529C >T change in the SPG7 gene, encoding the mutant p.Ala510Val paraplegin protein, was first described as a polymorphism in 1998. This was based on its frequency of 3 % and 4 % in two separate surveys of controls in the United Kingdom (UK) population. Subsequently, it has been found to co-segregate with disease in a number of different populations. Yeast expression studies support its having a deleterious effect. In this paper a consanguineous sibship is described in which four members who are homozygous for the p.Ala510Val variant present with a spectrum of disease. This spectrum encompasses moderately severe hereditary spastic paraparesis (HSP) with more minor ataxia in two siblings, moderately severe ataxia without spasticity in the third, and a very mild gait ataxia in the fourth. Two of the siblings also manifest vestibular failure. The remaining eight unaffected siblings are either heterozygous for the p.Ala510Val variant, or do not carry it at all. Homozygosity mapping using a high-density SNP array across the whole genome found just 11 genes (on two regions of chromosome 3) outside the SPG7 region on chromosome 16, which were homozygously shared by the affected siblings, but not shared by the unaffected siblings; none of them are likely to be causative. The weight of evidence is strongly in favour of the p.Ala510Val variant being a disease-causing mutation. We present additional data from the Auckland City Hospital neurogenetics clinic to show that the p.Ala510Val mutation is prevalent amongst HSP patients of UK extraction belying any suggestion that European p.Ala510Val haplotypes harbour a disease-causing mutation which the UK p.Ala510Val haplotypes do not. Taken together with previous findings of a carrier frequency of 3-4 % in the UK population (giving a homozygosity rate of 20-40/100,000), the data imply that the p.Ala510Val is the most common mutation causing neurogenetic disease in adults of UK ancestry, albeit the penetrance may be low or the disease caused may be mild.</AbstractText
|
[
[
"9892252",
"A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia.",
"In a preliminary dose-finding study, D-cycloserine, a partial agonist at the glycine modulatory site of the glutamatergic N-methyl-D-aspartate (NMDA) receptor, improved negative symptoms and cognitive function when added to conventional neuroleptics at a dose of 50 mg/d.</AbstractText Forty-seven patients with schizophrenia meeting criteria for deficit syndrome were randomized to D-cycloserine, 50 mg/d (n=23) or placebo (n=24) added to their conventional neuroleptic for an 8-week, double-blind trial. Clinical assessments were performed at baseline and at weeks 1, 2, 4, 6, and 8. Serum concentrations of D-cycloserine, relevant amino acids, and homovanillic acid were assayed at baseline and at weeks 4 and 8. A cognitive battery was performed at baseline and at week 8.</AbstractText Thirty-nine patients completed the 8-week trial. Seven dropouts occurred in the D-cycloserine group and 1 in the placebo group. The mean reduction in negative symptoms with D-cycloserine (23%) was significantly greater than with placebo (7%) as calculated by slopes representing Scale for the Assessment of Negative Symptoms (SANS) total scores. Improvement of negative symptoms was predicted by low neuroleptic dose and low baseline SANS total score. No differences were found in performance on any cognitive test between groups or in changes in any other clinical measure. Clinical response did not correlate significantly with serum amino acid concentrations at baseline or with concentrations of D-cycloserine at weeks 4 and 8.</AbstractText These results support the hypothesis that agents acting at the glycine modulatory site of the NMDA receptor improve primary negative symptoms.</AbstractText"
]
] |
[
[
"22998948",
"Glucocorticoid excess and the developmental origins of disease: two decades of testing the hypothesis--2012 Curt Richter Award Winner.",
"Low birthweight, a marker of an adverse in utero environment, is associated with cardiometabolic disease and brain disorders in adulthood. The adaptive changes made by the fetus in response to the intra-uterine environment result in permanent changes in physiology, structure and metabolism, a phenomenon termed early life programming. One of the key hypotheses to explain programming, namely over exposure of the developing fetus to glucocorticoids, was proposed nearly two decades ago, following the observation that the fetus was protected from high glucocorticoid levels in the mother by the actions of the placental barrier enzyme, 11β-hydroxysteroid dehydrogenase, which converts active glucocorticoids into inactive products. Numerous mechanistic studies in animal models have been carried out to test this hypothesis using manipulations to increase maternal glucocorticoids. Overall, these have resulted in offspring of lower birthweight, with an activated hypothalamic-pituitary-adrenal (HPA) axis and an adverse metabolic profile and behavioural phenotype in adulthood. Altered glucocorticoid activity or action is a good candidate mechanism in humans to link low birthweight with cardiometabolic and brain disorders. We have carried out detailed studies in men and women showing that high levels of endogenous glucocorticoids, or treatment with exogenous glucocorticoids, is associated with an adverse metabolic profile, increased cardiovascular disease and altered mood and cognitive decline. Our laboratory carried out the first translational studies in humans to test the glucocorticoid hypothesis, firstly demonstrating in studies of adult men and women, that low birthweight was associated with high fasting cortisol levels. We went on to dissect the mechanisms underlying the high fasting cortisol, demonstrating activation of the HPA axis, with increased cortisol responses to stimulation with exogenous adrenocorticotrophin hormone, lack of habituation to the stress of venepuncture, and increased cortisol responses to psychosocial stress. We have developed new dynamic tests to dissect the mechanisms regulating HPA axis central negative feedback sensitivity in humans, and demonstrated that this may be altered in obesity, one component of the metabolic syndrome. There are now studies in humans demonstrating that high circulating levels of maternal cortisol during pregnancy correlate negatively with birthweight, suggesting that excess glucocorticoids can by-pass the placental barrier. Deficiencies in the barrier enzyme, potentially increasing fetal glucocorticoid exposure, can also arise in association with maternal stress, malnutrition and disease, and can be inhibited by consumption of liquorice, which contains glycyrrhizin, an HSD inhibitor. Importantly, studies in humans have now demonstrated that high maternal cortisol in pregnancy and/or inhibition of HSD2 are associated with programmed outcomes in childhood including higher blood pressure, behavioural disorders as well as altered brain structure. We are investigating this further, using novel magnetic resonance imaging techniques to study the developing fetal brain in utero. The translational studies in support of the glucocorticoid hypothesis, and demonstrating that glucocorticoids are both mediators and targets of programming, are exciting and raise the question of whether this information can be used to identify those individuals most at risk of later life disease. In a recent study we showed that alterations in DNA methylation at genes important in regulating cortisol levels, tissue glucocorticoid action, blood pressure and fetal growth, are present in adulthood in association with both early life parameters and cardiometabolic risk factors. These preliminary data add to the limited literature in humans indicating a persisting epigenetic link between early life events and subsequent disease risk. Such findings open novel avenues for further exploration of the contribution of glucocorticoids to later life disease.</AbstractText"
]
] |
23908850
|
Cognitive decline and dementia in the oldest-old.
|
The oldest-old are the fastest growing segment of the Western population. Over half of the oldest-old will have dementia, but the etiology is yet unknown. Age is the only risk factor consistently associated with dementia in the oldest-old. Many of the risk and protective factors for dementia in the young elderly, such as ApoE genotype, physical activity, and healthy lifestyle, are not relevant for the oldest-old. Neuropathology is abundant in the oldest-old brains, but specific pathologies of Alzheimer's disease (AD) or vascular dementia are not necessarily correlated with cognition, as in younger persons. It has been suggested that accumulation of both AD-like and vascular pathologies, loss of synaptic proteins, and neuronal loss contribute to the cognitive decline observed in the oldest-old. Several characteristics of the oldest-old may confound the diagnosis of dementia in this age group. A gradual age-related cognitive decline, particularly in executive function and mental speed, is evident even in non-demented oldest-old. Hearing and vision losses, which are also prevalent in the oldest-old and found in some cases to precede/predict cognitive decline, may mechanically interfere in neuropsychological evaluations. Difficulties in carrying out everyday activities, observed in the majority of the oldest-old, may be the result of motor or physical dysfunction and of neurodegenerative processes. The oldest-old appear to be a select population, who escapes major illnesses or delays their onset and duration toward the end of life. Dementia in the oldest-old may be manifested when a substantial amount of pathology is accumulated, or with a composition of a variety of pathologies. Investigating the clinical and pathological features of dementia in the oldest-old is of great importance in order to develop therapeutic strategies and to provide the most elderly of our population with good quality of life.</AbstractText
|
[
[
"22708717",
"No evidence of intelligence improvement after working memory training: a randomized, placebo-controlled study.",
"Numerous recent studies seem to provide evidence for the general intellectual benefits of working memory training. In reviews of the training literature, Shipstead, Redick, and Engle (2010, 2012) argued that the field should treat recent results with a critical eye. Many published working memory training studies suffer from design limitations (no-contact control groups, single measures of cognitive constructs), mixed results (transfer of training gains to some tasks but not others, inconsistent transfer to the same tasks across studies), and lack of theoretical grounding (identifying the mechanisms responsible for observed transfer). The current study compared young adults who received 20 sessions of practice on an adaptive dual n-back program (working memory training group) or an adaptive visual search program (active placebo-control group) with a no-contact control group that received no practice. In addition, all subjects completed pretest, midtest, and posttest sessions comprising multiple measures of fluid intelligence, multitasking, working memory capacity, crystallized intelligence, and perceptual speed. Despite improvements on both the dual n-back and visual search tasks with practice, and despite a high level of statistical power, there was no positive transfer to any of the cognitive ability tests. We discuss these results in the context of previous working memory training research and address issues for future working memory training studies.</AbstractText"
]
] |
[
[
"23181011",
"Neuronal function is necessary but not sufficient for consciousness: consciousness is necessary for will.",
"Behavioral neuroscience has presented philosophers with the task of clarifying the relationship between neural determinism and free will. If neural functions encode information and govern decision-making, are the constructs of will, agency and indeed morality illusions of pre-scientific ignorance? This article will argue that neuronal function is necessary for representing distinct sensory-perceptual, cognitive, motivational, emotional states, and motor functions. However, neural transmission and action potentials are simply chemical-physical representations of these informational states but are not the embodiment of consciousness itself. By some yet undiscovered mechanism, consciousness \"reads\" the neuronal events into conscious experience. Absent a particular specialized brain region or sufficient relevant transmitters and receptors, relevant information cannot be processed and the individual cannot be conscious of that informational state. In natural and many artificial communication systems, communications proceed bi-directionally. By an argument of symmetry, if neuronal activity can communicate with consciousness, there is no reason to preclude consciousness from communicating back and influencing neuronal function. In the intervening conscious moment, information from diverse perceptual, motivational, cognitive, and emotional sources is weighted and will results. This process then biases resultant neural processes to actualize the willed target. This approach is limited in terms of operationalization into an experimental study because at present, there is no method to measure consciousness-independent of neuronal function and subjective report.</AbstractText"
]
] |
23261499
|
Neurochemical profiles of some novel psychoactive substances.
|
Fourteen substances from the class of drugs sometimes known as "legal highs" were screened against a battery of human receptors in binding assays, and their potencies as inhibitors of monoamine uptake determined in functional in vitro assays. Thirteen of the test substances acted as inhibitors of monoamine uptake at submicromolar concentrations, including 9 potent inhibitors of the dopamine transporter (DAT), 12 potent inhibitors of the norepinephrine transporter (NET) and 4 potent inhibitors of the serotonin transporter (SERT). Seven compounds acted as submicromolar inhibitors of both DAT and NET, and three substances 1-(benzofuran-5-yl)propan-2-amine (5-APB), 1-naphthalen-2-yl-2-pyrrolidin-1-ylpentan-1-one hydrochloride ("naphyrone") and 1-naphthalen-1-yl-2-pyrrolidin-1-ylpentan-1-one hydrochloride ("1-naphyrone") were submicromolar inhibitors of all three monoamine transporters. There was a lack of correlation between results of functional uptake experiments and in vitro binding assays for the monoamine transporters. There was also no correlation between the human behavioral effects of the substances and the results of bindings assays for a range of receptor targets, although 1-(benzofuran-5-yl)propan-2-amine (5-APB), 1-(benzofuran-6-yl)propan-2-amine hydrochloride (6-APB) and 5-iodo-2,3-dihydro-1H-inden-2-amine hydrochloride (5-iodo-aminoindane) exhibited <100 nM affinities for 5HT(2B) and α(2C) receptors. Functional assays revealed that 5-APB and 6-APB were potent full agonists at 5HT(2B) receptors.</AbstractText
|
[
[
"18773078",
"Spleen vagal denervation inhibits the production of antibodies to circulating antigens.",
"Recently the vagal output of the central nervous system has been shown to suppress the innate immune defense to pathogens. Here we investigated by anatomical and physiological techniques the communication of the brain with the spleen and provided evidence that the brain has the capacity to stimulate the production of antigen specific antibodies by its parasympathetic autonomic output.</AbstractText This conclusion was reached by successively demonstrating that: 1. The spleen receives not only sympathetic input but also parasympathetic input. 2. Intravenous trinitrophenyl-ovalbumin (TNP-OVA) does not activate the brain and does not induce an immune response. 3. Intravenous TNP-OVA with an inducer of inflammation; lipopolysaccharide (LPS), activates the brain and induces TNP-specific IgM. 4. LPS activated neurons are in the same areas of the brain as those that provide parasympathetic autonomic information to the spleen, suggesting a feed back circuit between brain and immune system. Consequently we investigated the interaction of the brain with the spleen and observed that specific parasympathetic denervation but not sympathetic denervation of the spleen eliminates the LPS-induced antibody response to TNP-OVA.</AbstractText These findings not only show that the brain can stimulate antibody production by its autonomic output, it also suggests that the power of LPS as adjuvant to stimulate antibody production may also depend on its capacity to activate the brain. The role of the autonomic nervous system in the stimulation of the adaptive immune response may explain why mood and sleep have an influence on antibody production.</AbstractText"
]
] |
[
[
"23200550",
"Next generation sequencing for neurological diseases: new hope or new hype?",
"Over the past year huge advances have been made in our ability to determine the genetic aetiology of many neurological diseases through the utilisation of next generation sequencing platforms. This technology is, on a daily basis, providing new breakthroughs in neurological disease. The aim of this article is to clearly describe the technological platforms, methods of data analysis, established breakthroughs, and potential future clinical and research applications of this innovative and exciting technique which has relevance to all those working within clinical neuroscience.</AbstractText"
]
] |
23226123
|
Identifying temporal and causal contributions of neural processes underlying the Implicit Association Test (IAT).
|
The Implicit Association Test (IAT) is a popular behavioral measure that assesses the associative strength between outgroup members and stereotypical and counterstereotypical traits. Less is known, however, about the degree to which the IAT reflects automatic processing. Two studies examined automatic processing contributions to a gender-IAT using a data driven, social neuroscience approach. Performance on congruent (e.g., categorizing male names with synonyms of strength) and incongruent (e.g., categorizing female names with synonyms of strength) IAT blocks were separately analyzed using EEG (event-related potentials, or ERPs, and coherence; Study 1) and lesion (Study 2) methodologies. Compared to incongruent blocks, performance on congruent IAT blocks was associated with more positive ERPs that manifested in frontal and occipital regions at automatic processing speeds, occipital regions at more controlled processing speeds and was compromised by volume loss in the anterior temporal lobe (ATL), insula and medial PFC. Performance on incongruent blocks was associated with volume loss in supplementary motor areas, cingulate gyrus and a region in medial PFC similar to that found for congruent blocks. Greater coherence was found between frontal and occipital regions to the extent individuals exhibited more bias. This suggests there are separable neural contributions to congruent and incongruent blocks of the IAT but there is also a surprising amount of overlap. Given the temporal and regional neural distinctions, these results provide converging evidence that stereotypic associative strength assessed by the IAT indexes automatic processing to a degree.</AbstractText
|
[
[
"17691351",
"An introduction to operative neuromodulation and functional neuroprosthetics, the new frontiers of clinical neuroscience and biotechnology.",
"Operative neuromodulation is the field of altering electrically or chemically the signal transmission in the nervous system by implanted devices in order to excite, inhibit or tune the activities of neurons or neural networks and produce therapeutic effects. It is a rapidly evolving biomedical and high-technology field on the cutting-edge of developments across a wide range of scientific disciplines. The authors review relevant literature on the neuromodulation procedures that are performed in the spinal cord or peripheral nerves in order to treat a considerable number of conditions such as (a) chronic pain (craniofacial, somatic, pelvic, limb, or due to failed back surgery), (b) spasticity (due to spinal trauma, multiple sclerosis, upper motor neuron disease, dystonia, cerebral palsy, cerebrovascular disease or head trauma), (c) respiratory disorders, (d) cardiovascular ischemia, (e) neuropathic bladder, and (f) bowel dysfunction of neural cause. Functional neuroprosthetics, a field of operative neuromodulation, encompasses the design, construction and implantation of artificial devices capable of generating electrical stimuli, thereby, replacing the function of damaged parts of the nervous system. The present article also reviews important literature on functional neuroprostheses, functional electrical stimulation (FES), and various emerging applications based on microsystems devices, neural engineering, neuroaugmentation, neurostimulation, and assistive technologies. The authors highlight promising lines of research such as endoneural prostheses for peripheral nerve stimulation, closed-loop systems for responsive neurostimulation or implanted microwires for microstimulation of the spinal cord to enable movements of paralyzed limbs. The above growing scientific fields, in combination with biological regenerative methods, are certainly going to enhance the practice of neuromodulation. The range of neuromodulatory procedures in the spine and peripheral nerves and the dynamics of the biomedical and technological domains which are reviewed in this article indicate that new breakthroughs are likely to improve substantially the quality of life of patients who are severely disabled by neurological disorders.</AbstractText"
]
] |
[
[
"23286166",
"Group-wise consistent fiber clustering based on multimodal connectional and functional profiles.",
"Fiber clustering is an essential step towards brain connectivity modeling and tract-based analysis of white matter integrity via diffusion tensor imaging (DTI) in many clinical neuroscience applications. A variety of methods have been developed to cluster fibers based on various types of features such as geometry, anatomy, connection, or function. However, identification of group-wise consistent fiber bundles that are harmonious across multi-modalities is rarely explored yet. This paper proposes a novel hybrid two-stage approach that incorporates connectional and functional features, and identifies group-wise consistent fiber bundles across subjects. In the first stage, based on our recently developed 358 dense and consistent cortical landmarks, we identified consistent backbone bundles with representative fibers. In the second stage, other remaining fibers are then classified into the existing backbone bundles using their correlations of resting state fMRI signals at the two ends of fibers. Our experimental results show that the proposed methods can achieve group-wise consistent fiber bundles with similar shapes and anatomic profiles, as well as strong functional coherences.</AbstractText"
]
] |
22794533
|
Infusing developmental neuroscience into school-based preventive interventions: implications and future directions.
