Robust but independent sex differences in human brain function, structure, and behavior

Bibliographic Collection: 
APE
Publication Type: Journal Article
Authors: Liu, Siyuan; Mahony, Bridget W.; Whitman, Ethan T.; Gotts, Stephen J.; Moraczewski, Dustin; Thomas, Adam; Martin, Alex; Raznahan, Armin
Year of Publication: 2026
Journal: Nature Communications
Date Published: 2026/05/21
Publication Language: eng
ISBN Number: 2041-1723
Abstract:

The neurobiological accompaniments of well-established sex differences in human behavior and disease remain unclear — in part due to a lack of large, diverse functional neuroimaging studies. We address this gap using over 700 h of fMRI data across seven tasks from 978 individuals with extensive structural and behavioral measures. We find that sex differences in task-activation are widespread (85% of cortex) and reproducible,  largely task-specific, of small to moderate effect size, and unaligned with brain volume differences. While machine learning can classify sex from brain activation, volume, or behavior, these data types provide orthogonal information. Brain-wide association studies reveal that links between brain activation and behavior are highly conserved between sexes. The few subtle sex differences in brain-behavior linkage that do exist are not preferentially localized to sex-biased behaviors. Our findings clarify the nature of sex differences in human brain function and their links with neuroanatomy and behavior, providing a useful foundation for future research.

DOI: http://dx.doi.org/10.1038/s41467-026-73262-2
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