ENIGMA Military Brain Injury: Altered Subcortical Volume in Chronic TBI Revealed by Mega-Analysis (P2.9-061)

Objective: To identify alterations in subcortical gray matter (GM) volume in Active Duty Service Members (ADSM) and Veterans of the United States military with history of traumatic brain injury (TBI), with greater power from multi-site mega-analysis. Background: TBI is one of the most common injuries affecting armed service members across the world. Injuries can affect combat readiness and can lead to long-term cognitive impairments and adverse health consequences. Altered subcortical GM volume may contribute to poor outcome. Reliable neuroimaging biomarkers of TBI have been elusive, often due to small sample size. Design/Methods: Participants were assessed through three different projects – DoD Alzheimer’s Disease Neuroimaging Initiative, Imaging Support of Study of Cognitive Rehabilitation Effectiveness in Mild Traumatic Brain Injury, and Chronic Effects of Neurotrauma Consortium, totaling 199 participants reporting at least one TBI (178M/21F) and 170 participants without history of TBI (153M/17F). Participants were between 18–83 years old. T1-weighted MR images were processed using FreeSurfer v5.3 and volume estimates of the thalamus, caudate, putamen, hippocampus, amygdala, nucleus accumbens, globus pallidus, and lateral ventricles were extracted using a standard protocol (http://enigma.usc.edu). TBI versus control effect sizes were calculated across sites using random effects to control for site effects, including age, sex, education, and intracranial volume as covariates. Results: We found significantly smaller left thalamic volume in the TBI group (t(367)=−3.0, p=0.0025). Within female participants (21 TBI/17 controls), those with TBI showed a larger putamen (t(36)=2.3, p=0.03). There was a sex-by-diagnosis effect in the left and right thalamus (left t(367)=2.8, p=0.0054; right t(367)=2.7, p=0.0066). Conclusions: We report reduced thalamic volume in Veterans and ADSM with history of TBI. Altered thalamic volume may contribute to motor, cognitive and other symptoms post-injury. Future studies on a larger sample need to verify a potential effect of sex. Future work will also examine associations of subcortical GM volume with clinical outcome measures. Disclosure: Dr. Dennis has nothing to disclose. Dr. Wilde has nothing to disclose. Dr. Zavaliangos-Petropulu has nothing to disclose. Dr. Newsome has nothing to disclose. Dr. Scheibel has nothing to disclose. Dr. Troyanskaya has nothing to disclose. Dr. Velez has nothing to disclose. Dr. Wade has nothing to disclose. Dr. Drennon has nothing to disclose. Dr. York has nothing to disclose. Dr. Bigler has nothing to disclose. Dr. Abildskov has nothing to disclose. Dr. Taylor has nothing to disclose. Dr. Jaramillo has nothing to disclose. Dr. Eapen has nothing to disclose. Dr. Belanger has nothing to disclose. Dr. Morey has nothing to disclose. Dr. Haswell has nothing to disclose. Dr. Bouchard has nothing to disclose. Dr. Adamson has nothing to disclose. Dr. Kang has nothing to disclose. Dr. Koerte has nothing to disclose. Dr. Shenton has nothing to disclose. Dr. Levin has nothing to disclose. Dr. Hinds has nothing to disclose. Dr. Walker has nothing to disclose. Dr. Thompson has nothing to disclose. Dr. Tate has nothing to disclose.