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.
Authors
- Dustin Moraczewski (ORCID: https://orcid.org/0000-0002-0422-3135)
- Ethan T. Whitman (ORCID: https://orcid.org/0000-0002-3208-171X)
- Adam Thomas
- Alex Martin (ORCID: https://orcid.org/0000-0002-3636-2498)
- Siyuan Liu (ORCID: https://orcid.org/0000-0003-3661-6248)
- Stephen J. Gotts (ORCID: https://orcid.org/0000-0002-7903-1832)
- Armin Raznahan (ORCID: https://orcid.org/0000-0002-5622-1190)
- Bridget W. Mahony
Institutions
- National Institute of Mental Health (US)
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
Funders
- National Institute of Mental Health