|
Recent advances in developmental neuroscience have the potential to significantly impact the behavioral and academic outcomes of adolescents. By adopting a translational approach, we aim to promote the transfer of knowledge related to neurological, cognitive, and emotion regulatory factors that underlie youth's ability to respond to educational and prevention programming.</AbstractText This article synthesizes basic and applied research from the field of developmental neuroscience to highlight the significance of this work for the creation, evaluation, and tailoring of school-based preventive interventions designed to address aggressive behavior problems. We draw on research related to stress, social-cognitive factors, emotional perception and regulation, and executive functioning to identify potential neurodevelopmental mediators and moderators of prevention program impacts.</AbstractText Findings suggest that a high level of brain plasticity characterizes early childhood and adolescent stages of development, providing optimal windows of opportunity for intervention. The available research emphasizes the importance of executive functioning and related emotional regulatory factors as potential mechanisms for change in educational and risk prevention models.</AbstractText Neuroscience research provides insights into underlying mechanisms that, when appropriately targeted, can help optimize the impact of social-emotional learning curricula. Recommendations are made for how to apply relevant findings from neuroscience and related disciplines to improve behavioral and academic outcomes for school-aged youth. Additional research areas are identified to inform the creation of neurodevelopmentally sensitive preventive interventions targeting aggressive behavior problems which, in turn, are expected to affect academic outcomes.</AbstractText
|
[
[
"19874855",
"Species differences in group size and electrosensory interference in weakly electric fishes: implications for electrosensory processing.",
"In animals with active sensory systems, group size can have dramatic effects on the sensory information available to individuals. In \"wave-type\" weakly electric fishes there is a categorical difference in sensory processing between solitary fish and fish in groups: when conspecifics are within about 1m of each other, the electric fields mix and produce interference patterns that are detected by electroreceptors on each individual. Neural circuits in these animals must therefore process two streams of information-salient signals from prey items and predators and social signals from nearby conspecifics. We investigated the parameters of social signals in two genera of sympatric weakly electric fishes, Apteronotus and Sternopygus, in natural habitats of the Napo River valley in Ecuador and in laboratory settings. Apteronotus were most commonly found in pairs along the Napo River (47% of observations; maximum group size 4) and produced electrosensory interference at rates of 20-300 Hz. In contrast, Sternopygus were alone in 80% of observations (maximum group size 2) in the same region of Ecuador. Similar patterns were observed in laboratory experiments: Apteronotus were in groups and preferentially approached conspecific-like signals in an electrotaxis experiment whereas Sternopygus tended to be solitary and did not approach conspecific-like electrosensory signals. These results demonstrate categorical differences in social electrosensory-related activation of central nervous system circuits that may be related to the evolution of the jamming avoidance response that is used in Apteronotus but not Sternopygus to increase the frequency of electrosensory interference patterns.</AbstractText"
]
] |
[
[
"23439731",
"Cerebellar pathology of a dual clinical diagnosis: patients with essential tremor and dystonia.",
"Clinical studies have implicated the cerebellum in the pathogenesis of essential tremor (ET), and recent postmortem studies have identified structural changes in the ET cerebellum. While the basal ganglia have traditionally been implicated in dystonia, cerebellar involvement has been suggested as well, and a recent study showed Purkinje cell (PC) loss. We conducted a detailed postmortem examination of the brain in four individuals with clinical diagnoses of ET and dystonia, and hypothesized that pathological changes in the cerebellum would be greater in these four ET cases than in published ET cases without dystonia.</AbstractText After a complete neuropathological assessment, a standard parasagittal neocerebellar tissue block was harvested in each brain. One 7-µm thick section was stained with luxol fast blue/hematoxylin and eosin, and one section with the Bielschowsky method. We quantified PCs, torpedoes, heterotopic PCs, PC dendritic swellings, and basket cell changes.</AbstractText Two ET+dystonia cases had more microscopic changes in the cerebellum than published ET cases; the other two cases had similar changes to published ET cases.</AbstractText This is the first report that uses human autopsy tissue to study patients with both ET and dystonia. The findings were heterogeneous. Additional studies, with larger samples, are needed.</AbstractText"
]
] |
23366259
|
Design of the multi-channel electroencephalography-based brain-computer interface with novel dry sensors.
|
The traditional brain-computer interface (BCI) system measures the electroencephalography (EEG) signals by the wet sensors with the conductive gel and skin preparation processes. To overcome the limitations of traditional BCI system with conventional wet sensors, a wireless and wearable multi-channel EEG-based BCI system is proposed in this study, including the wireless EEG data acquisition device, dry spring-loaded sensors, a size-adjustable soft cap. The dry spring-loaded sensors are made of metal conductors, which can measure the EEG signals without skin preparation and conductive gel. In addition, the proposed system provides a size-adjustable soft cap that can be used to fit user's head properly. Indeed, the results are shown that the proposed system can properly and effectively measure the EEG signals with the developed cap and sensors, even under movement. In words, the developed wireless and wearable BCI system is able to be used in cognitive neuroscience applications.</AbstractText
|
[
[
"19064491",
"Retention of high tactile acuity throughout the life span in blindness.",
"Previous studies of tactile acuity on the fingertip, using passive touch, have demonstrated an age-related decline in spatial resolution for both sighted and blind subjects. We have reexamined this age dependence with two newly designed tactile-acuity charts that require active exploration of the test symbols. One chart used dot patterns similar to braille, and the other used embossed Landolt rings. Groups of blind braille readers and sighted subjects ranging from 12 to 85 years old were tested in two experiments. We replicated previous findings for sighted subjects by showing an age-related decrease in tactile acuity by nearly 1% per year. Surprisingly, the blind subjects retained high acuity into old age, showing no age-related decline. For the blind subjects, tactile acuity did not correlate with braille reading speed, the amount of daily reading, or the age at which braille was learned. We conclude that when measured with active touch, blind subjects retain high tactile acuity into old age, unlike their aging sighted peers. We propose that blind people's use of active touch in daily activities, not specifically braille reading, results in preservation of tactile acuity across the life span.</AbstractText"
]
] |
[
[
"23060781",
"Using \"smart stimulators\" to treat Parkinson's disease: re-engineering neurostimulation devices.",
"Let's imagine the cruise control of your car locked at 120 km/h on any road in any condition (city, country, highway, sunny or rainy weather), or your car air conditioner set on maximum cold in any temperature condition (even during a snowy winter): would you find it efficient? That would probably not be the most optimal strategy for a proper and comfortable driving experience. As surprising as this may seem, this is a pretty accurate illustration of how deep brain stimulation is used today to treat Parkinson's disease motor symptoms and other neurological disorders such as essential tremor, obsessive-compulsive disorder, or epilepsy.</AbstractText"
]
] |
21840408
|
Modulating the brain at work using noninvasive transcranial stimulation.
|
This paper proposes a shift in the way researchers currently view and use transcranial brain stimulation technologies. From a neuroscience perspective, the standard application of both transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) has been mainly to explore the function of various brain regions. These tools allow for noninvasive and painless modulation of cortical tissue. In the course of studying the function of an area, many studies often report enhanced performance of a task during or following the stimulation. However, little follow-up research is typically done to further explore these effects. Approaching this growing pool of cognitive neuroscience literature with a neuroergonomics mindset (i.e., studying the brain at work), the possibilities of using these stimulation techniques for more than simply investigating the function of cortical areas become evident. In this paper, we discuss how cognitive neuroscience brain stimulation studies may complement neuroergonomics research on human performance optimization. And, through this discussion, we hope to shift the mindset of viewing transcranial stimulation techniques as solely investigatory basic science tools or possible clinical therapeutic devices to viewing transcranial stimulation techniques as interventional tools to be incorporated in applied science research and systems for the augmentation and enhancement of human operator performance.</AbstractText
|
[
[
"19298949",
"Perceptual simulation in conceptual combination: evidence from property generation.",
"In three experiments, participants received nouns or noun phrases for objects and verbally generated their properties (\"feature listing\"). Several sources of evidence indicated that participants constructed perceptual simulations to generate properties for the noun phrases during conceptual combination. First, the production of object properties for noun phrases depended on occlusion, with unoccluded properties being generated more often than occluded properties. Because a perceptual variable affected conceptual combination, perceptual simulations appeared central to combining the concepts for modifiers and head nouns. Second, neutral participants produced the same distributions of properties as participants instructed to describe images, suggesting that the conceptual representations used by neutral participants were similar to the mental images used by imagery participants. Furthermore, the property distributions for neutral and imagery participants differed from those for participants instructed to produce word associations. Third, participants produced large amounts of information about background situations associated with the object cues, suggesting that the simulations used to generate properties were situated. The experiments ruled out alternative explanations that simulation effects occur only for familiar noun phrases associated with perceptual memories and that rules associated with modifiers produce occlusion effects. A process model of the property generation task grounded in simulation mechanisms is presented. The possibility of integrating the simulation account of conceptual combination with traditional accounts and well-established findings is explored.</AbstractText"
]
] |
[
[
"23029114",
"Monitoring performance degradation of cerebellar functions using computational neuroscience methods: implications on neurological diseases.",
"Neurodegeneration is a major cause of human disease. Within the cerebellum, neuronal degeneration and/or dysfunction has been associated with many diseases, including several forms of cerebellar ataxia, since normal cerebellar function is paramount for proper motor coordination, balance, and motor learning. The cerebellum represents a well-established neural circuit. Determining the effects of neuronal loss is of great importance for understanding the fundamental workings of the cerebellum and disease-associated dysfunctions. This paper presents computational modeling of cerebellar function in relation to neurodegeneration either affecting a specific cerebellar cell type, such as granule cells or Purkinje cells, or more generally affecting cerebellar cells and the implications on effects in relation to performance degradation throughout the progression of cell death. The results of the models show that the overall number of cells, as a percentage of the total cell number in the model, of a particular type and, primarily, their proximity to the circuit output, and not the neuronal convergence due to the relative number of cells of a particular type, is the main indicator of the gravity of the functional deficit caused by the degradation of that cell type. Specifically, the greater the percentage loss of neurons of a specific type and the closer proximity of those cells to the deep cerebellar neurons, the greater the deficit caused by the neuronal cell loss. These findings contribute to the understanding of the functional consequences of neurodegeneration and the functional importance of specific connectivity within a neuronal circuit.</AbstractText"
]
] |
22969712
|
Neural systems supporting cognitive-affective interactions in adolescence: the role of puberty and implications for affective disorders.
|
Evidence from longitudinal studies suggests that adolescence may represent a period of vulnerability that, in the context of adverse events, could contribute to developmental trajectories toward behavioral and emotional health problems, including affective disorders. Adolescence is also a sensitive period for the development of neural systems supporting cognitive-affective processes, which have been implicated in the pathophysiology of affective disorders such as anxiety and mood disorders. In particular, the onset of puberty brings about a cascade of physical, hormonal, psychological, and social changes that contribute in complex ways to the development of these systems. This article provides a brief overview of neuroimaging research pertaining to the development of cognitive-affective processes in adolescence. It also includes a brief review of evidence from animal and human neuroimaging studies suggesting that sex steroids influence the connectivity between prefrontal cortical and subcortical limbic regions in ways that contribute to increased reactivity to emotionally salient stimuli. We integrate these findings in the context of a developmental affective neuroscience framework suggesting that the impact of rising levels of sex steroids during puberty on fronto-limbic connectivity may be even greater in the context of protracted development of prefrontal cortical regions in adolescence. We conclude by discussing the implications of these findings for future research aimed at identifying neurodevelopmental markers of risk for future onset of affective disorders.</AbstractText
|
[
[
"21677369",
"A cortical neural prosthesis for restoring and enhancing memory.",
"A primary objective in developing a neural prosthesis is to replace neural circuitry in the brain that no longer functions appropriately. Such a goal requires artificial reconstruction of neuron-to-neuron connections in a way that can be recognized by the remaining normal circuitry, and that promotes appropriate interaction. In this study, the application of a specially designed neural prosthesis using a multi-input/multi-output (MIMO) nonlinear model is demonstrated by using trains of electrical stimulation pulses to substitute for MIMO model derived ensemble firing patterns. Ensembles of CA3 and CA1 hippocampal neurons, recorded from rats performing a delayed-nonmatch-to-sample (DNMS) memory task, exhibited successful encoding of trial-specific sample lever information in the form of different spatiotemporal firing patterns. MIMO patterns, identified online and in real-time, were employed within a closed-loop behavioral paradigm. Results showed that the model was able to predict successful performance on the same trial. Also, MIMO model-derived patterns, delivered as electrical stimulation to the same electrodes, improved performance under normal testing conditions and, more importantly, were capable of recovering performance when delivered to animals with ensemble hippocampal activity compromised by pharmacologic blockade of synaptic transmission. These integrated experimental-modeling studies show for the first time that, with sufficient information about the neural coding of memories, a neural prosthesis capable of real-time diagnosis and manipulation of the encoding process can restore and even enhance cognitive, mnemonic processes.</AbstractText"
]
] |
[
[
"22344946",
"Answering the big questions in neuroscience: DoD's experimental research wing takes on massive, high-risk projects.",
"When the Defense Advanced Research Projects Agency (DARPA) asks research questions, it goes big. This is, after all, the same agency that put together teams of scientists and engineers to find a way to connect the worlds computers and, in doing so, developed the precursor to the Internet. DARPA, the experimental research wing of the U.S. Department of Defense, funds the types of research queries that scientists and engineers dream of tackling. Unlike a traditional granting agency that conservatively metes out its funding and only to projects with a good chance of success, DARPA puts its money on massive, multi-institutional projects that have no guarantees, but have enormous potential. In the 1990s, DARPA began its biological and medical science research to improve the safety, health, and well being of military personnel, according to DARPA program manager and Army Colonel Geoffrey Ling, Ph.D., M.D. More recently, DARPA has entered the realm of neuroscience and neurotechnology. Its focus with these projects is on its prime customer, the U.S. Department of Defense, but Ling acknowledged that technologies developed in its programs \"certainly have potential to cascade into civilian uses.\"</AbstractText"
]
] |
23129998
|
Supercomputers ready for use as discovery machines for neuroscience.
|
NEST is a widely used tool to simulate biological spiking neural networks. Here we explain the improvements, guided by a mathematical model of memory consumption, that enable us to exploit for the first time the computational power of the K supercomputer for neuroscience. Multi-threaded components for wiring and simulation combine 8 cores per MPI process to achieve excellent scaling. K is capable of simulating networks corresponding to a brain area with 10(8) neurons and 10(12) synapses in the worst case scenario of random connectivity; for larger networks of the brain its hierarchical organization can be exploited to constrain the number of communicating computer nodes. We discuss the limits of the software technology, comparing maximum filling scaling plots for K and the JUGENE BG/P system. The usability of these machines for network simulations has become comparable to running simulations on a single PC. Turn-around times in the range of minutes even for the largest systems enable a quasi interactive working style and render simulations on this scale a practical tool for computational neuroscience.</AbstractText
|
[
[
"21386006",
"Optogenetics in the teaching laboratory: using channelrhodopsin-2 to study the neural basis of behavior and synaptic physiology in Drosophila.",
"Here we incorporate recent advances in Drosophila neurogenetics and \"optogenetics\" into neuroscience laboratory exercises. We used the light-activated ion channel channelrhodopsin-2 (ChR2) and tissue-specific genetic expression techniques to study the neural basis of behavior in Drosophila larvae. We designed and implemented exercises using inexpensive, easy-to-use systems for delivering blue light pulses with fine temporal control. Students first examined the behavioral effects of activating glutamatergic neurons in Drosophila larvae and then recorded excitatory junctional potentials (EJPs) mediated by ChR2 activation at the larval neuromuscular junction (NMJ). Comparison of electrically and light-evoked EJPs demonstrates that the amplitudes and time courses of light-evoked EJPs are not significantly different from those generated by electrical nerve stimulation. These exercises introduce students to new genetic technology for remotely manipulating neural activity, and they simplify the process of recording EJPs at the Drosophila larval NMJ. Relatively little research work has been done using ChR2 in Drosophila, so students have opportunities to test novel hypotheses and make tangible contributions to the scientific record. Qualitative and quantitative assessment of student experiences suggest that these exercises help convey principles of synaptic transmission while also promoting integrative and inquiry-based studies of genetics, cellular physiology, and animal behavior.</AbstractText"
]
] |
[
[
"23391878",
"The dialectical law between coronary artery disease and stroke recurrence.",
"In this issue of Neuroendocrinology Letters Kováčik et al. reported that coronary artery disease is not associated with stroke recurrence. Although the data were analyzed by statistical methods and the analysis was extremely encouraging, the conclusion should be interpreted with caution.</AbstractText"
]
] |
22946114
|
Giuseppe Ferrario and the epidemiology of apoplexy during the 19th century.
