Persistent MRI Findings Unique to Blast and Repetitive Mild TBI: Analysis of the CENC/LIMBIC Cohort Injury Characteristics.

INTRODUCTION: MRI represents one of the clinical tools at the forefront of research efforts aimed at identifying diagnostic and prognostic biomarkers following traumatic brain injury (TBI). Both volumetric and diffusion MRI findings in mild TBI (mTBI) are mixed, making the findings difficult to interpret. As such, additional research is needed to continue to elucidate the relationship between the clinical features of mTBI and quantitative MRI measurements. MATERIAL AND METHODS: Volumetric and diffusion imaging data in a sample of 976 veterans and service members from the Chronic Effects of Neurotrauma Consortium and now the Long-Term Impact of Military-Relevant Brain Injury Consortium observational study of the late effects of mTBI in combat with and without a history of mTBI were examined. A series of regression models with link functions appropriate for the model outcome were used to evaluate the relationships among imaging measures and clinical features of mTBI. Each model included acquisition site, participant sex, and age as covariates. Separate regression models were fit for each region of interest where said region was a predictor. RESULTS: After controlling for multiple comparisons, no significant main effect was noted for comparisons between veterans and service members with and without a history of mTBI. However, blast-related mTBI were associated with volumetric reductions of several subregions of the corpus callosum compared to non-blast-related mTBI. Several volumetric (i.e., hippocampal subfields, etc.) and diffusion (i.e., corona radiata, superior longitudinal fasciculus, etc.) MRI findings were noted to be associated with an increased number of repetitive mTBIs versus. CONCLUSIONS: In deployment-related mTBI, significant findings in this cohort were only observed when considering mTBI sub-groups (blast mechanism and total number/dose). Simply comparing healthy controls and those with a positive mTBI history is likely an oversimplification that may lead to non-significant findings, even in consortium analyses.

Microstructural Organization of Distributed White Matter Associated With Fine Motor Control in US Service Members With Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is the most common form of brain injury. While most individuals recover from mTBI, roughly 20% experience persistent symptoms, potentially including reduced fine motor control. We investigate relationships between regional white matter organization and subcortical volumes associated with performance on the Grooved Pegboard (GPB) test in a large cohort of military Service Members and Veterans (SM&Vs) with and without a history of mTBI(s). Participants were enrolled in the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium. SM&Vs with a history of mTBI(s) (n = 847) and without mTBI (n = 190) underwent magnetic resonance imaging and the GPB test. We first examined between-group differences in GPB completion time. We then investigated associations between GPB performance and regional structural imaging measures (tractwise diffusivity, subcortical volumes, and cortical thickness) in SM&Vs with a history of mTBI(s). Lastly, we explored whether mTBI history moderated associations between imaging measures and GPB performance. SM&Vs with mTBI(s) performed worse than those without mTBI(s) on the non-dominant hand GPB test at a trend level (p < 0.1). Higher fractional anisotropy (FA) of tracts including the posterior corona radiata, superior longitudinal fasciculus, and uncinate fasciculus were associated with better GPB performance in the dominant hand in SM&Vs with mTBI(s). These findings support that the organization of several white matter bundles are associated with fine motor performance in SM&Vs. We did not observe that mTBI history moderated associations between regional FA and GPB test completion time, suggesting that chronic mTBI may not significantly influence fine motor control.

Phenotyping Depression After Mild Traumatic Brain Injury: Evaluating the Impact of Multiple Injury, Gender, and Injury Context.

The chronic mental health consequences of mild traumatic brain injury (TBI) are a leading cause of disability. This is surprising given the expectation of significant recovery after mild TBI, which suggests that other injury-related factors may contribute to long-term adverse outcomes. The objective of this study was to determine how number of prior injuries, gender, and environment/context of injury may contribute to depressive symptoms after mild TBI among deployed United States service members and veterans (SMVs). Data from the Long-term Impact of Military-Relevant Brain Injury Consortium Prospective Longitudinal Study was used to assess TBI injury characteristics and depression scores previously measured on the Patient Health Questionnaire-9 (PHQ-9) among a sample of 1456 deployed SMVs. Clinical diagnosis of mild TBI was defined via a multi-step process centered on a structured face-to-face interview. Logistical and linear regressions stratified by gender and environment of injury were used to model depressive symptoms controlling for sociodemographic and combat deployment covariates. Relative to controls with no history of mild TBI (n = 280), the odds ratios (OR) for moderate/severe depression (PHQ-9 ≥ 10) were higher for SMVs with one mild TBI (n = 358) OR: 1.62 (95% confidence interval [CI] 1.09-2.40, p = 0.016) and two or more mild TBIs (n = 818) OR: 1.84 (95% CI 1.31-2.59, p < 0.001). Risk differences across groups were assessed in stratified linear models, which found that depression symptoms were elevated in those with a history of multiple mild TBIs compared with those who had a single mild TBI (p < 0.001). Combat deployment-related injuries were also associated with higher depression scores than injuries occurring in non-combat or civilian settings (p < 0.001). Increased rates of depression after mild TBI persisted in the absence of post-traumatic stress disorder. Both men and women SMVs separately exhibited significantly increased depressive symptom scores if they had had combat-related mild TBI. These results suggest that contextual information, gender, and prior injury history may influence long-term mental health outcomes among SMVs with mild TBI exposure.

