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1.
Clin Med (Lond) ; 21(1): 53-58, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33479068

RESUMO

BACKGROUND: Fibromyalgia and myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are poorly understood conditions with overlapping symptoms, fuelling debate as to whether they are manifestations of the same spectrum or separate entities. Both are associated with hypermobility, but this remains significantly undiagnosed, despite impact on quality of life. OBJECTIVE: We planned to understand the relevance of hypermobility to symptoms in fibromyalgia and ME/CFS. METHOD: Sixty-three patient participants presented with a confirmed diagnosis of fibromyalgia and/or ME/CFS; 24 participants were healthy controls. Patients were assessed for symptomatic hypermobility. RESULTS: Evaluations showed exceptional overlap in patients between fibromyalgia and ME/CFS, plus 81% met Brighton criteria for hypermobility syndrome (odds ratio 7.08) and 18% met 2017 hypermobile Ehlers-Danlos syndrome (hEDS) criteria. Hypermobility scores significantly predicted symptom levels. CONCLUSION: Symptomatic hypermobility is particularly relevant to fibromyalgia and ME/CFS, and our findings highlight high rates of mis-/underdiagnosis. These poorly understood conditions have a considerable impact on quality of life and our observations have implications for diagnosis and treatment targets.

2.
Trends Neurosci ; 44(1): 39-51, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378656

RESUMO

Interoception, the sense of the body's internal physiological state, underpins homeostatic reflexes, motivational states, and sensations contributing to emotional experiences. The continuous nature of interoceptive processing, coupled to behavior, is implicated in the neurobiological construction of the sense of self. Aberrant integration and control of interoceptive signals, originating in the brain and/or the periphery, can perturb the whole system. Interoceptive abnormalities are implicated in the pathophysiology of psychiatric disorders and in the symptomatic expression of developmental, neurodegenerative, and neurological disorders. Moreover, interoceptive mechanisms appear central to somatic disorders of brain-body interactions, including functional digestive disorders, chronic pain, and comorbid conditions. The present article provides an overview of disorders of interoception and suggests future directions for better understanding, diagnosis, and management of these disorders.

4.
J Exp Psychol Gen ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33180532

RESUMO

Fear is coupled to states of physiological arousal. We tested how learning and memory of threat, specifically conditioned fear, is influenced by interoceptive signals. Forty healthy individuals were exposed to two threat (conditioned stimuli [CS+], paired with electrocutaneous shocks) and two safety (CS-) stimuli, time-locked to either cardiac ventricular systole (when arterial baroreceptors signal cardiovascular arousal to brainstem), or diastole (when these afferent signals are quiescent). Threat learning was indexed objectively using skin conductance responses (SCRs). During acquisition of threat contingencies, cardiac effects dominated: Stimuli (both CS+ and CS-) presented at systole evoked greater SCR responses, relative to stimuli (both CS+ and CS-) presented at diastole. This difference was amplified in more anxious individuals. Learning of conditioned fear was established by the end of the acquisition phase, which was followed by an extinction phase when unpaired CSs were presented at either the same or switched cardiac contingencies. One day later, electrocutaneous shocks triggered the reinstatement of fear responses. Subsequent presentation of stimuli previously encoded at systole evoked higher SCRs. Moreover, only those participants for whom stimuli had the same cardiac-contingency over both acquisition and extinction phases retained conditioned fear memory (i.e., CS+ > CS-). Our findings reveal two important cardiac afferent effects on threat learning and memory: 1) Cardiac signals bias processing toward threat; and 2) cardiac signals are a context for fear memory; altering this context can disrupt the memory. These observations suggest how threat reactivity may be reinforced and maintained by both acute and enduring states of cardiac arousal. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

5.
Psychophysiology ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33037836

RESUMO

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.

