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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

摘要

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.