Terra Incognita - Contributions of the Olivo-Cerebellar System to Autism Spectrum Disorder

The inferior olivary nuclei (ION), a key component of the olivo-cerebellar system, remain understudied in autism spectrum disorder (ASD) research despite evident cerebellar involvement. This perspective piece aims to elucidate the critical role of the ION in cerebellar microcircuitry and its potential implications in ASD pathophysiology. We review the olivo- cerebellar system and the structural and functional alterations of the ION in autism, highlighting findings from neuroanatomical, neuroimaging, and behavioral studies. ION disruptions, although underexplored, may have a major role in the symptomatology of ASD, particularly higher-order cognitive abilities, rapid stimuli processing, and motor coordination. Specifically, we highlight how anomalies in olivary neuron morphology and olivo-cerebellar connectivity patterns may underlie deficits in temporal processing and motor learning observed in ASD. Furthermore, we discuss the challenges in brainstem imaging and recent advancements in ultra-high field (UHF) 7 T MRI technology, as standard neuroimaging techniques. As these neuroimaging techniques continue to evolve, further investigation of the functional territories of the ION holds promise for providing essential understandings into ASD processes and may lead to pioneering therapeutic options targeting this crucial brainstem area.