Novel VPS13B Mutations in Three Large Pakistani Cohen Syndrome Families Suggests a Baloch Variant with Autistic-Like Features.

BackgroundCohen Syndrome (COH1) is a rare autosomal recessive disorder, principally identified by ocular, neural and muscular deficits. We identified three large consanguineous Pakistani families with intellectual disability and in some cases with autistic traits.MethodsClinical assessments were performed in order to allow comparison of clinical features with other VPS13B mutations. Homozygosity mapping followed by whole exome sequencing and Sanger sequencing strategies were used to identify disease-related mutations.ResultsWe identified two novel homozygous deletion mutations in VPS13B, firstly a 1 bp deletion, NM_017890.4:c.6879delT; p.Phe2293Leufs*24, and secondly a deletion of exons 37-40, which co-segregate with affected status. In addition to COH1-related traits, autistic features were reported in a number of family members, contrasting with the "friendly" demeanour often associated with COH1. The c.6879delT mutation is present in two families from different regions of the country, but both from the Baloch sub-ethnic group, and with a shared haplotype, indicating a founder effect among the Baloch population.ConclusionWe suspect that the c.6879delT mutation may be a common cause of COH1 and similar phenotypes among the Baloch population. Additionally, most of the individuals with the c.6879delT mutation in these two families also present with autistic like traits, and suggests that this variant may lead to a distinct autistic-like COH1 subgroup

Attribution de croyances chez l'enfant et l'adulte (mesures implicites et explicites et liens avec le raisonnement verbal)

Attribuer des croyances occupe chez l'adulte humain typique une place centrale dans la compréhension et la prédiction du comportement d'autrui. A partir du paradigme classique de fausse croyance, nous avons développé un matériel reposant sur des stimuli animés muets présentant des variations systématiques entre différentes conditions visant à mesurer la sensibilité aux croyances (SC), aux buts et aux causalités physiques (SBCP). Nous avons validé ce matériel dans un paradigme de choix forcé chez l'adulte et recherché des mesures implicites de la SC par l'analyse de mouvements oculaires (eye tracking). Une série d'expériences nous a amenés aux conclusions suivantes : Chez l'enfant, les résultats obtenus suggèrent que des processus distincts interviennent dans le développement de la SC et le développement de la SBCP et que les performances des enfants de 4 ans sont limitées par d'autres facteurs que les contraintes générales de la tâche. Dans une tâche de traitement perceptif des stimuli, l'attribution de croyances perturbe la performance de certains sujets, ce qui suggère son caractère irrépressible. Chez l'adulte typique, la suppression expérimentale de l'accès au raisonnement verbal par une tâche de langage dégrade les performances dans l'ensemble de la tâche mais n'entrave pas spécifiquement la SC, ce qui suggère que l'attribution de croyance ne repose pas spécifiquement sur un traitement verbal.Les résultats préliminaires chez des adultes avec un syndrome d'Asperger montrent des difficultés plus importantes avec la tâche de langage mais ne montrent pas d'effet différent sur la SC, ce qui n'est pas en faveur d'un rôle particulier du langage comme relais des processus intuitifs perturbés de cognition sociale. Ces données suggèrent une certaine autonomie entre SC et langage, chez l'enfant, chez l'adulte typique comme chez l'adulte avec syndrome d'Asperger, et invitent à explorer davantage les liens entre langage et autres processus cognitifs dans les troubles du spectre autistique.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Social behavioural adaptation in Autism.

Autism is still diagnosed on the basis of subjective assessments of elusive notions such as interpersonal contact and social reciprocity. We propose to decompose reciprocal social interactions in their basic computational constituents. Specifically, we test the assumption that autistic individuals disregard information regarding the stakes of social interactions when adapting to others. We compared 24 adult autistic participants to 24 neurotypical (NT) participants engaging in a repeated dyadic competitive game against artificial agents with calibrated reciprocal adaptation capabilities. Critically, participants were framed to believe either that they were competing against somebody else or that they were playing a gambling game. Only the NT participants did alter their adaptation strategy when they held information regarding others' competitive incentives, in which case they outperformed the AS group. Computational analyses of trial-by-trial choice sequences show that the behavioural repertoire of autistic people exhibits subnormal flexibility and mentalizing sophistication, especially when information regarding opponents' incentives was available. These two computational phenotypes yield 79% diagnosis classification accuracy and explain 62% of the severity of social symptoms in autistic participants. Such computational decomposition of the autistic social phenotype may prove relevant for drawing novel diagnostic boundaries and guiding individualized clinical interventions in autism

For autistic persons by autistic persons: Acceptability of a structured peer support service according to key stakeholders

