title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
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Effect of low-thoracic anodal tsDCS on PREP-induced pain intensity | pain | We observed a general increase of the subjective pain intensity caused by the cutaneous electrical stimuli using CE when eliciting PREP (evaluated by NRS) after anodal tsDCS compared to sham stimulation. However, this could not be shown separately for stimuli of the lower limb, so that we cannot recognize a connection ... | PMC10684856 | |
Limitations | NRS | STILL | Concerning the SEP, in our setup we only used one cortical recording electrode at a time and only evaluated the N20-P25-amplitude and N20-latency for the upper extremity and only the N30-P40-amplitude and N30-latency for the lower extremity. From this follows that we cannot rule out effects of tsDCS on other SEP values... | PMC10684856 |
Supplementary Information | The online version contains supplementary material available at 10.1038/s41598-023-47408-x. | PMC10684856 | ||
Acknowledgements | We thank the participants in this study for their consent and cooperation. | PMC10684856 | ||
Author contributions | F.E. contributed to the conception and design of the study, data collection, data analysis and drafted the manuscript, O.H. contributed to the conception of the study, data analysis and interpretation and revised the manuscript for intellectual content, E.E.K. contributed to data analysis and interpretation and revised... | PMC10684856 | ||
Funding | Open Access funding enabled and organized by Projekt DEAL. This work was supported by the Deutsche Forschungsgemeinschaft, SFB 874/A1 and A5, Project No.: 122679504. E. E.-K. holds an endowed professorship funded by the German Social Accident Insurance (DGUV) for the time of 6 years (2020–2026) and has received a grant... | PMC10684856 | ||
Data availability | The data collected or analyzed during this study are available from the corresponding author on reasonable request. | PMC10684856 | ||
Competing interests | The authors declare no competing interests. | PMC10684856 | ||
References | PMC10684856 | |||
Subject terms | psychiatric, attention-deficit/hyperactivity disorder, ADHD | DISORDERS | Methylphenidate is a widely used and effective treatment for attention-deficit/hyperactivity disorder (ADHD), yet the underlying neural mechanisms and their relationship to changes in behavior are not fully understood. Specifically, it remains unclear how methylphenidate affects brain and behavioral dynamics, and the i... | PMC10516959 |
Introduction | Attention-deficit/hyperactivity disorder, neurodevelopmental disorder, attentional deficits, ADHD | CORTEX | Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder that affects approximately 5–10% of children and adolescents worldwide [One of the most robust behavioral phenotypes associated with attentional deficits in childhood ADHD is intra-individual response variability (IIRV), w... | PMC10516959 |
Methods | PMC10516959 | |||
Participants and study design | neurological abnormalities, epilepsy, intellectual disability, TD, ADHD, head trauma | ARACHNOID CYSTS, EPILEPSY | This study involves re-analysis of a previous published dataset [Thirty-four children with ADHD and 65 TD children were recruited at the University of Fukui Hospital, Japan. Figure During the second visit, within 1 to 6 weeks after the first visit, children with ADHD underwent a resting-state fMRI scan and performed th... | PMC10516959 |
Assessment of attention and cognitive control | medication-induced, ADHD | A standardized CPT was administered to children with ADHD outside the MRI scanner under both methylphenidate and placebo conditions. The task consisted of a Go/NoGo paradigm in which children were presented with either a target or non-target stimulus on the screen for 100 msec, once every 2 s for 15 min across three 5-... | PMC10516959 | |
fMRI data acquisition | Functional images were acquired in a 3-T scanner (Discovery MR 750; General Electric Medical Systems, Milwaukee, WI) and a 32-channel head coil with a T2*-weighted gradient-echo echo-planar imaging sequence (TR = 2300 ms, TE = 30 ms, FA = 81°, FOV = 192 × 192 mm, matrix size = 64 × 64, voxel size = 3 × 3 mm). In total,... | PMC10516959 | ||