|
To analyze the pioneering research of Giuseppe Ferrario (1802-1870) on the epidemiology of apoplexy. To our knowledge, his work might have been the first to systematically investigate the epidemiology of cerebrovascular accidents, with the aim of shedding light on the underlying causes.</AbstractText A detailed analysis of the essay "Statistics of sudden deaths, more particularly of deaths from apoplexy, in the city and neighborhood of Milan, from 1750 to 1834," published by Ferrario in 1834.</AbstractText Ferrario conducted a large retrospective study on 13,360 people who died from apoplexy during an 84-year observational period. Analyzed data showed that these events were more frequent among men and during winter. Apoplexy was reported as mainly occurring at the age of 60; an increase in mortality was observed in young women aged between 21 and 30 years, probably due to an abuse of bloodletting. Ferrario introduced the term "hereditary apoplexy," being one of the first to hypothesize hereditary components in cerebrovascular diseases. He also tried to investigate the role of social conditions in the etiopathogenesis of these events, analyzing marital and employment status and suggesting to his colleagues that cultural and economic factors should be further examined.</AbstractText Giuseppe Ferrario may be considered as a pioneer of modern science and epidemiology and his work deserves consideration within the history of neurology and of neuroepidemiology.</AbstractText
|
[
[
"19120115",
"Chronic stress, combined with a high-fat/high-sugar diet, shifts sympathetic signaling toward neuropeptide Y and leads to obesity and the metabolic syndrome.",
"In response to stress, some people lose while others gain weight. This is believed to be due to either increased beta-adrenergic activation, the body's main fat-burning mechanism, or increased intake of sugar- and fat-rich \"comfort foods.\" A high-fat, high-sugar (HFS) diet alone, however, cannot account for the epidemic of obesity, and chronic stress alone tends to lower adiposity in mice. Here we discuss how chronic stress, when combined with an HFS diet, leads to abdominal obesity by releasing a sympathetic neurotransmitter, neuropeptide Y (NPY), directly into the adipose tissue. In vitro, when \"stressed\" with dexamethasone, sympathetic neurons shift toward expressing more NPY, which stimulates endothelial cell (angiogenesis) and preadipocyte proliferation, differentiation, and lipid-filling (adipogenesis) by activating the same NPY-Y2 receptors (Y2Rs). In vivo, chronic stress, consisting of cold water or aggression in HFS-fed mice, stimulates the release of NPY and the expression of Y2Rs in visceral fat, increasing its growth by 50% in 2 weeks. After 3 months, this results in metabolic syndrome-like symptoms with abdominal obesity, inflammation, hyperlipidemia, hyperinsulinemia, glucose intolerance, hepatic steatosis, and hypertension. Remarkably, local intra-fat Y2R inhibition pharmacologically or via adenoviral Y2R knock-down reverses or prevents fat accumulation and metabolic complications. These studies demonstrated for the first time that chronic stress, via the NPY-Y2R pathway, amplifies and accelerates diet-induced obesity and the metabolic syndrome. Our findings also suggest the use of local administration of Y2R antagonists for treatment of obesity and NPY-Y2 agonists for fat augmentation in other clinical applications.</AbstractText"
]
] |
[
[
"23383397",
"Interactions between oestrogen and the renin angiotensin system - potential mechanisms for gender differences in Alzheimer's disease.",
"Interactions between oestrogen and the renin angiotensin system (RAS) are reviewed and explored from the perspective where these interactions may modulate risk of developing Alzheimer's disease (AD). AD is more prevalent in women than men, partly attributed to women's increased life expectancy; however underlying vascular differences may also contribute to AD risk. The RAS is a key regulator of blood pressure (BP). Pharmacological inhibition of angiotensin converting enzyme (ACE) and blockade of angiotensin II type 1 receptors (AT1R) are widely used to treat hypertension. Variation in components of the RAS such as ACE, neprilysin (NEP) and AT1R have been reported in AD, some of which may also directly alter AD neuropathology with changes in amyloid beta (Aβ) levels, cognitive decline and neuroinflammation. Recently, RAS inhibiting drugs have been shown to attenuate the incidence, progression and pathology of AD. Oestrogen is also thought to prevent hypertension by reducing the vasoconstrictive actions of the RAS. Reduced oestrogen levels in women during the menopausal transition may therefore increase their risk of hypertension and/or RAS-mediated changes to cerebrovascular or AD pathology. Specifically, oestrogen prevents the production and action of angiotensin II (Ang II), thought to exert harmful effects of the RAS in both hypertension and AD, while also potentially facilitating RAS-mediated Aβ degradation. These oestrogen-RAS interactions may partly explain current conflicting findings regarding oestrogen depletion and hormone therapy with respect to AD risk. Clinical trials targeting either the RAS or oestrogen systems for AD prevention and treatment should perhaps give closer attention to key biochemical components of these pathways as potential confounders to primary and secondary outcome measures.</AbstractText"
]
] |
25205899
|
Neuroepidemiology of epilepsy in northwest India.
|
Epilepsy has a complex etiology characterised by recurring seizures.</AbstractText To study clinical profile of epilepsy patients with reference to type of epilepsy in northwest India. No previous Indian study has reported relative incidence of various types of seizures with reference to type of epilepsy.</AbstractText Data of 400 epilepsy patients (200 idiopathic and 200 symptomatic) was collected for their clinical characteristics. The classification of epilepsy into idiopathic and symptomatic types was done on the basis of findings of EEG, CT scan and MRI tests.</AbstractText The age of onset of seizures was less than 15 years in only one third of the total patients. The number of non-vegetarians was higher in SE (68.5%) than IE (58%). The male to female ratio was significantly higher (1.33:1 in IE and 1.47:1 in SE). No difference was seen for place of residence (urban vs rural) patients with epilepsy (PWE). The majority of patients (58.5% of symptomatic and 52.8% idiopathic) though reported no triggering factors, yet many of them, when questioned, had held supernatural powers to be the cause of the disease. Sleep deprivation was reported as a major triggering factor by 28.5% of idiopathic epilepsy (IE) and 25% of symptomatic epilepsy (SE) patients. The incidence of mental retardation (1.25%) and behavioral disorders (7%) was found to be relatively low. Loss of memory was reported in 46% of IE and 43.5% of SE and poor scholastic performance in 23% of IE and 16.5% of SE. A positive history was recorded in 11% first-degree relatives and 4% second-degree relatives. Generalized seizures were more common in IE patients (67.5%), while partial seizures with and without secondary generalization (50.5%), and generalized seizures (49.5%) were equally common in SE.</AbstractText The study demonstrates differences in the type of seizures between idiopathic and symptomatic epilepsies and not other demographic, clinical and psycho-social traits. The males were found to have higher risk of epilepsy than females. The epidemiological characteristics of epileptics show variations across populations and also within population.</AbstractText Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a disorder of the urea cycle and ornithine degradation pathway. Clinical manifestations and age of onset vary among individuals even in the same family. <i The biochemical diagnosis of HHH syndrome is established in a proband with the classic metabolic triad of episodic or postprandial hyperammonemia, persistent hyperornithinemia, and urinary excretion of homocitrulline. The molecular diagnosis of HHH syndrome is established in a symptomatic individual with or without suggestive metabolic/biochemical findings by identification of biallelic pathogenic variants in <i <i HHH syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the <i
|
[
[
"21466746",
"Study on the possible association of brain-derived neurotrophic factor polymorphism with the developmental course of symptoms of attention deficit and hyperactivity.",
"Several studies have, with conflicting results, investigated the relationship between the Val⁶⁶Met polymorphism in brain-derived neurotrophic factor (BDNF) and attention deficit hyperactivity disorder (ADHD). We assessed longitudinal, quantitative phenotypes of hyperactivity-impulsivity and inattention in order to determine whether the Val⁶⁶Met polymorphism is associated with age-specific and/or persistent symptoms of hyperactivity-impulsivity and/or inattention in a community-based cohort of 1236 Swedish individuals for which ADHD symptom data were collected when the participants were aged 8-9, 13-14 and 16-17 yr. The Met allele was associated with symptoms of ADHD at ages 8-9 and 13-14 yr. A multivariate regression analysis revealed that the observed effect of the Met allele on ADHD symptoms reflects an influence on persistent hyperactivity-impulsivity symptoms. The present findings support the hypothesis that BDNF is involved in the pathogenesis of ADHD. The results highlight the importance of distinguishing between hyperactivity-impulsivity and inattention, respectively, and demonstrate the value of using a longitudinal approach in genetic studies of ADHD symptoms.</AbstractText"
]
] |
[
[
"20425240",
"Advances in pediatric neurovirology.",
"Viral infections of the pediatric central nervous system (CNS) encompass a broad spectrum of both perinatally and postnatally acquired diseases with potentially devastating effects on the developing brain. In children, viral infections have been associated with chronic encephalopathy, encephalitis, demyelinating disease, tumors, and epilepsy. Older diagnostic techniques of biopsy, viral culture, electron microscopy, gel-based polymerase chain reaction (PCR), and viral titer quantification are being replaced with more rapid, sensitive, and specific real-time and microarray-based PCR technologies. Advances in neuroimaging technologies have provided for earlier recognition of CNS injury without elucidation of specific viral etiology. Although the mainstay therapy of many pediatric neurovirologic diseases, aside from HIV, includes intravenous acyclovir, much work is being done to develop novel antiviral immunotherapies aimed at both treating and preventing pediatric CNS viral disease.</AbstractText"
]
] |
22365959
|
Defining the genetic architecture of human developmental language impairment.
|
Language is a uniquely human trait, which poses limitations on animal models for discovering biological substrates and pathways. Despite this challenge, rapidly developing biotechnology in the field of genomics has made human genetics studies a viable alternative route for defining the molecular neuroscience of human language. This is accomplished by studying families that transmit both normal and disordered language across generations. The language disorder reviewed here is specific language impairment (SLI), a developmental deficiency in language acquisition despite adequate opportunity, normal intelligence, and without any apparent neurological etiology. Here, we describe disease gene discovery paradigms as applied to SLI families and review the progress this field has made. After review the evidence that genetic factors influence SLI, we discuss methods and findings from scans of the human chromosomes, including the main replicated regions on chromosomes 13, 16 and 19 and two identified genes, ATP2C2 and CMIP that appear to account for the language variation on chromosome 16. Additional work has been done on candidate genes, i.e., genes chosen a priori and not through a genome scanning studies, including several studies of CNTNAP2 and some recent work implicating BDNF as a gene x gene interaction partner of genetic variation on chromosome 13 that influences language. These recent developments may allow for better use of post-mortem human brain samples functional studies and animal models for circumscribed language subcomponents. In the future, the identification of genetic variation associated with language phenotypes will provide the molecular pathways to understanding human language.</AbstractText
|
[
[
"21893533",
"The multiple time scales of sleep dynamics as a challenge for modelling the sleeping brain.",
"A particular property of the sleeping brain is that it exhibits dynamics on very different time scales ranging from the typical sleep oscillations such as sleep spindles and slow waves that can be observed in electroencephalogram (EEG) segments of several seconds duration over the transitions between the different sleep stages on a time scale of minutes to the dynamical processes involved in sleep regulation with typical time constants in the range of hours. There is an increasing body of work on mathematical and computational models addressing these different dynamics, however, usually considering only processes on a single time scale. In this paper, we review and present a new analysis of the dynamics of human sleep EEG at the different time scales and relate the findings to recent modelling efforts pointing out both the achievements and remaining challenges.</AbstractText"
]
] |
[
[
"23077800",
"Occupational exposure to styrene in the fibreglass reinforced plastic industry: comparison between two different manufacturing processes.",
"Styrene is used in manufacturing fiberglass reinforced plastics: and occupational exposure was related to neurotoxicology and genotoxicity. The sum of the metabolites mandelic and phenylglyoxylic acids is the ACGIH biomarker for occupational exposure with a BEI of 400 mg/g of creatinine in end shift urine corresponding to a airborne styrene concentration of 85 mg/m3. There are two main molding processes, open and closed, the last more effective at controlling worker's styrene exposure.</AbstractText To compare the open molding process to the compression of fiber reinforced resin foils, a kind of closed molding, monitoring the styrene exposure of workers in two production sites (A and B).</AbstractText Environmental Monitoring was carried out by Radiello samplers and Biological Monitoring by means of the determination of MA and PGA with HPLC/MS/MS in 10 workers at Site A and 14 at Site B.</AbstractText The median values for styrene exposure resulted 31.1 mg/m3 for Site A and 24.4 mg/m for Site B, while the medians for the sum of the two metabolites in the end shift urine were 86.7 e 33.8 mg/g creatinine respectively. There is a significant linear correlation between personal styrene exposure and the excretion of styrene metabolites (R = 0.74).</AbstractText As expected the exposure markers of the workers of the two production sites resulted higher in the open process. The analytical results of both environmental and biological monitoring were all below the occupational exposure limits, confirming the efficacy of the protective devices.</AbstractText"
]
] |
37539014
|
Quantification of Speech Disfluency as a Marker of Medication-Induced Cognitive Impairment: An Application of Computerized Speech Analysis in Neuropharmacology.
|
We present the results of a study investigating the use of speech and language characteristics extracted from spontaneous spoken discourse to assess changes in cognitive function. Specifically, we investigated the use of automatic speech recognition technology to characterize spontaneous speech disfluency induced by topiramate, an anti-epileptic medication with language-related side-effects. We audio recorded spontaneous speech samples from 20 participants during several picture description tasks and analyzed the recordings automatically and manually to extract a range of spoken fluency measurements including speech discontinuities (e.g., filled pauses, false starts, and repetitions), silent pause duration, speaking rate and vowel lengthening. Our results indicate that some of these paralinguistic speech characteristics are a) sensitive to the effects of topiramate, b) are associated with topiramate concentrations in the blood, and c) complement standard neuropsychological tests typically used to investigate cognitive effects of medications. This work demonstrates the use of computational linguistic tools to assess cognitive effects in a more sensitive, objective and reproducible manner than is currently available with standard tests.</AbstractText
|
[
[
"21748284",
"A failure to normalize biochemical and metabolic insults during morphine withdrawal disrupts synaptic repair in mice transgenic for HIV-gp120.",
"Drug abuse in HIV-infected individuals accelerates the onset and progression of HIV-associated neurocognitive disorders (HAND). Opiates are a class of commonly abused drugs that have interactive effects with neurotoxic HIV proteins that facilitate glial dysfunction, neuronal damage and death. While the combined effects of neurotoxic HIV proteins and morphine have been extensively studied in the setting of chronic and acute morphine use, very little in known about the effects of HIV proteins during drug withdrawal. Since opiate withdrawal can induce considerable neuronal stress, we determined the effects of opiates (morphine) on brain redox balance, sphingolipid metabolism and synaptic integrity during both chronic and withdrawal conditions in non-transgenic mice (nTg), and in mice transgenic for the HIV-coat protein gp120 (gp120tg). In nTg mice, we found that chronic morphine increased brain oxidative capacity and induced synaptic damage that was largely reversed during drug withdrawal. Gp120tg mice showed a similar response to chronic morphine, but the diminished oxidative capacity and synaptic damage failed to normalize during drug withdrawal. In nTg mice, brain sphingolipid content was not affected by morphine during chronic or withdrawal conditions. In gp120tg mice there was a baseline perturbation in sphingolipid metabolism that manifest as decreased sphingomyelin with accumulations of the bioactive lipid ceramide. Sphingolipid metabolism was highly reactive to morphine in gp120tg mice. Chronic morphine increased sphingomyelin content with a consequent reduction in ceramide. During drug withdrawal, these effects reversed, and sphingomyelin levels were reduced with consequent increases of ceramide. We interpret these findings to suggest that neuronal repair during morphine withdrawal is inhibited in the setting of gp120 by mechanisms that involve sustained oxidative insult and accumulations of the highly reactive intermediate ceramide.</AbstractText"
]
] |
[
[
"23023166",
"The vagal innervation of the gut and immune homeostasis.",
"The central nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways. Recently, in animal models of sepsis, the vagus nerve (VN) has been proposed to play a crucial role in the regulation of the immune response, also referred to as the cholinergic anti-inflammatory pathway. The VN, through release of acetylcholine, dampens immune cell activation by interacting with α-7 nicotinic acetylcholine receptors. Recent evidence suggests that the vagal innervation of the gastrointestinal tract also plays a major role controlling intestinal immune activation. Indeed, VN electrical stimulation potently reduces intestinal inflammation restoring intestinal homeostasis, whereas vagotomy has the reverse effect. In this review, we will discuss the current understanding concerning the mechanisms and effects involved in the cholinergic anti-inflammatory pathway in the gastrointestinal tract. Deeper investigation on this counter-regulatory neuroimmune mechanism will provide new insights in the cross-talk between the nervous and immune system leading to the identification of new therapeutic targets to treat intestinal immune disease.</AbstractText"
]
] |
23219683
|
The effect of lead exposure on brain iron homeostasis and the expression of DMT1/FP1 in the brain in developing and aged rats.
|
The relation between lead (Pb) and iron (Fe) becomes increasingly concerned because they are both divalent metals that are absorbed by the same intestinal mechanism, and Pb exposure and Fe deficiency in the developmental brain, as well as Fe overload in the aged brain, can cause cognitive deficits. However, the interaction between Pb exposure and Fe status in the brain has not been established. Therefore, in the current study, we examined the effects of maternal ingestion of Pb in drinking water during gestation and lactation on the Fe status and the expression of divalent metal transporter 1 (DMT1) and ferroportin 1 (FP1) in the brain of offspring. The offspring were followed through old age, with measurements taken at postnatal week 3 (PNW3), 41 (PNW41) and 70 (PNW70). Pb exposure increases the Fe content in the old-aged rats' brain, which might be not subjected to DMT1 mediating, but may be associated with the decrease expression of FP1. Furthermore, the effect of Pb on FP1 expression is regulated at transcriptional and posttranscriptional levels. The perturbation in Fe homeostasis may contribute to the neurotoxicology consequences induced by Pb exposure, and FP1 may play a role in Pb-induced Fe cumulation in the brain.</AbstractText
|
[
[
"9526084",
"Category-specific semantic deficits in focal and widespread brain damage: a computational account.",
"Category-specific semantic impairments have been explained in terms of preferential damage to different types of features (e.g., perceptual vs. functional). This account is compatible with cases in which the impairments were the result of relatively focal lesions, as in herpes encephalitis. Recently, however, there have been reports of category-specific impairments associated with Alzheimer's disease, in which there is more widespread, patchy damage. We present experiments with a connectionist model that show how \"category-specific\" impairments can arise in cases of both localized and widespread damage; in this model, types of features are topographically organized, but specific categories are not. These effects mainly depend on differences between categories in the distribution of correlated features. The model's predictions about degree of impairment on natural kinds and artifacts over the course of semantic deterioration are shown to be consistent with existing patient data. The model shows how the probabilistic nature of damage in Alzheimer's disease interacts with the structure of semantic memory to yield different patterns of impairment between patients and categories over time.</AbstractText"
]
] |
[
[
"37539014",
"Quantification of Speech Disfluency as a Marker of Medication-Induced Cognitive Impairment: An Application of Computerized Speech Analysis in Neuropharmacology.",
"We present the results of a study investigating the use of speech and language characteristics extracted from spontaneous spoken discourse to assess changes in cognitive function. Specifically, we investigated the use of automatic speech recognition technology to characterize spontaneous speech disfluency induced by topiramate, an anti-epileptic medication with language-related side-effects. We audio recorded spontaneous speech samples from 20 participants during several picture description tasks and analyzed the recordings automatically and manually to extract a range of spoken fluency measurements including speech discontinuities (e.g., filled pauses, false starts, and repetitions), silent pause duration, speaking rate and vowel lengthening. Our results indicate that some of these paralinguistic speech characteristics are a) sensitive to the effects of topiramate, b) are associated with topiramate concentrations in the blood, and c) complement standard neuropsychological tests typically used to investigate cognitive effects of medications. This work demonstrates the use of computational linguistic tools to assess cognitive effects in a more sensitive, objective and reproducible manner than is currently available with standard tests.</AbstractText"
]
] |
23730352
|
Sleep, neuroengineering and dynamics.
