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 Ollinger; Jared 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

doi:10.1002/hbm.26179

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

Psychiatry & Behavioral Sciences

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	1888-1900
Number of pages	13
Journal	Human Brain Mapping
Volume	44
Issue number	5
DOIs	https://doi.org/10.1002/hbm.26179
State	Accepted/In press - 2022

Bibliographical note

Funding Information:
The views expressed in this article are those of the author(s) and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or US Government. Inga K. Koerte receives funding for a collaborative project unrelated to this article and serves as a paid scientific advisor for Abbott. She receives royalties for book chapters. Her spouse is an employee at Siemens AG. Paul M. Thompson received a research grant from Biogen, Inc., for research unrelated to this article.

Funding Information:
This work was supported by the NIH R61NS120249 K99NS096116; U.S. Army Medical Research and Materiel Command (USAMRMC) award 13129004; VA RR&D IK2RX002922; South Central VA Healthcare Network Veterans Health Administration; VA RR&D SPIRE Award I21RX001608; DOD PRARP; Dutch Ministry of Defence; R01AG058822 R01NS100973, DoD contract W81XWH‐18‐1‐0413, a grant from the James J. and Sue Femino Foundation, a Hanson‐Thorell Research Scholarship, the USC CURVE & SURE programs, and the Leonard Davis School of Gerontology; R01NS100952; European Research Council (ERC) (Starting Grant 804326); VA Rehabilitation Research and Development Service (VA RR&D) I01RX003443 I01RX003442; VA Health Services Research and Development Service Research Career Scientist Award IK6HX002608; Merit Review Award Number I01 CX001820 from the United States (U.S.) Department of Veterans Affairs Clinical Sciences R&D (CSRD) Service; VA CSR&D Career Development Award VA Career Development Award 5IK2CX001508; VA CSR&D Career Development Award 1IK2CX001772‐01; Defense and Veterans Brain Injury Centers, the U.S. Army Medical Research and Materiel Command (USAMRMC); W81XWH‐13‐2‐0025 and the Chronic Effects of Neurotrauma Consortium (CENC); PT108802‐SC104835 U54EB020403 K99 MH119314; (NIMH); NARSAD 27786. This work was supported by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense, through the Psychological Health/Traumatic Brain Injury Research Program LongTerm Impact of Military Relevant Brain Injury Consortium (LIMBIC) Award W81XWH18PH/TBIRPLIMBIC under Awards No. W81XWH1920067 W81XWH1320095, and by the U.S. Department of Veterans Affairs Awards No. I01 CX002097, I01 CX002096, I01 HX003155, I01 RX003444, I01 RX003443, I01 RX003442, I01 CX001135, I01 CX001246, I01 RX001774, I01 RX001135, I01 RX002076, I01 RX001880, I01 RX002172, I01 RX002173, I01 RX002171, I01 RX002174 I01 RX002170.

Publisher Copyright:
© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.

Keywords

DTI
military
traumatic brain injury

PubMed: MeSH publication types

Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Publisher link

10.1002/hbm.26179

Cite this

Dennis, E. L., Newsome, M. R., Lindsey, H. M., Adamson, M., Austin, T. A., Disner, S. G., Eapen, B. C., Esopenko, C., Franz, C. E., Geuze, E., Haswell, C., Hinds, S. R., Hodges, C. B., Irimia, A., Kenney, K., Koerte, I. K., Kremen, W. S., Levin, H. S., Morey, R. A., ... Wilde, E. A. (Accepted/In press). Altered lateralization of the cingulum in deployment-related traumatic brain injury: An ENIGMA military-relevant brain injury study. Human Brain Mapping, 44(5), 1888-1900. https://doi.org/10.1002/hbm.26179

