White Matter Asymmetry: A Reflection of Pathology in Traumatic Brain Injury.

Comparisons of white matter (WM) fractional anisotropy (FA) values between mild traumatic brain injury (mTBI) patients and controls have revealed inconsistencies in the directions of the resulting FA changes. To address these discrepancies, we examined hemispheric FA symmetry levels across WM tracts in 150 mTBI patients relative to 96 military controls. Automated fiber quantification was used to extract 18 WM tracts with 100 FA values, which were used to compute correlation strengths between the nine bilateral tract pairs. The Fisher z-transformed Pearson's r values were entered into an analysis of covariance examining the effects of group (mTBI and controls) and age on symmetry levels within each tract pair. The mTBI group displayed lower symmetry levels in the corticospinal tract and the inferior longitudinal fasciculus. Interactions between age and group were detected in the inferior fronto-occipital (IFOF), uncinate (UF), and superior longitudinal fasciculi (SLF). A similar pattern emerged in the IFOF and the UF, revealing age-related symmetry decreases in the mTBI patients despite stable levels of symmetry across ages in controls. In contrast, although the control group's symmetry levels actually increased with age in the SLF, no age-related symmetry changes were detected across the mTBI participants. Here, we proposed WM symmetry measures as a potential means of circumventing directional inconsistencies of trauma-related FA changes, as well as capturing more within-tract and within-subject variances of diffusion tensor imaging (DTI) metrics. Further, we demonstrated the method's utility in detecting mTBI-specific effects and their associated interactions with age.