|
Modeling of consciousness-related phenomena and neuroengineering are fields that are rapidly growing together. We review recent approaches and developments and point out some promising directions of future research: Understanding the dynamics of consciousness states and associated oscillations, pathological oscillations as well as their treatment by stimulation, neuroprosthetics and brain-computer-interface approaches, and stimulation approaches that probe, influence and strengthen memory consolidation. In all these fields, computational models connect theory, neurophysiology and neuroengineering research and pave a way towards medical applications.</AbstractText
|
[
[
"20800054",
"Kisspeptins: bridging energy homeostasis and reproduction.",
"Body energy reserves and metabolic state are relevant modifiers of puberty onset and fertility; forms of metabolic stress ranging from persistent energy insufficiency to morbid obesity are frequently linked to reproductive disorders. The mechanisms for such a close connection between energy balance and reproduction have been the subject of considerable attention; however, our understanding of the neurobiological basis for this phenomenon is still incomplete. In mid 1990s, the adipose-hormone, leptin, was proven as an essential signal for transmitting metabolic information onto the centers governing puberty and reproduction; yet, the ultimate mode of action of leptin on GnRH neurons has remained contentious for years. More recently, kisspeptins, a family of neuropeptides encoded by the Kiss1 gene, have emerged as conduits for the metabolic regulation of reproduction and putative effectors of leptin actions on GnRH neurons. This review recapitulates the experimental evidence obtained to date, mostly in laboratory rodents, supporting the function of kisspeptins in bridging energy balance and reproduction, with special emphasis on recent developments in this field, such as the recognition of mTOR (mammalian target of rapamycin) and Crtc1 (Creb1-regulated transcription coactivator-1) as putative mediators for leptin regulation of Kiss1 expression, as well as the identification of other potential metabolic modulators of kisspeptin signaling, such as ghrelin, neuropeptide Y (NPY) and melanin-concentrating hormone (MCH).</AbstractText"
]
] |
[
[
"23166484",
"Functional connectivity and tuning curves in populations of simultaneously recorded neurons.",
"How interactions between neurons relate to tuned neural responses is a longstanding question in systems neuroscience. Here we use statistical modeling and simultaneous multi-electrode recordings to explore the relationship between these interactions and tuning curves in six different brain areas. We find that, in most cases, functional interactions between neurons provide an explanation of spiking that complements and, in some cases, surpasses the influence of canonical tuning curves. Modeling functional interactions improves both encoding and decoding accuracy by accounting for noise correlations and features of the external world that tuning curves fail to capture. In cortex, modeling coupling alone allows spikes to be predicted more accurately than tuning curve models based on external variables. These results suggest that statistical models of functional interactions between even relatively small numbers of neurons may provide a useful framework for examining neural coding.</AbstractText"
]
] |
23576843
|
Possibilities offered by implantable miniaturized cuff-electrodes for insect neurophysiology.
|
Recent advances in microsystems technology led to a miniaturization of cuff-electrodes, which suggests these electrodes not just for long-term neuronal recordings in mammalians, but also in medium-sized insects. In this study we investigated the possibilities offered by cuff-electrodes for neuroethology using insects as a model organism. The implantation in the neck of a tropical bushcricket resulted in high quality extracellular nerve recordings of different units responding to various acoustic, vibratory, optical and mechanical stimuli. In addition, multi-unit nerve activity related to leg movements was recorded in insects walking on a trackball. A drawback of bi-polar nerve recordings obtained during tethered flight was overlay of nerve activity with large amplitude muscle potentials. Interestingly, cuff-electrode recordings were robust to withstand walking and flight activity so that good quality nerve recordings were possible even three days after electrode implantation. Recording multi-unit nerve activity in intact insects required an elaborate spike sorting algorithm in order to discriminate neuronal units responding to external stimuli from background activity. In future, a combination of miniaturized cuff-electrodes and light-weight amplifiers equipped with a wireless transmitter will allow the investigation of neuronal processes underlying natural behavior in freely moving insects. By this means cuff-electrodes may contribute to the development of realistic neuronal models simulating neuronal processes underlying natural insect behavior, such like mate choice and predator avoidance.</AbstractText
|
[
[
"11222789",
"Paraplegin gene analysis in hereditary spastic paraparesis (HSP) pedigrees in northeast England.",
"To identify the frequency and characterize the phenotype of paraplegin mutations in the hereditary spastic paraparesis (HSP) population in the northeast of England.</AbstractText HSP is a disorder that shows both clinical and genetic heterogeneity. To date, 13 loci have been associated with an HSP phenotype, with the causative gene having been identified in four of these. Two autosomal genes have been identified, paraplegin and spastin, and two X-linked genes have been identified, L1CAM (cell adhesion molecule) and proteolipid protein.</AbstractText Thirty HSP pedigrees from the northeast of England were analyzed for mutation in each of the 17 exons of the paraplegin gene.</AbstractText A single family with a paraplegin mutation was identified in which the paraplegin mutation co-segregates with an HSP phenotype in an apparent dominant manner. The authors also describe frequent polymorphism in the paraplegin gene in both the HSP and control populations.</AbstractText Mutations in the paraplegin gene are not a common cause of HSP in the northeast of England. The phenotype of the paraplegin-related HSP family described had several striking features including amyotrophy, raised creatine kinase, sensorimotor peripheral neuropathy, and oxidative phosphorylation defect on muscle biopsy.</AbstractText"
]
] |
[
[
"23252730",
"The physiology of fish behaviour: a selective review of developments over the past 40 years(§).",
"During the past 40 years many new techniques have emerged that have been pivotal in furthering understanding of the physiology of fish behaviour. Behavioural studies have been enhanced by video recording systems and software for computerized event recording analysis, fine scale anatomical studies by fluorescence confocal microscopy, neurophysiological studies by visualisation and neuroendocrinology with techniques for identifying, localizing and quantifying many neurochemicals within the central nervous system. This array of approaches has been complemented by developments in molecular biology that include the ability to monitor expression profiles for known genes in specific neural structures and within the whole transcriptome. This article explores how the deployment of new techniques during the last four decades has advanced the understanding of two extensively studied systems. The first of these is the fast-start escape response, concentrating on work on goldfish Carassius auratus and zebrafish Danio rerio. The second is the link between social experience and neuroendocrinology and how this relates to life-history traits in the cichlid Burton's mouthbrooder Astatotilapia burtoni. These two case studies are then used to explore the extent to which the behaviour of animals can be explained in terms of underlying physiological mechanisms.</AbstractText"
]
] |
23341313
|
Absence of verbal recall or memory for symptom acquisition in fear and trauma exposure: a conceptual case for fear conditioning and learned nonuse in assessment and treatment.
|
Absence of memory or verbal recall for symptom acquisition in fear and trauma exposure, as well as absence of successful coping behavior for life events, is associated with a number of diagnoses, including traumatic brain injury, posttraumatic stress disorder, pain, and anxiety. The difficulty with diagnosis and treatment planning based on the absence of recall, memory, and successful coping behavior is threefold: (1) these assessments do not distinguish between disruption of behavior and lack of capacity, (2) the absence of verbal recall and memory complicates cognitive-based treatment, and (3) a confounding issue is the same absent behavior can be observed at different times and contexts. While memory of the specific details of the initial traumatic event(s) may not be available to verbal report, the existence of time- and context-dependent relationships for the initial as well as subsequent experiences is arguable. The absence of memory or lack of verbal recall does not rule out measurable physiological bodily responses for the initial trauma(s), nor does it help to establish the effects of subsequent experiences for symptom expression. Also, the absence of memory must include the prospect of fear-based learning that does not require or involve the cortex. It is posited that the literatures of fear conditioning and learned nonuse provide complementary illustrations of how the time and context of the initial trauma(s) and subsequent experiences affect behavior, which is not dependent on the effected individual being able to provide a memory-based verbal report. The replicated clinical application demonstrates that, without scientific demonstration, neither neuroanatomy nor verbal report can be assumed sufficient to predict overt behavior or physiologic responses. For example, while commonly assumed to be predictively so, autonomic nervous system innervation is insufficient to define the unique stimulus- and context-dependent physiological responses of an individual. By recording simultaneous physiological responses to the controlled presentation of a context-dependent stimulus, the unique relationships of physiology and overt behaviors for the individual can be demonstrated. Using this process also allows more complex virtual reality or other in vivo stimulus assessments to be incorporated for the development of individually tailored assessments and therapeutic plans. Thus, with or without memory or verbal recall, the use of multiple time- and context-specific simultaneous physiological measures and overt behavior can guide clinical effort as well as serve to objectively assess the ongoing treatment and its outcome.</AbstractText
|
[
[
"21749991",
"Acetazolamide-responsive exercise-induced episodic ataxia associated with a novel homozygous DARS2 mutation.",
"Leukoencephalopathy with brain stem and spinal cord involvement and brain lactate elevation (LBSL) was recently shown to be caused by mutations in the DARS2 gene, encoding a mitochondrial aspartyl-tRNA synthetase. So far, affected individuals were invariably compound heterozygous for two mutations in DARS2, and drug treatments have remained elusive.</AbstractText Prospective 2-year follow-up of the natural history of the main presenting symptoms in a homozygous DARS2 mutation carrier, followed by a 60 day treatment with acetazolamide in two different doses and with two random treatment interruptions.</AbstractText The patient presented with exercise-induced paroxysmal gait ataxia and areflexia as an atypical phenotype associated with a novel homozygous DARS2 mutation. These features showed an excellent dose-dependent, sustained treatment response to a carbonic anhydrase inhibitor. Pathogenic mutations in episodic ataxia genes were excluded, thus making it highly unlikely that this phenotype was because of episodic ataxia as a second disorder besides LBSL.</AbstractText This case demonstrates that DARS2 mutation homozygosity is not lethal, as suggested earlier, but compatible with a rather benign disease course. More importantly, it extends the phenotypic spectrum of LBSL and reveals that at least some DARS2-associated phenotypic features might be readily treatable. However, future observations of paroxsymal ataxia and, possibly, areflexia in other DARS2-mutated patients are warranted to further corroborate our finding that DARS2 mutations can lead to a paroxsymal ataxia phenotype.</AbstractText"
]
] |
[
[
"23176028",
"Iranians' contribution to world literature on neuroscience.",
"The purpose of this study is to analyse Iranian scientific publications in the neuroscience subfields by librarians and neuroscientists, using Science Citation Index Expanded (SCIE) via Web of Science data over the period, 2002-2008.</AbstractText Data were retrieved from the SCIE. Data were collected from the 'subject area' of the database and classified by neuroscience experts into 14 subfields. To identify the citation patterns, we applied the 'impact factor' and the 'number of publication'. Data were also analysed using HISTCITE, Excel 2007 and SPSS.</AbstractText Seven hundred and thirty-four papers have been published by Iranian between 2002 and 2008. Findings showed a growing trend of neuroscience papers in the last 3 years with most papers (264) classified in the neuropharmacology subfield. There were fewer papers in neurohistory, psychopharmacology and artificial intelligence. International contributions of authors were mostly in the neurology subfield, and 'Collaboration Coefficient' for the neuroscience subfields in Iran was 0.686 which is acceptable. Most international collaboration between Iranians and developed countries was from USA. Eighty-seven percent of the published papers were in journals with the impact factor between 0 and 4; 25% of papers were published by the researchers affiliated to Tehran University of Medical Sciences.</AbstractText Progress of neuroscience in Iran is mostly seen in the neuropharmacology and the neurology subfields. Other subfields should also be considered as a research priority by health policymakers. As this study was carried out by the collaboration of librarians and neuroscientists, it has been proved valuable for both librarians and policymakers. This study may be encouraging for librarians from other developing countries.</AbstractText"
]
] |
20360360
|
Introduction of green fluorescent protein (GFP) into hippocampal neurons through viral infection.
|
Expression of green fluorescent protein (GFP), its more fluorescent mutant forms (e.g., EGFP [enhanced GFP]), or their fusion protein derivatives, affords a number of informative possibilities in cellular neuroscience. EGFP is a soluble protein and appears to be homogeneously distributed within the cytosol of neurons when expressed. Thus, it reveals the structure of the neuron, including the cell body, and axonal and dendritic arbors. It is also sufficiently bright to reveal detailed structures such as axonal boutons and dendritic spines. When expressed as a fusion protein, EGFP can provide information about the distribution characteristics of the proteins within neurons. Furthermore, during single-cell electrophysiological studies, such expression can direct the investigator to record from a cell carrying a foreign gene. In this protocol, we describe the use of the Sindbis pseudovirus expression system to deliver GFP to neurons. Sindbis is a member of the alphaviruses, which are plus-stranded RNA viruses. This protocol uses the DH(26S) strain, which preferentially infects neurons over glia (50:1). Two infection methods are given: one for dissociated hippocampal cultured neurons and one for organotypic hippocampal slices.</AbstractText
|
[
[
"11377409",
"Double-blind naltrexone and placebo comparison study in the treatment of pathological gambling.",
"The authors' goal was to assess the efficacy and tolerability of naltrexone in the treatment of pathologic gambling disorder.</AbstractText Eighty-three subjects who met criteria for DSM-IV pathologic gambling disorder were enrolled in a 1-week single-blind placebo lead-in followed by an 11-week double-blind naltrexone or placebo trial. Naltrexone was started at 25 mg/day and titrated upward until maximum symptom improvement or 250 mg/day was achieved. Gambling symptom change was assessed with the patient-rated Clinical Global Impression (PG-CGI-PT), clinician-rated CGI (PG-CGI-MD), and the Gambling Symptom Rating Scale (G-SAS). Side effects were monitored weekly and liver function tests biweekly.</AbstractText Data from 45 patients were analyzed. Using random regression analysis, significant improvement was noted in all three gambling symptom measures: patient-rated Clinical Global Impression, p <.001; clinician-rated CGI, p <.001; Gambling Symptom Rating Scale, p <.019. At study end, 75% of subjects taking naltrexone were much or very much improved on both the PE-CEI PT and the PG-CGI-MD, compared with only 24% of those on placebo. Elevated liver enzymes occurred in four subjects who were taking analgesics concurrently. Nausea was common during the first week of treatment.</AbstractText Results suggest that naltrexone is effective in reducing the symptoms of pathologic gambling. Until further studies corroborate the present findings, our report should be interpreted cautiously.</AbstractText"
]
] |
[
[
"20976129",
"The picture of the linguistic brain: how sharp can it be? Reply to Fedorenko & Kanwisher.",
"What is the best way to learn how the brain analyzes linguistic input? Two popular methods have attempted to segregate and localize linguistic processes: analyses of language deficits subsequent to (mostly focal) brain disease, and functional Magnetic Resonance Imaging (fMRI) in health. A recent Compass article by Fedorenko and Kanwisher (FK, 2009) observes that these methods group together data from many individuals through methods that rely on variable anatomical landmarks, and that results in a murky picture of how language is represented in the brain. To get around the variability problem, FK propose to import into neurolinguistics a method that has been successfully used in vision research - one that locates functional Regions Of Interest (fROIs) in each individual brain.In this note, I propose an alternative perspective. I first take issue with FK's reading of the literature. I point out that, when the neurolinguistic landscape is examined with the right linguistic spectacles, the emerging picture - while intriguingly complex - is not murky, but rather, stable and clear, parsing the linguistic brain into functionally and anatomically coherent pieces. I then examine the potential value of the method that FK propose, in light of important micro-anatomical differences between language and high-level vision areas, and conclude that as things stand the method they propose is not very likely to bear much fruit in neurolinguistic research.</AbstractText"
]
] |
20419352
|
Blue moon neurovirology: the merits of studying rare CNS diseases of viral origin.
|
While measles virus (MV) continues to have a significant impact on human health, causing 150,000-200,000 deaths worldwide each year, the number of fatalities that can be attributed to MV-triggered central nervous system (CNS) diseases are on the order of a few hundred individuals annually (World Health Organization 2009). Despite this modest impact, substantial effort has been expended to understand the basis of measles-triggered neuropathogenesis. What can be gained by studying such a rare condition? Simply stated, the wealth of studies in this field have revealed core principles that are relevant to multiple neurotropic pathogens, and that inform the broader field of viral pathogenesis. In recent years, the emergence of powerful in vitro systems, novel animal models, and reverse genetics has enabled insights into the basis of MV persistence, the complexity of MV interactions with neurons and the immune system, and the role of immune and CNS development in virus-triggered disease. In this review, we highlight some key advances, link relevant measles-based studies to the broader disciplines of neurovirology and viral pathogenesis, and propose future areas of study for the field of measles-mediated neurological disease.</AbstractText
|
[
[
"942927",
"Morphine suppression of ethanol withdrawal in mice.",
"The acute administration of morphine, alcohol or dopamine results in a pronounced suppression of the convulsions produced by alcohol in mice. The suppressive action of morphine on alcohol withdrawal in the mouse apparently is not a product of morphine intoxication, but rather to some other specific interaction between alcohol and morphine in the central nervous system. The conclusion suggest that dopamine may play a significant role as a modulator in convulsions produced during alcohol withdrawal.</AbstractText"
]
] |
[
[
"20826300",
"Neuroscience and education: an ideal partnership for producing evidence-based solutions to Guide 21(st) Century Learning.",
"Neuro-Education is a nascent discipline that seeks to blend the collective fields of neuroscience, psychology, cognitive science, and education to create a better understanding of how we learn and how this information can be used to create more effective teaching methods, curricula, and educational policy. Though still in its infancy as a research discipline, this initiative is already opening critical new dialog between teachers, administrators, parents, and brain scientists.</AbstractText"
]
] |
20739175
|
Micro-scale and microfluidic devices for neurobiology.