Dennis, EL, Newsome, MR, Lindsey, HM, Adamson, M, Austin, TA, Disner, SG, Eapen, BC, Esopenko, C, Franz, CE, Geuze, E, Haswell, C, Hinds, SR, Hodges, CB, Irimia, A, Kenney, K, Koerte, IK, Kremen, WS, Levin, HS, Morey, RA, Ollinger, J, Rowland, JA, Scheibel, RS, Shenton, ME, Sullivan, DR, Talbert, LD, Thomopoulos, SI, Troyanskaya, M, Walker, WC, Wang, X, Ware, AL, Werner, JK, Williams, W, Thompson, PM, Tate, DF & Wilde, EA 2022, 'Altered lateralization of the cingulum in deployment-related traumatic brain injury: An ENIGMA military-relevant brain injury study', Human Brain Mapping, vol. 44, no. 5, pp. 1888-1900. https://doi.org/10.1002/hbm.26179

@article{ca869c4cab724b11a58a0e7f850057ce,

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

abstract = "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.",

keywords = "DTI, military, traumatic brain injury",

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

note = "Funding Information: The views expressed in this article are those of the author(s) and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or US Government. Inga K. Koerte receives funding for a collaborative project unrelated to this article and serves as a paid scientific advisor for Abbott. She receives royalties for book chapters. Her spouse is an employee at Siemens AG. Paul M. Thompson received a research grant from Biogen, Inc., for research unrelated to this article. Funding Information: This work was supported by the NIH R61NS120249 K99NS096116; U.S. Army Medical Research and Materiel Command (USAMRMC) award 13129004; VA RR&D IK2RX002922; South Central VA Healthcare Network Veterans Health Administration; VA RR&D SPIRE Award I21RX001608; DOD PRARP; Dutch Ministry of Defence; R01AG058822 R01NS100973, DoD contract W81XWH‐18‐1‐0413, a grant from the James J. and Sue Femino Foundation, a Hanson‐Thorell Research Scholarship, the USC CURVE & SURE programs, and the Leonard Davis School of Gerontology; R01NS100952; European Research Council (ERC) (Starting Grant 804326); VA Rehabilitation Research and Development Service (VA RR&D) I01RX003443 I01RX003442; VA Health Services Research and Development Service Research Career Scientist Award IK6HX002608; Merit Review Award Number I01 CX001820 from the United States (U.S.) Department of Veterans Affairs Clinical Sciences R&D (CSRD) Service; VA CSR&D Career Development Award VA Career Development Award 5IK2CX001508; VA CSR&D Career Development Award 1IK2CX001772‐01; Defense and Veterans Brain Injury Centers, the U.S. Army Medical Research and Materiel Command (USAMRMC); W81XWH‐13‐2‐0025 and the Chronic Effects of Neurotrauma Consortium (CENC); PT108802‐SC104835 U54EB020403 K99 MH119314; (NIMH); NARSAD 27786. This work was supported by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense, through the Psychological Health/Traumatic Brain Injury Research Program LongTerm Impact of Military Relevant Brain Injury Consortium (LIMBIC) Award W81XWH18PH/TBIRPLIMBIC under Awards No. W81XWH1920067 W81XWH1320095, and by the U.S. Department of Veterans Affairs Awards No. I01 CX002097, I01 CX002096, I01 HX003155, I01 RX003444, I01 RX003443, I01 RX003442, I01 CX001135, I01 CX001246, I01 RX001774, I01 RX001135, I01 RX002076, I01 RX001880, I01 RX002172, I01 RX002173, I01 RX002171, I01 RX002174 I01 RX002170. Publisher Copyright: {\textcopyright} 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.",

year = "2022",

doi = "10.1002/hbm.26179",

language = "English (US)",

volume = "44",

pages = "1888--1900",

journal = "Human Brain Mapping",

issn = "1065-9471",

publisher = "Wiley-Liss Inc.",

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TY - JOUR

T1 - Altered lateralization of the cingulum in deployment-related traumatic brain injury

T2 - An ENIGMA military-relevant brain injury study

AU - Dennis, Emily L.

