Whole-brain correlates of post-traumatic stress disorder in military-related mild traumatic brain injury: A voxel-wise meta-analysis

Resting-state functional magnetic resonance imaging (rs-fMRI) is widely used in studying mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) among military service personnel (MSP). The risk for PTSD is greater after mTBI than after non-mTBI trauma, and PTSD is associated with worse biological, psychological, and social (biopsychosocial) outcomes after mTBI. Studying the neural correlates of mTBI-related PTSD in this population may provide insights into the pathophysiology of both conditions and help identify MSPs most at risk of developing persistent symptoms. This voxel-wise meta-analysis aimed to examine the current literature on rs-fMRI in mTBI-related PTSD, collect neuroimaging data, and perform a voxel-wise meta-analysis to identify significant nodes of functional connectivity across studies. We searched the literature using PubMed, EMBASE, and ScienceDirect. The database query yielded 1455 articles, narrowed with specified eligibility criteria to a final cohort of 33 studies, with 1521 experiment group participants and 1369 controls. Article quality was assessed using the QUADAS-2 instrument. Our meta-analysis revealed a robust correlation between PTSD-mTBI and increased whole-brain resting-state functional connectivity (rsFC) in the amygdala. Our meta-analysis also showed strong correlations between PTSD-mTBI and decreased whole-brain rsFC across regions implicated in speech and language processing. Our meta-regression highlighted robust correlations between less time after a recent mTBI and increased whole-brain rsFC in posterior regions of the default mode network. Our meta-regression also showed strong correlations between increased PTSD symptom severity, increased connectivity in the amygdala, and decreased connectivity in Broca's area.