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Objective: To examine the association between employment status and neuropsychological functioning in veterans with a history of remote mild traumatic brain injury (mTBI) using 2 approaches to assess cognitive performance: (a) standard, traditional mean cognitive performance; and (b) across-test intraindividual variability (IIV)., Setting: Outpatient Veterans Affairs (VA) hospital., Participants: Eligibility criteria included veterans with a history of mTBI who performed adequately on performance validity tests. Participants (N = 75; 37 employed, 38 unemployed) were evaluated, on average, about 5.5 years after their most recent mTBI., Design: Observational cohort study; all participants completed a clinical interview and a comprehensive neuropsychological assessment., Main Measures: Primary outcomes of interest included mean cognitive composite test scores and IIV scores on tasks of memory, attention/processing speed, and executive functioning., Results: Logistic regression models showed that mean cognitive performance was not predictive of employment status; however, IIV indices were ( = 7.88, P = .048) and accounted for 13% of the variance. Greater memory-IIV was significantly associated with being unemployed (β = -.16, SE = .07, P = .020, Exp(B) = 0.85; 95% CI, 0.74-0.98)., Conclusion: These findings build upon prior work showing that IIV, or cognitive dispersion, is associated with important functional outcomes following mTBI, including employment status. Future studies are needed to verify these findings, but the present study suggests that IIV indices offer a clinically meaningful marker of cognitive functioning and should be considered when evaluating functional outcomes following head trauma., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Objective: Posttraumatic stress disorder (PTSD), history of mild traumatic brain injury (mTBI), and executive function (EF) difficulties are prevalent in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans. We evaluated the contributions of injury variables, lower-order cognitive component processes (processing speed/attention), and psychological symptoms to EF., Participants: OEF/OIF Veterans (N = 65) with PTSD and history of mTBI were administered neuropsychological tests of EF and self-report assessments of PTSD and depression., Results: Those impaired on one or more EF measures had higher PTSD and depression symptoms and lower processing speed/attention performance than those with intact performance on all EF measures. Across participants, poorer attention/processing speed performance and higher psychological symptoms were associated with worse performance on specific aspects of EF (eg, inhibition and switching) even after accounting for injury variables. Although direct relationships between EF and injury variables were equivocal, there was an interaction between measures of injury burden and processing speed/attention such that those with greater injury burden exhibited significant and positive relationships between processing speed/attention and inhibition/switching, whereas those with lower injury burden did not., Conclusion: Psychological symptoms as well as lower-order component processes of EF (attention and processing speed) contribute significantly to executive dysfunction in OEF/OIF Veterans with PTSD and history of mTBI. However, there may be equivocal relationships between injury variables and EF that warrant further study. Results provide groundwork for more fully understanding cognitive symptoms in OEF/OIF Veterans with PTSD and history of mTBI that can inform psychological and cognitive interventions in this population.

Objective: To investigate white matter microstructure compromise in Veterans with a history of traumatic brain injury (TBI) and its possible contribution to posttraumatic stress disorder (PTSD) symptomatology and neuropsychological functioning via diffusion tensor imaging., Participants and Methods: Thirty-eight Veterans with mild (n = 33) and moderate (n = 5) TBI and 17 military control participants without TBI completed neuropsychological testing and psychiatric screening and underwent magnetic resonance imaging an average of 4 years following their TBI event(s). Fractional anisotropy (FA) and diffusivity measures were extracted from 9 white matter tracts., Results: Compared with military control participants, TBI participants reported higher levels of PTSD symptoms and performed worse on measures of memory and psychomotor-processing speed. Traumatic brain injury was associated with lower FA in the genu of the corpus callosum and left cingulum bundle. Fractional anisotropy negatively correlated with processing speed and/or executive functions in 7 of the 8 tracts. Regional FA did not correlate with memory or PTSD symptom ratings., Conclusion: Results suggest that current PTSD symptoms are independent of TBI-related white matter alterations, as measured by diffusion tensor imaging. In addition, white matter microstructural compromise may contribute to reduced processing speed in our sample of participants with history of neurotrauma. Findings of the current study add insight into the factors associated with complicated recovery from mild to moderate TBI.

