Adverse Outcome Following Mild Traumatic Brain Injury Is Associated with Microstructure Alterations at the Gray and White Matter Boundary

Lara Pankatz; Philine Rojczyk; Johanna Seitz-Holland; Sylvain Bouix; Leonard B Jung; Tim L T Wiegand; Elena M Bonke; Nico Sollmann; Elisabeth Kaufmann; Holly Carrington; Twishi Puri; Yogesh Rathi; Michael J Coleman; Ofer Pasternak; Mark S George; Thomas W McAllister; Ross Zafonte; Murray B Stein; Christine E Marx; Martha E Shenton; Inga K Koerte

doi:10.3390/jcm12165415

Adverse Outcome Following Mild Traumatic Brain Injury Is Associated with Microstructure Alterations at the Gray and White Matter Boundary

J Clin Med. 2023 Aug 21;12(16):5415. doi: 10.3390/jcm12165415.

Authors

Lara Pankatz^{1

2}, Philine Rojczyk^{1

2}, Johanna Seitz-Holland^{1

3}, Sylvain Bouix^{1

4}, Leonard B Jung^{1

2}, Tim L T Wiegand^{1

2}, Elena M Bonke^{1

2

5}, Nico Sollmann^{1

2

6

7

8}, Elisabeth Kaufmann^{1

2

9}, Holly Carrington^{1

10}, Twishi Puri¹, Yogesh Rathi¹, Michael J Coleman¹, Ofer Pasternak^{1

11}, Mark S George^{12

13}, Thomas W McAllister¹⁴, Ross Zafonte^{15

16}, Murray B Stein^{17

18

19}, Christine E Marx^{20

21}, Martha E Shenton^{1

11}, Inga K Koerte^{1

2

3

5}

Affiliations

¹ Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Somerville, MA 02145, USA.
² cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatic and Psychotherapy, Ludwig-Maximilians-Universität, 80336 Munich, Germany.
³ Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
⁴ Département de génie logiciel et TI, École de Technologie Supérieure, Université du Québec, Montreal, QC H3C 1K3, Canada.
⁵ Graduate School of Systemic Neuroscience, Ludwig-Maximilians-Universität, 82152 Planegg, Germany.
⁶ Department of Diagnostic and Interventional Radiology, University Hospital Ulm, 89081 Ulm, Germany.
⁷ Department of Diagnostic and Interventional Neuroradiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany.
⁸ TUM-Neuroimaging Center, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany.
⁹ Department of Neurology, University Hospital, LMU, 81377 Munich, Germany.
¹⁰ Brain Injury Research Center of Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
¹¹ Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
¹² Psychiatry Department, Medical University of South Carolina, Charleston, SC 29425, USA.
¹³ Ralph H. Johnson VA Medical Center, Charleston, SC 29401, USA.
¹⁴ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
¹⁵ Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
¹⁶ Department of Physical Medicine and Rehabilitation, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
¹⁷ Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.
¹⁸ School of Public Health, University of California San Diego, La Jolla, CA 92093, USA.
¹⁹ Psychiatry Service, VA San Diego Healthcare System, San Diego, CA 92161, USA.
²⁰ VA Mid-Atlantic Mental Illness Research and Clinical Center (MIRECC) and Durham VA Medical Center, Durham, NC 27705, USA.
²¹ Department of Psychiatry and Behavior Sciences, Duke University School of Medicine, Durham, NC 27710, USA.

Abstract

The gray matter/white matter (GM/WM) boundary of the brain is vulnerable to shear strain associated with mild traumatic brain injury (mTBI). It is, however, unknown whether GM/WM microstructure is associated with long-term outcomes following mTBI. The diffusion and structural MRI data of 278 participants between 18 and 65 years of age with and without military background from the Department of Defense INTRuST study were analyzed. Fractional anisotropy (FA) was extracted at the GM/WM boundary across the brain and for each lobe. Additionally, two conventional analytic approaches were used: whole-brain deep WM FA (TBSS) and whole-brain cortical thickness (FreeSurfer). ANCOVAs were applied to assess differences between the mTBI cohort (n = 147) and the comparison cohort (n = 131). Associations between imaging features and post-concussive symptom severity, and functional and cognitive impairment were investigated using partial correlations while controlling for mental health comorbidities that are particularly common among military cohorts and were present in both the mTBI and comparison group. Findings revealed significantly lower whole-brain and lobe-specific GM/WM boundary FA (p < 0.011), and deep WM FA (p = 0.001) in the mTBI cohort. Whole-brain and lobe-specific GM/WM boundary FA was significantly negatively correlated with post-concussive symptoms (p < 0.039), functional (p < 0.016), and cognitive impairment (p < 0.049). Deep WM FA was associated with functional impairment (p = 0.002). Finally, no significant difference was observed in cortical thickness, nor between cortical thickness and outcome (p > 0.05). Findings from this study suggest that microstructural alterations at the GM/WM boundary may be sensitive markers of adverse long-term outcomes following mTBI.

Keywords: cognitive impairment; diffusion tensor imaging; fractional anisotropy; magnetic resonance imaging; mild traumatic brain injury; post-concussion symptoms.

Abstract

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