Sex differences in functional connectivity during fetal brain development

ABSTRACT Sex-related differences in brain and behavior are apparent across the life course, but the exact set of processes that guide their emergence in utero remains a topic of vigorous scientific inquiry. Here, we evaluate sex and gestational age (GA)-related change in functional connectivity (FC) within and between brain wide networks. Using resting-state functional magnetic resonance imaging we examined FC in 118 human fetuses between 25.9 and 39.6 weeks GA (70 male; 48 female). Infomap was applied to the functional connectome to identify discrete prenatal brain networks in utero . A consensus procedure produced an optimal model comprised of 16 distinct fetal neural networks distributed throughout the cortex and subcortical regions. We used enrichment analyses to assess network-level clustering of strong FC-GA correlations separately in each sex group, and to identify network pairs exhibiting distinct patterns of GA-related change in FC between males and females. We discovered both within and between network FC-GA associations that varied with sex. Specifically, associations between GA and posterior cingulate-temporal pole and fronto-cerebellar FC were observed in females only, whereas the association between GA and increased intracerebellar FC was stronger in males. These observations confirm that sexual dimorphism in functional brain systems emerges during human gestation.