Sex dimorphism in the white matter: fractional anisotropy and brain size

To examine sex differences in fractional anisotropy of the white matter across the whole brain, controlling for head size variation.

A total of 238 normal subjects aged 40-49 years were included in this study. Diffusion tensor images were acquired at 3 Tesla using a single-shot spin-echo echo-planar sequence. With use of tract-based spatial statistics (TBSS), sex differences in fractional anisotropy of the white matter were examined across the whole brain, without and with adjustment of total intracranial volume. Voxelwise analyses of the processed fractional anisotropy data were performed using permutation-based, voxelwise nonparametric testing.

TBSS analysis without adjustment for total intracranial volume showed several regions with a significant effect of sex on fractional anisotropy; these included the splenium of the corpus callosum, bilateral superior corona radiata, and posterior limbs of the internal capsule, midbrain, and cerebellum. Significantly higher fractional anisotropy was seen in males compared with females in these regions. TBSS analysis with adjustment for total intracranial volume, however, showed a greatly reduced number of such regions.

The results of our study suggest that sex differences in fractional anisotropy of the white matter reported by previous studies may partly reflect differences in head size, not microscopic differences.