Brain volume changes following blast-related mild TBI in service members and veterans: a LIMBIC-CENC study

ImportanceBlast-related mild traumatic brain injuries (bTBI), the "signature injury" of post-9/11 conflicts, are associated with clinically-relevant long-term cognitive, psychological, and behavioral dysfunction and disability; however, the underlying neural mechanisms remain unclear. ObjectiveTo investigate associations between a history of remote bTBI and regional brain volume in a sample of United States (U.S.) Veterans and Active Duty Service Members (VADSM). DesignProspective case-control study of U.S. VADSM of participants from the Long-term Impact of Military-relevant Brain Injury Consortium - Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC), which enrolled over 1,500 participants at five sites used in this analysis between 2014-2023. SettingParticipants were recruited from Veterans Affairs medical centers across the U.S. ParticipantsSeven hundred and seventy-four VADSM of the U.S. military met eligibility criteria for this analysis. ExposureAll participants had combat exposure, and 82% had one or more lifetime mild TBIs with variable injury mechanisms. Main Outcomes and MeasuresRegional brain volume was calculated using tensor-based morphometry on 3D T1-weighted magnetic resonance imaging scans. TBI history, including history of blast-related injury (bTBI), was assessed by structured clinical interview. Cognitive performance and psychiatric symptoms were assessed with a battery of validated instruments. We hypothesized that regional volume would be smaller in the bTBI group, and that this would be associated with cognitive performance. ResultsIndividuals with a history of bTBI had smaller brain volumes in several clusters, with the largest centered bilaterally in the superior corona radiata and globus pallidus. Greater volume deficits were associated with a larger number of lifetime bTBIs. Additionally, causal mediation analysis revealed that these volume differences significantly mediated the association between bTBI and performance on measures of working memory and processing speed. Conclusions and RelevanceOur results reveal robust volume differences associated with bTBI. Magnetic resonance elastography atlases reveal that the specific regions affected include the stiffest tissues in the brain, which may underlie their vulnerability to pressure waves from blast exposures. Furthermore, these volume differences significantly mediated the association between bTBI and cognitive function, indicating that this may be a helpful biomarker in tracking outcome after bTBI and suggesting potential treatment targets to prevent or limit chronic dysfunction.