Cortico-Cerebellar Neurodynamics during Social Interaction in Autism Spectrum Disorder

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. ### Competing Interest Statement D.E. is a full-time employee of F. Hoffmann-La Roche Ltd. All other authors report no biomedical financial interests or potential conflicts of interest. ### Funding Statement This study was funded by Fondation de France (2015-00059547) and Institut Pasteur. A.B. was supported by a fellowship of the French Ministry of Foreign Affairs. G.D. was supported by the Institute for Data Valorization (IVADO) Professor Startup and Operational Funds and by Fonds de la Recherche en Sante du Québec (FRSQ) junior 1 salary award. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of the Robert Debré Hospital gave ethical approval for this work (study approval no. 08-029). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.