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

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.

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Publication Details

Journal
Nature Communications
Published
2026-05-21
DOI
https://doi.org/10.1038/s41467-026-73262-2
Primary Topic
Functional Brain Connectivity Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Dustin Moraczewski, Ethan T. Whitman, Adam Thomas, Alex Martin et al.
Nature Communications
Functional Brain Connectivity Studies
article

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

Dustin Moraczewski, Ethan T. Whitman, Adam Thomas, Alex Martin, Siyuan Liu, Stephen J. Gotts, Armin Raznahan, Bridget W. Mahony
article en

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.

Nature Communications
National Institute of Mental Health (US)
National Institute of Mental Health
Gender equality
Openalex Percentile: Top 5%
Functional Brain Connectivity Studies
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