The progression of sex differences in brain networks across the lifespan

Abstract

Sex differences in brain connectivity are well documented, yet how these differences evolve across the human lifespan remains poorly understood. Rigorously assessing sex-dependent trajectories of brain network organization is challenging due to difficulty in acquiring, processing, and modeling high-dimensional connectomes. Here, we analyzed 15 types of functional and structural connectivity networks from 1286 healthy individuals aged 8-100+ years, using our new AI-based Krakencoder to derive a low-dimensional multimodal "fusion" connectome representation. Sex differences were minimal in early childhood, pronounced in young to mid-adulthood, and diverged across modalities in later life: functional connectivity grew less distinct and structural connectivity grew more distinct from midlife onward. Functional differences were driven predominantly by higher-order association networks (default mode, control), while structural differences concentrated in lower-order cerebellar and subcortical pathways. These findings provide a lifespan-wide, multimodal map of sex differences in brain networks which may help inform sex-specific vulnerability and resilience to brain disorders.