Enhanced motor noise in an autism subtype with poor motor skills

Early motor difficulties are a common in many, but not all, autistic individuals. These difficulties tend to be highly present in individuals carrying rare genetic mutations with high penetrance for autism. Many of these rare genetic mechanisms also cause neurophysiological dysregulation of excitation-inhibition balance (E:I). A predicted downstream consequence of E:I imbalance in motor circuitry would translate behaviorally into enhanced ‘motor noise’ – that is, increased variability in execution of motor actions. Here we tested the hypothesis that autistic individuals with the most pronounced motor difficulties would be most affected by enhanced motor noise. Unsupervised data-driven clustering on a standardized test of motor skills (n=156, age = 3-16 years) identified the presence of two robust and highly stable autism motor subtypes described by relatively intact versus highly impaired motor skills. With motor kinematics data recorded during a simple reach-to-drop task, we observed that enhanced motor noise is a specific characteristic of the autism subtype with highly impaired motor skills. Autistic individuals with poor motor skills may be differentially affected by E:I imbalance within motor circuitry. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme under grant agreement No 755816 (AUTISMS) (ERC Starting Grant to MVL). Data collection and research from IRCCS-MEDEA has been funded by grants from the Italian Ministry of Health to AC (Ricerca Finalizzata GR-2011-02348929; Ricerca Corrente 2023, Progetto Mosaico) ### 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: Data from this work is a re-analysis of data that is either publicly available from the National Institute of Mental Health Data Archive (NDA) or in-house data collected by the authors at IRCCS Medea. For the IRCCS Medea dataset re-analysis, written parental informed consent was obtained for all participants, and the protocol was approved by the Eugenio Medea Scientific Institute's the ethics committee. 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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Publicly available data re-analyzed for this work can be found on the National Institute of Mental Health Data Archive (NDA). All other in-house data from the present study are available upon reasonable request to the authors.