|
The precise spatial and temporal control afforded by microfluidic devices make them uniquely suited as experimental tools for cellular neuroscience. Micro-structures have been developed to direct the placement of cells and small organisms within a device. Microfluidics can precisely define pharmacological microenvironments, mimicking conditions found in vivo with the advantage of defined parameters which are usually difficult to control and manipulate in vivo. These devices are compatible with high-resolution microscopy, are simple to assemble, and are reproducible. In this review we will focus on microfluidic devices that have recently been developed for small, whole organisms such as C. elegans and dissociated cultured neurons. These devices have improved control over the placement of cells or organisms and allowed unprecedented experimental access, enabling novel investigations in neurobiology.</AbstractText
|
[
[
"20665248",
"Developmental changes in the expression of kisspeptin mRNA in rat hypothalamus.",
"Kisspeptin is a family of neuropeptides and the natural ligands of G protein-coupled receptor (GPR)-54. Kisspeptin/GPR-54 system is known to play a pivotal role in puberty onset and in the regulation of reproductive functions. To clarify the postnatal ontogeny of kisspeptin neurons in rat hypothalamus, we analyzed the expression patterns of kisspeptin mRNA from neonate to adult by in situ hybridization. In anteroventral periventricular nucleus (AVPV), kisspeptin mRNA were first detected at postnatal day (PND) 7 and postnatal week 3 in males and females, respectively, and the number of kisspeptin mRNA-expressing neurons increased during development in both sexes. In the arcuate nucleus (ARC), kisspeptin mRNA was present from PND3. In males, the number of kisspeptin mRNA-expressing neurons gradually increased during development. In females, the number of kisspeptin mRNA-expressing neurons in neonates was greater than in males; it significantly decreased at juvenile stages and then increased toward adulthood. These results indicate that the increase in kisspeptin mRNA expression in ARC across puberty might be involved in the onset of puberty. We also demonstrate that the kisspeptin mRNA-expressing neurons in ARC appear earlier than those in AVPV and show clear sex differences in their numbers during neonatal period.</AbstractText"
]
] |
[
[
"20802854",
"Optical mapping of release properties in synapses.",
"Synapses are important functional units that determine how information flows through the brain. Understanding their biophysical properties and the molecules that underpin them is an important goal of cellular neuroscience. Thus, it is of interest to develop protocols that allow easy measurement of synaptic parameters in model systems that permit molecular manipulations. Here, we used a sensitive and high-time resolution optical approach that allowed us to characterize two functional parameters critical to presynaptic efficacy: vesicle fusion probability (Pv) and readily-releasable pool size (RRP). We implemented two different approaches to determine the RRP size that were in broad agreement: depletion of the RRP by high-frequency stimulation and saturation of the calcium sensor during single action potential stimuli. Our methods are based on reporters that provide a robust, quantitative, purely presynaptic readout and present a new avenue to study molecules that affect synaptic vesicle exocytosis.</AbstractText"
]
] |
23666281
|
[What can microscopy teach us on suicide?].
|
The fine neuroanatomy of mood disorders and suicide is a relatively recent field of investigation. Together with neuroimaging, molecular biology and biochemistry, histological analyses of post-mortem brain regions implicated in mood regulation allow gaining a better understanding of the cellular and molecular mechanisms underlying major depression and suicide. In this article, the author discusses recent studies conducted in his laboratory on the fine neuroanatomy of the anterior cingular cortex (ACC). In particular, he presents data showing that ACC white matter fibrous astrocytes are hypertrophic in depressed suicides compared to matched sudden-death controls. These data are interpreted in the context of the neuroimmune hypothesis of major depression and suicide.</AbstractText
|
[
[
"21312401",
"Functional brain imaging in schizophrenia: selected results and methods.",
"Functional brain imaging studies of patients with schizophrenia may be grouped into those that assume that the signs and symptoms of schizophrenia are due to disordered circuitry within a critical brain region and studies that assume that the signs and symptoms are due to disordered connections among brain regions. Studies have investigated the disordered functional brain anatomy of both the positive and negative symptoms of schizophrenia. Studies of spontaneous hallucinations find that although hallucinations are associated with abnormal brain activity in primary and secondary sensory areas, disordered brain activation associated with hallucinations is not limited to sensory systems. Disordered activation in non-sensory regions appear to contribute to the emotional strength and valence of hallucinations, to be a factor underlying an inability to distinguish ongoing mental processing from memories, and to reflect the brain's attempt to modulate the intensity of hallucinations and resolve conflicts with other processing demands. Brain activation studies support the view that auditory/verbal hallucinations are associated with an impaired ability of internal speech plans to modulate neural activation in sensory language areas. In early studies, negative symptoms of schizophrenia were hypothesized to be associated with impaired function in frontal brain areas. In support of this hypothesis meta-analytical studies have found that resting blood flow or metabolism in frontal cortex is reduced in schizophrenia, though the magnitude of the effect is only small to moderate. Brain activation studies of working memory (WM) functioning are typically associated with large effect sizes in the frontal cortex, whereas studies of functions other than WM generally reveal smaller effects. Findings from some functional connectivity studies have supported the hypothesis that schizophrenia patients experience impaired functional connections between frontal and temporal cortex, although the nature of the disordered connectivity is complex. More recent studies have used functional brain imaging to study neural compensation in schizophrenia, to serve as endophenotypes in genetic studies and to provide biomarkers in drug development studies. These emerging trends in functional brain imaging research are likely to help stimulate the development of a general neurobiological theory of the complex symptoms of schizophrenia.</AbstractText"
]
] |
[
[
"22905274",
"Toxocariasis and epilepsy: systematic review and meta-analysis.",
"Human toxocariasis is a zoonotic infection caused by the larval stages of Toxocara canis (T. canis) and less frequently Toxocara cati (T. cati). A relationship between toxocariasis and epilepsy has been hypothesized. We conducted a systematic review and a meta-analysis of available data to evaluate the strength of association between epilepsy and Toxocara spp. seropositivity and to propose some guidelines for future surveys.</AbstractText Electronic databases, the database from the Institute of Neuroepidemiology and Tropical Neurology of the University of Limoges (http://www-ient.unilim.fr/) and the reference lists of all relevant papers and books were screened up to October 2011.</AbstractText We performed a systematic review of literature on toxocariasis (the exposure) and epilepsy (the outcome). Two authors independently assessed eligibility and study quality and extracted data. A common odds ratio (OR) was estimated using a random-effects meta-analysis model of aggregated published data.</AbstractText Seven case-control studies met the inclusion criteria, for a total of 1867 participants (850 cases and 1017 controls). The percentage of seropositivity (presence of anti-Toxocara spp. antibodies) was higher among people with epilepsy (PWE) in all the included studies even if the association between epilepsy and Toxocara spp. seropositivity was statistically significant in only 4 studies, with crude ORs ranging 2.04-2.85. Another study bordered statistical significance, while in 2 of the included studies no significant association was found. A significant (p < 0.001) common OR of 1.92 [95% confidence interval (CI) 1.50-2.44] was estimated. Similar results were found when meta-analysis was restricted to the studies considering an exclusively juvenile population and to surveys using Western Blot as confirmatory or diagnostic serological assay.</AbstractText Our results support the existence of a positive association between Toxocara spp. seropositivity and epilepsy. Further studies, possibly including incident cases, should be performed to better investigate the relationship between toxocariasis and epilepsy.</AbstractText"
]
] |
23110153
|
Prediction of muscle activities from electrocorticograms in primary motor cortex of primates.
|
Electrocorticography (ECoG) has drawn attention as an effective recording approach for brain-machine interfaces (BMI). Previous studies have succeeded in classifying movement intention and predicting hand trajectories from ECoG. Despite such successes, however, there still remains considerable work for the realization of ECoG-based BMIs as neuroprosthetics. We developed a method to predict multiple muscle activities from ECoG measurements. We also verified that ECoG signals are effective for predicting muscle activities in time varying series when performing sequential movements. ECoG signals were band-pass filtered into separate sensorimotor rhythm bands, z-score normalized, and smoothed with a Gaussian filter. We used sparse linear regression to find the best fit between frequency bands of ECoG and electromyographic activity. The best average correlation coefficient and the normalized root-mean-square error were 0.92±0.06 and 0.06±0.10, respectively, in the flexor digitorum profundus finger muscle. The δ (1.5∼4Hz) and γ2 (50∼90Hz) bands contributed significantly more strongly than other frequency bands (P<0.001). These results demonstrate the feasibility of predicting muscle activity from ECoG signals in an online fashion.</AbstractText
|
[
[
"12716950",
"Hierarchical processing in spoken language comprehension.",
"Understanding spoken language requires a complex series of processing stages to translate speech sounds into meaning. In this study, we use functional magnetic resonance imaging to explore the brain regions that are involved in spoken language comprehension, fractionating this system into sound-based and more abstract higher-level processes. We distorted English sentences in three acoustically different ways, applying each distortion to varying degrees to produce a range of intelligibility (quantified as the number of words that could be reported) and collected whole-brain echo-planar imaging data from 12 listeners using sparse imaging. The blood oxygenation level-dependent signal correlated with intelligibility along the superior and middle temporal gyri in the left hemisphere and in a less-extensive homologous area on the right, the left inferior frontal gyrus (LIFG), and the left hippocampus. Regions surrounding auditory cortex, bilaterally, were sensitive to intelligibility but also showed a differential response to the three forms of distortion, consistent with sound-form-based processes. More distant intelligibility-sensitive regions within the superior and middle temporal gyri, hippocampus, and LIFG were insensitive to the acoustic form of sentences, suggesting more abstract nonacoustic processes. The hierarchical organization suggested by these results is consistent with cognitive models and auditory processing in nonhuman primates. Areas that were particularly active for distorted speech conditions and, thus, might be involved in compensating for distortion, were found exclusively in the left hemisphere and partially overlapped with areas sensitive to intelligibility, perhaps reflecting attentional modulation of auditory and linguistic processes.</AbstractText"
]
] |
[
[
"23237463",
"Interactions between tactile and proprioceptive representations in haptics.",
"Neuroprosthetic limbs, regardless of their sophisticated motor control, require sensory feedback to viably interact with the environment. Toward that aim, the authors examined interrelationships between tactile and proprioceptive sensations. Through human psychophysics experiments, they evaluated error patterns of subjects estimating hand location in a horizontal 2-dimensional workspace under 3 tactile conditions. While tactile cues did not significantly affect the structure of the pattern of errors, touching the workspace reduced estimation errors. During neurophysiological experiments, a macaque grasped textured objects using 2 hand postures. Sensory coding showed dependence on both roughness of the manipulandum and posture. In summary, the authors suggest that tactile sensations underlying haptics are processed in a stable spatial reference frame provided by a proprioceptive system, and that tactile and proprioceptive inputs can be encoded simultaneously by individual cells. Such insights will be useful for providing stable, adaptive sensory feedback for neuroprosthetics.</AbstractText"
]
] |
23853342
|
HermesD: A High-Rate Long-Range Wireless Transmission System for Simultaneous Multichannel Neural Recording Applications.
|
HermesD is a high-rate, low-power wireless transmission system to aid research in neural prosthetic systems for motor disabilities and basic motor neuroscience. It is the third generation of our "Hermes systems" aimed at recording and transmitting neural activity from brain-implanted electrode arrays. This system supports the simultaneous transmission of 32 channels of broadband data sampled at 30 ks/s, 12 b/sample, using frequency-shift keying modulation on a carrier frequency adjustable from 3.7 to 4.1 GHz, with a link range extending over 20 m. The channel rate is 24 Mb/s and the bit stream includes synchronization and error detection mechanisms. The power consumption, approximately 142 mW, is low enough to allow the system to operate continuously for 33 h, using two 3.6-V/1200-mAh Li-SOCl2 batteries. The transmitter was designed using off-the-shelf components and is assembled in a stack of three 28 mm ? 28-mm boards that fit in a 38 mm ? 38 mm ? 51-mm aluminum enclosure, a significant size reduction over the initial version of HermesD. A 7-dBi circularly polarized patch antenna is used as the transmitter antenna, while on the receiver side, a 13-dBi circular horn antenna is employed. The advantages of using circularly polarized waves are analyzed and confirmed by indoor measurements. The receiver is a stand-alone device composed of several submodules and is interfaced to a computer for data acquisition and processing. It is based on the superheterodyne architecture and includes automatic frequency control that keeps it optimally tuned to the transmitter frequency. The HermesD communications performance is shown through bit-error rate measurements and eye-diagram plots. The sensitivity of the receiver is -83 dBm for a bit-error probability of 10(-9). Experimental recordings from a rhesus monkey conducting multiple tasks show a signal quality comparable to commercial acquisition systems, both in the low-frequency (local field potentials) and upper-frequency bands (action potentials) of the neural signals. This system can be easily scaled up in terms of the number of channels and data rate to accommodate future generations of Hermes systems.</AbstractText
|
[
[
"23493966",
"Exploring sensory neuroscience through experience and experiment.",
"Many phenomena that we take for granted are illusions - color and motion on a TV or computer monitor, for example, or the impression of space in a stereo music recording. Even the stable image that we perceive when looking directly at the real world is illusory. One of the important lessons from sensory neuroscience is that our perception of the world is constructed rather than received. Sensory illusions effectively capture student interest, but how do you then move on to substantive discussion of neuroscience? This article illustrates several illusions, attempts to connect them to neuroscience, and shows how students can explore and experiment with them. Even when (as is often the case) there is no agreed-upon mechanistic explanation for an illusion, students can form hypotheses and test them by manipulating stimuli and measuring their effects. In effect, students can experiment with illusions using themselves as subjects.</AbstractText"
]
] |
[
[
"20377146",
"Saccadic peak velocity sensitivity to variations in mental workload.",
"For research and applications in the field of (neuro)ergonomics, it is of increasing importance to have reliable methods for measuring mental workload. In the present study we examined the hypothesis that saccadic eye movements can be used for an online assessment of mental workload.</AbstractText Saccadic main sequence (amplitude, duration and peak velocity) was used as a diagnostic measure of mental workload in a virtual driving task with three complexity levels. We tested 18 drivers in the SIRCA driving simulator while their eye movements were recorded. The Wickens' multiple resources model was used as theoretical framework. Changes in mental workload between the complexity levels were evaluated multidimensionally, using subjective rating, performance in a secondary task, and other behavioral indices.</AbstractText Saccadic peak velocity decreased (7.2 visual degrees/s) as the mental workload increased, as measured by scores of mental workload test (15.2 scores) and the increase of the reaction time on the secondary task (46 ms).</AbstractText Saccadic peak velocity is affected by variations in mental workload during ecologically valid tasks. We conclude that saccadic peak velocity could be a useful diagnostic index for the assessment of operators' mental workload and attentional state in hazardous environments.</AbstractText"
]
] |
23494679
|
Electroretinograms in Drosophila: a robust and genetically accessible electrophysiological system for the undergraduate laboratory.
|
Laboratory courses in neurophysiology fulfill a critical need for inquiry-based training in undergraduate programs in neuroscience and biology. These courses typically use classical electrophysiological preparations to explore the basic features of neuronal function. However, current neuroscience research also focuses on elucidating the molecular and genetic mechanisms of neuronal function, using model systems that include mutant and transgenic animals. To bridge laboratory training in neurophysiology with modern molecular genetics, we describe a teaching model based on electroretinography of the fruit fly Drosophila melanogaster, a long-established model system for basic neuroscience research. Drosophila are easily maintained, economical, and have hundreds of neurophysiologically relevant mutant strains and genetic tools readily available. The Drosophila electroretinogram (ERG) is a simple and accessible extracellular recording of a neural signal in the fly eye in response to flashes of light. The signal is multifaceted and the response is sensitive to stimulation parameters such as intensity, duration and wavelength, thus forming a rich source of analysis for students. Most importantly, different mutations affecting key components of intracellular signaling, synaptic transmission or neuronal function can affect the ERG waveform in characteristic ways. Recording wild type and mutant ERGs allows students to examine firsthand the connection between genetics, biochemical pathways, and electrophysiology. This neurophysiology laboratory course can facilitate and enhance an understanding of the cellular and molecular contributions to neurophysiological recordings.</AbstractText
|
[
[
"19669582",
"Monitoring health implications of pesticide exposure in factory workers in Pakistan.",
"The study aimed to determine the hazardous health effects of pesticides exposure in the factory workers by measuring plasma cholinesterase (PChE), pesticides residues, and renal and hepatic biochemical markers. In addition, we also assessed the knowledge, attitudes, and safety practices adopted by the industrial workers. The study was conducted in three different sizes of factories located in Lahore (large), Multan (medium), and Karachi (small) in Pakistan. Total 238 adult males consisting of 184 pesticide industrial workers (exposed group) from large-sized (67), medium-sized (61), small-sized (56) industrial formulation factories, and 54 controls (unexposed) were included in the study. All the participants were male of aged 18 to 58 years. PChE levels were estimated by Ellmann's method. Plasma pesticides residue analysis was performed by using reverse phase C-18 on high-performance liquid chromatograph and GC with NPD detector. Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, urea, and gamma glutamyltransferase (GGT) were measured on Selectra E auto analyzer. Plasma and C-reactive protein was analyzed by Immulite 1000. The results revealed a significant decrease in plasma post exposure PChE levels (<30%) as compared to baseline in the workers of small (29%) and medium (8%) industrial units (p < 0.001). Plasma cypermethrin, endosulfan, imidacloprid, thiodicarb, carbofuran, and methamidophos levels were found to be higher than allowable daily intake. Serum AST, ALT, creatinine GGT, malondialdehyde, total antioxidant, and CRP were significantly raised among the workers of small and medium pesticide formulation factories as compared to large industrial unit and controls (p < 0.001). The study demonstrated that unsafe practices among small- and medium-sized pesticides industrial workers cause significant increase in pesticide exposure, oxidative stress, and derangement of hepatic and renal function.</AbstractText"
]
] |
[
[
"23671950",
"Effect of head circumference on parameters of pattern reversal visual evoked potential in healthy adults of central India.",
"Visual evoked response testing has been one of the most exciting clinical tools to be developed from neurophysiologic research in recent years and has provided us with an objective method of identifying abnormalities of the afferent visual pathways. Investigation were carried out to see whether the head circumference influence the pattern reversal visual evoked potential (PRVEP) parameters. The study comprised of pattern reversal visual evoked potential (PRVEP) recordings in 400 eyes of 200 normal subjects. Two hundred fourty eight eyes were males and 152 eyes were from 76 female subjects recruited from the Central Indian population in the age range of 40-79 years. Visual evoked potential (VEP) recordings were performed in accordance to the standardized methodology of International Federation of Clinical Neurophysiology (IFCN) Committee Recommendations and International Society for Clinical Electrophysiology of Vision (ISCEV) Guidelines and montages were kept as per 10-20 International System of EEG Electrode placements. The stimulus configuration in this study consisted of the transient pattern reversal method in which a black and white checker board was generated (full field) and displayed on a VEP Monitor by an electronic pattern regenerator inbuilt in an Evoked Potential Recorder (RMS EMG EP MARK II). VEP latencies, duration and amplitude were measured in all subjects and the data were analyzed. The correlation of all the electrophysiological parameters with head circumference was evaluated by Pearson's correlation co-efficient (r) and its statistical significance was evaluated. The prediction equations for all the VEP parameters with respect to head circumference were derived. We found a positive correlation of P 100 latency and N 155 latency with mean head circumference, while a highly significant negative correlation were noted of P 100 amplitude with head circumference. N 70 latency was significantly correlated with head circumference. P 100 duration showed in negative correlation with head circumference. These findings suggest that VEP latencies, duration and amplitude are influenced by the head circumference of the individual in a sample of healthy subjects and head circumference can be a useful predictor of VEP peak latencies, amplitude and duration.</AbstractText"
]
] |
25419230
|
Improving Executive Function and its Neurobiological Mechanisms through a Mindfulness-Based Intervention: Advances within the Field of Developmental Neuroscience.