7.
Neuroimage Clin ; 27: 102322, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645662

RESUMO

Individuals who engage in binge drinking behaviors may show evidence of impaired cognitive function and emotional dysregulation. Impaired empathy, characterized by a reduced ability to understand and respond appropriately to feelings of others, is increasingly recognized for its role in Alcohol Use Disorders (AUD). The present study examined a population of young adult social drinkers to compare individuals who show binge drinking behavior to those who do not on measures of empathic processing and associated neural responses. A secondary aim explored similarities and differences between binge drinkers living in the UK and France. Alcohol drinking history and impulsivity ratings were recorded from seventy-one participants [(37 UK (Binge drinkers N = 19); 34 France (Binge drinkers N = 17)], who then underwent a neuroimaging study. During functional magnetic resonance imaging, participants viewed images of bodily pain (vs. no-pain), while adopting the perspective of self (pain recipient) or other (observer of someone else experiencing pain). Anterior midcingulate cortex (aMCC) and insula activation distinguished pain from no-pain conditions. Binge drinkers showed stronger regional neural activation than non-binge drinkers within a cluster spanning fusiform gyrus and inferior temporal gyrus, encompassing the Fusiform Body Area. Binge drinkers compared to non-binge drinkers also took longer to respond when viewing pictures depicting pain, in particular when adopting the perspective of self. Relationships between changes in brain activation and behavioural responses in pain versus no pain conditions (self or other perspective) indicated that whereas non-binge drinkers engage areas supporting self to other distinction, binge drinkers do not. Our findings suggest that alcohol binge drinking is associated with different empathy-related behavioral and brain responses, consistent with the proposed importance of empathy in the development of AUD.

8.
Neurosci Biobehav Rev ; 116: 283-300, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32610178

RESUMO

Loneliness can be operationalized as the actual or perceived absence of those social relationships that serve to meet basic emotional needs. In contrast to solitude, a chosen state of being without company, loneliness is associated with negative affect and emotional distress. Loneliness can have detrimental effects on mental and physical wellbeing, expressed as an increased risk of morbidity and mortality. Higher rates of loneliness are observed in patients suffering from chronic health conditions, mental health conditions, cardiovascular problems, and neurodivergent populations, including autistic individuals. While the link between poor health and loneliness is established, the identification of relevant underlying mechanisms is a difficult endeavor. In this narrative review, we provide an overview of published research and related literature describing the manifold interactions between loneliness, affective symptomatology, neural and embodied processing relevant to physical health, mental health, and neurodiversity. We propose a framework that can inform the identification of psychophysiological mechanisms underlying the link between loneliness and affective symptomatology that may represent interventional targets to mitigate the associated cycle of biopsychosocial morbidity.

9.
Front Behav Neurosci ; 14: 111, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670033

RESUMO

Knowledge of brain mechanisms underlying self-regulation can provide valuable insights into how people regulate their thoughts, behaviors, and emotional states, and what happens when such regulation fails. Self-regulation is supported by coordinated interactions of brain systems. Hence, behavioral dysregulation, and its expression as impulsivity, can be usefully characterized using functional connectivity methodologies applied to resting brain networks. The current study tested whether individual differences in trait impulsivity are reflected in the functional architecture within and between resting-state brain networks. Thirty healthy individuals completed a self-report measure of trait impulsivity and underwent resting-state functional magnetic resonance imaging. Using Probabilistic Independent Components Analysis in FSL MELODIC, we identified across participants 10 networks of regions (resting-state networks) with temporally correlated time courses. We then explored how individual expression of these spatial networks covaried with trait impulsivity. Across participants, we observed that greater self-reported impulsivity was associated with decreased connectivity of the right lateral occipital cortex (peak mm 46/-70/16, FWE 1-p = 0.981) with the somatomotor network. No supratheshold differences were observed in between-network connectivity. Our findings implicate the somatomotor network, and its interaction with sensory cortices, in the control of (self-reported) impulsivity. The observed "decoupling" may compromise effective integration of early perceptual information (from visual and somatosensory cortices) with behavioral control programs, potentially resulting in negative consequences.