fMRI data pre-processing | Resting state fMRI data were analyzed using SPM12 ( | PMC10516959 | ||
Region of interest (ROI) and time series | Eleven ROIs were determined from a previous study of attention and cognitive control [Time series of the 1 | PMC10516959 | ||
Bayesian switching dynamical systems (BSDS) model | TD, ADHD | We used a BSDS model [ROI timeseries from typically developing (TD) children, children with ADHD under placebo (Placebo) and methylphenidate (MPH) conditions were grouped together and analyzed in a common BSDS model. This yielded latent states common to all three groups. Key measures extracted from BSDS include occupan... | PMC10516959 | |
Brain state dynamics in relation to behavioral performance | REGRESSION | To understand the relationship between the latent dynamic brain state and out-of-scanner behavioral performance, we used multiple linear regression models to examine whether occupancy rates and mean lifetime of each brain is related to behavioral performance. Other potential confounds such as age, social-economic statu... | PMC10516959 | |
Functional connectivity of time-varying latent brain states | To determine which dynamic functional connections are important for distinguishing different brain states, we conducted paired t-tests to examine medication effect on the covariance matrix between latent brain states derived from BSDS analysis and two-sample t-tests to examine group differences. The results were thresh... | PMC10516959 | ||
Medication effect on functional connectivity in relation to its effect on IIRV | To determine whether medication effect on functional connectivity between the SN, FPN and DMN contributes to its effect on sustained attention, we first conducted | PMC10516959 | ||
Results | PMC10516959 | |||
Participants and demographic information | neurological abnormalities, excessive head motion, psychiatric comorbidity, TD, ADHD, handedness | Ninety-nine children, including 34 boys with a clinical diagnosis of ADHD and 65 TD boys (6–15 years old) completed the study. Children with ADHD were enrolled in a double-blind, placebo-controlled crossover design as described previously (39–41). Children with ADHD were scanned twice using resting-state functional MRI... | PMC10516959 | |
Methylphenidate effects on sustained attention | ADHD | Children with ADHD completed a standardized continuous performance task [ | PMC10516959 | |
Aberrant latent brain state dynamics in children with ADHD | TD, ADHD | CORTEX | Latent state variables play a crucial role in characterizing the dynamics of brain activity. We used BSDS to probe latent state dynamics of a cognitive control system comprising key nodes of the SN, FPN, and DMN: bilateral anterior insula, middle frontal gyrus, frontal eye fields, inferior parietal lobe, posterior cing... | PMC10516959 |
Methylphenidate normalizes aberrant latent brain states. | TD, aberrancy, ADHD | Occupancy rate (OR) of the latent brain state S2 was significantly higher in children with ADHD than TD children (We conducted a similar ANOVA analysis to examine group differences on mean lifetimes across all the latent brain states but did not find significant interaction and main effects of group and state (all Thes... | PMC10516959 | |
Methylphenidate normalizes aberrant state dynamics in children with ADHD | TD, ADHD | Next, we tested whether methylphenidate could normalize abnormal state dynamics in children with ADHD. A two-way ANOVA with factors medication (placebo, methylphenidate) and state (S1, S2, S3, S4 and S5) revealed a significant main effect of state (Because the occupancy rate of state S2 was significantly different betw... | PMC10516959 | |
Relationship between methylphenidate-induced changes in brain state dynamics and response variability | Methylphenidate-induced, medication-induced, ADHD | REGRESSION | We then determined whether methylphenidate-induced changes in brain state dynamics are associated with changes in IIRV in the CPT. We focused on state S2 which we found to be aberrant in children with ADHD, as detailed above. Specifically, we conducted a multiple linear regression analysis to evaluate the relationship ... | PMC10516959 |
