Coordinating Global Multi-Site Studies of Military-Relevant Traumatic Brain Injury: Opportunities, Challenges, and Harmonization Guidelines

David F. Tate, Emily L. Dennis, John T. Adams, Maheen M. Adamson, Heather G. Belanger, Erin D. Bigler, Heather C. Bouchard, Alexandra L. Clark, Lisa M. Delano-Wood, Seth G. Disner, Blessen C. Eapen, Carol E. Franz, Elbert Geuze, Naomi J. Goodrich-Hunsaker, Kihwan Han, Jasmeet P. Hayes, Sidney R. Hinds, Cooper B. Hodges, Elizabeth S. Hovenden, Andrei IrimiaKimbra Kenney, Inga K. Koerte, William S. Kremen, Harvey S. Levin, Hannah M. Lindsey, Rajendra A. Morey, Mary R. Newsome, John Ollinger, Mary Jo Pugh, Randall S. Scheibel, Martha E. Shenton, Danielle R. Sullivan, Brian A. Taylor, Maya Troyanskaya, Carmen Velez, Benjamin Sc Wade, Xin Wang, Ashley L. Ware, Ross Zafonte, Paul M. Thompson, Elisabeth A. Wilde

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Traumatic brain injury (TBI) is common among military personnel and the civilian population and is often followed by a heterogeneous array of clinical, cognitive, behavioral, mood, and neuroimaging changes. Unlike many neurological disorders that have a characteristic abnormal central neurologic area(s) of abnormality pathognomonic to the disorder, a sufficient head impact may cause focal, multifocal, diffuse or combination of injury to the brain. This inconsistent presentation makes it difficult to establish or validate biological and imaging markers that could help improve diagnostic and prognostic accuracy in this patient population. The purpose of this manuscript is to describe both the challenges and opportunities when conducting military-relevant TBI research and introduce the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Military Brain Injury working group. ENIGMA is a worldwide consortium focused on improving replicability and analytical power through data sharing and collaboration. In this paper, we discuss challenges affecting efforts to aggregate data in this patient group. In addition, we highlight how “big data” approaches might be used to understand better the role that each of these variables might play in the imaging and functional phenotypes of TBI in Service member and Veteran populations, and how data may be used to examine important military specific issues such as return to duty, the late effects of combat-related injury, and alteration of the natural aging processes.

Original languageEnglish (US)
Pages (from-to)585-613
Number of pages29
JournalBrain Imaging and Behavior
Volume15
Issue number2
DOIs
StatePublished - Apr 2021

Bibliographical note

Funding Information:
VA R&D SPIRE AWARD to MA. K99NS096116 to ELD. VA RR&D IK2RX002922-01A1 to SGD. Dutch Ministry of Defence. R01AG058822 to JPH. R01NS100973 and DoD contract W81XWH-18-1-0413 to AI. VA Rehabilitation Research and Development Service I01RX003443, I01RX003442; VA Health Services Research and Development Service Research Career Scientist Award IK6HX002608 to MJP. This work was supported (or supported in part) by 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 1IK2CX001772-01 to DRS. 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) to DFT. UL1TR002649 to BAT. U54EB020403 to PMT. Department of Defense, Chronic Effects of Neurotrauma Consortium (CENC) Award W81XWH-13-2-0095, 5 I01 RX002174 to EAW.

Funding Information:
VA and DoD research projects are also funded through a number of different peer reviewed mechanisms. DoD has both intramural and extramural funding opportunities, while the United States VA system only funds intramural investigations. Practically, this means that principal investigators for VA funds must have a VA appointment and be employed by the VA for a minimum of 5/8ths time. Principal investigators funded by DoD grants can be active duty military, civil service employees, academic, or other private industry personnel qualified to conduct the research. In addition, guidelines for expenditure limits, both overall and in certain categories, may differ between these funding agencies. While these factors may influence the kinds of research submitted to each agency, judicious use of these mechanisms can facilitate the ability to address research questions using diverse funding mechanisms.

Funding Information:
VA R&D SPIRE AWARD to MA. K99NS096116 to ELD. VA RR&D IK2RX002922-01A1 to SGD. Dutch Ministry of Defence. R01AG058822 to JPH. R01NS100973 and DoD contract W81XWH-18-1-0413 to AI. VA Rehabilitation Research and Development Service I01RX003443, I01RX003442; VA Health Services Research and Development Service Research Career Scientist Award IK6HX002608 to MJP. This work was supported (or supported in part) by 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 1IK2CX001772-01 to DRS. 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) to DFT. UL1TR002649 to BAT. U54EB020403 to PMT. Department of Defense, Chronic Effects of Neurotrauma Consortium (CENC) Award W81XWH-13-2-0095, 5 I01 RX002174 to EAW.

Funding Information:
Dr. Adamson is on the scientific advisory board for TruGenomics, a start-up developing a biomarker for PTSD. Dr. Zafonte received royalties from 1) Oakstone for an educational CD- Physical Medicine and Rehabilitation a Comprehensive Review; 2) Demos publishing for serving as co-editor of the text Brain Injury Medicine. Dr. Zafonte also serves on the Scientific Advisory Board of Myomo, Oxeia Biopharma, Biodirection and ElMINDA. He also evaluates patients in the MGH Brain and Body-TRUST Program which is funded by the NFL Players Association. 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, Department of Veterans Affairs, or the U.S. Government.

Publisher Copyright:
© 2021, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

Keywords

  • blast injury
  • ENIGMA
  • military
  • TBI
  • traumatic brain injury
  • veteran

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