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. 2024 Nov 4;7(11):e2443416.
doi: 10.1001/jamanetworkopen.2024.43416.

Differences in Brain Volume in Military Service Members and Veterans After Blast-Related Mild TBI: A LIMBIC-CENC Study

Emily L Dennis  1   2 , Jared A Rowland  3   4 , Carrie Esopenko  5 , Nicholas J Tustison  6 , Mary R Newsome  1   2   7 , Elizabeth S Hovenden  1   2 , Brian B Avants  6 , Jessica Gill  8   9 , Sidney R Hinds 2nd  10 , Kimbra Kenney  10   11 , Hannah M Lindsey  1   2 , Sarah L Martindale  3   4 , Mary Jo Pugh  12   13 , Randall S Scheibel  7   14 , Pashtun-Poh Shahim  15 , Robert Shih  16 , James R Stone  6 , Maya Troyanskaya  7   14 , William C Walker  17   18 , Kent Werner  10 , Gerald E York  19 , David X Cifu  17 , David F Tate  1   2 , Elisabeth A Wilde  1   2   7
Affiliations

Differences in Brain Volume in Military Service Members and Veterans After Blast-Related Mild TBI: A LIMBIC-CENC Study

Emily L Dennis et al. JAMA Netw Open. .

Abstract

Importance: Blast-related mild traumatic brain injuries (TBIs), 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.

Objective: To investigate associations between a history of remote blast-related mild TBI and regional brain volume in a sample of US veterans and active duty service members.

Design, setting, and participants: Prospective cohort study of US veterans and active duty service members from the Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC), which enrolled more than 1500 participants at 5 sites used in this analysis between 2014 and 2023. Participants were recruited from Veterans Affairs medical centers across the US; 774 veterans and active duty service members of the US military met eligibility criteria for this secondary analysis. Assessment dates were from January 6, 2015, to March 31, 2023; processing and analysis dates were from August 1, 2023, to January 15, 2024.

Exposure: All participants had combat exposure, and 82% had 1 or more lifetime mild TBIs with variable injury mechanisms.

Main outcomes and measures: Regional brain volume was calculated using tensor-based morphometry on 3-dimensional, T1-weighted magnetic resonance imaging scans; history of TBI, including history of blast-related mild TBI, 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 blast-related mild TBI group and that this would be associated with cognitive performance.

Results: A total of 774 veterans (670 [87%] male; mean [SD] age, 40.1 [9.8] years; 260 [34%] with blast-related TBI) were included in the sample. Individuals with a history of blast-related mild TBI had smaller brain volumes than individuals without a history of blast-related mild TBI (which includes uninjured individuals and those with non-blast-related mild TBI) in several clusters, with the largest centered bilaterally in the superior corona radiata and subcortical gray and white matter (cluster peak Cohen d range, -0.23 to -0.38; mean [SD] Cohen d, 0.28 [0.03]). Additionally, causal mediation analysis revealed that these volume differences significantly mediated the association between blast-related mild TBI and performance on measures of working memory and processing speed.

