Fetal functional connectivity prospectively associates with autistic traits in toddlerhood

Accumulating evidence from neuroimaging studies has implicated widespread disruptions in brain connectivity in autism spectrum disorder (ASD), with altered connectivity patterns reported as early as infancy. However, it remains unexplored whether functional connectivity differences are evident prior to birth in the brain of fetuses who will later exhibit autistic traits in early childhood. In this study, we leveraged a longitudinal sample of 62 children with both quality-assured fetal brain resting-state MRI data and a parent-report measure of autistic traits at age 3 years. Enrichment analysis was employed to identify network pairs significantly correlated with autistic traits. Specificity analysis was conducted by additionally controlling for other childhood psychopathology. Our results demonstrated significant correlations between autistic traits and functional connectivity in the cingulate-left temporal and right prefrontal-left operculum network pairs in both the primary and specificity analyses. Visual network connectivity with prefrontal and opercular regions was also implicated. These network pairs demonstrated positive associations with autistic traits, indicating that stronger connectivity between these network pairs was associated with higher autistic traits. In contrast, weaker cerebellum-right operculum connectivity was associated with higher autistic traits, uniquely in the specificity analysis. This study provides the first in vivo evidence prospectively linking variation in functional network connectivity in the fetal brain to autistic traits in toddlerhood. These findings extend the current understanding of the prenatal brain origins of ASD and highlight the potential of fetal rs-fMRI as a tool to identify neural signatures related to social-emotional development and ASD likelihood.