Regional sex differences in human cortical anatomy vary in their morphometric bases and overlap with sex chromosomal and gonadal influences
- Hyo M. Lee
- Siyuan Liu
- Elisa Guma
- Elizabeth Levitis
- Rebecca Shafee
- Gabrielle Dugan
- François M. Lalonde
- Liv Clasen
- Alex DeCasien
- M. Mallar Chakravarty
- Jason P. Lerch
- Konrad Wagstyl
- Angela Delaney
- Armin Raznahan
2026-06-13
Humans show reproducible sex differences in regional cortical volume (CV), but it remains unclear how these relate to the two biologically dissociable determinants of CV – surface area (SA) and cortical thickness (CT) – or to potentially causal sex chromosomal and gonadal effects. Here, we analyze neuroimaging data in two independent human cohorts ( N = 1754) to identify and interrelate highly reproducible sex differences in regional CV, SA and CT – as well as their alignment with distinct functional networks and histomolecular signatures. Integrating neuroimaging data from clinical cohorts with sex chromosome aneuploidy and isolated gonadotropin-releasing hormone deficiency (N = 313) establishes that regions of sex-biased cortical anatomy are enriched for congruent effects of X-chromosome dosage (e.g., primary sensory and insular cortices) and gonadal hormones (e.g., dorsal parietal regions and angular gyrus). This work refines maps of sex-biased human cortical organization and helps to narrow hypotheses regarding their potential genetic and endocrine causes.