Open AccessThe sexual brain, genes, and cognition: A machine‐predicted brain sex score explains individual differences in cognitive intelligence and genetic influence in young children
Author(s) -
Kim Kakyeong,
Joo Yoonjung Yoonie,
Ahn Gun,
Wang HeeHwan,
Moon SeoYoon,
Kim Hyeonjin,
Ahn WooYoung,
Cha Jiook
Publication year - 2022
Publication title -
human brain mapping
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.005
H-Index - 191
eISSN - 1097-0193
pISSN - 1065-9471
DOI - 10.1002/hbm.25888
Subject(s) - cognition , sexual dimorphism , sex characteristics , psychology , brain morphometry , effects of sleep deprivation on cognitive performance , brain size , fluid and crystallized intelligence , developmental psychology , medicine , neuroscience , magnetic resonance imaging , fluid intelligence , working memory , radiology
Sex impacts the development of the brain and cognition differently across individuals. However, the literature on brain sex dimorphism in humans is mixed. We aim to investigate the biological underpinnings of the individual variability of sexual dimorphism in the brain and its impact on cognitive performance. To this end, we tested whether the individual difference in brain sex would be linked to that in cognitive performance that is influenced by genetic factors in prepubertal children ( N = 9,658, ages 9–10 years old; the Adolescent Brain Cognitive Development study). To capture the interindividual variability of the brain, we estimated the probability of being male or female based on the brain morphometry and connectivity features using machine learning (herein called a brain sex score). The models accurately classified the biological sex with a test ROC–AUC of 93.32%. As a result, a greater brain sex score correlated significantly with greater intelligence ( p fdr < .001, η p 2 = .011–.034; adjusted for covariates) and higher cognitive genome‐wide polygenic scores (GPSs) ( p fdr < .001, η p 2 < .005). Structural equation models revealed that the GPS‐intelligence association was significantly modulated by the brain sex score, such that a brain with a higher maleness score (or a lower femaleness score) mediated a positive GPS effect on intelligence (indirect effects = .006–.009; p = .002–.022; sex‐stratified analysis). The finding of the sex modulatory effect on the gene–brain–cognition relationship presents a likely biological pathway to the individual and sex differences in the brain and cognitive performance in preadolescence.