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Fatigue Is Associated With Global and Regional Thalamic Morphometry in Veterans With a History of Mild Traumatic Brain Injury

Clark, Alexandra L., MS; Sorg, Scott F., PhD; Holiday, Kelsey, BA; Bigler, Erin D., PhD; Bangen, Katherine J., PhD; Evangelista, Nicole D., BS; Bondi, Mark W., PhD; Schiehser, Dawn M., PhD; Delano-Wood, Lisa, PhD

Section Editor(s): Caplan, Bruce PhD, ABPP; Bogner, Jennifer PhD, ABPP; Brenner, Lisa PhD, ABPP; Malec, James PhD, ABPP

The Journal of Head Trauma Rehabilitation: November/December 2018 - Volume 33 - Issue 6 - p 382–392
doi: 10.1097/HTR.0000000000000377
Focus on Clinical Research and Practice

Objective: Fatigue is a complex, multidimensional phenomenon that commonly occurs following traumatic brain injury (TBI). The thalamus—a structure vulnerable to both primary and secondary injuries in TBI—is thought to play a pivotal role in the manifestation of fatigue. We explored how neuroimaging markers of local and global thalamic morphometry relate to the subjective experience of fatigue post-TBI.

Methods: Sixty-three Veterans with a history of mild TBI underwent structural magnetic resonance imaging and completed questionnaires related to fatigue and psychiatric symptoms. FMRIB's Software (FSL) was utilized to obtain whole brain and thalamic volume estimates, as well as to perform regional thalamic morphometry analyses.

Results: Independent of age, sex, intracranial volume, posttraumatic stress disorder, and depressive symptoms, greater levels of self-reported fatigue were significantly associated with decreased right (P = .026) and left (P = .046) thalamic volumes. Regional morphometry analyses revealed that fatigue was significantly associated with reductions in the anterior and dorsomedial aspects of the right thalamic body (P < .05). Similar trends were observed for the left thalamic body (P < .10).

Conclusions: Both global and regional thalamic morphometric changes are associated with the subjective experience of fatigue in Veterans with a history of mild TBI. These findings support a theory in which disruption of thalamocorticostriatal circuitry may result in the manifestation of fatigue in individuals with a history of neurotrauma.

San Diego State University/University of California San Diego (SDSU/UCSD) Joint Doctoral Program in Clinical Psychology (Mss Clark and Holiday); VA San Diego Healthcare System (VASDHS), San Diego, California (Mss Clark, Holiday, and Evangelista and Drs Sorg, Bangen, Bondi, Schiehser, and Delano-Wood); Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, California (Drs Schiehser and Delano-Wood); Department of Psychiatry, School of Medicine, University of California San Diego (Drs Sorg, Bangen, Bondi, Schiehser, and Delano-Wood); Department of Radiology, University of California San Diego, La Jolla; and Department of Psychology and the Neuroscience Center, Brigham Young University, Provo Utah (Dr Bigler).

Corresponding Author: Lisa Delano-Wood, PhD, VA San Diego Healthcare System (151B), 3350 La Jolla Village Dr, San Diego, CA 92161 (

Dawn M. Schiehser and Lisa Delano-Wood contributed equally to this work.

All procedures involved in this study were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975. Informed consent was obtained from all patients included in the study.

This work was supported by Veterans Affairs grants awarded to Drs Delano-Wood (829-MR-NB-25860), Schiehser (CDA-2-065-10S), and Sorg (CDA-2- CX001508). This work was further supported by grants awarded by the Department of Defense (W81XWH-10-2-0169) to Dr Delano-Wood and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (F31NS09870) to Ms Clark.

The authors declare no conflicts of interest.

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