Gender differences in functional brain connectivity are present in utero

A new study from American researchers confirmed the results of some previous works which demonstrated that gender differences in functional brain connectivity are present in utero.

About gender-specific differences in brain structure and function

The last decades of neuroscience research have provided considerable evidence that gender-specific differences in the brain are found at all levels of neuroscience. At the molecular and cellular level, brain sexual dimorphism has been observed in neural processes such as neurogenesis, cell growth, migration, formation of synapses, expression of receptors, apoptosis, and plasticity.

For the most part, gender-related brain dimorphism results from a cascade of events, beginning with the role of the gender-determining genes and continuing with the actions of gonadal hormones in embryonic, neonatal, peripubertal and adult life. A critical period for the organizational effects of testosterone on brain structure in humans is thought to be from 8 to 24 weeks of gestation. Testosterone acts to masculinise and defeminise the circuitry of the male brain. In contrast, a female phenotype develops in the absence of the androgenic hormones of the testes. Thus, estrogen actions in the female brain activate the functions that have been allowed to develop in the absence of testosterone.

Neuroimaging studies have demonstrated gender-specific differences in the structural and functional level; in the complexity and thickness of the brain cortex, in the connectivity between brain areas, within and outside traditional “reproductive” centers.

In their pioneering volumetric analysis of the fetal brains DeLacoste et al. (1991) showed a greater weight of the right hemisphere in the male brains and a greater weight of the left hemisphere in the female brains. These findings were in line with the original theory of cerebral lateralization of Geschwind and Galaburda (1987), who stated that a smaller left hemisphere is one of the consequences of higher levels of testosterone in utero.

In 2014, Li aet al. using magnetic resonance imaging (MRI) provided the evidence of significant gender-related dimorphism of the cortical structural asymmetry in newborns. They found a more prominent asymmetry of sulcal depth around the planum temporale and superior temporal sulcus in males than in females.

Wheelock et al. (2019) used resting-state functional MRI (fMRI) to explore, for the first time, the gender-specific differences in the functional connectivity within and between networks in 118 human fetuses across the gestation. They found that early in gestation (between 25 and 38 weeks) female fetuses showed greater change in long range functional connectivity, while male fetuses showed greater change in local functional connectivity.

Ingalhalikar et al. (2014) used diffusion tensor imaging methods to assess human connectome in a very large population of 949 young people aged 8 to 22 years. They identified fundamental gender-specific differences in the structural architecture of the human brain. The males had higher within-hemispheric connectivity ratio in the frontal, temporal and parietal lobes bilaterally, whereas the female brains rather tend to show higher inter-hemispheric connectivity and greater across- lobe connectivity, mainly between the lobes in different hemispheres. The modularity and transitivity were higher in males compared to females. The authors found the most pronounced gender-specific differences in the brains of adolescents (aged 13.4 to 17 years) which indicates an early separation of the developmental trajectories between the genders. According to the authors, men’s brains are optimized for communication within the hemispheres, while women’s brains are optimized for interhemispheric communication.

Gender-specific differences in brain structure and function observed throughout the development are believed to contribute to differences in behavior, cognition, and the presentation of neurodevelopmental disorders. Limited research is focused on this topic, mainly on changes in the levels of gonadal hormones early in gestation, as well as on differences in brain structure apparent at birth.

About the study

In the present study, the research team used resting state fMRI scans of 95 human fetuses, performed between 19 and 40 weeks of gestation.

The results showed that functional brain connectivity patterns classified fetal gender with 73% accuracy. Across support vector machine models, the researchers identified features (functional connections) that reliably differentiated fetal gender. Highly consistent predictors included connections in the somatomotor and frontal areas alongside the hippocampus, cerebellum, and basal ganglia.

Moreover, high consistency features also implicated a greater magnitude of interregional connections in females, while male weighted features were predominately within anatomically bounded regions. These findings indicate that differences, which were observed later in childhood, as presented in the study of Ingalhalikar et al (2014), are present and reliably detectable even before birth.

The scientists concluded that their findings have shown that gender differences arise before birth in a way that is consistent and reliable enough to be highly identifiable.

The study findings were published in the scientific journal Cerebral Cortex.Cook KM et al. Robust gender differences in functional brain connectivity are present in utero, Cerebral Cortex, 2022., May 31.