Hyper-connectivity of the DMN in aberrant brain state in children with ADHD | TD, ADHD | We sought to determine differences in functional connectivity associated with S2, the aberrant latent brain states in children with ADHD. Here we leveraged the ability of BSDS to identify connectivity patterns associated with each brain state in each individual. Compared to TD children, children with ADHD under placebo... | PMC10516959 | |
Methylphenidate reduces aberrant state-specific hyper-connectivity. | ADHD | Children with ADHD under placebo condition showed ( | PMC10516959 | |
Methylphenidate influences functional connectivity of aberrant brain state in children with ADHD | ADHD | Next, we examined the effect of methylphenidate on functional connectivity in the aberrant brain state, S2, in children with ADHD. We found that the medication reduces hyper-connectivity between PCC and VMPFC in children with ADHD ( | PMC10516959 | |
Methylphenidate modulation on SN-DMN functional connectivity predicts its effect on IIRV | medication-induced, ADHD | Finally, we examined whether methylphenidate-induced changes in functional connectivity of the aberrant brain state, S2, are associated with medication-induced changes in IIRV. We found that medication-induced changes in functional connectivity between left AI node of the SN and PCC node of the DMN in state S2 is signi... | PMC10516959 | |
State-specific effects of methylphenidate on brain and behavioral dynamics. | Methylphenidate effect on the functional connectivity of lAI and PCC of the latent brain state S2 was significantly associated with the medication effect on the IIRV ( | PMC10516959 | ||
Robustness of findings | comorbidity, ADHD, autism | REGRESSION | We conducted additional analyses to determine the robustness of our findings. Specifically, we examined whether medication effects on brain-behavior association are stable with respect to head motion, exclusion of IQ as covariates in the regression model. We also examined whether results were influenced by comorbidity ... | PMC10516959 |
Discussion | inattention symptoms, medication-induced, ADHD | Methylphenidate is a commonly used stimulant for treating inattention symptoms in children with ADHD. We used a novel state-space approach to investigate aberrancies in latent brain states associated with dynamics of cognitive control networks in childhood ADHD and then determined whether methylphenidate normalizes the... | PMC10516959 | |
Methylphenidate normalizes aberrant brain state dynamics in children with ADHD | TD, ADHD | One prominent neurocognitive model proposes that higher levels of attentional fluctuations in individuals with ADHD may arise from abnormal brain dynamics [The current study overcomes these limitations by using a novel BSDS algorithm to uncover latent brain states characterized by unique spatiotemporal circuit properti... | PMC10516959 | |
Methylphenidate normalizes state-specific hyper-connectivity of the DMN in children with ADHD | ADHD-related dysfunction, ADHD | CORTEX | Our next goal was to uncover latent space features that define the abnormal state S2 in children with ADHD and determine whether methylphenidate can normalize these features. Each latent brain state is characterized by distinct patterns of functional connectivity between the key nodes of the SN, FPN and DMN. These netw... | PMC10516959 |
Methylphenidate’s modulation on SN-DMN connectivity contributes to its effect on attention | attention and cognitive control, ADHD | Our last goal was to determine whether changes in functional connectivity induced by methylphenidate in the abnormal state S2 were linked to medication’s impact on sustained attention. We used IIRV from a sustained attention task as high response variability is a hallmark of inattention. We found that methylphenidate’s... | PMC10516959 | |
Limitations | We acknowledge several limitations in this study. Our study participants were all male, not all drug naïve, and spanned a wide range from 6 to 15. To control for the effects of psychostimulants, all participants were medication-free for at least 5 half-lives prior to the MRI scans. For ethical reasons, participants wer... | PMC10516959 | ||