|
Poor executive function (EF) has been associated with a host of short- and long-term problems across the lifespan, including elevated rates of attention deficit hyperactivity disorder, depression, drug abuse, and antisocial behavior. Mindfulness-based interventions that focus on increasing awareness of one's thoughts, emotions, and actions have been shown to improve specific aspects of EF, including attention, cognitive control, and emotion regulation. In this article, we apply a developmental neuroscience perspective to review research relevant to one specific mindfulness-based intervention, Integrative Body-Mind Training (IBMT). Randomized controlled trials of IBMT indicate improvements in specific EF components, and uniquely highlight the role of neural circuitry specific to the anterior cingulate cortex (ACC) and the autonomic nervous system (ANS) as two brain-based mechanisms that underlie IBMT-related improvements. The relevance of improving specific dimensions of EF through short-term IBMT to prevent a cascade of risk behaviors for children and adolescents is described and future research directions are proposed.</AbstractText
|
[
[
"23017085",
"The maps problem and the mapping problem: two challenges for a cognitive neuroscience of speech and language.",
"Research on the brain basis of speech and language faces theoretical and empirical challenges. Most current research, dominated by imaging, deficit-lesion, and electrophysiological techniques, seeks to identify regions that underpin aspects of language processing such as phonology, syntax, or semantics. The emphasis lies on localization and spatial characterization of function. The first part of the paper deals with a practical challenge that arises in the context of such a research programme. This maps problem concerns the extent to which spatial information and localization can satisfy the explanatory needs for perception and cognition. Several areas of investigation exemplify how the neural basis of speech and language is discussed in those terms (regions, streams, hemispheres, networks). The second part of the paper turns to a more troublesome challenge, namely how to formulate the formal links between neurobiology and cognition. This principled problem thus addresses the relation between the primitives of cognition (here speech, language) and neurobiology. Dealing with this mapping problem invites the development of linking hypotheses between the domains. The cognitive sciences provide granular, theoretically motivated claims about the structure of various domains (the \"cognome\"); neurobiology, similarly, provides a list of the available neural structures. However, explanatory connections will require crafting of computationally explicit linking hypotheses at the right level of abstraction. For both the practical maps problem and the principled mapping problem, developmental approaches and evidence can play a central role in the resolution.</AbstractText"
]
] |
[
[
"23505339",
"Baby Steps to Superintelligence: Neuroprosthetics and Children.",
"Children surviving neural injuries face challenges not seen by their adult counterparts, namely that they experience neural injury before reaching neurodevelopmental maturity. Neural prostheses offer one possible path to recovery, along with the potential for functional outcomes that could exceed expectations. Although the first cochlear implant was placed more than fifty years ago, the field of neuroprosthetics is still relatively young. Several types of neural prostheses are in development stages ranging from animal models to (adult) human trials. In this paper, I discuss how neural prostheses may assist recovery for children surviving neural injury. I argue that approaching the use of neural prosthetics in children with considerations derived from transhumanism alongside traditional bioethics can provide an opportunity to reframe adult-focused ethics toward a child/family focus and to strip away the prejudicial metaphor of cyborgization.</AbstractText"
]
] |
23137683
|
Behavioral neuroscience: learning to suckle with signature odor.
|
A new study in mice reveals that an apparently innate behavior, suckling, is triggered not by a classical pheromone but by the pup learning the complex signature odor of its mother.</AbstractText
|
[
[
"17947337",
"Word-finding difficulty: a clinical analysis of the progressive aphasias.",
"The patient with word-finding difficulty presents a common and challenging clinical problem. The complaint of 'word-finding difficulty' covers a wide range of clinical phenomena and may signify any of a number of distinct pathophysiological processes. Although it occurs in a variety of clinical contexts, word-finding difficulty generally presents a diagnostic conundrum when it occurs as a leading or apparently isolated symptom, most often as the harbinger of degenerative disease: the progressive aphasias. Recent advances in the neurobiology of the focal, language-based dementias have transformed our understanding of these processes and the ways in which they breakdown in different diseases, but translation of this knowledge to the bedside is far from straightforward. Speech and language disturbances in the dementias present unique diagnostic and conceptual problems that are not fully captured by classical models derived from the study of vascular and other acute focal brain lesions. This has led to a reformulation of our understanding of how language is organized in the brain. In this review we seek to provide the clinical neurologist with a practical and theoretical bridge between the patient presenting with word-finding difficulty in the clinic and the evidence of the brain sciences. We delineate key illustrative speech and language syndromes in the degenerative dementias, compare these syndromes with the syndromes of acute brain damage, and indicate how the clinical syndromes relate to emerging neurolinguistic, neuroanatomical and neurobiological insights. We propose a conceptual framework for the analysis of word-finding difficulty, in order both better to define the patient's complaint and its differential diagnosis for the clinician and to identify unresolved issues as a stimulus to future work.</AbstractText"
]
] |
[
[
"22284580",
"Christfried Jakob's late views (1930-1949) on the psychogenetic function of the cerebral cortex and its localization: culmination of the neurophilosophical thought of a keen brain observer.",
"This article follows the culmination of the scientific thought of the neurobiologist Christfried Jakob (1866-1956) during the later part of his career, based on publications from 1930 to 1949, when he was between 64 and 83 years of age. Jakob emphasized the necessity of bridging philosophy to the biological sciences, neurobiology in particular. Thus, we consider him as one of the early protagonists in the emergence of neurophilosophy in the 20th century. The topics that occupied his mind were the foundations for a future philosophy of the brain, and the 'neurobiogenetic', 'neurodynamic', and 'neuropsychogenetic' problems in relation to how consciousness emerges. Jakob's views have many elements in common with great thinkers of philosophy and psychology, including Immanuel Kant, William James, Edmund Husserl, Henri Bergson, Jean Piaget and Willard Quine. A common denominator can also be discerned between Jakob's dynamic approach and certain aspects of cybernetics and neurophenomenology. Jakob propounded the interdisciplinarity of sciences as an indispensable tool for ultimately solving the enigma of consciousness.</AbstractText"
]
] |
23010511
|
Transcriptome analysis of Drosophila CNS midline cells reveals diverse peptidergic properties and a role for castor in neuronal differentiation.
|
One of the key aspects of neuronal differentiation is the array of neurotransmitters and neurotransmitter receptors that each neuron possesses. One important goal of developmental neuroscience is to understand how these differentiated properties are established during development. In this paper, we use fluorescence activated cell sorting and RNA-seq to determine the transcriptome of the Drosophila CNS midline cells, which consist of a small number of well-characterized neurons and glia. These data revealed that midline cells express 9 neuropeptide precursor genes, 13 neuropeptide receptor genes, and 31 small-molecule neurotransmitter receptor genes. In situ hybridization and high-resolution confocal analyses were carried-out to determine the midline cell identity for these neuropeptides and the neuropeptide receptors. The results revealed a surprising level of diversity. Neuropeptide genes are expressed in a variety of midline cell types, including motoneurons, GABAergic interneurons, and midline glia. These data revealed previously unknown functional differences among the highly-related iVUM neurons. There also exist segmental differences in expression for the same neuronal sub-type. Similar experiments on midline-expressed neuropeptide receptor genes reveal considerable diversity in synaptic inputs. Multiple receptor types were expressed in midline interneurons and motoneurons, and, in one case, link feeding behavior to gut peristalsis and locomotion. There were also segmental differences, variations between the 3 iVUMs, and three hormone receptor genes were broadly expressed in most midline cells. The Drosophila Castor transcription factor is present at high levels in iVUM5, which is both GABAergic and expresses the short neuropeptide F precursor gene. Genetic and misexpression experiments indicated that castor specifically controls expression of the short neuropeptide F precursor gene, but does not affect iVUM cell fate or expression of Gad1. This indicates a novel function for castor in regulating neuropeptide gene expression.</AbstractText
|
[
[
"18457512",
"Timing, storage, and comparison of stimulus duration engage discrete anatomical components of a perceptual timing network.",
"The temporal discrimination paradigm requires subjects to compare the duration of a probe stimulus to that of a sample previously stored in working or long-term memory, thus providing an index of timing that is independent of a motor response. However, the estimation process itself comprises several component cognitive processes, including timing, storage, retrieval, and comparison of durations. Previous imaging studies have attempted to disentangle these components by simply measuring brain activity during early versus late scanning epochs. We aim to improve the temporal resolution and precision of this approach by using rapid event-related functional magnetic resonance imaging to time-lock the hemodynamic response to presentation of the sample and probe stimuli themselves. Compared to a control (color-estimation) task, which was matched in terms of difficulty, sustained attention, and motor preparation requirements, we found selective activation of the left putamen for the storage (\"encoding\") of stimulus duration into working memory (WM). Moreover, increased putamen activity was linked to enhanced timing performance, suggesting that the level of putamen activity may modulate the depth of temporal encoding. Retrieval and comparison of stimulus duration in WM selectively activated the right superior temporal gyrus. Finally, the supplementary motor area was equally active during both sample and probe stages of the task, suggesting a fundamental role in timing the duration of a stimulus that is currently unfolding in time.</AbstractText"
]
] |
[
[
"23355814",
"What is social about social perception research?",
"A growing consensus in social cognitive neuroscience holds that large portions of the primate visual brain are dedicated to the processing of social information, i.e., to those aspects of stimuli that are usually encountered in social interactions such as others' facial expressions, actions, and symbols. Yet, studies of social perception have mostly employed simple pictorial representations of conspecifics. These stimuli are social only in the restricted sense that they physically resemble objects with which the observer would typically interact. In an equally important sense, however, these stimuli might be regarded as \"non-social\": the observer knows that they are viewing pictures and might therefore not attribute current mental states to the stimuli or might do so in a qualitatively different way than in a real social interaction. Recent studies have demonstrated the importance of such higher-order conceptualization of the stimulus for social perceptual processing. Here, we assess the similarity between the various types of stimuli used in the laboratory and object classes encountered in real social interactions. We distinguish two different levels at which experimental stimuli can match social stimuli as encountered in everyday social settings: (1) the extent to which a stimulus' physical properties resemble those typically encountered in social interactions and (2) the higher-level conceptualization of the stimulus as indicating another person's mental states. We illustrate the significance of this distinction for social perception research and report new empirical evidence further highlighting the importance of mental state attribution for perceptual processing. Finally, we discuss the potential of this approach to inform studies of clinical conditions such as autism.</AbstractText"
]
] |
22807662
|
Coding conspecific identity and motion in the electric sense.
|
Interactions among animals can result in complex sensory signals containing a variety of socially relevant information, including the number, identity, and relative motion of conspecifics. How the spatiotemporal properties of such evolving naturalistic signals are encoded is a key question in sensory neuroscience. Here, we present results from experiments and modeling that address this issue in the context of the electric sense, which combines the spatial aspects of vision and touch, with the temporal aspects of audition. Wave-type electric fish, such as the brown ghost knifefish, Apteronotus leptorhynchus, used in this study, are uniquely identified by the frequency of their electric organ discharge (EOD). Multiple beat frequencies arise from the superposition of the EODs of each fish. We record the natural electrical signals near the skin of a "receiving" fish that are produced by stationary and freely swimming conspecifics. Using spectral analysis, we find that the primary beats, and the secondary beats between them ("beats of beats"), can be greatly influenced by fish swimming; the resulting motion produces low-frequency envelopes that broaden all the beat peaks and reshape the "noise floor". We assess the consequences of this motion on sensory coding using a model electroreceptor. We show that the primary and secondary beats are encoded in the afferent spike train, but that motion acts to degrade this encoding. We also simulate the response of a realistic population of receptors, and find that it can encode the motion envelope well, primarily due to the receptors with lower firing rates. We discuss the implications of our results for the identification of conspecifics through specific beat frequencies and its possible hindrance by active swimming.</AbstractText
|
[
[
"21731699",
"Recognition of 5-hydroxymethylcytosine by the Uhrf1 SRA domain.",
"Recent discovery of 5-hydroxymethylcytosine (5hmC) in genomic DNA raises the question how this sixth base is recognized by cellular proteins. In contrast to the methyl-CpG binding domain (MBD) of MeCP2, we found that the SRA domain of Uhrf1, an essential factor in DNA maintenance methylation, binds 5hmC and 5-methylcytosine containing substrates with similar affinity. Based on the co-crystal structure, we performed molecular dynamics simulations of the SRA:DNA complex with the flipped cytosine base carrying either of these epigenetic modifications. Our data indicate that the SRA binding pocket can accommodate 5hmC and stabilizes the flipped base by hydrogen bond formation with the hydroxyl group.</AbstractText"
]
] |
[
[
"22922354",
"Selective interactions of spinophilin with the C-terminal domains of the δ- and μ-opioid receptors and G proteins differentially modulate opioid receptor signaling.",
"Previous studies have shown that the intracellular domains of opioid receptors serve as platforms for the formation of a multi-component signaling complex consisting of various interacting partners (Leontiadis et al., 2009, Cell Signal. 21, 1218-1228; Georganta et al., 2010, Neuropharmacology, 59(3), 139-148). In the present study we demonstrate that spinophilin a dendritic-spine enriched scaffold protein associates with δ- and μ-opioid receptors (δ-ΟR, μ-OR) constitutively in HEK293 an interaction that is altered upon agonist administration and enhanced upon forskolin treatment for both μ-OR and δ-ΟR. Spinophilin association with the opioid receptors is mediated via the third intracellular loop and a conserved region of the C-terminal tails. The portion of spinophilin responsible for interaction with the δ-OR and μ-OR is narrowed to a region encompassing amino acids 151-444. Spinophilin, RGS4, Gα and Gβγ subunits of G proteins form a multi-protein complex using specific regions of spinophilin and a conserved amino acid stretch of the C-terminal tails of both δ-μ-ORs. Expression of spinophilin in HEK293 cells potentiated DPDPE-mediated adenylyl-cyclase inhibition of δ-OR leaving unaffected the levels of cAMP accumulation mediated by the μ-OR. Moreover, measurements of extracellular signal regulated kinase (ERK1,2) phosphorylation indicated that the presence of spinophilin attenuated agonist-driven ERK1,2 phosphorylation mediated upon activation of the δ-OR but not the μ-OR. Collectively, these findings suggest that spinophilin associates with both δ- and μ-ΟR and G protein subunits in HEK293 cells participating in a multimeric signaling complex that displays a differential regulatory role in opioid receptor signaling.</AbstractText"
]
] |
23161463
|
Recent advances in clinical neurogenetics.
|
Herein, I review the main papers in neurogenetic research published in the Journal of Neurology over the last year.</AbstractText
|
[
[
"15050709",
"Tactile discrimination activates the visual cortex of the recently blind naive to Braille: a functional magnetic resonance imaging study in humans.",
"The occipital cortex of blind subjects is known to be activated during tactile discrimination tasks such as Braille reading. To investigate whether this is due to long-term learning of Braille or to sensory deafferentation, we used fMRI to study tactile discrimination tasks in subjects who had recently lost their sight and never learned Braille. The occipital cortex of the blind subjects without Braille training was activated during the tactile discrimination task, whereas that of control sighted subjects was not. This finding suggests that the activation of the visual cortex of the blind during performance of a tactile discrimination task may be due to sensory deafferentation, wherein a competitive imbalance favors the tactile over the visual modality.</AbstractText"
]
] |
[
[
"23280856",
"Intrahippocampal infusion of the Ih blocker ZD7288 slows evoked theta rhythm and produces anxiolytic-like effects in the elevated plus maze.",
"Hippocampal theta rhythm has been associated with a number of behavioral processes, including learning and memory, spatial behavior, sensorimotor integration and affective responses. Suppression of hippocampal theta frequency has been shown to be a reliable neurophysiological signature of anxiolytic drug action in tests using known anxiolytic drugs (i.e., correlational evidence), but only one study to date (Yeung et al. (2012) Neuropharmacology 62:155-160) has shown that a drug with no known effect on either hippocampal theta or anxiety can in fact separately suppress hippocampal theta and anxiety in behavioral tests (i.e., prima facie evidence). Here, we attempt a further critical test of the hippocampal theta model by performing intrahippocampal administrations of the Ih blocker ZD7288, which is known to disrupt theta frequency subthreshold oscillations and resonance at the membrane level but is not known to have anxiolytic action. Intrahippocampal microinfusions of ZD7288 at high (15 µg), but not low (1 µg) doses slowed brainstem-evoked hippocampal theta responses in the urethane anesthetized rat, and more importantly, promoted anxiolytic action in freely behaving rats in the elevated plus maze. Taken together with our previous demonstration, these data provide converging, prima facie evidence of the validity of the theta suppression model.</AbstractText"
]
] |
22940423
|
HIV immune complexes prevent excitotoxicity by interaction with NMDA receptors.
|
Human immunodeficiency virus-1 (HIV)-associated neurocognitive disorder (HAND) is a neurodegenerative disease for which there is no available neuroprotective therapy. Viral proteins, such as Tat, have been implicated as agents of neurotoxicity via multiple mechanisms, including effects by directly binding to the NMDA receptor. We evaluated the ability of the immune response against Tat to modulate neurotoxicity at glutamate receptors.</AbstractText Neurotoxicity was measured in primary neuronal-glial cultures and in hippocampal slice cultures. We used immunoprecipitation experiments to demonstrate interaction between Tat, NMDA receptor, and anti-Tat antibody. Using known structures of Tat and NMDA receptors, we developed a model of their interactions.</AbstractText Antibodies to Tat attenuated Tat-mediated neurotoxicity. Interestingly, Tat immune complexes also blocked neurotoxicity caused by NMDA receptor agonists but not kainate/AMPA receptor agonists. Neither Tat nor antibody alone blocked the excitotoxic effect, nor did an unrelated antigen-antibody complex. The protective effect of the Tat immune complexes was also lost when Tat was modified by nitrosylation or by using a deletion mutant of Tat.</AbstractText The ability of viral immune complexes to interact with NMDA receptors and prevent excitotoxicity represents a novel host defense mechanism. Host immune responses may influence host susceptibility to various effects of viral proteins, modulating HIV complications, such as onset of HAND. These observations provide rationale for development of vaccine therapies targeting Tat for prevention of HAND.</AbstractText
|
[
[
"17959477",
"Increasing the performance of cortically-controlled prostheses.",
"Neural prostheses have received considerable attention due to their potential to dramatically improve the quality of life of severely disabled patients. Cortically-controlled prostheses are able to translate neural activity from cerebral cortex into control signals for guiding computer cursors or prosthetic limbs. Non-invasive and invasive electrode techniques can be used to measure neural activity, with the latter promising considerably higher levels of performance and therefore functionality to patients. We review here some of our recent experimental and computational work aimed at establishing a principled design methodology to increase electrode-based cortical prosthesis performance to near theoretical limits. Studies discussed include translating unprecedentedly brief periods of \"plan\" activity into high information rate (6.5 bits/s)control signals, improving decode algorithms and optimizing visual target locations for further performance increases, and recording from chronically implanted arrays in freely behaving monkeys to characterize neuron stability. Taken together, these results should substantially increase the clinical viability of cortical prostheses.</AbstractText"
]
] |
[
[
"23273129",
"Phase synchronization of neuronal noise in mouse hippocampal epileptiform dynamics.",
"Organized brain activity is the result of dynamical, segregated neuronal signals that may be used to investigate synchronization effects using sophisticated neuroengineering techniques. Phase synchrony analysis, in particular, has emerged as a promising methodology to study transient and frequency-specific coupling effects across multi-site signals. In this study, we investigated phase synchronization in intracellular recordings of interictal and ictal epileptiform events recorded from pairs of cells in the whole (intact) mouse hippocampus. In particular, we focused our analysis on the background noise-like activity (NLA), previously reported to exhibit complex neurodynamical properties. Our results show evidence for increased linear and nonlinear phase coupling in NLA across three frequency bands [theta (4-10 Hz), beta (12-30 Hz) and gamma (30-80 Hz)] in the ictal compared to interictal state dynamics. We also present qualitative and statistical evidence for increased phase synchronization in the theta, beta and gamma frequency bands from paired recordings of ictal NLA. Overall, our results validate the use of background NLA in the neurodynamical study of epileptiform transitions and suggest that what is considered \"neuronal noise\" is amenable to synchronization effects in the spatiotemporal domain.</AbstractText"
]
] |
23183130
|
Nanopsychiatry--the potential role of nanotechnologies in the future of psychiatry: a systematic review.
