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 brain white matter, suggesting distinct structural connectivity patterns between females and males. Diffusion MRI tractography is an important tool in assessing white matter connectivity and brain tissue microstructure across different populations. Whole brain tractography analysis for group statistical comparison is a challenging task due to the large number of white matter connections. This work studies whole-brain white matter connectivity differences between females and males using dMRI tractography. We study a large cohort of 707 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 analyze tracts in the cerebral cortex and understudied pathways like those connecting to the cerebellum. We identify several tracts with significant sex differences in terms of their fractional anisotropy and/or mean diffusivity. These include deep tracts like the arcuate fasciculus, corticospinal tract, and corpus callosum, superficial tracts in the frontal lobe, and cerebellar tracts. Finally, a canonical correlation analysis (CCA) that identifies covariance patterns between white matter and behavior measures reveals that these white matter differences are associated with a range of neurobehavioral measures, with the strongest and most consistent associations observed for motor function, suggesting motor circuits as a potential key focus for future research.