Cognitive "success" in the setting of performance validity test failure.

BACKGROUND: Although studies have shown unique variance contributions from performance invalidity, it is difficult to interpret the meaning of cognitive data in the setting of performance validity test (PVT) failure. The current study aimed to examine cognitive outcomes in this context. METHOD: Two hundred and twenty-two veterans with a history of mild traumatic brain injury referred for clinical evaluation completed cognitive and performance validity measures. Standardized scores were characterized as Within Normal Limits (≥16th normative percentile) and Below Normal Limits (<16th percentile). Cognitive outcomes are examined across four commonly used PVTs. Self-reported employment and student status were used as indicators of "productivity" to assess potential functional differences related to lower cognitive performance. RESULTS: Among participants who performed in the invalid range on Test of Memory Malingering trial 1, Word Memory Test, Wechsler Adult Intelligence Scale-Fourth Edition Digit Span aged corrected scaled score, and the California Verbal Learning Test-Second Edition Forced Choice index, 16-88% earned broadly within normal limits scores across cognitive testing. Depending on which PVT measure was applied, the average number of cognitive performances below the 16th percentile ranged from 5 to 7 of 14 tasks. There were no differences in the total number of below normal limits performances on cognitive measures between "productive" and "non-productive" participants (T = 1.65, p = 1.00). CONCLUSIONS: Results of the current study suggest that the range of within normal limits cognitive performance in the context of failed PVTs varies greatly. Importantly, our findings indicate that neurocognitive data may still provide important practical information regarding cognitive abilities, despite poor PVT outcomes. Further, given that rates of below normal limits cognitive performance did not differ among "productivity" groups, results have important implications for functional abilities and recommendations in a clinical setting.

Putting the pieces together to understand anger in combat veterans and service members: Psychological and physical contributors.

Dysregulated anger can result in devastating health and interpersonal consequences for individuals, families, and communities. Compared to civilians, combat veterans and service members (C-V/SM) report higher levels of anger and often have risk factors for anger including posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), pain, alcohol use, and impaired sleep. The current study examined the relative contributions of established variables associated with anger (e.g., combat exposure, current PTSD symptoms, history of TBI, pain interference, and hazardous alcohol use) in 1263 C-V/SM. Sleep impairments, represented by poor sleep quality and obstructive sleep apnea (OSA) risk, were also evaluated as potential mediators of the relationships between established risk factors and anger, and therefore potential modifiable treatment targets. Multiple regression model results revealed that PTSD symptoms (ß = 0.517, p < .001), OSA risk (ß = 0.057, p = .016), pain interference (ß = 0.214, p < .001), and hazardous alcohol use (ß = 0.054, p = .009) were significantly associated with anger. Results of the mediation models revealed that OSA risk accounted for the association between PTSD and anger, in addition to the association between pain interference and anger. The current study extends previous literature by simultaneously examining factors associated with anger using a multivariable model in a large sample of C-V/SM. Additionally, treating OSA may be a novel way to reduce anger in C-V/SM who have PTSD and/or pain interference.

Varying failure criteria on performance validity tests influences interpretation of cognitive outcomes.

