New Insights into Sex Differences in Human Cortical Organization

Strategic Insights -

Human brains exhibit reproducible sex differences in regional cortical volume (CV), but the underlying mechanisms remain unclear. Researchers have been studying the role of surface area (SA) and cortical thickness (CT) in shaping these differences. A recent investigation published in bioRxiv provides new findings on the causal drivers of sex differences in the human cortex. The study, led by Siyuan Liu from the National Institute of Mental Health (NIMH), used structural neuroimaging data from two independent human cohorts to quantify and spatially resolve the differential contributions of SA and CT to observed sex differences in CV.

Key Takeaways:

  • The study found that humans show reproducible sex differences in regional cortical volume (CV), with surface area (SA) and cortical thickness (CT) being the two biologically dissociable determinants of CV.
  • The researchers used structural neuroimaging data from two independent human cohorts (combined N=1,754; 967 females) to quantify and spatially resolve the differential contributions of SA and CT to observed sex differences in CV.
  • The study found that the dissociable facets of sex-biased cortical organization are highly reproducible and align with distinct functional networks and histo-molecular signatures.
  • By leveraging complementary neuroimaging data in clinical case-control cohorts (combined N=313) featuring variations in X and Y chromosome dosage (sex chromosome aneuploidies) and testicular hormone production (isolated GnRH deficiency), the researchers established that regions of sex-biased CV, SA, and CT in humans are enriched for congruent anatomical effects of X-chromosome dosage (e.g., primary sensory and insular cortices) and gonadal hormones (e.g., dorsomedial frontal and temporo-parietal-occipital regions).
  • The study concluded that regions of sex-biased CV, SA, and CT in humans are enriched for congruent anatomical effects of X-chromosome dosage (e.g., primary sensory and insular cortices) and gonadal hormones (e.g., dorsomedial frontal and temporo-parietal-occipital regions).

Statistics:

  • 1,754 participants were included in the structural neuroimaging data analysis.
  • 967 females were part of the combined N=1,754 cohort.
  • 313 participants were included in the clinical case-control cohorts.
  • The study focused on sex differences in regional cortical volume (CV), surface area (SA), and cortical thickness (CT).
  • The research identified distinct functional networks and histo-molecular signatures associated with sex-biased cortical organization.

Sources:

  • Liu, S., Lee, H. M., Guma, E., Levitis, E., Shafee, R., Dugan, G., ... & Raznahan, A. (2025). Fractionation of sex differences in human cortical anatomy. bioRxiv.
  • NewsRx. New Life Science Findings from National Institute of Mental Health (NIMH) Outlined (Fractionation of sex differences in human cortical anatomy). Health & Medicine Week, October 24, 2025; p 3279.