Conclusion | psychiatric, behavioral instability, ADHD | DISORDERS | Our study sheds new light on the mechanisms by which methylphenidate improves attention and cognitive control in children with ADHD. Using a Bayesian dynamic systems model, we investigated how methylphenidate modulates the dynamics of latent brain states and how this modulation affects behavioral variability. We found ... | PMC10516959 |
Supplementary information | The online version contains supplementary material available at 10.1038/s41386-023-01668-3. | PMC10516959 | ||
Acknowledgements | We thank Drs. Kai Makita and Shinichiro Takiguchi for their assistance with data collection. | PMC10516959 | ||
Author contributions | YM and AT designed the experiments and collected data; WC and VM designed the data analysis strategy; WC and YM analyzed the data; WC and VM wrote the manuscript; all authors edited the manuscript. | PMC10516959 | ||
Funding | BRAIN | This work was supported by Japan Society for the Promotion of Science (JSPS) Overseas Research Fellowships (#201960003), a Grant-in-Aid for Scientific Research (A)(B), Challenging Exploratory Research, and Young Scientists from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (#17K198... | PMC10516959 | |
Code availability | All code will be shared on SCSNL GitHub upon publication. | PMC10516959 | ||
Competing interests | The authors declare no competing interests. | PMC10516959 | ||
References | PMC10516959 | |||
Methods | fungal sensitization, allergic fungal airway disease, asthma | ASTHMA | Key inclusion criteria required participants of ≥18 years of age with a documented diagnosis of moderate-to-severe asthma (≥12 months) treated with inhaled corticosteroid and long-acting β2-agonist (≥4 months); evidence of allergic fungal airway disease (fungal sensitization to | PMC9897512 |
Results | deaths | Participants (n = 17) were randomized to GSK3772847 (n = 8) or placebo (n = 9) for 12 weeks and included in efficacy and safety analyses. This study was terminated early due to the high rate of screen failure, low enrollment, and unlikely feasibility of timely study completion. There were no differences observed in blo... | PMC9897512 | |
Conclusions | Lack of clinical benefits with GSK3772847 was likely due to the small sample size, highlighting the need for larger prospective studies. | PMC9897512 | ||
Data Availability | For reasons of privacy protection for study participants, GSK offers access to data and materials via controlled access. Anonymized individual participant data from this study plus the annotated case report form, protocol, reporting and analysis plan, data set specifications, raw dataset, analysis-ready dataset, and cl... | PMC9897512 | ||
Introduction | allergic fungal airway disease, asthma | ASTHMA | Thermotolerant fungal species can colonize the airways of patients with asthma, causing a range of clinical presentations grouped together as allergic fungal airway disease (AFAD) [Interleukin-33 (IL-33) levels are increased in lung epithelial cells and blood serum in patients with asthma [In a recently reported Phase ... | PMC9897512 |
Methods | PMC9897512 | |||
Study design | This was a 28-week randomized, multicenter, double-blind, sponsor-open, comparative study (see | PMC9897512 | ||
Inclusion criteria | fungal sensitization, asthma | ASTHMA, ASTHMA | Eligible participants were aged ≥18 years with documented diagnosis of moderate-to-severe asthma (≥12 months) treated with inhaled corticosteroid and long-acting β2-agonist (≥4 months); pre-bronchodilator forced expiratory volume in 1 second 35–79% of predicted, FeNO ≥25 parts per billion, Asthma Control Questionnaire-... | PMC9897512 |
Study endpoints | SECONDARY | Primary endpoints were change from baseline (Week 0) to Week 12 in blood eosinophils and FeNO. Key secondary endpoints were pharmacokinetics, serum levels of free soluble ST2 (sST2), and safety. | PMC9897512 | |
Statistical analysis | RECRUITMENT | Given the exploratory nature of the study, no formal sample size calculation was performed. Twenty participants per arm was estimated to provide an adequate level of precision for treatment differences for the primary endpoints.Enrollment was terminated early due to recruitment issues and the unlikely unfeasibility of ... | PMC9897512 | |