Abstract Introduction Social support is a protective factor in the mental health of autistic people. Furthermore, prejudice regarding autistic people is a constraint for the development of social support programmes by autistic peers. Methods The objective of this study is to describe the anticipated acceptability of structured peer support programmes for and by autistic persons. Fifteen key stakeholders (six autistic adults, four caregivers and five service providers) participated in in‐depth semistructured interviews. A qualitative thematic analysis of the content of the verbatim was carried out. Findings We found that while a structured peer social support programme is acceptable to autistic people and caregivers, there was no consensus among service providers. The latter expressed doubts about the ability of autistic people to offer support. The framing of discussions between peers, the training of peer helpers, the support for autistic leadership and an organization that considers the communicational and sensory characteristics of autistic persons, could influence adherence to such a programme. Moreover, a space without service providers is an important condition for the acceptability of a peer support programme. Conclusion A structured peer support service for and by autistic persons could be an innovative way to answer the unmet support needs of autistic people. It seems essential to anticipate potential barriers and facilitators and to communicate among health professionals to promote this approach and reduce possible prejudice about the ability of autistic people to offer support to their peers. More studies are necessary. Patient or Public Contribution Fifteen key stakeholders who are involved in autistic people's trajectory of service and support participated in this research. We are a research team composed of healthcare professionals and researchers, in addition to one member of our team being an autistic advocate and a mental health peer‐support mentor. Two members of our team are also parents of autistic children. The comprehensibility of the questions for the interview was consulted and discussed with one autistic advocate‐collaborator

The Impact of Verbal Capacity on Theory of Mind in Deaf and Hard of Hearing Children

International audienc

The functional database of the ARCHI project: Potential and perspectives

International audienceMore than two decades of functional magnetic resonance imaging (fMRI) of the human brain have succeeded to identify, with a growing level of precision, the neural basis of multiple cognitive skills within various domains (perception, sensorimotor processes, language, emotion and social cognition …). Progress has been made in the comprehension of the functional organization of localized brain areas. However, the long time required for fMRI acquisition limits the number of experimental conditions performed in a single individual. As a consequence, distinct brain localizations have mostly been studied in separate groups of participants, and their functional relationships at the individual level remain poorly understood. To address this issue, we report here preliminary results on a database of fMRI data acquired on 78 individuals who each performed a total of 29 experimental conditions, grouped in 4 cross-domains functional localizers. This protocol has been designed to efficiently isolate, in a single session, the brain activity associated with language, numerical representation, social perception and reasoning, premotor and visuomotor representations. Analyses are reported at the group and at the individual level, to establish the ability of our protocol to selectively capture distinct regions of interest in a very short time. Test-retest reliability was assessed in a subset of participants. The activity evoked by the different contrasts of the protocol is located in distinct brain networks that, individually, largely replicate previous findings and, taken together, cover a large proportion of the cortical surface. We provide detailed analyses of a subset of regions of relevance: the left frontal, left temporal and middle frontal cortices. These preliminary analyses highlight how combining such a large set of functional contrasts may contribute to establish a finer-grained brain atlas of cognitive functions, especially in regions of high functional overlap. Detailed structural images (structural connectivity, micro-structures, axonal diameter) acquired in the same individuals in the context of the ARCHI database provide a promising situation to explore functional/structural interdependence. Additionally, this protocol might also be used as a way to establish individual neurofunctional signatures in large cohorts

Disconnecting force from money: effects of basal ganglia damage on incentive motivation.

International audienceBilateral basal ganglia lesions have been reported to induce a particular form of apathy, termed auto-activation deficit (AAD), principally defined as a loss of self-driven behaviour that is reversible with external stimulation. We hypothesized that AAD reflects a dysfunction of incentive motivation, a process that translates an expected reward (or goal) into behavioural activation. To investigate this hypothesis, we designed a behavioural paradigm contrasting an instructed (externally driven) task, in which subjects have to produce different levels of force by squeezing a hand grip, to an incentive (self-driven) task, in which subjects can win, depending on their hand grip force, different amounts of money. Skin conductance was simultaneously measured to index affective evaluation of monetary incentives. Thirteen AAD patients with bilateral striato-pallidal lesions were compared to thirteen unmedicated patients with Parkinson's; disease (PD), which is characterized by striatal dopamine depletion and regularly associated with apathy. AAD patients did not differ from PD patients in terms of grip force response to external instructions or skin conductance response to monetary incentives. However, unlike PD patients, they failed to distinguish between monetary incentives in their grip force. We conclude that bilateral striato-pallidal damage specifically disconnects motor output from affective evaluation of potential rewards

Novel VPS13B Mutations in Three Large Pakistani Cohen Syndrome Families Suggests a Baloch Variant with Autistic-Like Features.

BackgroundCohen Syndrome (COH1) is a rare autosomal recessive disorder, principally identified by ocular, neural and muscular deficits. We identified three large consanguineous Pakistani families with intellectual disability and in some cases with autistic traits.MethodsClinical assessments were performed in order to allow comparison of clinical features with other VPS13B mutations. Homozygosity mapping followed by whole exome sequencing and Sanger sequencing strategies were used to identify disease-related mutations.ResultsWe identified two novel homozygous deletion mutations in VPS13B, firstly a 1 bp deletion, NM_017890.4:c.6879delT; p.Phe2293Leufs*24, and secondly a deletion of exons 37-40, which co-segregate with affected status. In addition to COH1-related traits, autistic features were reported in a number of family members, contrasting with the "friendly" demeanour often associated with COH1. The c.6879delT mutation is present in two families from different regions of the country, but both from the Baloch sub-ethnic group, and with a shared haplotype, indicating a founder effect among the Baloch population.ConclusionWe suspect that the c.6879delT mutation may be a common cause of COH1 and similar phenotypes among the Baloch population. Additionally, most of the individuals with the c.6879delT mutation in these two families also present with autistic like traits, and suggests that this variant may lead to a distinct autistic-like COH1 subgroup