July 28, 2020

Sex differences in brain anatomy

At a Glance

  • An analysis of more than 2,000 brain scans showed sex differences in the volume of certain regions in the human brain.
  • The findings shed light on the mechanisms that may contribute to sex-based differences in brain disease and behavior.
Silhouettes of a man and woman with gears in heads Scientists found differences in the volume of certain brain regions between the sexes. Youst / DigitalVision Vectors / Getty Images

While there are many similarities between men and women, sex can make a difference for some health risks and behaviors. For example, women are more likely to have certain mental health conditions, like depression. Men are more likely to have certain neurodevelopmental conditions, such as autism spectrum disorder. Studies have also shown sex differences in certain cognitive tasks, like the ability to recognize faces. But what underlies these differences isn’t fully understood.

Researchers have observed sex differences in the volume of certain brain regions in animals. Some studies suggest these anatomical differences are largely due to the effects of sex hormones on brain development. More recent research suggests that the activity, or “expression” of genes on the sex chromosomes plays a role in shaping these anatomical differences. Each cell in your body carries a pair of sex chromosomes, including your brain cells. Females have two X chromosomes, and males have one X and one Y.

To explore sex differences in the human brain, a team led by Drs. Siyuan Liu and Armin Raznahan at NIH’s National Institute of Mental Health (NIMH) analyzed neuroimaging data collected from two independent databanks. The Human Connectome Project involved 976 healthy adults between the ages of 22 and 35. The UK Biobank neuroimaging dataset was from 1,120 adults, ages 44 to 50. Results were published on July 20, 2020 in the Proceedings of the National Academy of Sciences.

On average, males and females showed greater volume in different areas of the cortex, the outer brain layer that controls thinking and voluntary movements. Females had greater volume in the prefrontal cortex, orbitofrontal cortex, superior temporal cortex, lateral parietal cortex, and insula. Males, on average, had greater volume in the ventral temporal and occipital regions. Each of these regions is responsible for processing different types of information.

The team cross-referenced their anatomical findings with publicly available maps of gene expression in the brain. These maps are based on more than 1,300 postmortem tissue samples from six human donors. The spatial pattern of sex differences in cortical volume was similar to the spatial pattern of sex-chromosome gene expression in the cortex. Regions with relatively high expression of sex-chromosome genes tended to have greater cortical volume in males than females.

The researchers also compared the anatomical findings with data from more than 11,000 functional neuroimaging studies. Such studies examine brain activation during specific activities or conditions. Of 50 cognitive categories, five were associated with anatomical differences: visual object recognition, face processing, cognitive control, inhibition, and conflict. Facial processing showed the strongest association.

“Developing a clearer understanding of sex differences in human brain organization has great importance for how we think about well-established sex differences in cognition, behavior, and risk for psychiatric illness,” Raznahan says. “We were inspired by new findings on sex differences in animal models and wanted to try to close the gap between these animal data and our models of sex differences in the human brain.”

More research is needed to determine whether these anatomical distinctions play any role in sex differences in cognition and behavior.

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References: Integrative structural, functional, and transcriptomic analyses of sex-biased brain organization in humans. Liu S, Seidlitz J, Blumenthal JD, Clasen LS, Raznahan A. Proc Natl Acad Sci U S A. 2020 Jul 20:201919091. doi: 10.1073/pnas.1919091117. Online ahead of print. PMID: 32690678.

Funding: National Institute of Mental Health (NIMH).