Generalizable sex differences in functional brain organization follow the cortical hierarchy in youth
Year: 2026
Type: preprint
Abstract: 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: Audrey C. Luo, Meike D. Hettwer, Aaron F. Alexander-Bloch, Joëlle Bagautdinova, Deanna M. Barch, Matthew Cieslak, Elizabeth A. Flook, Alexandre R. Franco, Raquel E. Gur, Ruben C. Gur, Arielle S. Keller, Gregory Kiar, Michael P. Milham, Laura Pritschet, Armin Raznahan, Taylor Salo, Giovanni A. Salum, Golia Shafiei, Russell T. Shinohara, Leah H. Somerville, Valerie J. Sydnor, Simon N. Vandekar, Xinyu Zhang, Sheila Shanmugan, Theodore D. Satterthwaite
Institutions: University of Pennsylvania, Children's Hospital of Philadelphia, University of Pennsylvania Health System, Washington University in St. Louis, Nathan Kline Institute for Psychiatric Research, Child Mind Institute, New York University, University of Connecticut, Connecticut Institute for the Brain and Cognitive Sciences, National Institute of Mental Health, Harvard University, University of Pittsburgh, University of Pittsburgh Medical Center, Vanderbilt University Medical Center, University of California, Santa Barbara
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
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
OpenAlex ID: W7225402798