OBJECTIVE: The present study examined the effects of applying various performance validity tests (PVT) failure criteria on the relationship between cognitive outcomes and posttraumatic stress (PTS) symptomology. METHOD: One hundred and ninety-nine veterans with a history of mild traumatic brain injury referred for clinical evaluation completed cognitive tests, PVTs, and self-report measures of PTS symptoms and symptom exaggeration. Normative T scores of select cognitive tests were averaged into memory, attention/processing speed, and executive functioning composites. Separate one way analyses of variance assessed differences among high PTS (n = 140) versus low PTS (n = 59) groups and were repeated excluding participants based on varying combinations of PVT failure criteria. RESULTS: When no PVTs were considered, the high PTS group demonstrated worse performance across all three cognitive domains. Excluding those who failed two or more stand-alone, or two or more embedded validity measures resulted in group differences across all cognitive composites. When participants were excluded based on failure of any one embedded and any one stand-alone PVT measure combined, the high PTS group performed worse on the executive functioning and attention/processing speed composites. The remaining three proposed methods to control for performance validity resulted in null PTS-cognition relationships. Results remained largely consistent after controlling for symptom exaggeration. CONCLUSIONS: Methods of defining PVT failure can greatly influence differences in cognitive function between groups defined by PTS symptom levels. Findings highlight the importance of considering performance validity when interpreting cognitive data and warrant future investigation of PVT failure criteria in other conditions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Harmonizing PTSD severity scales across instruments and sites.

OBJECTIVE: The variety of instruments used to assess posttraumatic stress disorder (PTSD) allows for flexibility, but also creates challenges for data synthesis. The objective of this work was to use a multisite mega analysis to derive quantitative recommendations for equating scores across measures of PTSD severity. METHOD: Empirical Bayes harmonization and linear models were used to describe and mitigate site and covariate effects. Quadratic models for converting scores across PTSD assessments were constructed using bootstrapping and tested on hold out data. RESULTS: We aggregated 17 data sources and compiled an n = 5,634 sample of individuals who were assessed for PTSD symptoms. We confirmed our hypothesis that harmonization and covariate adjustments would significantly improve inference of scores across instruments. Harmonization significantly reduced cross-dataset variance (28%, p < .001), and models for converting scores across instruments were well fit (median R² = 0.985) with an average root mean squared error of 1.46 on sum scores. CONCLUSIONS: These methods allow PTSD symptom severity to be placed on multiple scales and offers interesting empirical perspectives on the role of harmonization in the behavioral sciences. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Altered lateralization of the cingulum in deployment-related traumatic brain injury: An ENIGMA military-relevant brain injury study.

Traumatic brain injury (TBI) in military populations can cause disruptions in brain structure and function, along with cognitive and psychological dysfunction. Diffusion magnetic resonance imaging (dMRI) can detect alterations in white matter (WM) microstructure, but few studies have examined brain asymmetry. Examining asymmetry in large samples may increase sensitivity to detect heterogeneous areas of WM alteration in mild TBI. Through the Enhancing Neuroimaging Genetics Through Meta-Analysis Military-Relevant Brain Injury working group, we conducted a mega-analysis of neuroimaging and clinical data from 16 cohorts of Active Duty Service Members and Veterans (n = 2598). dMRI data were processed together along with harmonized demographic, injury, psychiatric, and cognitive measures. Fractional anisotropy in the cingulum showed greater asymmetry in individuals with deployment-related TBI, driven by greater left lateralization in TBI. Results remained significant after accounting for potentially confounding variables including posttraumatic stress disorder, depression, and handedness, and were driven primarily by individuals whose worst TBI occurred before age 40. Alterations in the cingulum were also associated with slower processing speed and poorer set shifting. The results indicate an enhancement of the natural left laterality of the cingulum, possibly due to vulnerability of the nondominant hemisphere or compensatory mechanisms in the dominant hemisphere. The cingulum is one of the last WM tracts to mature, reaching peak FA around 42 years old. This effect was primarily detected in individuals whose worst injury occurred before age 40, suggesting that the protracted development of the cingulum may lead to increased vulnerability to insults, such as TBI.

Associations Between Sociodemographic, Mental Health, and Mild Traumatic Brain Injury Characteristics With Lifetime History of Criminal Justice Involvement in Combat Veterans and Service Members.

