ESPE Yearbook of Paediatric Endocrinology

Brief Summary:This study used functional MRI to investigate brain organization with a spatiotemporal deep neural network model and explainable AI (XAI) analytics. It found highly significant differences between the male and female brain on a large number of healthy young probands. It reveals that sex differences in functional brain dynamics are replicable, generalizable and related to sex-specific behavior.

Human brain development is affected by the sex (hormones) throughout life. Sex differences in brain functioning have been found in many disorders, e.g. neurological and psychiatric diseases. While females exhibit more often multiple sclerosis, dementia, anxiety, eating disorders and depression, males are more likely to suffer from Parkinsons, attention-deficit hyperactivity disorder, autism and schizophrenia.

So far, our understanding of brain sex differences has been largely based on anatomical studies and structural brain imaging showing clear sex-specific patterns. However, it was unclear how these structural differences correlate with functional sex differences. Although studies using fMRI seem able to address this question by connectivity analyses, data so far were inconsistent mostly due to methodological issues. To overcome these challenges, this study used data of three (larger) cohorts of healthy, age-‘restricted’ probands and a refined model to analyze fMRI combined with novel XAI. They claim that there are i) reliable, ii) reproducible, iii) interpretable differences in functional brain organization between typical biological males and females, that iv) clearly relate to sex-specific behavior.

Overall, this study highlights biological sex as an important determinant of human brain organization and challenges the hypothesis that male-female brain organization is a continuum. As this study was performed on young adults aged 20–35 years, it will be very interesting to see similar studies performed on newborns, through childhood and puberty informing on sex development of the human brain. Maybe such studies will also help in understanding sex- and gender-specific behavior and preferences. Further studies could address effects of endogenous and exogenous hormones on brain organization and this might be informative for understanding and managing gender incongruence.