Reframing sexual differentiation of the brain
20th century linear model for brain sex
"For the past 50 years, the prevailing view of sexual differentiation of the brain has been a linear model in which chromosomal sex determines gonadal sex, which determines brain sex. (...) This iconic model based on the organizational/activational hypothesis14 has proved a sturdy framework for elucidating some, but not all, of the aspects of sexual differentiation of the brain."
(image source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165173/figure/F1/)
21st century model for brain sex
"Redefining sexual differentiation. In a twenty-first-century view of sexual differentiation of the brain, the importance of genetics and environment are incorporated along with the effects of hormones to provide a more nuanced portrayal of the types of variables that cause sex differences. Included in this view are the principles that hormones, sex chromosome genes and sex-specific environments have independent parallel differentiating effects that can interact with each other, often synergistically, to cause sex differences in the brain. However, there are also compensatory sex-specific variables that act to reduce sex differences rather than induce them. The result is that some aspects of male and female brain, behavior and physiology are unique from each other, whereas others are highly similar. Two important aspects of the redefined view are not illustrated here: sex differences are pervasive throughout the brain and not restricted to reproductively relevant neural circuits, and variability in the degree to which brain regions are masculinized or feminized in one individual results in a mosaic of relative maleness or femaleness and thereby greatly increases the variance between individuals of the same sex in a population."
(image source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165173/figure/F4/)
(McCarthy, Margaret M., and Arthur P. Arnold. "Reframing sexual differentiation of the brain." Nature neuroscience 14.6 (2011): 677-683.)
Sexual differentiation of the brain not only because of (prenatal) hormones, but also neuroimmunology and epigenetics
"Recent research in rodent models has led to dramatic shifts in our views of the mechanisms underlying the sexual differentiation of the brain. These include the surprising discoveries of a role for immune cells and inflammatory mediators in brain masculinization and a role for epigenetic suppression in brain feminization. How and to what degree these findings will translate to human brain development will be questions of central importance in future research in this field."(McCarthy, Margaret M., Bridget M. Nugent, and Kathryn M. Lenz. "Neuroimmunology and neuroepigenetics in the establishment of sex differences in the brain." Nature Reviews Neuroscience (2017).)
Immune cells co-responsible for brain sex differentiation
"These studies demonstrate that immune cells in the brain interact with the nervous and endocrine systems during development, and are crucial for sexual differentiation of brain and behavior."
(Lenz, Kathryn M., et al. "Microglia are essential to masculinization of brain and behavior." Journal of Neuroscience 33.7 (2013): 2761-2772.)
AI detects differences between male and female brain rhythms
"The electric brain signals, measured by using EEG, of males and females show differences. The difference can't be detected by visual inspection, not even by the trained eye of a neurologist. A 'deep learning' computer is able to find it. (...) The main difference is in the 'beta activity', a frequency range between 20 and 25 Hz. These rhythms have to do with cognition and with tasks that are emotionally positive or negative. It is known from previous research that females are better capable of recognizing emotion: this could indicate a difference in beta activity. Within the context of this research project, this has not been elaborated further."
(University of Twente. "Male and female brain rhythms show differences." ScienceDaily. ScienceDaily, 15 February 2018.)
MRI shows significant differences in brain development between male and female fetuses
"However, models of relative growth accounting for global measures revealed a complex temporal form, with strikingly similar cortical development in males and females at lobe scales. In contrast, local cortical growth patterns and larger scale white matter volume and surface measures differed significantly between male and female. Many proportional differences were maintained during neurogenesis and over 18 weeks of growth. These indicate sex related sculpting of neuroanatomy begins early in development, before cortical folding, potentially influencing postnatal development."
(Studholme, C., Kroenke, C. D., & Dighe, M. (2020). Motion corrected MRI differentiates male and female human brain growth trajectories from mid-gestation. Nature Communications, 11(1), 1-16.)