10.
J Med Internet Res ; 22(6): e15171, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32519676

RESUMO

BACKGROUND: The written format and literacy competence of screen-based texts can interfere with the perceived trustworthiness of health information in online forums, independent of the semantic content. Unlike in professional content, the format in unmoderated forums can regularly hint at incivility, perceived as deliberate rudeness or casual disregard toward the reader, for example, through spelling errors and unnecessary emphatic capitalization of whole words (online shouting). OBJECTIVE: This study aimed to quantify the comparative effects of spelling errors and inappropriate capitalization on ratings of trustworthiness independently of lay insight and to determine whether these changes act synergistically or additively on the ratings. METHODS: In web-based experiments, 301 UK-recruited participants rated 36 randomized short stimulus excerpts (in the format of information from an unmoderated health forum about multiple sclerosis) for trustworthiness using a semantic differential slider. A total of 9 control excerpts were compared with matching error-containing excerpts. Each matching error-containing excerpt included 5 instances of misspelling, or 5 instances of inappropriate capitalization (shouting), or a combination of 5 misspelling plus 5 inappropriate capitalization errors. Data were analyzed in a linear mixed effects model. RESULTS: The mean trustworthiness ratings of the control excerpts ranged from 32.59 to 62.31 (rating scale 0-100). Compared with the control excerpts, excerpts containing only misspellings were rated as being 8.86 points less trustworthy, those containing inappropriate capitalization were rated as 6.41 points less trustworthy, and those containing the combination of misspelling and capitalization were rated as 14.33 points less trustworthy (P<.001 for all). Misspelling and inappropriate capitalization show an additive effect. CONCLUSIONS: Distinct indicators of incivility independently and additively penalize the perceived trustworthiness of online text independently of lay insight, eliciting a medium effect size.

11.
Epilepsia ; 61(6): 1156-1165, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32501547

RESUMO

OBJECTIVE: Dissociative traits represent a disturbance in selfhood that may predispose to, and trigger, functional seizures (FSs). The predictive representation and control of the internal physiological state of the body (interoception) are proposed to underpin the integrity of the sense of self ("minimal selfhood"). Therefore, discrepancies between objective and subjective aspects of interoception may relate to symptom expression in patients with FSs. Here, we tested whether individual differences in trait measures of interoception relate to dissociative symptoms, and whether state interoceptive deficits predict FS occurrence. METHODS: Forty-one participants with FSs and 30 controls completed questionnaire ratings of dissociation, and measures of (1) interoceptive accuracy (IA)-objective performance on heartbeat detection tasks; (2) trait interoceptive sensibility-subjective sensitivity to internal sensations (using the Porges Body Perception Questionnaire); and (3) state interoceptive sensibility-subjective trial-by-trial measures of confidence in heartbeat detection. Interoceptive trait prediction error (ITPE) was calculated from the discrepancy between IA and trait sensibility, and interoceptive state prediction error (ISPE) from the discrepancy between IA and state sensibility. RESULTS: Patients with FSs had significantly lower IA and greater trait interoceptive sensibility than healthy controls. ITPE was the strongest predictor of dissociation after controlling for trait anxiety and depression in a regression model. ISPE correlated significantly with FS frequency after controlling for state anxiety. SIGNIFICANCE: Patients with FSs have disturbances in interoceptive processing that predict both dissociative traits reflecting the disrupted integrity of self-representation, and the expression of FSs. These findings provide insight into the pathophysiology of functional neurological disorder, and could lead to novel diagnostic and therapeutic approaches.


Assuntos
Conscientização/fisiologia , Transtornos Dissociativos/diagnóstico , Transtornos Dissociativos/psicologia , Interocepção/fisiologia , Convulsões/diagnóstico , Convulsões/psicologia , Adulto , Ansiedade/diagnóstico , Ansiedade/fisiopatologia , Ansiedade/psicologia , Transtornos Dissociativos/fisiopatologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Testes Neuropsicológicos , Convulsões/fisiopatologia
12.
Hum Brain Mapp ; 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32596977

RESUMO

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.

13.
Cortex ; 128: 88-106, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32325277

RESUMO

Autism symptomology has a profound impact on cognitive and affective functioning, yet we know relatively little about how it shapes patterns of ongoing thought. In an exploratory study in a large population of neurotypical individuals, we used experience sampling to characterise the relationship between ongoing cognition and self-reported autistic traits. We found that with increasing autistic symptom score, cognition was characterised by thinking more in words than images. Analysis of structural neuroimaging data found that autistic traits linked to social interaction were associated with greater cortical thickness in a region of lingual gyrus (LG) within the occipital cortex. Analysis of resting state functional neuroimaging data found autistic traits were associated with stronger connectivity between the LG and a region of motor cortex. Importantly, the strength of connectivity between the LG and motor cortex moderated the link between autistic symptoms and thinking in words: individuals showing higher connectivity showed a stronger association between autistic traits and thinking in words. Together we provide behavioural and neural evidence linking autistic traits to the tendency to think in words which may be rooted in underlying cortical organisation. These observations lay the groundwork for research into the form and content of self-generated thoughts in individuals with the established diagnosis of autism.

