White matter abnormalities in mild traumatic brain injury with and without post-traumatic stress disorder: a subject-specific diffusion tensor imaging study

Abstract

Mild traumatic brain injuries (mTBIs) are often associated with posttraumatic stress disorder (PTSD). In cases of chronic mTBI, accurate diagnosis can be challenging due to the overlapping symptoms this condition shares with PTSD. Furthermore, mTBIs are heterogeneous and not easily observed using conventional neuroimaging tools, despite the fact that diffuse axonal injuries are the most common injury. Diffusion tensor imaging (DTI) is sensitive to diffuse axonal injuries and is thus more likely to detect mTBIs, especially when analyses account for the inter-individual variability of these injuries. Using a subject-specific approach, we compared fractional anisotropy (FA) abnormalities between groups with a history of mTBI (n = 35), comorbid mTBI and PTSD (mTBI + PTSD; n = 22), and healthy controls (n = 37). We compared all three groups on the number of abnormal FA clusters derived from subject-specific injury profiles (i.e., individual z-score maps) along a common white matter skeleton. The mTBI + PTSD group evinced a greater number of abnormally low FA clusters relative to both the healthy controls and the mTBI group without PTSD (p < .05). Across the groups with a history of mTBI, increased numbers of abnormally low FA clusters were significantly associated with PTSD symptom severity, depression, post-concussion symptoms, and reduced information processing speed (p < .05). These findings highlight the utility of subject-specific microstructural analyses when searching for mTBI-related brain abnormalities, particularly in patients with PTSD. This study also suggests that patients with a history of mTBI and comorbid PTSD, relative to those without PTSD, are at increased risk of FA abnormalities.

Keywords: Diffusion tensor imaging; Fractional anisotropy; Magnetic resonance imaging; Mild traumatic brain injury; Post-traumatic stress disorder.

Fig. 1

Results from preliminary analysis of healthy controls (n = 112) across all six INTRuST sites. Note: FA = fractional anisotropy. In this study, we analyzed data acquired from sites 3 and 4 (Phillips Achieva scanners).

Fig. 2

Group-wise mean number of clusters of five or more voxels with z-scores of 3 and more (or −3 and less in the case of clusters of low FA). We applied a square-root transformation to the means to remove positive skew of original distributions. Error bars represent the standard error of the mean. A) The groups did not differ with respect to overall FA abnormalities (i.e., absolute FA; p < .05), B) The groups did not differ in terms of mean number of clusters with abnormally high FA, C) The MTBI+PTSD group had a significantly greater number of clusters of abnormally low FA compared to mTBI and HCs (p < .05).

Fig. 3

Axial slices (z = 9) of different participants from the mTBI+PTSD group illustrating heterogeneity of fractional anisotropy (FA) potholes. Red indicates regions of z-scores with values of −3 or less along the FA skeleton. FSL script tbss_fill used to thicken results for illustrative purposes.

Fig. 4

Relationships between clusters of abnormally low fractional anisotropy (FA) and clinical measures in the mTBI and mTBI+PTSD participants. The number of clusters was square-root transformed to account for positive skew of the original distribution. We conducted these analyses on an exploratory basis, and the p-values we report were not adjusted for multiple comparisons. When we applied a Holm-Bonferroni correction (Holm, 1979), significant relationships (for the number of abnormally negative clusters) remained with PTSD symptom severity and depression, although those with postconcussive symptoms, Trails B, and WAIS coding were lost.