Investigating Sexual Dimorphism of Human White Matter in a Harmonized, Multisite Diffusion Magnetic Resonance Imaging Study

Cereb Cortex. 2021 Jan 1;31(1):201-212. doi: 10.1093/cercor/bhaa220.


Axonal myelination and repair, critical processes for brain development, maturation, and aging, remain controlled by sexual hormones. Whether this influence is reflected in structural brain differences between sexes, and whether it can be quantified by neuroimaging, remains controversial. Diffusion-weighted magnetic resonance imaging (dMRI) is an in vivo method that can track myelination changes throughout the lifespan. We utilize a large, multisite sample of harmonized dMRI data (n = 551, age = 9-65 years, 46% females/54% males) to investigate the influence of sex on white matter (WM) structure. We model lifespan trajectories of WM using the most common dMRI measure fractional anisotropy (FA). Next, we examine the influence of both age and sex on FA variability. We estimate the overlap between male and female FA and test whether it is possible to label individual brains as male or female. Our results demonstrate regionally and spatially specific effects of sex. Sex differences are limited to limbic structures and young ages. Additionally, not only do sex differences diminish with age, but tracts within each subject become more similar to one another. Last, we show the high overlap in FA between sexes, which implies that determining sex based on WM remains open.

Keywords: connectivity; diffusion-weighted MRI; female; fractional anisotropy; male.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aging
  • Anisotropy
  • Axons / physiology
  • Child
  • Diffusion Magnetic Resonance Imaging
  • Diffusion Tensor Imaging
  • Female
  • Humans
  • Limbic System / diagnostic imaging
  • Limbic System / physiology
  • Male
  • Middle Aged
  • Myelin Sheath / physiology
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / physiology
  • Sex Characteristics*
  • White Matter / anatomy & histology*
  • White Matter / diagnostic imaging*
  • Young Adult