14.
Sci Rep ; 10(1): 4184, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144304

RESUMO

Interoceptive signals concerning the internal physiological state of the body influence motivational feelings and action decisions. Cardiovascular arousal may facilitate inhibition to mitigate risks of impulsive actions. Baroreceptor discharge at ventricular systole underpins afferent signalling of cardiovascular arousal. In a modified Go/NoGo task, decisions to make or withhold actions on 'Choose' trials were not influenced by cardiac phase, nor individual differences in heart rate variability. However, cardiac interoceptive awareness and insight predicted how frequently participants chose to act, and their speed of action: Participants with better awareness and insight tended to withhold actions and respond slower, while those with poorer awareness and insight tended to execute actions and respond faster. Moreover, self-reported trait urgency correlated negatively with intentional inhibition rates. These findings suggest that lower insight into bodily signals is linked to urges to move the body, putatively by engendering noisier sensory input into motor decision processes eliciting reactive behaviour.


Assuntos
Comportamento Impulsivo/fisiologia , Interocepção/fisiologia , Adolescente , Adulto , Conscientização , Eletrocardiografia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Adulto Jovem
15.
Addict Biol ; 25(4): e12796, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31222868

RESUMO

Even at low to moderate doses, ingestion of the widely used recreational drug alcohol (ethanol) can impact cognitive and emotional processing. Recent studies show that the sense of agency (SoA; ie, the subjective experience of voluntary control over actions) can be modulated by specific pharmacological manipulations. The SoA, as quantified by the intentional binding (IB) paradigm, is enhanced by direct or indirect dopaminergic agonists in patients with Parkinson's disease and by ketamine (an N-methyl-D-aspartate (NMDA) receptor antagonist) in healthy individuals. These findings implicate dopaminergic and glutamatergic neurotransmission in mechanisms underlying SoA. Alcohol has a complex set of actions, including disinhibition of dopaminergic neurotransmission and allosteric antagonism at NMDA receptors. Here, we tested the hypothesis that low to moderate doses of alcohol would enhance SoA, and impact impulsivity and subjective emotional state. We conducted two experiments in 59 healthy male and female social drinkers, who ingested either a placebo "vehicle," or one of two doses of ethanol: 0.4 and 0.6 g/kg. In both experiments, we observed increased SoA/IB at both doses of alcohol exposure, relative to the placebo condition. We found no correlation between the effects of alcohol on IB and on impulsivity or subjective emotional state. Our findings might have implications for social and legal responsibility related to alcohol use, particularly in states prior to overt intoxication. Further studies are necessary to investigate the effects of alcohol and other addictive substances on the SoA.

16.
BJPsych Bull ; 44(2): 60-66, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31685068

RESUMO

Advances in digital technology have a profound impact on conventional healthcare systems. We examine the trailblazing use of online interventions to enable autonomous psychological care which can greatly enhance individual- and population-level access to services. There is strong evidence supporting online cognitive-behavioural therapy and more engaging programmes are now appearing so as to reduce user 'attrition'. The next generation of autonomous psychotherapy programmes will implement adaptive and personalised responses, moving beyond impersonalised advice on cognitive and behavioural techniques. This will be a more authentic form of psychotherapy that integrates therapy with the actual relationship experiences of the individual user.

17.
Psychiatry Res Neuroimaging ; 295: 111020, 2020 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-31790922

RESUMO

Perseverative cognition (i.e. rumination and worry) describes intrusive, uncontrollable, repetitive thoughts. These negative affective experiences are accompanied by physiological arousal, as if the individual were facing an external stressor. Perseverative cognition is a transdiagnostic symptom, yet studies of neural mechanisms are largely restricted to specific clinical populations (e.g. patients with major depression). The present study applied activation likelihood estimation (ALE) meta-analyses to 43 functional neuroimaging studies of perseverative cognition to elucidate the neurobiological substrates across individuals with and without psychopathological conditions. Task-related and resting state functional connectivity studies were examined in separate meta-analyses. Across task-based studies, perseverative cognition engaged medial frontal gyrus, cingulate gyrus, insula, and posterior cingulate cortex. Resting state functional connectivity studies similarly implicated posterior cingulate cortex together with thalamus and anterior cingulate cortex (ACC), yet the involvement of ACC distinguished between perseverative cognition in healthy controls (HC) and clinical groups. Perseverative cognition is accompanied by the engagement of prefrontal, insula and cingulate regions, whose interaction may support the characteristic conjunction of self-referential and affective processing with (aberrant) cognitive control and embodied (autonomic) arousal. Within this context, ACC engagement appears critical for the pathological expression of rumination and worry.