Conclusions and relevance: In this cohort study of 774 veterans and active duty service members, robust volume differences associated with blast-related TBI were identified. Furthermore, these volume differences significantly mediated the association between blast-related mild TBI and cognitive function, indicating that this pattern of brain differences may have implications for daily functioning.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Rowland reported receiving grants from the Department of Defense (DoD), a Chronic Effects of Neurotrauma Consortium Award, and grants from the Department of Veterans Affairs during the conduct of the study. Dr Esopenko reported receiving speaker honoraria from the Brain Injury Association of New York State and the Women’s Operational Military Exposure Network. Dr Hinds reported receiving personal fees as an employee of SCS Consulting LLC, which has financial affiliations with the Major League Soccer Players Association, Nano DX, Owl Therapeutics, Prevent Biometrics, the Collaborative Neuropathology Network Characterizing Outcomes of TBI, the US Army Medical Research and Development Command’s Congressionally Directed Medical Research Programs, and the National Football League Players Association. Dr Hinds serves as a co-principal investigator but does receive financial compensation for his work with Long-Term Impact of Military-Relevant Brain Injury Consortium (LIMBIC)–Chronic Effects of Neurotrauma Consortium; he is a member of Concussion Legacy Foundation’s Veterans Advisory Board; an advisory board member to the University of Michigan Concussion Center; an advisor to Gryphon Bio; an advisory board member of 2508 Biosciences; an ad hoc reviewer for VA Brain Health Research; an invited reviewer to the Congressionally Directed Medical Research Programs; a contributor to the National Academy of Science, Engineering, and Medicine “Accelerating Progress in TBI Research and Care”; a National Academies of Sciences, Engineering, and Medicine TBI Forum committee member (currently inactive); and a former contributor to the Post-traumatic Epilepsy Research Program. His former Department of Defense work includes NFL Scientific Advisory Board member; NCAA-DoD CARE Medical Advisory Board Member; DoD Brain Health Research Coordinating Officer and Medical Advisor to the Principal Assistant for Research and Technology, US Army Medical Research and Development Command; Ex Officio National Advisory Neurological Disorders and Stroke Council Member; and Congressionally Directed Medical Research Program’s Peer Reviewed Alzheimer’s Disease Research Program. Dr Martindale reported receiving grants from the Department of Veterans Affairs during the conduct of the study. Dr Pugh reported receiving grants from and was employed at the Department of Veterans Affairs during the conduct of the study and receiving grants from Sanofi Pharmaceuticals outside the submitted work. Dr Stone reported receiving grants from the Department of Veterans Affairs during the conduct of the study. Dr Walker reported receiving a DoD Long-Term Impact of Military-Relevant Brain Injury Consortium Award during the conduct of the study. Dr Tate reported receiving grants from the DoD and the Department of Veteran Affairs during the conduct of the study. Dr Wilde reported receiving grants from the University of Utah and from the Department of Veteran Affairs during the conduct of the study and grants from the University of Utah outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Differences in Regional Volume Between Participants With and Those Without a History of Blast-Related Mild Traumatic Brain Injury
Blue clusters showing significantly smaller volumes are presented, with colors corresponding to Cohen d. Left in image is right in brain. Orange clusters indicate larger volumes, most of which are not visible from this view.
Figure 2.
Figure 2.. Causal Mediation Analyses
Results of causal mediation analyses run in R using the mediation package. For these analyses, the initial variable was blast-related mild traumatic brain injury (TBI) (yes or no), the mediator was volume of either the superior corona radiata or subcortical clusters (derived as described in the Primary Analysis subsection and depicted in Figure 1), and the outcome variables were the Trail-Making Test–B (TMT-B) completion time, the TMT-B and TMT-A completion time, or the Total Digit Span. M mediates the relationship between X and Y.
See this image and copyright information in PMC

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References

    1. Warden D. Military TBI during the Iraq and Afghanistan wars. J Head Trauma Rehabil. 2006;21(5):398-402. doi:10.1097/00001199-200609000-00004 - DOI - PubMed
    1. Mac Donald CL, Johnson AM, Cooper D, et al. . Detection of blast-related traumatic brain injury in U.S. military personnel. N Engl J Med. 2011;364(22):2091-2100. doi:10.1056/NEJMoa1008069 - DOI - PMC - PubMed
    1. Martindale SL, Shura RD, Rostami R, Taber KH, Rowland JA. Research letter: blast exposure and brain volume. J Head Trauma Rehabil. 2021;36(6):424-428. doi:10.1097/HTR.0000000000000660 - DOI - PubMed
    1. Bryden DW, Tilghman JI, Hinds SR II. Blast-related traumatic brain injury: current concepts and research considerations. J Exp Neurosci. 2019;13:1179069519872213. doi:10.1177/1179069519872213 - DOI - PMC - PubMed
    1. DePalma RG, Hoffman SW. Combat blast related traumatic brain injury (TBI): decade of recognition; promise of progress. Behav Brain Res. 2018;340:102-105. doi:10.1016/j.bbr.2016.08.036 - DOI - PubMed

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