Cerebellar Crus I and Crus II Structure and Excitation/Inhibition Balance in Autism Spectrum Disorder

PURPOSE: Cerebro-cerebellar network dynamics are highly implicated in autism spectrum disorder (ASD), particularly the posterolateral cerebellar hemispheres. Cellular alterations in the cerebellum are also consistently reported in post-mortem research, suggesting potential impacts on the balance between excitatory glutamatergic (Glu) and inhibitory GABAergic signaling (E/I). Emerging evidence further indicates that the cerebellum supports multiple cognitive and behavioral domains associated with the diagnostic criteria for ASD. METHODS: H MR spectroscopy data (MEGA-SPECIAL) to examine neurometabolites of Glu and GABA from the cerebellar hemispheres of autistic (n=13) and neurotypical children (n =16). We also explored preliminary comparisons with autistic adolescents (n=7) and assessed relationships for social communication, restricted and repetitive behaviors, and sensory processing differences. RESULTS: Crus I and II were significantly thinner in autistic children compared to neurotypical children. While there were no significant group differences in the subset of participants with quality neurometabolite measurements, p > 0.05, there were salient relationships between E/I, cerebellar structure, and core ASD domains. Thinner Crus I grey matter and smaller Crus II volume were correlated with higher E/I, especially for Glu in left Crus I and right Crus II. Morphometric properties and E/I were also associated with self-injurious and other restricted and repetitive behaviors. CONCLUSION: Our preliminary findings are limited by the small sample size but suggest a potential relationship between cerebellar structure, the balance of excitation-inhibition in cerebro-cerebellar networks, and the core domains of autism spectrum disorder.