The brain of women and men
Researchers investigate differences between the sexes and the role of sex hormones on brain development
It is widely known in neuroscience that males have larger brains than females on average. However, how the brain differs functionally between the sexes is less well understood. Based on the premise that brain structure supports function, Bianca Serio and Sofie Valk from the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig and Forschungszentrum Jülich investigated whether sex differences in the functional organization of the brain could be explained by differences in brain size, brain microstructure and the distance of functional connections along the cortical surface. Their results suggest that sex differences in functional brain organization instead reflect small differences in functional networks and connections. In a second study, Svenja Küchenhoff from Sofie Valk's team was further able to show the extent to which sex hormones influence the structure of the brain.
“We wanted to know whether sex differences in brain size explain sex differences in brain function. In other words, whether differences in brain structure reflect differences in the propagation of the functional signal,” Bianca Serio explains the idea behind her study and goes on to emphasize: ”However, a few points are important to note: First, functional signal in the brain as measured by fMRI primarily reflects physiological and metabolic mechanisms, namely through regional changes in blood flow. It would therefore be wrong to automatically assume that sex differences in functional brain signal explain observable differences in cognition or behavior, rather than simply reflecting basic physiological and metabolic differences. Second, sex differences in brain structure and function are generally rather small – for example, there may be larger differences within a sex group than between the sexes for some brain features. Individual brains share general principles of functional organization, but exhibit a certain degree of variability across individuals. We therefore used the characteristic of biological sex to divide our study participants into two groups and performed a statistical analysis to explore whether sex differences in the basic functional organization of the brain can be partly explained by differences in structural features of the brain.”
For their analyses, the researchers used the publicly available Human Connectome Project dataset, which includes brain data from 1000 study participants. “Contrary to our expecttions, we found that differences in brain size, microstructure and the distance of functional connections along the cortical surface do not reflect functional differences between the sexes. We therefore further investigated which specific features of brain function could explain the observed sex differences in fundamental functional brain organization. Here we found small sex differences in the connections within and between functional networks, which could explain to some degree the small differences in functional network topography between the sexes. The differences are small, but small effects can sometimes help to explain some meaningful differences in mechanisms. Because we did not test cognitive and behavioral associations in our study, we should be very cautious not to speculate what these brain differences might mean for observable differences between the sexes. A more general question that intrigues me personally, however, is why women are statistically twice as likely as men to be diagnosed with depression. Sex hormones may for example play a significant role in modulating brain organization, and a colleague from our team has looked at this in more detail,” Serio continues. “I hope that our basic research on the general principles of brain organization can help us make progress towards a better understanding of such important topics.”
Female data gap
Svenja Küchenhoff, whose study Bianca Serio is referring to, also believes that this kind of research is urgently needed. “Unfortunately, we still have a 'female data gap' - also in neuroscience. The male body is seen as the standard and many medical solutions may therefore not suitable for women. To understand what is really behind medical problems that disproportionately affect men or women, it is important to look at the underlying factors - such as variation in hormone levels.” This is why, in a study, she and Sofie Valk investigated the extent to which sex hormones influence brain structure. Sex hormone receptors are widely distributed in both neurons and glial cells, which enables them to interact with the most important cell groups in the brain via various molecular mechanisms. These mechanisms lead to sex-specific differences in brain structure as well as hormone-induced plasticity, both due to exogenous and endogenous sex hormones, as Svenja Küchenhoff describes. “We looked at the regional differences in the microstructure of the cerebral cortex using magnetic resonance imaging in over 1000 healthy women and men. In a first step, we showed in the study that there are sex-specific regional differences in the microstructure of the cerebral cortex and the hippocampus. However, these sex-specific differences change depending on which hormone profile is considered in the women - in some cases they even disappear completely or are reversed. In addition, we find these effects primarily in brain regions where genes of estrogen receptors and the synthesis of sex hormones are particularly strongly expressed. Taken together, we can therefore say that sex hormones play an important role in the modulation and plasticity of the brain's microstructure.”
Both researchers emphasize that biological sex is not binary either: The complex interaction of sex chromosomes, hormones and sex organs suggests that sex -as a biological construct- is better defined by a continuum. In their view, more research is needed to investigate the cause of observable sex differences in the brain and its significance for differences in health and cognition.