Objective: Failure on performance validity tests (PVTs) is common in Veterans with histories of mild traumatic brain injury (mTBI), leading to questionable validity of clinical presentations., Participants: Using diffusion tensor imaging, we investigated white matter (WM) integrity and cognition in 79 Veterans with history of mTBI who passed PVTs (n = 43; traumatic brain injury [TBI]-passed), history of mTBI who failed at least 1 PVT (n = 13; TBI-failed), and military controls (n = 23; MCs) with no history of TBI., Results: The TBI-failed group demonstrated significantly lower cognitive scores relative to MCs and the TBI-passed group; however, no such differences were observed between MCs and the TBI-passed group. On a global measure of WM integrity (ie, WM burden), the TBI-failed group showed more overall WM abnormalities than the other groups. However, no differences were observed between the MCs and TBI-passed group on WM burden. Interestingly, regional WM analyses revealed abnormalities in the anterior internal capsule and cingulum of both TBI subgroups relative to MCs. Moreover, compared with the TBI-passed group, the TBI-failed group demonstrated significantly decreased WM integrity in the corpus callosum., Conclusions: Findings revealed that, within our sample, WM abnormalities are evident in those who fail PVTs. This study adds to the burgeoning PVT literature by suggesting that poor PVT performance does not negate the possibility of underlying WM abnormalities in military personnel with history of mTBI., Competing Interests: The authors report no conflicts of interests.

Objective: To assess the relationship between postconcussive symptoms and quality of life (QOL) in Veterans with mild to moderate traumatic brain injury (TBI)., Methods: Sixty-one Operation Enduring Freedom/Operation Iraqi Freedom/Persian Gulf War Veterans with a history of mild or moderate TBI, more than 6 months postinjury, and 21 demographically matched Veteran controls were administered self-report measures of QOL (World Health Organization Quality of Life-BREF) and postconcussive symptom severity (Neurobehavioral Symptom Inventory)., Results: Perceived QOL was significantly worse in Veterans with mild-moderate TBI than in controls. In the TBI group, QOL was predominantly associated with affective symptoms, and moderate to strong correlations with fatigue and depression were evident across all QOL areas. Multivariate analyses revealed depression and fatigue to be the best predictors of Psychological, Social, and Environmental QOL, whereas sleep difficulty best predicted Physical QOL in mild-moderate TBI., Conclusion: Veterans with post-acute mild-moderate TBI evidence worse QOL than demographically matched Veteran controls. Affective symptoms, and specifically those of fatigue, depression, and sleep difficulty, appear to be the most relevant postconcussive symptoms predicting QOL in this population. These findings underscore the importance of examining specific symptoms as they relate to post-acute TBI QOL and provide guidance for treatment and intervention studies.

Objective: To evaluate the validity of the Modified Fatigue Impact Scale (MFIS) in veterans with a history of mild to moderate traumatic brain injury (TBI)., Participants: Veterans (N = 106) with mild (92%) or moderate (8%) TBI., Setting: Veterans Administration Health System., Procedure: Factor structure, internal consistency, convergent validity, sensitivity, and specificity of the MFIS were examined., Results: Principal component analysis identified 2 viable MFIS factors: a Cognitive subscale and a Physical/Activities subscale. Item analysis revealed high internal consistency of the MFIS Total scale and subscale items. Strong convergent validity of the MFIS scales was established with 2 Beck Depression Inventory II fatigue items. Receiver operating characteristic curve analysis revealed good to excellent accuracy of the MFIS in classifying fatigued versus nonfatigued individuals., Conclusion: The MFIS is a valid multidimensional measure that can be used to evaluate the impact of fatigue on cognitive and physical functioning in individuals with mild to moderate TBI. The psychometric properties of the MFIS make it useful for evaluating fatigue and provide the potential for improving research on fatigue in this population.

Objective: We investigated using diffusion tensor imaging (DTI) and the association between white matter integrity and executive function (EF) performance in postacute mild traumatic brain injury (mTBI). In addition, we examined whether injury severity, as measured by loss of consciousness (LOC) versus alterations in consciousness (AOC), is related to white matter microstructural alterations and neuropsychological outcome., Participants: Thirty Iraq and Afghanistan War era veterans with a history of mTBI and 15 healthy veteran control participants., Results: There were no significant overall group differences between control and mTBI participants on DTI measures. However, a subgroup of mTBI participants with EF decrements (n = 13) demonstrated significantly decreased fractional anisotropy of prefrontal white matter, corpus callosum, and cingulum bundle structures compared with mTBI participants without EF decrements (n = 17) and control participants. Participants having mTBI with LOC were more likely to evidence reduced EF performances and disrupted ventral prefrontal white matter integrity when compared with either mTBI participants without LOC or control participants., Conclusions: Findings suggest that altered white matter integrity contributes to reduced EF in subgroups of veterans with a history of mTBI and that LOC may be a risk factor for reduced EF as well as associated changes to ventral prefrontal white matter.