Task-based functional connectivity in striato-motor-cortical system in autism: Associations with sex and executive function

Previously we found that female autistic youth (Aut-F) showed reduced brain response in dorsal striatum (putamen) when viewing human motion, alongside larger rare copy number variants that included genes expressed in early striatal development. Thus, striatal differences may characterize Aut-F, but broader systems-level and behavioral implications of these differences remain unexplored. We conducted secondary data analysis of the sex-balanced cohort (8–17 y) in which we first discovered these patterns, in order to: 1) understand how functional connectivity between putamen and frontal targets might vary from the non-autistic population, and differ by sex; and 2) explore which brain connectivity and phenotypic features best predicted executive function. Using psychophysiological interaction analysis ( N = 184), we found that Aut-F youth ( n = 45) showed reduced functional connectivity between left anterior putamen (Pa) and dorsal premotor cortex/pre-supplementary motor area versus matched non-autistic female peers (NAut-F; n = 45), suggesting reduced engagement of a typical Pa-frontal pathway for attentional regulation. Best subsets regression ( N = 200) indicated that left Pa-left dorsolateral prefrontal functional connectivity explained significant variance in executive functioning across all participants, controlling for neurotype. These results suggest that striatal differences in Aut-F may have adaptive consequences in part due to impacts on connectivity between Pa and frontal regions important for attentional control.