Results | PMC9897512 | |||
Participant disposition and baseline demographics | Between 18 April 2018 and 6 January 2020, 115 participants were screened, of which 17 participants who met the inclusion criteria were randomized and included in efficacy and safety analyses: placebo, n = 9 (6 male); GSK3772847, n = 8 (6 male). The CONSORT flow diagram is shown in | PMC9897512 | ||
CONSORT flow diagram. | *1 patient withdrew; 5 patients did not meet continuation criteria. †1 patient within this group was subsequently re-randomized and went on to complete the study. | PMC9897512 | ||
Baseline demographics and characteristics. | SD, standard deviation. | PMC9897512 | ||
Pharmacokinetics, target engagement, and efficacy | Mean C | PMC9897512 | ||
Ratio to baseline in free soluble ST2 levels*. | *This figure includes on- and off-treatment data (on-treatment defined window is 28 days). CI, confidence interval; ST2, suppressor of tumorigenicity 2. The raw data for this figure are provided as | PMC9897512 | ||
Change from baseline to Week 12 in eosinophils and FeNO. | *Lower CV, coefficient of variation; FeNO, fractional exhaled nitric oxide; ppb, parts per billion; Min, minimum; Max, maximum; Q, quartile. | PMC9897512 | ||
Safety | deaths, nasopharyngitis, headache | ADVERSE EVENT, NASOPHARYNGITIS, PROSTATE CANCER | Adverse events (AEs) were experienced by 3/8 (38%) participants with GSK3772847 and 7/9 (78%) participants with placebo, most commonly nasopharyngitis (GSK3772847, n = 1; placebo, n = 2) and headache (GSK3772847, n = 1; placebo, n = 2). No drug-related AEs or serious AEs were reported in the GSK3772847 arm. In the plac... | PMC9897512 |
Discussion | epithelial damage, deaths, asthma | ASTHMA | This study was terminated early due to the high rate of screen failure, low enrollment, and unlikely feasibility of timely study completion. While other factors such as viruses, pollens, and chitin can induce or trigger IL-33 release, the choice to restrict the study to a single population (asthma) with a specific comm... | PMC9897512 |
Supporting information | PMC9897512 | |||
CONSORT checklist. | (DOC)Click here for additional data file. | PMC9897512 | ||
Full study protocol. | (PDF)Click here for additional data file. | PMC9897512 | ||
Raw data for | (DOCX)Click here for additional data file.The authors thank Daniel Bratton for his contribution to the statistical analysis and Catherine Charron for her input in the study setup and protocol development. The authors also thank all investigators and study staff. Editorial support (in the form of writing assistance, inc... | PMC9897512 | ||
References | PMC9897512 | |||
Resumo | Potencial conflito de interesseNão há conflito com o presente artigo. | PMC10263431 | ||
Fundamento | O exercício exerce um papel positivo na evolução da doença cardíaca isquêmica, melhorando a capacidade funcional e prevenindo o remodelamento ventricular. | PMC10263431 | ||
Objetivo | Investigar o impacto do exercício sobre a mecânica de contração do ventrículo esquerdo (VE) após um infarto agudo do miocárdio (IAM) não complicado. | PMC10263431 | ||
Métodos | Um total de 53 pacientes foram incluídos e alocados aleatoriamente em um programa de treinamento supervisionado (grupo TREINO, n=27) ou em um grupo CONTROLE (n=26) que recebeu recomendações usuais sobre a prática de exercício físico após um IAM. Todos os pacientes realizaram um teste cardiopulmonar e um ecocardiograma... | PMC10263431 | ||
Resultados | Não foram encontradas diferenças nas análises dos parâmetros de | PMC10263431 | ||
Conclusões | ventricular nessa população | A atividade física não causou melhora significativa nos parâmetros de deformação longitudinal, radial ou circunferencial do VE. No entanto, o exercício teve um impacto significativo sobre a mecânica de torção do VE, que consistiu em uma redução na rotação basal, na velocidade de twist, na torção, e na velocidade de to... | PMC10263431 | |
: Influência do Exercício Físico sobre a Mecânica de Contração do Ventrículo Esquerdo após Infarto do Miocárdio | PMC10263431 | |||
