Study of Sex Differences in the Whole Brain White Matter Using Diffusion MRI Tractography and Suprathreshold Fiber Cluster Statistics

Sex-specific characteristics demonstrate a substantial influence on the human brain white matter, suggesting distinct brain structural connectivity patterns between females and males. Diffusion MRI (dMRI) tractography is an important tool in assessing white matter connectivity and brain tissue microstructure across different populations. Whole brain white matter analysis using dMRI tractography for group statistical comparison is a challenging task due to the large number of white matter connections. In this work, we study whole-brain white matter connectivity differences between females and males using dMRI tractography. We study a large cohort of 707 healthy adult subjects from the Human Connectome Project Young Adult dataset. By applying a well-established fiber clustering pipeline and a suprathreshold fiber cluster statistical method, we evaluated tracts in the cerebral cortex, as well as those connecting to regions such as the cerebellum, which have been relatively less studied using dMRI tractography. We identified several tracts that differed significantly between females and males in terms of their fractional anisotropy and/or mean diffusivity. These included several deep white matter tracts (e.g., arcuate fasciculus, corticospinal tract, and corpus callosum) that have been previously shown to have sex differences, as well as superficial white matter tracts in the frontal lobe. However, there were relatively few cortical association tracts that exhibited significant sex differences. We also identified cerebellar tracts with sex differences. Finally, correlation analysis revealed that these white matter differences were linked to a range of neurobehavioral measures, with the strongest and most consistent associations observed for motor function. Overall, these findings provide characterizations of sex differences in the white matter and indicate that the circuits underlying motor function may be an important focus of future work on sex differences in the human brain.