Regional associations of white matter integrity and neurological, post-traumatic stress disorder and autonomic symptoms in Veterans with and without history of loss of consciousness in mild TBI

Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) share overlapping symptom presentations and are highly comorbid conditions among Veteran populations. Despite elevated presentations of PTSD after mTBI, mechanisms linking the two are unclear, although both have been associated with alterations in white matter and disruptions in autonomic regulation. The present study aimed to determine if there is regional variability in white matter correlates of symptom severity and autonomic functioning in a mixed sample of Veterans with and without PTSD and/or mTBI (N = 77).Diffusion-weighted images were processed to extract fractional anisotropy (FA) values for major white matter structures. The PTSD Checklist-Military version (PCL-M) and Neurobehavioral Symptom Inventory (NSI) were used to determine symptom domains within PTSD and mTBI. Autonomic function was assessed using continuous blood pressure and respiratory sinus arrythmia during a static, standing angle positional test. Mixed-effect models were used to assess the regional specificity of associations between symptom severity and white matter, with FA, global symptom severity (score), and white matter tract (tract) as predictors. Additional interaction terms of symptom domain (i.e., NSI and PCL-M subscales) and loss of consciousness (LoC) were added to evaluate potential moderating effects. A parallel analysis was conducted to explore concordance with autonomic functioning.Results from the two-way Score × Tract interaction suggested that global symptom severity was associated with FA in the cingulum angular bundle (positive) and uncinate fasciculus (negative) only, without variability by symptom domain. We also found regional specificity in the relationship between FA and autonomic function, such that FA was positively associated with autonomic function in all tracts except the cingulum angular bundle. History of LoC moderated the association for both global symptom severity and autonomic function.Our findings are consistent with previous literature suggesting that there is significant overlap in the symptom presentation in TBI and PTSD, and white matter variability associated with LoC in mTBI may be associated with increased PTSD-spectra symptoms. Further research on treatment response in patients with both mTBI history and PTSD incorporating imaging and autonomic assessment may be valuable in understanding the role of brain injury in treatment outcomes and inform treatment design.