The progression of sex differences in brain networks across the lifespan.

Publication Type Preprint
Authors Huang K, Jamison K, Jacobs E, Miolane N, Kuceyeski A
Journal bioRxiv
Date Published 01/31/2026
ISSN 2692-8205
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.
DOI 10.64898/2026.01.30.702608
PubMed ID 41659512
PubMed Central ID PMC12874019
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