|
Nanomedicine is defined as the area using nanotechnology's concepts for the benefit of human beings' health and well being. In this article, we aimed to provide an overview of areas where nanotechnology is applied and how they could be extended to care for psychiatric illnesses. The main applications of nanotechnology in psychiatry are (i) pharmacology. There are two main difficulties in neuropharmacology: drugs have to pass the blood-brain barrier and then to be internalized by targeted cells. Nanoparticles could increase drugs bioavailability and pharmacokinetics, especially improving safety and efficacy of psychotropic drugs. Liposomes, nanosomes, nanoparticle polymers, nanobubbles are some examples of this targeted drug delivery. Nanotechnologies could also add new pharmacological properties, like nanoshells and dendrimers (ii) living analysis. Nanotechnology provides technical assistance to in vivo imaging or metabolome analysis (iii) central nervous system modeling. Research teams have succeeded to modelize inorganic synapses and mimick synaptic behavior, a step essential for further creation of artificial neural systems. Some nanoparticle assemblies present the same small worlds and free-scale networks architecture as cortical neural networks. Nanotechnologies and quantum physics could be used to create models of artificial intelligence and mental illnesses. We are not about to see a concrete application of nanomedicine in daily psychiatric practice. Even if nanotechnologies are promising, their safety is still inconsistent and this must be kept in mind. However, it seems essential that psychiatrists do not forsake this area of research the perspectives of which could be decisive in the field of mental illness.</AbstractText
|
[
[
"17506923",
"Neuropsychological and behavioural disinhibition in adult ADHD compared to borderline personality disorder.",
"Although attention-deficit/hyperactivity disorder (ADHD) is thought to be an inhibitory disorder, the question remains of how specific the inhibitory deficit is in adults and whether it distinguishes ADHD from borderline personality disorder (BPD), with which it shares several clinical features, particularly impulsiveness.</AbstractText The study assessed various motor and cognitive inhibitory functions (inhibition of prepotent, ongoing and interfering responses) in addition to working memory in adult ADHD patients with and without BPD, compared to subjects with BPD alone and controls. In addition, questionnaire data on various aspects of impulsiveness and anger regulation were assessed in all groups.</AbstractText ADHD patients performed worse than BPD individuals and controls in two inhibitory tasks: the stop signal task and the conflict module of the Attentional Network Task (ANT). In addition, they exhibited longer reaction times (RTs) and higher intra-individual variance in nearly all attentional tasks. The co-morbid group exhibited poor performance on the stop signal task but not on the conflict task. The BPD group barely differed from controls in neuropsychological performance but overlapped with ADHD in some behavioural problems, although they were less severe on the whole.</AbstractText Impaired inhibition is a core feature in adults with ADHD. In addition, slow RTs and high intra-individual variance in performance may reflect deficits in the regulation of activation and effort in ADHD patients. ADHD and BPD share some symptoms of behavioural dysregulation without common cognitive deficits, at least in the attentional realm.</AbstractText"
]
] |
[
[
"23161463",
"Recent advances in clinical neurogenetics.",
"Herein, I review the main papers in neurogenetic research published in the Journal of Neurology over the last year.</AbstractText"
]
] |
23303059
|
Using standardized fMRI protocols to identify patterns of prefrontal circuit dysregulation that are common and specific to cognitive and emotional tasks in major depressive disorder: first wave results from the iSPOT-D study.
|
Functional neuroimaging studies have implicated dysregulation of prefrontal circuits in major depressive disorder (MDD), and these circuits are a viable target for predicting treatment outcomes. However, because of the heterogeneity of tasks and samples used in studies to date, it is unclear whether the central dysfunction is one of prefrontal hyperreactivity or hyporeactivity. We used a standardized battery of tasks and protocols for functional magnetic resonance imaging, to identify the common vs the specific prefrontal circuits engaged by these tasks in the same 30 outpatients with MDD compared with 30 matched, healthy control participants, recruited as part of the International Study to Predict Optimized Treatment in Depression (iSPOT-D). Reflecting cognitive neuroscience theory and established evidence, the battery included cognitive tasks designed to assess functions of selective attention, sustained attention-working memory and response inhibition, and emotion tasks to assess explicit conscious and implicit nonconscious viewing of facial emotion. MDD participants were distinguished by a distinctive biosignature of: hypoactivation of the dorsolateral prefrontal cortex during working memory updating and during conscious negative emotion processing; hyperactivation of the dorsomedial prefrontal cortex during working memory and response inhibition cognitive tasks and hypoactivation of the dorsomedial prefrontal during conscious processing of positive emotion. These results show that the use of standardized tasks in the same participants provides a way to tease out prefrontal circuitry dysfunction related to cognitive and emotional functions, and not to methodological or sample variations. These findings provide the frame of reference for identifying prefrontal biomarker predictors of treatment outcomes in MDD.</AbstractText
|
[
[
"20012068",
"Astrocytes: biology and pathology.",
"Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.</AbstractText"
]
] |
[
[
"23955619",
"An autopsy case of the Marburg variant of multiple sclerosis (acute multiple sclerosis).",
"We herein report an autopsy case of the Marburg variant of multiple sclerosis (MS). A 29-year-old woman developed acute and progressive neurological symptoms. A diagnosis of MS was suspected based on the patient's clinical background and brain MRI findings and the lack of evidence of malignancy on a brain biopsy. Despite the administration of typical treatment for MS, a fatal outcome occurred three months after disease onset. The autopsy revealed multiple inflammatory demyelinating lesions in the central nervous system. In addition, two noteworthy histopathological features were observed compared with prototypical MS. We evaluate the pathogenic differences between the Marburg type and prototypical MS by discussing the neuropathology and cerebrospinal fluid (CSF) findings of our case.</AbstractText"
]
] |
22922354
|
Selective interactions of spinophilin with the C-terminal domains of the δ- and μ-opioid receptors and G proteins differentially modulate opioid receptor signaling.
|
Previous studies have shown that the intracellular domains of opioid receptors serve as platforms for the formation of a multi-component signaling complex consisting of various interacting partners (Leontiadis et al., 2009, Cell Signal. 21, 1218-1228; Georganta et al., 2010, Neuropharmacology, 59(3), 139-148). In the present study we demonstrate that spinophilin a dendritic-spine enriched scaffold protein associates with δ- and μ-opioid receptors (δ-ΟR, μ-OR) constitutively in HEK293 an interaction that is altered upon agonist administration and enhanced upon forskolin treatment for both μ-OR and δ-ΟR. Spinophilin association with the opioid receptors is mediated via the third intracellular loop and a conserved region of the C-terminal tails. The portion of spinophilin responsible for interaction with the δ-OR and μ-OR is narrowed to a region encompassing amino acids 151-444. Spinophilin, RGS4, Gα and Gβγ subunits of G proteins form a multi-protein complex using specific regions of spinophilin and a conserved amino acid stretch of the C-terminal tails of both δ-μ-ORs. Expression of spinophilin in HEK293 cells potentiated DPDPE-mediated adenylyl-cyclase inhibition of δ-OR leaving unaffected the levels of cAMP accumulation mediated by the μ-OR. Moreover, measurements of extracellular signal regulated kinase (ERK1,2) phosphorylation indicated that the presence of spinophilin attenuated agonist-driven ERK1,2 phosphorylation mediated upon activation of the δ-OR but not the μ-OR. Collectively, these findings suggest that spinophilin associates with both δ- and μ-ΟR and G protein subunits in HEK293 cells participating in a multimeric signaling complex that displays a differential regulatory role in opioid receptor signaling.</AbstractText
|
[
[
"21312401",
"Functional brain imaging in schizophrenia: selected results and methods.",
"Functional brain imaging studies of patients with schizophrenia may be grouped into those that assume that the signs and symptoms of schizophrenia are due to disordered circuitry within a critical brain region and studies that assume that the signs and symptoms are due to disordered connections among brain regions. Studies have investigated the disordered functional brain anatomy of both the positive and negative symptoms of schizophrenia. Studies of spontaneous hallucinations find that although hallucinations are associated with abnormal brain activity in primary and secondary sensory areas, disordered brain activation associated with hallucinations is not limited to sensory systems. Disordered activation in non-sensory regions appear to contribute to the emotional strength and valence of hallucinations, to be a factor underlying an inability to distinguish ongoing mental processing from memories, and to reflect the brain's attempt to modulate the intensity of hallucinations and resolve conflicts with other processing demands. Brain activation studies support the view that auditory/verbal hallucinations are associated with an impaired ability of internal speech plans to modulate neural activation in sensory language areas. In early studies, negative symptoms of schizophrenia were hypothesized to be associated with impaired function in frontal brain areas. In support of this hypothesis meta-analytical studies have found that resting blood flow or metabolism in frontal cortex is reduced in schizophrenia, though the magnitude of the effect is only small to moderate. Brain activation studies of working memory (WM) functioning are typically associated with large effect sizes in the frontal cortex, whereas studies of functions other than WM generally reveal smaller effects. Findings from some functional connectivity studies have supported the hypothesis that schizophrenia patients experience impaired functional connections between frontal and temporal cortex, although the nature of the disordered connectivity is complex. More recent studies have used functional brain imaging to study neural compensation in schizophrenia, to serve as endophenotypes in genetic studies and to provide biomarkers in drug development studies. These emerging trends in functional brain imaging research are likely to help stimulate the development of a general neurobiological theory of the complex symptoms of schizophrenia.</AbstractText"
]
] |
[
[
"23055474",
"The Hodgkin-Huxley heritage: from channels to circuits.",
"The Hodgkin-Huxley studies of the action potential, published 60 years ago, are a central pillar of modern neuroscience research, ranging from molecular investigations of the structural basis of ion channel function to the computational implications at circuit level. In this Symposium Review, we aim to demonstrate the ongoing impact of Hodgkin's and Huxley's ideas. The Hodgkin-Huxley model established a framework in which to describe the structural and functional properties of ion channels, including the mechanisms of ion permeation, selectivity, and gating. At a cellular level, the model is used to understand the conditions that control both the rate and timing of action potentials, essential for neural encoding of information. Finally, the Hodgkin-Huxley formalism is central to computational neuroscience to understand both neuronal integration and circuit level information processing, and how these mechanisms might have evolved to minimize energy cost.</AbstractText"
]
] |
23504446
|
Using equivalence-based instruction to increase efficiency in teaching neuroanatomy.
|
A goal of all instruction is to efficiently allocate time spent teaching -- balancing redundancy that enhances learning with redundancy that is irrelevant to increasing student understanding. Efficient allocation of time allows the instructor to present additional material and go into more detail about the information being presented. Here we borrow laboratory research on concept formation and apply these formal principles in teaching introductory neuroanatomy within a lecture course on Behavioral Neuroscience. Concept formation is taught by pairing multiple stimuli, for instance brain name, location, and function, in such a way that novel associations within a category emerge without direct training. This study demonstrates that careful selection of associations by the instructor can encourage the spontaneous emergence of novel associations within a concept or category, thereby increasing efficiency of teaching and by extension, the depth of material that can be taught.</AbstractText
|
[
[
"9626715",
"The role of defeat and entrapment (arrested flight) in depression: an exploration of an evolutionary view.",
"The social rank theory of psychopathology suggests that with the evolution of social hierarchies various psychobiological mechanisms became attuned to the success or failure in conflict situations. Specifically, subordinates and those who have lost status are at greater risk of pathology than winners and those of higher status. In this theory concepts of defeat and entrapment are seen to be of special relevance to the study of depression. We outline the role of defeat and entrapment within the social rank theory of depression.</AbstractText New self-report measures of entrapment and defeat were developed and used to test predictions of the social rank theory of depression. Both a sample of students and depressed patients were assessed with these new scales and other social rank measures (e.g. social comparison and submissive behaviour).</AbstractText The entrapment and defeat measures were found to have good psychometric properties and significantly correlated with depression. They were also strongly associated with other rank variables. Defeat maintained a strong association with depression even after controlling for hopelessness (r = 0.62), whereas the relationship between hopelessness and depression was substantially reduced when controlling for defeat. Entrapment and defeat added substantially to the explained variance of depression after controlling for the other social rank variables.</AbstractText Defeat and entrapment appear to be promising variables for the study of depression. These variables may also help to develop linkages between human and animal models of psychopathology.</AbstractText"
]
] |
[
[
"23248404",
"Neuroprotective activity of Stereospermum suaveolens DC against 6-OHDA induced Parkinson's disease model.",
"To evaluate the neuroprotective effect of Stereospermum suaveolens DC on 6-hydroxy dopamine induced Parkinson's disease model.</AbstractText The study was conducted on Sprague-Dawley rats where parkinson's disease was induced by producing the striatal 6-hydroxy dopamine lesions. The test animals received methanolic extract of Stereospermum suaveolens at dose of 125, 250 and 500 mg/kg for 42 days. Behavioral assessment, spontaneous locomotor activity and muscular coordination were studied. Antioxidant levels, striatal infraction area were assessed and histopathological studies were carried out.</AbstractText The Stereospermum suaveolens DC methanolic extract showed significant dose dependent increase in behavioral activity, improved muscular coordination. Significant reduction of lipid peroxidation (LPO), increased antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT) and non-enzymatic activity of glutathione (GSH) and total thiol levels in extract treated groups was observed in test groups as compared to control group. Striatal infarction area was significantly reduced in extract treated groups as compared to control group.</AbstractText The methanolic extract of Stereospermum suaveolens DC showed neuroprotective activity against 6-hydroxy dopamine induced Parkinson's disease in rats.</AbstractText"
]
] |
23371266
|
[Funcion sparing surgery in uro-oncology: germ cell tumors of the testis].
|
Surgery in germ cell tumors of the testis (TGT) may result in andrological disorders, both after orchiectomy and after retroperitoneal lymphadenectomy (RPLND). Bilateral orchiectomy suppresses both testicular functions: exocrine and endocrine. In selected cases with bilateral TGT (metachronous/synchronous), or in the case of TGT in monorchid patients, partial orchiectomy (enucleation of the tumor) can preserve both functions with a low risk of relapse in residual testicular parenchyma, in the absence of intraepithelial neoplasia (TIN). In cases of TIN and normal testosterone levels (80%), the fertility is maintained in 50% of patients. In these cases the use of radiotherapy on the residual testicular parenchyma can prevent the future development of invasive cancer, though compromising the hormonal function. The RPLND (open or laparoscopic) can produce major side effects, such as retrograde ejaculation. Knowledge of the adrenergic fiber retroperitoneal neuroanatomy enables to implement a "nerve sparing" surgery with an almost total reduction of this serious side effect, but that option is only available in few centers of excellence. Semen cryopreservation has become a common practice performed before any treatment that might impact on the andrological function of patients.</AbstractText
|
[
[
"8490989",
"Epidemiology of epilepsy in developing countries.",
"Epilepsy is an important health problem in developing countries, where its prevalence can be up to 57 per 1000 population. This article reviews the epidemiology of epilepsy in developing countries in terms of its incidence, prevalence, seizure type, mortality data, and etiological factors. The prevalence of epilepsy is particularly high in Latin America and in several African countries, notably Liberia, Nigeria, and the United Republic of Tanzania. Parasitic infections, particularly neurocysticercosis, are important etiological factors for epilepsy in many of these countries. Other reasons for the high prevalence include intracranial infections of bacterial or viral origin, perinatal brain damage, head injuries, toxic agents, and hereditary factors. Many of these factors are, however, preventable or modifiable, and the introduction of appropriate measures to achieve this could lead to a substantial decrease in the incidence of epilepsy in developing countries.</AbstractText"
]
] |
[
[
"23476081",
"Framing Nicotine Addiction as a \"Disease of the Brain\": Social and Ethical Consequences.",
"In this article, we seek to better understand how a genomic vision of addiction may influence drug prevention and treatment. Though <i We explore the emerging view of addiction as a \"disease of the brain\" in open-ended interviews with 86 stakeholders from the fields of nicotine research and tobacco control. Interview data were analyzed using standard qualitative techniques.</AbstractText Most stakeholders hold a medicalized view of addiction. Though environmental variables are understood to be a primary cause of smoking initiation, the speed and strength with which addiction occurs is understood to be a largely biological process. Though stakeholders believe that an increased focus on addiction as a disease of the brain is not likely to lead to widespread unrealistic expectations for cessation therapies, they remain concerned that it may reinforce teenagers' expectations that quitting is not difficult. Finally, stakeholder responses indicate that genetic and neuroscientific research is unlikely to increase or decrease stigmatization, but will be used by interest groups to buttress their existing views of the stigma associated with smoking.</AbstractText We argue that the main potential harms of focusing on biological etiology stem from a concept of addiction that is disassociated from social context. Focusing on genetic testing and brain scans may lead one to overemphasize pharmaceutical \"magic bullet cures\" and underemphasize, and underfund, more traditional therapies and public health prevention strategies that have proven to be effective. Genetic research on addiction may fundamentally change our conception of deviance and our identities, and may thus transform our susceptibility to substance use into something isolated in our biology, not embedded in a biosocial context.</AbstractText"
]
] |
23167712
|
Affect-specific modulation of the N1m to shock-conditioned tones: magnetoencephalographic correlates.
