Sex Differences of the Brain Structural Adaptation to Hypoxic Environment

Background: Different physiological and pathological patterns have been found in the two sexes at high altitude. However, sex differences in brains remain unknown. Methods: T1-weighted MRI scanned in 61 Tibetan males and 68 Tibetan females aged 17-23, and Freesurfer was used to detect brain structures. Neuropsychological tests were also performed. Matched lowland Han subjects were controls. Results: Both Tibetan and Han males had larger global gray matter (GM) volume and white matter volume than females, while Tibetan but not Han female brains contained a larger proportion of GM than male brains. Tibetan females had significant smaller regional GM volume in the left rostral middle frontal gyrus, pars opercularis, and right caudal middle frontal gyrus, and moreover, GM volume in the left pars opercularis positively correlated with digit span score. However, Tibetans females had significantly thicker cortices in the left rostral middle frontal gyrus, left pars triangularis, right rostral middle frontal gyrus, and right pars triangularis than males and cortical thickness in these regions negatively correlated with altitude. In Tibetan females but not males, the negative correlation of cortical thickness with altitude has been testified by global analysis. Conversely, Han subjects showed discrepant sex differences in brains with Tibetans, showing larger regional GM volume and thicker cortices in different brain areas. Conclusion: A distinct pattern of sex differences exists between Tibetan and Han brains. Female brains may be more tolerable to hypoxia. Sex differences in the brains of Tibetans may be related to different neuropsychiatric performances in the two sexes.