AU - Newsome, Mary R.

AU - Lindsey, Hannah M.

AU - Adamson, Maheen

AU - Austin, Tara A.

AU - Disner, Seth G.

AU - Eapen, Blessen C.

AU - Esopenko, Carrie

AU - Franz, Carol E.

AU - Geuze, Elbert

AU - Haswell, Courtney

AU - Hinds, Sidney R.

AU - Hodges, Cooper B.

AU - Irimia, Andrei

AU - Kenney, Kimbra

AU - Koerte, Inga K.

AU - Kremen, William S.

AU - Levin, Harvey S.

AU - Morey, Rajendra A.

AU - Ollinger, John

AU - Rowland, Jared A.

AU - Scheibel, Randall S.

AU - Shenton, Martha E.

AU - Sullivan, Danielle R.

AU - Talbert, Leah D.

AU - Thomopoulos, Sophia I.

AU - Troyanskaya, Maya

AU - Walker, William C.

AU - Wang, Xin

AU - Ware, Ashley L.

AU - Werner, John Kent

AU - Williams, Wright

AU - Thompson, Paul M.

AU - Tate, David F.

AU - Wilde, Elisabeth A.

N1 - Funding Information: The views expressed in this article are those of the author(s) and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or US Government. Inga K. Koerte receives funding for a collaborative project unrelated to this article and serves as a paid scientific advisor for Abbott. She receives royalties for book chapters. Her spouse is an employee at Siemens AG. Paul M. Thompson received a research grant from Biogen, Inc., for research unrelated to this article. Funding Information: This work was supported by the NIH R61NS120249 K99NS096116; U.S. Army Medical Research and Materiel Command (USAMRMC) award 13129004; VA RR&D IK2RX002922; South Central VA Healthcare Network Veterans Health Administration; VA RR&D SPIRE Award I21RX001608; DOD PRARP; Dutch Ministry of Defence; R01AG058822 R01NS100973, DoD contract W81XWH‐18‐1‐0413, a grant from the James J. and Sue Femino Foundation, a Hanson‐Thorell Research Scholarship, the USC CURVE & SURE programs, and the Leonard Davis School of Gerontology; R01NS100952; European Research Council (ERC) (Starting Grant 804326); VA Rehabilitation Research and Development Service (VA RR&D) I01RX003443 I01RX003442; VA Health Services Research and Development Service Research Career Scientist Award IK6HX002608; Merit Review Award Number I01 CX001820 from the United States (U.S.) Department of Veterans Affairs Clinical Sciences R&D (CSRD) Service; VA CSR&D Career Development Award VA Career Development Award 5IK2CX001508; VA CSR&D Career Development Award 1IK2CX001772‐01; Defense and Veterans Brain Injury Centers, the U.S. Army Medical Research and Materiel Command (USAMRMC); W81XWH‐13‐2‐0025 and the Chronic Effects of Neurotrauma Consortium (CENC); PT108802‐SC104835 U54EB020403 K99 MH119314; (NIMH); NARSAD 27786. This work was supported by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense, through the Psychological Health/Traumatic Brain Injury Research Program LongTerm Impact of Military Relevant Brain Injury Consortium (LIMBIC) Award W81XWH18PH/TBIRPLIMBIC under Awards No. W81XWH1920067 W81XWH1320095, and by the U.S. Department of Veterans Affairs Awards No. I01 CX002097, I01 CX002096, I01 HX003155, I01 RX003444, I01 RX003443, I01 RX003442, I01 CX001135, I01 CX001246, I01 RX001774, I01 RX001135, I01 RX002076, I01 RX001880, I01 RX002172, I01 RX002173, I01 RX002171, I01 RX002174 I01 RX002170. Publisher Copyright: © 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - DTI

KW - military

KW - traumatic brain injury

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DO - 10.1002/hbm.26179

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

Abstract

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Keywords

PubMed: MeSH publication types

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