Generalizable sex differences in functional brain organization follow the cortical hierarchy in youth
It remains unknown if sex differences in human functional connectivity follow a generalizable overarching principle. Here, we tested whether sex differences in functional connectivity during childhood and adolescence are organized along the sensorimotor-association (S-A) axis, a cortical hierarchy spanning unimodal sensorimotor to transmodal association cortex. We analyzed four large-scale, independent datasets of youth ages 5-23 years (total N = 3,355). Across datasets, males showed greater connectivity between functional networks, whereas females showed greater connectivity within networks, most prominently within the default mode network. More broadly, the sensorimotor and association ends of the S-A axis were more segregated in females and more integrated in males. This difference extended to macroscale cortical organization: the cortical hierarchy was expanded in females relative to males along the principal gradient of functional connectivity. Together, these findings identify the S-A axis as a generalizable organizing principle of sex differences in functional brain organization during youth.
Authors
- Leah H. Somerville (ORCID: https://orcid.org/0000-0002-3747-6884)
- Alexandre R. Franco (ORCID: https://orcid.org/0000-0002-1552-1090)
- Laura Pritschet (ORCID: https://orcid.org/0000-0003-4701-1017)
- Raquel E. Gur (ORCID: https://orcid.org/0000-0002-4082-8502)
- Aaron F. Alexander‐Bloch (ORCID: https://orcid.org/0000-0001-6554-1893)
- Deanna M. Barch (ORCID: https://orcid.org/0000-0003-1693-8506)
- Arielle S. Keller (ORCID: https://orcid.org/0000-0003-4708-1672)
- Sheila Shanmugan (ORCID: https://orcid.org/0000-0001-7633-163X)
- Audrey C. Luo (ORCID: https://orcid.org/0000-0001-6798-1876)
- Joëlle Bagautdinova (ORCID: https://orcid.org/0000-0001-7201-467X)
- Theodore Daniel Satterthwaite (ORCID: https://orcid.org/0000-0001-7072-9399)
- Golia Shafiei (ORCID: https://orcid.org/0000-0002-2036-5571)
- Michael Peter Milham (ORCID: https://orcid.org/0000-0003-3532-1210)
- Gregory Kiar (ORCID: https://orcid.org/0000-0001-8915-496X)
- Matthew Cieslak (ORCID: https://orcid.org/0000-0002-1931-4734)
- Armin Raznahan (ORCID: https://orcid.org/0000-0002-5622-1190)
- Valerie J. Sydnor (ORCID: https://orcid.org/0000-0002-8640-668X)
- Meike D. Hettwer (ORCID: https://orcid.org/0000-0002-7973-6752)
- Simon Vandekar (ORCID: https://orcid.org/0000-0002-7457-9073)
- Taylor Salo (ORCID: https://orcid.org/0000-0001-9813-3167)
- Elizabeth A. Flook (ORCID: https://orcid.org/0000-0002-0192-0496)
- Ruben C. Gur (ORCID: https://orcid.org/0000-0002-4082-8502)
- Russel T. Shinohara
- Xinyu Zhang (ORCID: https://orcid.org/0009-0008-5545-8138)
- Giovanni A. Salum
Institutions
- Nathan Kline Institute for Psychiatric Research (US)
- Children's Hospital of Philadelphia (US)
- Harvard University (US)
- University of Connecticut (US)
- University of California, Santa Barbara (US)
- University of Pittsburgh (US)
- Washington University in St. Louis (US)
- Child Mind Institute (US)
- University of Pittsburgh Medical Center (US)
- University of Pennsylvania Health System (US)
- National Institute of Mental Health (US)
- Connecticut Institute for the Brain and Cognitive Sciences (US)
- New York University (US)
- University of Pennsylvania (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-11-06
- DOI
- https://doi.org/10.64898/2026.11.05.762913
- Primary Topic
- Functional Brain Connectivity Studies
- Type
- preprint
Funders
- Burroughs Wellcome Fund
- University of Pennsylvania
- National Alliance for Research on Schizophrenia and Depression
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- National Institute on Aging
- National Institute on Drug Abuse
- National Institute of Biomedical Imaging and Bioengineering