Scientific analysis of more than 2,000 scans of the brain showed that there are strong sex differences in volume of certain areas of the human brain. This pattern of gender differences in the brain volume corresponds to the gene expression patterns of sex chromosomes observed in autopsy samples of cerebral cortex, suggesting that sex chromosomes can affect the anatomical structure of the brain during growth and development. The study was conducted under the guidance of American scientists from the National Institute of mental health (NIMH) at the National institutes of health (NIH), and the results were published in the journal Proceedings of the National Academy of Sciences.
“A clearer understanding of gender differences in the tissues of the human brain is very important because it helps us understand the established gender differences in the perception, behaviour and risk of mental illness. Inspired by the discovered sex differences found in experimental animal models, we wanted to try to bridge the gap between these data about animals and our patterns of sex differences in the human brain,” said Armin Raznahan (Armin Raznahan), head of Section, developing neurogenomics NIMH, which took an active part in the study.
For a long time researchers have observed gender differences in subcortical structures of the brain of mice. Some studies suggest that these anatomical differences are largely due to the influence of sex hormones, and push “gonadorelin” theory to explain sex differences in the brain development process. However, more recent studies in mice revealed also persistent sex differences in the cortical structures. At the same time, data on gene expression suggest that sex chromosomes may play a role in the formation of these anatomical sex differences. Although there are many similarities between the mouse brain and human brain, it is unclear whether it applies key insights about mice and people.
To explore the neurobiological basis of gender differences in human brain Raznahan, the study’s lead author Dr. Liu XIYUAN and their colleagues first analyzed the neuroimaging data collected in the framework of the project the Human Connectome Project (HCP). These data were obtained from 976 healthy adults aged 22 to 35 years, and sustainable results revealed gender differences in the volume of certain cortical structures. On average, women had relatively larger volume of cortex in the medial and lateral prefrontal cortex, orbitofrontal cortex, superior temporal sulcus and the lateral parietal sulcus, whereas in men was, on average, a relatively larger volume of cortex in the ventral temporal and occipital regions, including the temporal pole, fusiform gyrus and primary visual cortex.
Then Liu XIYUAN and his colleagues used two complementary approaches to determine the reproducibility of these results. First, the researchers randomly divided the data set HCP in two parts at 1000 units, and then compared the results of both halves, finding that the pattern of sex differences in volume of cerebral cortex was very stable. Then the researchers obtained consistent results with the findings of the HCP in a disjoint set of neuroimaging data from the UK Biobank. Although the data sets had a noticeable demographic and methodological differences, the researchers found that the overall picture of gender differences in volume of cerebral cortex was very consistent.
After that, Liu XIYUAN and his co-authors tied their anatomical data from publicly available maps of gene expression in the brain, which are based on 1317 post-mortem tissue samples from six donors-people. The results showed that the spatial pattern of sex differences in the volume of the crust was similar to the spatial pattern of gene expression of sex chromosomes in the cerebral cortex. In particular, the cortical area with a relatively high gene expression of sex chromosomes usually have a larger volume of the cortex in men than in women.
This correspondence cortical gene expression of sex chromosomes is also consistent with the results of previous studies on mice. Studies have shown that gender differences in the anatomy of the brain can at least partially be explained by genetic mechanisms that have been preserved throughout the evolution of mammals. These data show that sex differences in the volume of the cerebral cortex can influence genes located in sex chromosomes X and Y.
“Men and women differ in many genetic factors and environmental factors, and these factors can potentially affect brain development. Since experimentation on humans is difficult, we often rely on observational data to conclude about potential genetic factors or the environmental factors influencing sex differences of the brain, said Raznahan. — We observed a very high level of reproducibility of the anatomical sex differences in different groups of men and women, as well as the relationship between these differences and gene expression of sex chromosomes. All the above facts show that these differences probably do not result from only environmental influences”.
The researchers also compared their anatomical data with more than 11 thousand studies functional neuroimaging. The results show that there is spatial overlap between the brain regions that showed sex differences in the volume of crust in the dataset HCP, and brain regions associated with face recognition in functional neuroimaging studies.
Using these results as a “road map”, future research can better explore the causes and consequences of sex differences in the human brain.