High-fidelity measures of whole-brain functional connectivity and white matter integrity mediate relationships between traumatic brain injury and post-traumatic stress disorder symptoms

Evan M. Gordon, Randall S. Scheibel, Laura Zambrano-Vazquez, Meilin Jia-Richards, Geoffrey J. May, Eric C. Meyer, Steven M. Nelson

Research output: Contribution to journalArticlepeer-review

Abstract

Traumatic brain injury (TBI) disrupts brain communication and increases risk for post-traumatic stress disorder (PTSD). However, mechanisms by which TBI-related disruption of brain communication confers PTSD risk have not been successfully elucidated in humans. This may be in part because functional MRI (fMRI), the most common technique for measuring functional brain communication, is unreliable for characterizing individual patients. However, this unreliability can be overcome with sufficient within-individual data. Here, we examined whether relationships could be observed among TBI, structural and functional brain connectivity, and PTSD severity by collecting ∼3.5 hours of resting-state fMRI and diffusion tensor imaging (DTI) data in each of 26 United States military veterans. We observed that a TBI history was associated with decreased whole-brain resting-state functional connectivity (RSFC), while the number of lifetime TBIs was associated with reduced whole-brain fractional anisotropy (FA). Both RSFC and FA explained independent variance in PTSD severity, with RSFC mediating the TBI-PTSD relationship. Finally, we showed that large amounts of per-individual data produced highly reliable RSFC measures, and that relationships among TBI, RSFC/FA, and PTSD could not be observed with typical data quantities. These results demonstrate links among TBI, brain connectivity, and PTSD severity, and illustrate the need for precise characterization of individual patients using high-data fMRI scanning.

Original languageEnglish (US)
Pages (from-to)767-779
Number of pages13
JournalJournal of neurotrauma
Volume35
Issue number5
DOIs
StatePublished - Mar 2018
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank Ramy Sweidan, Brad Gary, Staley Justice, Krupa George, Janani Srikanth, Allison McGinnis, Robert Athey, and Joel Reid for their assistance in data collection and behavioral data coding. This work was supported by grants RX000304-04A1 (E.C.M.), B1320-I (R.S.S.), and O1062-I (R.S.S.) from the United States Department of Veterans Affairs Rehabilitation Research and Development Service, and by VISN17 Center of Excellence pilot funding. The contents of this manuscript do not represent the views of the United States Department of Veterans Affairs or the United States Government.

Publisher Copyright:
© Copyright 2018, Mary Ann Liebert, Inc.

Keywords

  • FC
  • high-data MRI
  • PTSD
  • TBI
  • white matter integrity

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