High-fidelity measures of whole-brain functional connectivity and white matter integrity mediate relationships between TBI and PTSD symptoms

Traumatic brain injury (TBI) disrupts brain communication and increases risk for posttraumatic stress disorder (PTSD). However, mechanisms by which TBI-related disruption of brain communication confers PTSD risk have not been successfully elucidated in humans. This may be in part because fMRI, the most common technique for measuring brain function, is unreliable for characterizing individual patients. However, this unreliability can be overcome with sufficient within-individual data. Here, we examined whether relationships could be observed between TBI, structural and functional brain connectivity, and PTSD severity by collecting ~3.5 hours of resting-state fMRI and DTI data in each of 26 US military veterans. We observed that a TBI history was associated with decreased whole-brain resting-state functional connectivity (RSFC), while the number of lifetime TBIs was associated with reduced whole-brain fractional anisotropy (FA). Both RSFC and FA explained independent variance in PTSD severity, with RSFC med...