Sex differences in functional connectivity during fetal brain development

Area of Science:

• Neuroscience
• Developmental Neuroscience
• Human Fetal Development

Background:

• Sex-related differences in brain and behavior are observed throughout life.
• The precise developmental processes driving these differences in utero are not fully understood.
• Understanding prenatal brain development is crucial for identifying potential neurodevelopmental variations.

Purpose of the Study:

• To investigate sex and gestational age-related changes in functional connectivity (FC) within and between prenatal brain networks.
• To identify specific fetal brain networks exhibiting sex-specific patterns of FC development.
• To confirm the emergence of sexual dimorphism in functional brain systems during human gestation.

Main Methods:

• Resting-state functional magnetic resonance imaging (fMRI) was used to examine FC in 118 human fetuses (70 male, 48 female) between 25.9 and 39.6 weeks gestational age (GA).
• Infomap algorithm applied to the functional connectome to identify 16 discrete prenatal brain networks.
• Enrichment analysis used to assess sex-specific correlations between FC and GA, and identify distinct patterns of GA-related FC change between sexes.

Main Results:

• Both within-network and between-network FC-GA associations varied significantly with sex.
• Associations between GA and posterior cingulate-temporal pole and fronto-cerebellar FC were observed exclusively in females.
• The association between GA and increased intracerebellar FC was found to be stronger in males.

Conclusions:

• Functional brain systems exhibit sex-specific developmental trajectories during human gestation.
• Sexual dimorphism in brain connectivity begins to emerge in the prenatal period.
• These findings provide critical insights into the early origins of sex-related brain differences.