Assuntos
Encéfalo/diagnóstico por imagem , Giro do Cíngulo/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Ruminação Cognitiva/fisiologia , Adulto , Nível de Alerta/fisiologia , Encéfalo/fisiopatologia , Cognição/fisiologia , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Masculino
18.
Neuroimage ; 202: 116072, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31386920

RESUMO

The dynamic embodiment of psychological processes is evident in the association of health outcomes, behavioural traits and psychological functioning with Heart Rate Variability (HRV). The dominant high-frequency component of HRV is an index of the central neural control of heart rhythm, mediated via the parasympathetic vagus nerve. HRV provides a potential objective measure of action policies for the adaptive and predictive allostatic regulation of homeostasis within the cardiovascular system. In its support, a network of brain regions (referred to as the 'central autonomic network') maps internal state, and controls autonomic responses. This network includes regions of prefrontal cortex, anterior cingulate cortex, insula, amygdala, periaqueductal grey, pons and medulla. Human neuroimaging studies of neural activation and functional connectivity broadly endorse this architecture, and its link with cardiac regulation at rest and dysregulation in clinical states that include affective disorders. In this review, we appraise neuroimaging research and related evidence for HRV as an informative marker of autonomic integration with affect and cognition, taking a perspective on function and organisation. We consider evidence for the utility of HRV as a metric to inform targeted interventions to improve autonomic and affective dysregulation, and suggest research questions for further investigation.


Assuntos
Sistema Nervoso Autônomo/fisiologia , Encéfalo/fisiologia , Frequência Cardíaca/fisiologia , Homeostase/fisiologia , Transtornos do Humor/fisiopatologia , Animais , Humanos , Vias Neurais/fisiologia , Neuroimagem
19.
Biol Psychol ; 146: 107711, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31163190

RESUMO

The sensing of internal bodily signals, a process known as interoception, contributes to subjective emotional feeling states that can guide empathic understanding of the emotions of others. Individuals with Autism Spectrum Conditions (ASC) typically show an attenuated intuitive capacity to recognise and interpret other peoples' emotional signals. Here we test directly if differences in interoceptive processing relate to the ability to perceive emotional signals from the intonation of speech (affective prosody) in ASC adults. We employed a novel prosody paradigm to compare emotional prosody recognition in ASC individuals and a group of neurotypical controls. Then, in a larger group of ASC individuals, we tested how recognition of affective prosody related to objective, subjective and metacognitive (awareness) psychological dimensions of interoception. ASC individuals showed reduced recognition of affective prosody compared to controls. Deficits in performance on the prosody task were mitigated by greater interoceptive awareness, so that ASC individuals were better able to judge the prosodic emotion if they had better insight into their own interoceptive abilities. This data links the ability to access interoceptive representations consciously to the recognition of emotional expression in others, suggesting a crossmodal target for interventions to enhance interpersonal skills.


Assuntos
Transtorno do Espectro Autista/psicologia , Emoções/fisiologia , Interocepção/fisiologia , Adulto , Conscientização , Compreensão , Empatia , Feminino , Humanos , Masculino , Metacognição , Percepção da Fala , Adulto Jovem
20.
Front Psychiatry ; 10: 29, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30890965

RESUMO

Tourette syndrome is a hyperkinetic movement disorder. Characteristic features include tics, recurrent movements that are experienced as compulsive and "unwilled"; uncomfortable premonitory sensations that resolve through tic release; and often, the ability to suppress tics temporarily. We demonstrate how these symptoms and features can be understood in terms of aberrant predictive (Bayesian) processing in hierarchical neural systems, explaining specifically: why tics arise, their "unvoluntary" nature, how premonitory sensations emerge, and why tic suppression works-sometimes. In our model, premonitory sensations and tics are generated through over-precise priors for sensation and action within somatomotor regions of the striatum. Abnormally high precision of priors arises through the dysfunctional synaptic integration of cortical inputs. These priors for sensation and action are projected into primary sensory and motor areas, triggering premonitory sensations and tics, which in turn elicit prediction errors for unexpected feelings and movements. We propose experimental paradigms to validate this Bayesian account of tics. Our model integrates behavioural, neuroimaging, and computational approaches to provide mechanistic insight into the pathophysiological basis of Tourette syndrome.

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