|
Despite its fundamental relevance for representing the emotional world surrounding us, human affective neuroscience research has widely neglected the auditory system, at least in comparison to the visual domain. Here, we have investigated the spatiotemporal dynamics of human affective auditory processing using time-sensitive whole-head magnetoencephalography. A novel and highly challenging affective associative learning procedure, 'MultiCS conditioning', involving multiple conditioned stimuli (CS) per affective category, was adopted to test whether previous findings from intramodal conditioning of multiple click-tones with an equal number of auditory emotional scenes (Bröckelmann et al., 2011 J. Neurosci., 31, 7801) would generalise to crossmodal conditioning of multiple click-tones with an electric shock as single aversive somatosensory unconditioned stimulus (UCS). Event-related magnetic fields were recorded in response to 40 click-tones before and after four contingent pairings of 20 CS with a shock and the other half remaining unpaired. In line with previous findings from intramodal MultiCS conditioning we found an affect-specific modulation of the auditory N1m component 100-150 ms post-stimulus within a distributed frontal-temporal-parietal neural network. Increased activation for shock-associated tones was lateralised to right-hemispheric regions, whereas unpaired safety-signalling tones were preferentially processed in the left hemisphere. Participants did not show explicit awareness of the contingent CS-UCS relationship, yet behavioural conditioning effects were indicated on an indirect measure of stimulus valence. Our findings imply converging evidence for a rapid and highly differentiating affect-specific modulation of the auditory N1m after intramodal as well crossmodal MultiCS conditioning and a correspondence of the modulating impact of emotional attention on early affective processing in vision and audition.</AbstractText
|
[
[
"17030182",
"The vagus nerve: a tonic inhibitory influence associated with inflammatory bowel disease in a murine model.",
"The recently proposed Inflammatory Reflex describes an interaction between the vagus nerve and peripheral macrophages, resulting in attenuation of proinflammatory cytokine release in response to systemic exposure to bacterial endotoxin. The purpose of this study was to determine whether a similar vagus/macrophage axis modulates the inflammatory responses in the colon in mice.</AbstractText We assessed the Disease Activity Index (DAI), macroscopic and histologic damage, serum amyloid-P level, and myeloperoxidase activity in colitis induced by administration of dextran sodium sulfate (DSS) in healthy and vagotomized C57BL/6 and in mice deficient in macrophage-colony stimulating factor (M-CSF)-induced and in hapten-induced colitis. A pyloroplasty was performed in vagotomized mice.</AbstractText DAI, macroscopic and histologic scores, myeloperoxidase activity, levels of serum amyloid-P, and colonic tissue levels of interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha were increased significantly in vagotomized mice 5 days post-DSS and 3 days after hapten-induced colitis compared with sham-operated mice that received DSS or the hapten. Pretreatment with nicotine significantly decreased each of these markers in vagotomized mice with DSS colitis, and all markers except DAI and IL-6 in sham-operated DSS-treated mice. Conversely, hexamethonium treatment significantly increased each of these markers in the sham-operated DSS-treated mice. Vagotomy had no effect on the colitis in M-CSF-deficient mice.</AbstractText The vagus nerve plays a counterinflammatory role in acute colitis via a macrophage-dependent mechanism, involving hexamethonium-sensitive nicotinic receptors. The identification of a counterinflammatory neural pathway would open new therapeutic avenues for treating acute exacerbations of inflammatory bowel disease.</AbstractText"
]
] |
[
[
"23245219",
"Ventral striatum activation to prosocial rewards predicts longitudinal declines in adolescent risk taking.",
"Adolescence is a period of intensified emotions and an increase in motivated behaviors and passions. Evidence from developmental neuroscience suggests that this heightened emotionality occurs, in part, due to a peak in functional reactivity to rewarding stimuli, which renders adolescents more oriented toward reward-seeking behaviors. Most prior work has focused on how reward sensitivity may create vulnerabilities, leading to increases in risk taking. Here, we test whether heightened reward sensitivity may potentially be an asset for adolescents when engaged in prosocial activities. Thirty-two adolescents were followed over a one-year period to examine whether ventral striatum activation to prosocial rewards predicts decreases in risk taking over a year. Results show that heightened ventral striatum activation to prosocial stimuli relates to longitudinal declines in risk taking. Therefore, the very same neural region that has conferred vulnerability for adolescent risk taking may also be protective against risk taking.</AbstractText"
]
] |
23095170
|
High yield derivation of enriched glutamatergic neurons from suspension-cultured mouse ESCs for neurotoxicology research.
|
Recently, there has been a strong emphasis on identifying an in vitro model for neurotoxicity research that combines the biological relevance of primary neurons with the scalability, reproducibility and genetic tractability of continuous cell lines. Derived neurons should be homotypic, exhibit neuron-specific gene expression and morphology, form functioning synapses and consistently respond to neurotoxins in a fashion indistinguishable from primary neurons. However, efficient methods to produce neuronal populations that are suitable alternatives to primary neurons have not been available.</AbstractText With the objective of developing a more facile, robust and efficient method to generate enriched glutamatergic neuronal cultures, we evaluated the neurogenic capacity of three mouse embryonic stem cell (ESC) lines (R1, C57BL/6 and D3) adapted to feeder-independent suspension culture. Neurogenesis and neuronal maturation were characterized as a function of time in culture using immunological, genomic, morphological and functional metrics. The functional responses of ESNs to neurotropic toxins with distinctly different targets and mechanisms of toxicity, such as glutamate, α-latrotoxin (LTX), and botulinum neurotoxin (BoNT), were also evaluated.</AbstractText Suspension-adapted ESCs expressed markers of pluripotency through at least 30 passages, and differentiation produced 97×106 neural progenitor cells (NPCs) per 10-cm dish. Greater than 99% of embryonic stem cell-derived neurons (ESNs) expressed neuron-specific markers by 96 h after plating and rapidly developed complex axodendritic arbors and appropriate compartmentalization of neurotypic proteins. Expression profiling demonstrated the presence of transcripts necessary for neuronal function and confirmed that ESN populations were predominantly glutamatergic. Furthermore, ESNs were functionally receptive to all toxins with sensitivities and responses consistent with primary neurons.</AbstractText These findings demonstrate a cost-effective, scalable and flexible method to produce a highly enriched glutamatergic neuron population. The functional characterization of pathophysiological responses to neurotropic toxins and the compatibility with multi-well plating formats were used to demonstrate the suitability of ESNs as a discovery platform for molecular mechanisms of action, moderate-throughput analytical approaches and diagnostic screening. Furthermore, for the first time we demonstrate a cell-based model that is sensitive to all seven BoNT serotypes with EC50 values comparable to those reported in primary neuron populations. These data providing compelling evidence that ESNs offer a neuromimetic platform suitable for the evaluation of molecular mechanisms of neurotoxicity.</AbstractText
|
[
[
"20012068",
"Astrocytes: biology and pathology.",
"Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.</AbstractText"
]
] |
[
[
"22520647",
"European study of research and development in mobility technology for persons with disabilities.",
"\\In the fall of 2010, the National Science Foundation, the National Institutes of Health and the U.S. Veteran's Administration jointly supported a review of mobility technology in Europe. A delegation of American Scientists traveled to Europe to visit a number of research centers and engaged in a demonstration and dialogue related to the global state-of-the-art for mobility impairment rectification and augmentation. From the observations and exchanges between the U.S. delegation and host institutions, the researchers were able to derive a series of papers which are now published in this thematic series of Journal of NeuroEngineering and Rehabilitation. The papers describe the main themes of the European mobility technology research activities showing a healthy picture of research and innovation in the field.</AbstractText"
]
] |
29913996
|
The attenuation of pain behaviour and serum interleukin-6 concentration by nimesulide in a rat model of neuropathic pain.
|
Background Evidence for a role of immune system in hyperalgesic pain states is increasing. Recent work in neuroimmunology suggests that the immune system does more than simply perform its well known functions of recognizing and removing invading pathogens and tumors. Interest in neuroinflammation and neuroimmune activation has grown rapidly in recent years with the recognition of the role of central nervous system inflammatiom and immune responses in the aetiology of pain states. Among various theories, the role of inflammatory responses of the injured nerve has recently received attention. Cytokines are heterogenous group of polypeptides that activate the immune system and mediate inflammatory responses, acting on a variety of tissue, including the peripheral and central nervous system. Interleukin-6 (IL-6) a pro-inflammatory cytokine, is potentially important in pain aetiology, have pronociceptive actions. Neuropathic pain may be due to a primary insult to the peripheral or central nervous system. Substances released during inflammation from immune cells play an important role in the development and maintenance of chronic pain. Nimesulide, a highly selective cox-2 inhibitor, effectively reduces hyperalgesia due to peripherally administration of inflammatory agents like formalin. The safety of nimesulide was reported for some conditions in which other NSAIDs are contraindicated. Here we have determined the effect of nimesulide on pain behaviour and serum IL-6 level in chronic constriction injury (CCI) model of neuropathic pain. Methods Experiments were carried out on male Wistar rats, (weight 150-200 g, n = 8). Rats were divided into 3 different groups: 1-CCI + saline 0.9% 2Sham + saline 0.9% (control) 3CCI + drug. Nimesulide (1.25, 2.5, 5 mg/kg, i.p.) was injected 1h before surgery and continued daily to day 14 post-ligation. 42 °C water for thermal hyperalgesia, von Frey filaments for mechanical allodynia, acetone test for cool allodynia and 10 °C water for cold hyperalgesia were respectively used as pain behavioural tests. Behavioural tests were recorded before surgery and on postoperative days 1, 3, 5, 7, 10, 14 and the serum concentration of IL-6 was determined at the day 14. Results The results of this study showed a decrease in hyperalgesia and allodynia following nimesulide administration. Conclusions It appears that nimesulide was able to reduce pain behaviour due to nerve inflammation and a parallel decrease in the serum IL-6 concentration was observed. Implications The immune system is an important mediator in the cascade of events that ultimately results in hyperalgesia. Cytokines contribute to the patheogenesis of neuropathic pain, therefore drugs that inhibit cytokine release from immune cells may reduce inflammatory pain states.</AbstractText
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[
[
"21391760",
"The default network distinguishes construals of proximal versus distal events.",
"Humans enjoy a singular capacity to imagine events that differ from the \"here-and-now.\" Recent cognitive neuroscience research has linked such simulation processes to the brain's \"default network.\" However, extant cognitive theories suggest that perceivers reliably simulate only relatively proximal experiences-those that seem nearby, soon, likely to happen, or relevant to a close other. Here, we test these claims by examining spontaneous engagement of the default network while perceivers consider experiencing events from proximal and distal perspectives. Across manipulations of perspective in four dimensions, two regions of the default network-medial prefrontal cortex and retrosplenial cortex-were more active for proximal than distal events, supporting cognitive accounts that perceivers only richly simulate experiences that seem immediate and that perceivers represent different dimensions of distance similarly. Moreover, stable individual differences in default activity when thinking about distal events correlated with individual variability in an implicit measure of psychological distance, suggesting that perceivers naturally vary in their tendency to simulate far-off or unlikely experiences.</AbstractText"
]
] |
[
[
"20817916",
"Neuroscience: viable applications in education?",
"As a relatively young science, neuroscience is still finding its feet in potential collaborations with other disciplines. One such discipline is education, with the field of neuroeducation being on the horizon since the 1960s. However, although its achievements are now growing, the partnership has not been as successful as first hopes suggested it should be. Here the authors discuss the theoretical barriers and potential solutions to this, which have been suggested previously, with particular focus on levels of research in neuroscience and their applicability to education. Moreover, they propose that these theoretical barriers are driven and maintained by practical barriers surrounding common language and research literacy. They propose that by overcoming these practical barriers through appropriate training and shared experience, neuroeducation can reach its full potential.</AbstractText"
]
] |
22905274
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Toxocariasis and epilepsy: systematic review and meta-analysis.
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Human toxocariasis is a zoonotic infection caused by the larval stages of Toxocara canis (T. canis) and less frequently Toxocara cati (T. cati). A relationship between toxocariasis and epilepsy has been hypothesized. We conducted a systematic review and a meta-analysis of available data to evaluate the strength of association between epilepsy and Toxocara spp. seropositivity and to propose some guidelines for future surveys.</AbstractText Electronic databases, the database from the Institute of Neuroepidemiology and Tropical Neurology of the University of Limoges (http://www-ient.unilim.fr/) and the reference lists of all relevant papers and books were screened up to October 2011.</AbstractText We performed a systematic review of literature on toxocariasis (the exposure) and epilepsy (the outcome). Two authors independently assessed eligibility and study quality and extracted data. A common odds ratio (OR) was estimated using a random-effects meta-analysis model of aggregated published data.</AbstractText Seven case-control studies met the inclusion criteria, for a total of 1867 participants (850 cases and 1017 controls). The percentage of seropositivity (presence of anti-Toxocara spp. antibodies) was higher among people with epilepsy (PWE) in all the included studies even if the association between epilepsy and Toxocara spp. seropositivity was statistically significant in only 4 studies, with crude ORs ranging 2.04-2.85. Another study bordered statistical significance, while in 2 of the included studies no significant association was found. A significant (p < 0.001) common OR of 1.92 [95% confidence interval (CI) 1.50-2.44] was estimated. Similar results were found when meta-analysis was restricted to the studies considering an exclusively juvenile population and to surveys using Western Blot as confirmatory or diagnostic serological assay.</AbstractText Our results support the existence of a positive association between Toxocara spp. seropositivity and epilepsy. Further studies, possibly including incident cases, should be performed to better investigate the relationship between toxocariasis and epilepsy.</AbstractText
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[
[
"17322880",
"Mapping autism risk loci using genetic linkage and chromosomal rearrangements.",
"Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.</AbstractText"
]
] |
[
[
"23077800",
"Occupational exposure to styrene in the fibreglass reinforced plastic industry: comparison between two different manufacturing processes.",
"Styrene is used in manufacturing fiberglass reinforced plastics: and occupational exposure was related to neurotoxicology and genotoxicity. The sum of the metabolites mandelic and phenylglyoxylic acids is the ACGIH biomarker for occupational exposure with a BEI of 400 mg/g of creatinine in end shift urine corresponding to a airborne styrene concentration of 85 mg/m3. There are two main molding processes, open and closed, the last more effective at controlling worker's styrene exposure.</AbstractText To compare the open molding process to the compression of fiber reinforced resin foils, a kind of closed molding, monitoring the styrene exposure of workers in two production sites (A and B).</AbstractText Environmental Monitoring was carried out by Radiello samplers and Biological Monitoring by means of the determination of MA and PGA with HPLC/MS/MS in 10 workers at Site A and 14 at Site B.</AbstractText The median values for styrene exposure resulted 31.1 mg/m3 for Site A and 24.4 mg/m for Site B, while the medians for the sum of the two metabolites in the end shift urine were 86.7 e 33.8 mg/g creatinine respectively. There is a significant linear correlation between personal styrene exposure and the excretion of styrene metabolites (R = 0.74).</AbstractText As expected the exposure markers of the workers of the two production sites resulted higher in the open process. The analytical results of both environmental and biological monitoring were all below the occupational exposure limits, confirming the efficacy of the protective devices.</AbstractText"
]
] |
22937517
|
Optogenetics: a novel optical manipulation tool for medical investigation.
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Optogenetics is a new and rapidly evolving gene and neuroengineering technology that allows optical control of specific populations of neurons without affecting other neurons in the brain at high temporal and spatial resolution. By heterologous expression of the light-sensitive membrane proteins, cell type-specific depolarization or hyperpolarization can be optically induced on a millisecond time scale. Optogenetics has the higher selectivity and specificity compared to traditional electrophysiological techniques and pharmaceutical methods. It has been a novel promising tool for medical research. Because of easy handling, high temporal and spatial precision, optogenetics has been applied to many aspects of nervous system research, such as tactual neural circuit, visual neural circuit, auditory neural circuit and olfactory neural circuit, as well as research of some neurological diseases. The review highlights the recent advances of optogenetics in medical study.</AbstractText
|
[
[
"18448316",
"A critical look at the embodied cognition hypothesis and a new proposal for grounding conceptual content.",
"Many studies have demonstrated that the sensory and motor systems are activated during conceptual processing. Such results have been interpreted as indicating that concepts, and important aspects of cognition more broadly, are embodied. That conclusion does not follow from the empirical evidence. The reason why is that the empirical evidence can equally be accommodated by a 'disembodied' view of conceptual representation that makes explicit assumptions about spreading activation between the conceptual and sensory and motor systems. At the same time, the strong form of the embodied cognition hypothesis is at variance with currently available neuropsychological evidence. We suggest a middle ground between the embodied and disembodied cognition hypotheses--grounding by interaction. This hypothesis combines the view that concepts are, at some level, 'abstract' and 'symbolic', with the idea that sensory and motor information may 'instantiate' online conceptual processing.</AbstractText"
]
] |
[
[
"21723668",
"Steroid sulfatase-deficient mice exhibit endophenotypes relevant to attention deficit hyperactivity disorder.",
"Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental condition characterised by inattention, impulsivity and hyperactivity; it is frequently co-morbid with anxiety and conduct disorders, sleep perturbation and abnormal consummatory behaviours. Recent studies have implicated the neurosteroid-modulating enzyme steroid sulfatase (STS) as a modulator of ADHD-related endophenotypes. The effects of steroid sulfatase deficiency on homecage activity, feeding/drinking behaviours, anxiety-related behaviours (assayed in light-dark box and open field paradigms), social dominance and serum steroid hormone levels were determined by comparing 40,XY and 39,X(Y*)O mice. Subsequently, mice administered the steroid sulfatase inhibitor COUMATE acutely were compared to vehicle-treated mice on behavioural tasks sensitive to enzyme deficiency to dissociate between its developmental and ongoing effects. 39,X(Y*)O mice exhibited heightened reactivity to a novel environment, hyperactivity in the active phase, and increased water (but not food) consumption relative to 40,XY mice during a 24h period; the former group also demonstrated evidence for heightened emotional reactivity. There was no difference in social dominance between the 40,XY and 39,X(Y*)O mice. COUMATE administration had no effect on homecage activity, water consumption or anxiety measures in the open field. 39,X(Y*)O mice exhibited significantly lower dehydroepiandrosterone (DHEA) serum levels than 40,XY mice, but equivalent corticosterone levels. Together with previous data, the present results suggest that steroid sulfatase may influence core and associated ADHD behavioural endophenotypes via both developmental and ongoing mechanisms, and that the 39,X(Y*)O model may represent a useful tool for elucidating the neurobiological basis of these endophenotypes.</AbstractText"
]
] |
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