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White matter abnormalities in mild traumatic brain injury with and without post-traumatic stress disorder: a subject-specific diffusion tensor imaging study

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Abstract

Mild traumatic brain injuries (mTBIs) are often associated with posttraumatic stress disorder (PTSD). In cases of chronic mTBI, accurate diagnosis can be challenging due to the overlapping symptoms this condition shares with PTSD. Furthermore, mTBIs are heterogeneous and not easily observed using conventional neuroimaging tools, despite the fact that diffuse axonal injuries are the most common injury. Diffusion tensor imaging (DTI) is sensitive to diffuse axonal injuries and is thus more likely to detect mTBIs, especially when analyses account for the inter-individual variability of these injuries. Using a subject-specific approach, we compared fractional anisotropy (FA) abnormalities between groups with a history of mTBI (n = 35), comorbid mTBI and PTSD (mTBI + PTSD; n = 22), and healthy controls (n = 37). We compared all three groups on the number of abnormal FA clusters derived from subject-specific injury profiles (i.e., individual z-score maps) along a common white matter skeleton. The mTBI + PTSD group evinced a greater number of abnormally low FA clusters relative to both the healthy controls and the mTBI group without PTSD (p < .05). Across the groups with a history of mTBI, increased numbers of abnormally low FA clusters were significantly associated with PTSD symptom severity, depression, post-concussion symptoms, and reduced information processing speed (p < .05). These findings highlight the utility of subject-specific microstructural analyses when searching for mTBI-related brain abnormalities, particularly in patients with PTSD. This study also suggests that patients with a history of mTBI and comorbid PTSD, relative to those without PTSD, are at increased risk of FA abnormalities.

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Authors and Affiliations

  1. Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, 1249 Boylston St, Boston, MA, 02215, USA

    Christian Lepage, Amicie de Pierrefeu, Inga K. Koerte, Michael J. Coleman, Ofer Pasternak, Martha E. Shenton & Sylvain Bouix

  2. Department of Psychology, University of Ottawa, Ottawa, Canada

    Christian Lepage

  3. School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

    Amicie de Pierrefeu

  4. Department of Child and Adolescent Psychiatry, Psychosomatic, and Psychotherapy, Ludwig-Maximilian-University, Munich, Germany

    Inga K. Koerte

  5. Stanford University Medical Center, Palo Alto, CA, USA

    Gerald Grant

  6. Duke University, Durham, NC, USA

    Gerald Grant

  7. Duke University Medical Center and VA Mid-Atlantic MIRECC, Durham, NC, USA

    Christine E. Marx & Rajendra A. Morey

  8. Geisel School of Medicine at Dartmouth, Hanover, NH, USA

    Laura A. Flashman & Thomas W. McAllister

  9. Medical University of South Carolina, Ralph H. Johnson VA Medical Center, Charleston, SC, USA

    Mark S. George

  10. Indiana University School of Medicine, Indianapolis, IN, USA

    Thomas W. McAllister

  11. Department of Neurosurgery, Mayfield Clinic, University of Cincinnati (UC) College of Medicine, Neurotrauma Center at UC Neuroscience Institute, Cincinnati, OH, USA

    Norberto Andaluz

  12. University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Lori Shutter

  13. University of Cincinnati, Pittsburgh, PA, USA

    Lori Shutter

  14. Department of Surgery, University of California, San Diego, CA, USA

    Raul Coimbra

  15. Spaulding Rehabilitation Hospital, Massachusetts General Hospital, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Ross D. Zafonte

  16. Department of Psychiatry and Department of Family Medicine & Public Health, University of California, San Diego, La Jolla, CA, USA

    Murray B. Stein

  17. Department of Radiology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA

    Martha E. Shenton

  18. VA Boston Healthcare System, Brockton Division, Brockton, MA, USA

    Martha E. Shenton

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  1. Christian Lepage
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  2. Amicie de Pierrefeu
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  3. Inga K. Koerte
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  4. Michael J. Coleman
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  5. Ofer Pasternak
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  6. Gerald Grant
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  7. Christine E. Marx
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  8. Rajendra A. Morey
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  9. Laura A. Flashman
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  10. Mark S. George
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  11. Thomas W. McAllister
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  12. Norberto Andaluz
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  13. Lori Shutter
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  14. Raul Coimbra
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  15. Ross D. Zafonte
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  16. Murray B. Stein
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  17. Martha E. Shenton
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  18. Sylvain Bouix
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Corresponding author

Correspondence to Sylvain Bouix.

Ethics declarations

This study was conducted according to the principles expressed in the Declaration of Helsinki and approved by Brigham and Women’s Hospital institutional review board. All participants provided written, informed consent

Funding

CL was supported by the Canadian Institutes of Health Research Frederick Banting and Charles Best Doctoral Award, which was awarded in support of his PhD in clinical psychology from the University of Ottawa. The authors would like to acknowledge the following grants that, in part, supported this work: W81XWH-08-2-0159 (Imaging core PI: Shenton, Consortium PI: Stein, Site PIs: George, Grant, Marx, McAllister, and Zafonte).

Conflict of interest

The authors declare they have no conflicts of interest.

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Lepage, C., de Pierrefeu, A., Koerte, I.K. et al. White matter abnormalities in mild traumatic brain injury with and without post-traumatic stress disorder: a subject-specific diffusion tensor imaging study. Brain Imaging and Behavior 12, 870–881 (2018). https://doi.org/10.1007/s11682-017-9744-5

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