Sexual dimorphism of white-matter functional connectome in healthy young adults

Sexual dimorphism in human brain has garnered significant attention in neuroscience research. Although multiple investigations have examined sexual dimorphism in gray matter (GM) functional connectivity (FC), the research of white matter (WM) FC remains relatively limited.

Utilizing resting-state fMRI data from 569 healthy young adults, we investigated sexual dimorphism in the WM functional connectome. We constructed both WM-WM and GM-WM FC networks and subsequently analyzed their FC strength, functional connectivity density, and network topological properties. Based on identified dimorphic features, a radial basis function support vector machine model was employed for sex prediction and classification. Validation analyses confirmed the reproducibility of our findings.

Our analyses revealed significant sexual dimorphism in FC within both the WM-WM and GM-WM networks. Notably, females generally exhibited stronger connection strengths across numerous pathways compared to males. Topologically, females displayed greater global system aggregation (higher clustering coefficient) in the WM-WM network. Similarly, within the GM-WM connectome, females showed enhanced network integration, specifically higher global and local efficiency in the frontoparietal network and increased clustering coefficient in the attention network. Critically, these dimorphic WM features proved effective for sex classification using machine learning; an integrated model combining WM-WM and GM-WM FCs achieved superior predictive performance over models using individual feature sets, highlighting the unique information encoded in WM functional dynamics.

This finding extends our understanding of brain sex differences beyond gray matter and provides novel insights into the neurological mechanisms potentially underlying sex-specific patterns in cognition, behavior, and susceptibility to brain disorders.