Disrupted Cerebrocerebellar Intrinsic Functional Connectivity in Young Adults with High-Functioning Autism Spectrum Disorder: A Data-Driven, Whole-Brain, High-Temporal Resolution Functional Magnetic Resonance Imaging Study

Abstract

This study examines the resting-state functional-connectivity (RsFc) in young adults with high-functioning autism spectrum disorder (HF-ASD) using state-of-the-art fMRI data acquisition and analysis techniques. High temporal resolution fMRI using simultaneous multi-slice acquisition aided unbiased whole-brain connectome-wide multivariate pattern analysis (MVPA) techniques for assessing RsFc. MVPA revealed two clusters (Crus I/II and lobule IX) of abnormal connectivity in the cerebellum that are consistent with the notion of a triple representation of nonmotor processing in the cerebellum. Whole-brain seed-based RsFc analyses informed by these clusters showed significant under connectivity between the cerebellar and social, emotional, and language brain regions in the HF-ASD group compared to healthy controls. The results we report are coherent with existing structural, functional, and RsFc literature in autism, extend previous literature reporting cerebellar abnormalities in the neuropathology of autism, and highlight the cerebellum as a potential target for therapeutic, diagnostic, predictive, and prognostic developments in HF-ASD. The description of functional connectivity abnormalities reported in this study using whole-brain, data-driven analyses has the potential to crucially advance the development of ASD biomarkers, targets for therapeutic interventions, and neural predictors for measuring treatment response.