Executive Dysfunction in Autism Spectrum Disorder Is Associated With Increased Cerebro-Cerebellar Resting-State Functional Connectivity.

This study examined the correlation between the cerebellar functional status and the executive function (EF) scores and explored alterations of functional connectivity (FC) among autism spectrum disorder (ASD) individuals compared to typically developing (TD) subjects. Individuals from the Autism Brain Imaging Data Exchange II dataset (ABIDE II) with complete cerebellum scanning coverage and available Behavior Rating Inventory of EF (BRIEF) t-scores were included, yielding a final sample of 71 ASD (age: 11.50 ± 2.77) and 149 TD (age:11.48 ± 1.60) individuals. Four cerebellar ROIs (left Lobule VI, left Crus I, right Crus I, and left VIIB) were defined from a meta-analysis. We quantified cerebellar intrinsic activity using percent amplitude of fluctuation (PerAF) and assessed seed-based FC within cerebro-cerebellar circuits. We found no between-group differences in PerAF across the four ROIs, and PerAF showed no significant association with global executive composite (GEC) scores within the ASD group. In contrast, FC analyses revealed predominantly increased cerebro-cerebellar connectivity in ASD. Notably, stronger FC between left Lobule VI and right inferior frontal gyrus, pars opercularis (IFGoper), as well as between left Crus I and left IFGoper were positively correlated with BRIEF Shift scores, indicating that greater coupling within these loops was associated with poorer cognitive flexibility. These results suggest that EF impairment among ASD individuals might be reflected in part by alterations in functional interconnections within the cerebro-cerebellar system. These findings help to understand the potential role of the cerebellum in EF among ASD individuals and might provide ideas for therapeutic interventions.