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Background. Repetitive and restricted behaviors and interests (RRBI) are core symptoms of autism with a complex entity and are commonly categorized into ‘motor-driven’ and ‘cognitively-driven’. RRBI symptomatology depends on the individual’s clinical environment limiting the understanding of RRBI physiology, particularly their associated neuroanatomical structures. The complex RRBI heterogeneity needs to explore the whole RRBI spectrum by integrating the clinical context (autistic individuals, their relatives and typical developing (TD) individuals). We hypothesized that different RRBI dimensions would emerge by exploring the whole spectrum of RRBI, and that these dimensions are associated with neuroanatomical signatures - involving cortical & subcortical areas. Method. A sample of 792 individuals composed of 267 autistic subjects, their 370 first-degree relatives and 155 TD individuals was enrolled in the study. We assessed the whole patterns of RRBI in each individual by using the Repetitive Behavior Scale-Revised and the Yale-Brown Obsessive Compulsive Scale. We estimated brain volumes using MRI scanner for a subsample of the subjects (n=152, 42 ASD, 89 relatives and 13 TD). We first investigated the dimensionality of RRBI by performing a principal component analysis on all items of these scales and included all the sampling population. We then explored the relationship between RRBI-derived factors with brain volumes using linear regression models. Results. We identified 3 main factors (with 30.3% of the RRBI cumulative variance): Factor 1 (FA1, 12.7%) reflected mainly the ‘motor-driven’ RRBI symptoms; Factor 2 and 3 (respectively 8.8% and 7.9%) gathered mainly Y-BOCS related items and represented the ‘cognitively-driven’ RRBI symptoms. These three factors were significantly associated with the right/left putamen volumes but with opposite effects: FA1 was negatively associated with an increased volume of the right/left putamen conversely to FA2 & FA3 (all uncorrected pConclusion. Our results suggested 3 coherent RRBI dimensions involving the putamen commonly and other structures according to the RRBI dimension. The exploration of the putamen’s integrative role in RSBI needs to be strengthened in further studies.

BackgroundExploring neural network dynamics during social interaction could help to identify biomarkers of Autism Spectrum Disorders (ASD). Recently, the cerebellum, a brain structure that plays a key role in social cognition, has attracted growing interest. Here, we investigated the electrophysiological activity of the cortico-cerebrum network during real-time social interaction in ASD. We focused our analysis on theta oscillations (3-8 Hz), which have been associated with large-scale coordination of distant brain areas and might contribute to interoception, motor control, and social event anticipation, all skills known to be altered in ASD.MethodsWe combined the Human Dynamic Clamp, a paradigm for studying realistic social interactions using a virtual avatar, with high-density electroencephalography (HD-EEG). Using source reconstruction, we investigated power in the cortex and the cerebellum, along with coherence between the cerebellum and three cortical areas, and compared our findings in a sample of participants with ASD and with typical development (TD) (n = 140). We developed an open-source pipeline to analyse neural dynamics at the source level from HD-EEG data.ResultsIndividuals with ASD showed a significant increase in theta band power during social interaction compared to resting state, unlike individuals with TD. In particular, we observed a higher theta power over the cerebellum and the frontal and temporal cortices in the ASD group compared to the TD group, alongside bilateral connectivity alterations between the cerebellum and the sensorimotor and parietal cortices.ConclusionsThis study uncovered ASD-specific alterations in the theta dynamics, especially in a network between the cerebellum and social-associated cortical networks.

Literature reference for the preprint first posted on medRxiv: https://www.medrxiv.org/content/10.1101/19013771v1; Background: The Human Dynamic Clamp (HDC) is a human-machine interface for studying realistic social interaction under controlled and reproducible conditions. Here, we propose to probe the validity of the HDC as psychometric instrument for quantifying social abilities in children with Autism Spectrum Disorder (ASDs) and neurotypical development. Methods: To study behavioral synchrony, we derived from interaction with the HDC avatar, five standardized scores following a gradient from sensory-motor and motor to higher socio-cognitive skills, in a sample of 155 individuals (113 with ASDs, 42 typically developing participants; aged 5 to 25 years; IQ>70). Results: We conducted regression analyses with normative modeling on global scores according to four sub-conditions (avatar behavior "cooperative/competitive", human task "in-phase/anti-phase", diagnosis and age at inclusion). Children with ASDs tend to have significant lower scores than controls for motor skills. Independently of the phenotype, socio-cognitive skills increase with developmental age, while being affected by the ongoing task and the behavior of the avatar.Discussion: The weaker performance in participants with ASDs for motor skills suggests convergent validity for this score of the HDC during social interaction. Results provide additional evidence of a relationship between sensory-motor and socio-cognitive skills. As we found a significant main effect of age at inclusion, HDC may be used as a marker of aging of socio-cognitive skills during real-time social interaction. Conclusion: Through its standardized and objective evaluation, the HDC not only represents a valid paradigm for the study of interpersonal synchrony but also a clinically relevant psychometric instrument for the evaluation and stratification of socio-motor dysfunctions.

The validity of the standard version of the Liege Intra-Nuclear Cascade (INCL4) model, which has been shown to be quite successful for the description of spallation reactions, is limited to an upper incident energy of ∼2 GeV, because inelastic elementary processes are restricted to the excitation and de-excitation of the Delta resonance. In this paper, the INCL4 model is extended to higher incident energy by including other inelastic elementary collisions. However, excitation of heavier baryonic resonances is replaced by direct multipion production in elementary nucleon–nucleon and pion–nucleon collisions. The predictions of the modified model for production of charged pions by proton and pion beams off nuclei are compared with experimental data of the HARP Collaboration for beam energies between 2 and 12 GeV. The apparent duality between the approach based on excitation of numerous baryonic resonances and our approach is briefly discussed.

The Li` ege intranuclear cascade model has been improved by allowing for multipion production in nucleon- nucleon collisions, a feature that is more and more relevant in nucleon-induced spallation reactions when the incident kinetic energy exceeds 2 GeV or so. A phase space model is presented for multipion production and tested by comparing with experimental data.

Background: Exploring neural network dynamics during social interaction could help to identify biomarkers of Autism Spectrum Disorders (ASD). Recently, the cerebellum, a brain structure that plays a key role in social cognition, has attracted growing interest. Here, we investigated the electrophysiological activity of the cortico-cerebrum network during real-time social interaction in ASD. We focused our analysis on theta oscillations (3-8 Hz), which have been associated with large-scale coordination of distant brain areas and might contribute to interoception, motor control, and social event anticipation, all skills known to be altered in ASD. Methods: We combined the Human Dynamic Clamp, a paradigm for studying realistic social interactions using a virtual avatar, with high-density electroencephalography (HD-EEG). Using source reconstruction, we investigated power in the cortex and the cerebellum, along with coherence between the cerebellum and three cortical areas, and compared our findings in a sample of participants with ASD and with typical development (TD) (n = 140). We developed an open-source pipeline to analyse neural dynamics at the source level from HD-EEG data. Results: Individuals with ASD showed a significant increase in theta band power during social interaction compared to resting state, unlike individuals with TD. In particular, we observed a higher theta power over the cerebellum and the frontal and temporal cortices in the ASD group compared to the TD group, alongside bilateral connectivity alterations between the cerebellum and the sensorimotor and parietal cortices.Conclusions: This study uncovered ASD-specific alterations in the theta dynamics, especially in a network between the cerebellum and social-associated cortical networks.