Introdução | TEM | Os benefícios do exercício após um infarto agudo do miocárdio (IAM) têm sido investigados por muitos anos, e a maioria das publicações demonstraram um melhor prognóstico com essa prática.Tais benefícios têm sido demonstrado em casos de IAM com maior envolvimento contrátil do ventrículo esquerdo (VE), marcado por disfun... | PMC10263431 | |
Métodos | PMC10263431 | |||
Delineamento e população do estudo | Este foi um estudo prospectivo, longitudinal, randomizado e controlado. Pacientes com um IAM não complicado, admitidos na Unidade de Doença Coronariana Aguda do Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo (InCor/HCFMUSP), que concordaram em participar do programa, foram separados aleatori... | PMC10263431 | ||
Ecocardiograma convencional | O ecocardiograma foi realizado por um único operador experiente, cego quanto ao grupo de alocação. Um aparelho de ecocardiografia comercialmente disponível (Vivid E9; GE Medical Systems, Milwaukee, WI, EUA) foi usado, equipado com transdutores lineares de banda larga, com uma frequência de 5-2 MHz. As medidas, análise ... | PMC10263431 | ||
Aquisição e análise das imagens por | Para a aquisição das imagens e análise subsequente pela técnica Análises
| PMC10263431 | ||
– A) exemplo de medida de rotação apical. B) representação gráfica da torção do ventrículo esquerdo; FVA: fechamento da valva aórtica. | PMC10263431 | |||
Teste cardiopulmonar | O TCP foi realizado em um cicloergômetro eletromagnético (Medfit 400L, Medical Fitness Equipment, Maarn, Holanda), seguindo um protocolo de rampa, com uma velocidade de 60 rotações por minuto (rpm) e aumentos de carga de 10w a 20w por minuto, até atingir a exaustão física. Os participantes foram conectados a um ventila... | PMC10263431 | ||
Análise estatística | As variáveis contínuas foram apresentadas em média ± desvio padrão (DP) ou mediana e intervalos interquartis (IIQs), de acordo com a normalidade da distribuição avaliada pelo teste de Shapiro-Wilk. As variáveis categóricas foram apresentadas em números e porcentagens. Para o cálculo do tamanho amostral, considerou-se o... | PMC10263431 | ||
Resultados | PMC10263431 | |||
Características clínicas | De 2016 a 2019, 76 pacientes foram recrutados. Desses, 23 foram excluídos por várias razões, sendo a baixa adesão ao exercício a principal (
| PMC10263431 | ||
– Fluxograma de inclusão dos pacientes; SCA: síndrome coronariana aguda. | As características da população estão apresentadas na
| PMC10263431 | ||
Teste cardiopulmonar | A
| PMC10263431 | ||
Ecocardiograma convencional | Os dados ecocardiográficos estão apresentados na | PMC10263431 | ||
Análise da mecânica na contração do VE | PMC10263431 | |||
Corte apical | PMC10263431 | |||
Strain e strain radial (SR) | Não foram observadas diferenças significativas no
| PMC10263431 | ||
Eixo transversal | PMC10263431 | |||
Twist e torção do VE | Resultados das análises do twist a da torção do VE estão apresentados na | PMC10263431 | ||
Análise de correlação | A análise de correlação linear de Pearson foi realizada para avaliar a correlação entre os deltas de VO | PMC10263431 | ||
Discussão | O presente estudo investigou a hipótese de que a reabilitação cardiovascular, por meio de um programa de exercício supervisionado, teria um impacto sobre a mecânica de contração do VE em uma população após um IAM não complicado. Há poucos estudos investigando o real benefício do exercício sobre o remodelamento do VE, c... | PMC10263431 | ||
Limitações | Primeiro, o tamanho relativamente pequeno da amostra, a curta duração do programa de exercício, o pequeno número de sessões de treinamento para os pacientes no grupo TREINO (duas vezes por semana), e a baixa adesão de alguns pacientes ao programa pode ter diminuído o poder do estudo em demonstrar possíveis diferenças e... | PMC10263431 | ||
Conclusão | Em nosso estudo, o exercício não causou melhora significativa nos parâmetros de deformação longitudinal, radial ou circunferencial. Contudo, o exercício foi associado a uma redução na rotação basal, na velocidade de twist, na torção e na velocidade de torção. Esse desfecho pode ser interpretado como uma “reserva” da to... | PMC10263431 |
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