title: Brainstem white matter integrity is related to loss of consciousness and postconcussive symptomatology in veterans with chronic mild to moderate traumatic brain injury.
abstract: We investigated associations between DTI indices of three brainstem white matter tracts, traumatic brain injury (TBI) injury characteristics, and postconcussive symptomatology (PCS) in a well-characterized sample of veterans with history of mild to moderate TBI (mTBI). 58 military veterans (mTBI: n = 38, mean age = 33.2, mean time since injury = 90.9 months; military controls [MC]; n = 20; mean age = 29.4) were administered 3T DTI scans as well as a comprehensive neuropsychiatric evaluation including evaluation of TBI injury characteristics and PCS symptoms (e.g., negative mood, dizziness, balance and coordination difficulties). Tractography was employed by seeding ROIs along 3 brainstem white matter tracts (i.e., medial lemniscus-central tegmentum tract [ML-CTT]; corticospinal tracts [CST], and pontine tegmentum [PT]), and mean DTI values were derived from fractional anisotropic (FA) maps. Results showed that there were no significant difference in FA between the MC and TBI groups across the 3 regions of interest; however, among the TBI group, CST FA was significantly negatively associated with LOC duration. Additionally, lower FA of certain tracts-most especially the PT-was significantly associated with increased PCS symptoms (i.e., more severe vestibular symptoms, poorer physical functioning, and greater levels of fatigue), even after adjusting for PTSD symptoms. Our findings show that, in our sample of veterans with mTBI, tractography-based DTI indices of brainstem white matter tracts of interest are related to the presence and severity of PCS symptoms. Findings are promising as they show linkages between brainstem white matter integrity and injury severity (LOC), and they raise the possibility that the pontine tegmentum in particular may be a useful marker of PCS symptoms. Collectively, these data point to important neurobiological substrates of the chronic and complex constellation of symptoms following the 'signature injury' of our combat-exposed veterans.
authors.affiliation: Veterans Affairs San Diego Healthcare System (116B), 3350 La Jolla Village Drive, San Diego, CA, 92161, USA. ldelano@ucsd.edu.|Center of Excellence for Stress and Mental Health (CESAMH), San Diego, CA, 92161, USA. ldelano@ucsd.edu.|Department of Psychiatry, University of California, La Jolla, San Diego, CA, 92093, USA. ldelano@ucsd.edu.
authors.forename: L
authors.initials: L
authors.lastname: Delano-Wood
authors.affiliation: Veterans Affairs San Diego Healthcare System (116B), 3350 La Jolla Village Drive, San Diego, CA, 92161, USA.|Department of Psychiatry, University of California, La Jolla, San Diego, CA, 92093, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Bangen
authors.affiliation: Veterans Affairs San Diego Healthcare System (116B), 3350 La Jolla Village Drive, San Diego, CA, 92161, USA.|Center of Excellence for Stress and Mental Health (CESAMH), San Diego, CA, 92161, USA.|Department of Psychiatry, University of California, La Jolla, San Diego, CA, 92093, USA.
authors.forename: S F
authors.initials: SF
authors.lastname: Sorg
authors.affiliation: San Diego (SDSU/UCSD) Joint Doctoral Program in Clinical Psychology, San Diego State University/University of California, San Diego, CA, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Clark
authors.affiliation: Veterans Affairs San Diego Healthcare System (116B), 3350 La Jolla Village Drive, San Diego, CA, 92161, USA.|Center of Excellence for Stress and Mental Health (CESAMH), San Diego, CA, 92161, USA.|Department of Psychiatry, University of California, La Jolla, San Diego, CA, 92093, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Schiehser
authors.affiliation: Veterans Affairs San Diego Healthcare System (116B), 3350 La Jolla Village Drive, San Diego, CA, 92161, USA.|Center of Excellence for Stress and Mental Health (CESAMH), San Diego, CA, 92161, USA.
authors.forename: N
authors.initials: N
authors.lastname: Luc
authors.affiliation: Veterans Affairs San Diego Healthcare System (116B), 3350 La Jolla Village Drive, San Diego, CA, 92161, USA.|Department of Psychiatry, University of California, La Jolla, San Diego, CA, 92093, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Bondi
authors.affiliation: San Diego (SDSU/UCSD) Joint Doctoral Program in Clinical Psychology, San Diego State University/University of California, San Diego, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Werhane
authors.affiliation: Veterans Affairs San Diego Healthcare System (116B), 3350 La Jolla Village Drive, San Diego, CA, 92161, USA.|Center of Excellence for Stress and Mental Health (CESAMH), San Diego, CA, 92161, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Kim
authors.affiliation: Department of Psychology & Neuroscience Centre, Brigham Young University, Provo, UT, USA.|Department of Psychiatry & The Brain Institute of Utah, University of Utah, Salt Lake City, UT, USA.
authors.forename: E D
authors.initials: ED
authors.lastname: Bigler
mesh_terms: D000328:Adult; D016880:Anisotropy; D001933:Brain Stem / Q000473:pathology*; D002908:Chronic Disease; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D008889:Military Personnel; D009483:Neuropsychological Tests; D038223:Post-Concussion Syndrome / Q000473:pathology* / Q000503:physiopathology*; D012720:Severity of Illness Index; D013997:Time Factors; D014474:Unconsciousness / Q000473:pathology* / Q000503:physiopathology; D014728:Veterans; D066127:White Matter / Q000473:pathology*
keywords: Brainstem; DTI; Diffusion tensor imaging; PCS; Postconcussive syndrome; TBI; Traumatic brain injury; White matter