Generalizable sex differences in functional brain organization follow the cortical hierarchy in youth
- 1Penn Lifespan Informatics and Neuroimaging Center (PennLINC), University of Pennsylvania, Philadelphia, PA, USA.; Department of Psychiatry, Perelman School of M
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.
Related
- Functional organization and natural scene responses across mouse visual cortical areas revealed with encoding manifolds
- Functional Network Organization Underlying Individual Differences in False Feedback Susceptibility: A Graph Theoretical Analysis.
- Individualized morphometric-similarity deviations in autism linked to cortical hierarchy and microarchitecture
- Cortical Hierarchy Dynamically Organizes Large-Scale Neural Propagation
- Structure-function tethering of human locus coeruleus connectivity reveals a noradrenergic cortical hierarchy
BibTeX
@misc{luo2026generalizable,
title = {{Generalizable sex differences in functional brain organization follow the cortical hierarchy in youth}},
author = {A. C. Luo and M. D. Hettwer and A. F. Alexander-Bloch and J. Bagautdinova and D. M. Barch and M. Cieslak and E. A. Flook and A. R. Franco and R. E. Gur and R. C. Gur and A. S. Keller and G. Kiar and M. P. Milham and L. Pritschet and A. Raznahan and T. Salo and G. A. Salum and G. Shafiei and R. T. Shinohara and L. H. Somerville and V. J. Sydnor and S. N. Vandekar and X. Zhang and S. Shanmugan and T. D. Satterthwaite},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.05.762913},
url = {https://www.biorxiv.org/content/10.64898/2026.11.05.762913v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Generalizable sex differences in functional brain organization follow the cortical hierarchy in youth
AU - A. C. Luo
AU - M. D. Hettwer
AU - A. F. Alexander-Bloch
AU - J. Bagautdinova
AU - D. M. Barch
AU - M. Cieslak
AU - E. A. Flook
AU - A. R. Franco
AU - R. E. Gur
AU - R. C. Gur
AU - A. S. Keller
AU - G. Kiar
AU - M. P. Milham
AU - L. Pritschet
AU - A. Raznahan
AU - T. Salo
AU - G. A. Salum
AU - G. Shafiei
AU - R. T. Shinohara
AU - L. H. Somerville
AU - V. J. Sydnor
AU - S. N. Vandekar
AU - X. Zhang
AU - S. Shanmugan
AU - T. D. Satterthwaite
PY - 2026
DA - 2026/11/05
PB - bioRxiv
DO - 10.64898/2026.11.05.762913
UR - https://www.biorxiv.org/content/10.64898/2026.11.05.762913v1
AB - 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.
ER -