Altered lateralization of the cingulum in deployment-related traumatic brain injury: An ENIGMA military-relevant brain injury study

Emily L. Dennis*, Mary R. Newsome, Hannah M. Lindsey, Maheen Adamson, Tara A. Austin, Seth G. Disner, Blessen C. Eapen, Carrie Esopenko, Carol E. Franz, Elbert Geuze, Courtney Haswell, Sidney R. Hinds, Cooper B. Hodges, Andrei Irimia, Kimbra Kenney, Inga K. Koerte, William S. Kremen, Harvey S. Levin, Rajendra A. Morey, John OllingerJared A. Rowland, Randall S. Scheibel, Martha E. Shenton, Danielle R. Sullivan, Leah D. Talbert, Sophia I. Thomopoulos, Maya Troyanskaya, William C. Walker, Xin Wang, Ashley L. Ware, John Kent Werner, Wright Williams, Paul M. Thompson, David F. Tate, Elisabeth A. Wilde

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Traumatic brain injury (TBI) in military populations can cause disruptions in brain structure and function, along with cognitive and psychological dysfunction. Diffusion magnetic resonance imaging (dMRI) can detect alterations in white matter (WM) microstructure, but few studies have examined brain asymmetry. Examining asymmetry in large samples may increase sensitivity to detect heterogeneous areas of WM alteration in mild TBI. Through the Enhancing Neuroimaging Genetics Through Meta-Analysis Military-Relevant Brain Injury working group, we conducted a mega-analysis of neuroimaging and clinical data from 16 cohorts of Active Duty Service Members and Veterans (n = 2598). dMRI data were processed together along with harmonized demographic, injury, psychiatric, and cognitive measures. Fractional anisotropy in the cingulum showed greater asymmetry in individuals with deployment-related TBI, driven by greater left lateralization in TBI. Results remained significant after accounting for potentially confounding variables including posttraumatic stress disorder, depression, and handedness, and were driven primarily by individuals whose worst TBI occurred before age 40. Alterations in the cingulum were also associated with slower processing speed and poorer set shifting. The results indicate an enhancement of the natural left laterality of the cingulum, possibly due to vulnerability of the nondominant hemisphere or compensatory mechanisms in the dominant hemisphere. The cingulum is one of the last WM tracts to mature, reaching peak FA around 42 years old. This effect was primarily detected in individuals whose worst injury occurred before age 40, suggesting that the protracted development of the cingulum may lead to increased vulnerability to insults, such as TBI.

Original languageEnglish
Pages (from-to)1888-1900
Number of pages13
JournalHuman Brain Mapping
Issue number5
Publication statusPublished - 1 Apr 2023


  • DTI
  • military
  • traumatic brain injury


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