INTRODUCTION: Veterans and service members (V/SM) may have more risk factors for arrest and felony incarceration (e.g., posttraumatic stress disorder and at-risk substance use) but also more protective factors (e.g., access to health care) to mitigate behaviors that may lead to arrest. As such, understanding which factors are associated with criminal justice involvement among V/SM could inform prevention and treatment efforts. The current study examined relationships between lifetime history of arrests and felony incarceration and sociodemographic, psychological, and brain injury characteristics factors among combat V/SM. MATERIALS AND METHODS: The current study was a secondary data analysis from the Chronic Effects of Neurotrauma Consortium multicenter cohort study, approved by local institutional review boards at each study site. Participants were V/SM (N = 1,540) with combat exposure (19% active duty at time of enrollment) who were recruited from eight Department of Veterans Affairs and DoD medical centers and completed a baseline assessment. Participants were predominantly male (87%) and white (72%), with a mean age of 40 years (SD = 9.7). Most (81%) reported a history of at least one mild traumatic brain injury, with one-third of those experiencing three or more mild traumatic brain injuries (33%). Participants completed a self-report measure of lifetime arrest and felony incarceration history, a structured interview for all potential concussive events, the post-traumatic stress disorder checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and the Alcohol Use Disorders Identification Test-Consumption. Three groups were compared on self-reported level of lifetime history of criminal justice system involvement: (1) no history of arrest or incarceration (65%); (2) history of arrest but no felony incarceration (32%); and (3) history of felony incarceration (3%). RESULTS: Ordinal regression analyses revealed that hazardous alcohol consumption (ß = .44, P < .001; odds ratio = 1.56) was positively associated with increased criminal justice involvement after adjusting for all other variables. Being married or partnered (ß = -.44, P < .001; odds ratio = 0.64) was negatively associated with decreased criminal justice involvement. CONCLUSIONS: The rate of lifetime arrest (35%) in this V/SM sample was consistent with rates of arrests in the U.S. general population. One modifiable characteristic associated with lifetime arrest and felony incarceration was hazardous alcohol consumption. Alcohol use should be a top treatment target for V/SM at risk for arrest and those with history of criminal justice involvement.

Can mild traumatic brain injury alter cognition chronically? A LIMBIC-CENC multicenter study.

OBJECTIVE: While outcome from mild traumatic brain injury (mTBI) is generally favorable, concern remains over potential negative long-term effects, including impaired cognition. This study examined the link between cognitive performance and remote mTBIs within the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) multicenter, observational study of Veterans and service members (SMs) with combat exposure. METHOD: Baseline data of the participants passing all cognitive performance validity tests (n = 1,310) were used to conduct a cross-sectional analysis. Using multivariable regression models that adjusted for covariates, including age and estimated preexposure intellectual function, positive mTBI history groups, 1-2 lifetime mTBIs (nonrepetitive, n = 614), and 3 + lifetime mTBIs (repetitive; n = 440) were compared to TBI negative controls (n = 256) on each of the seven cognitive domains computed by averaging Z scores of prespecified component tests. Significance levels were adjusted for multiple comparisons. RESULTS: Neither of the mTBI positive groups differed from the mTBI negative control group on any of the cognitive domains in multivariable analyses. Findings were also consistently negative across sensitivity analyses (e.g., mTBIs as a continuous variable, number of blast-related mTBIs, or years since the first and last mTBI). CONCLUSIONS: Our findings demonstrate that the average veteran or SM who experienced one or more mTBIs does not have postacute objective cognitive deficits due to mTBIs alone. A holistic health care approach including comorbidity assessment is indicated for patients reporting chronic cognitive difficulties after mTBI(s), and strategies for addressing misattribution may be beneficial. Future study is recommended with longitudinal designs to assess within-subjects decline from potential neurodegeneration. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A pilot study of olfactory function in veterans with a history of deployment-related mild traumatic brain injury.

Olfactory impairment in military populations is highly prevalent and often attributed to the long-term effects of mild traumatic brain injury (mTBI) and chronic psychiatric disorders. The main goal of this investigation was to examine olfactory function in a cohort of combat veterans using a quantitative smell test.Participants underwent a neurological examination, completed performance validity testing (PVT), provided deployment history, and their medical records were reviewed.Participants were 38 veterans with a deployment-related mTBI who passed the PVT and did not have ongoing substance misuse issues. Olfactory examination revealed normosmia in 20 participants and various degrees of deficit in 18. The groups did not differ in demographics, post-injury interval, or current clinical (non-psychiatric) conditions. Participants with hyposmia frequently reported being exposed to a higher number of blasts and being positioned closer to the nearest primary blast, and more often endorsed a period of loss of consciousness after the most serious mTBI. In addition, they more often reported tympanic membrane perforation, extracranial injuries, and histories of both blast and blunt force mTBI. Comorbid diagnoses of posttraumatic stress disorder, depression, chronic headaches, and pain were more common among them as well.Several blast exposure and injury-related characteristics increase the likelihood of long-term olfactory impartments, comorbid psychiatric conditions, and chronic pain among veterans with history of deployment-related mTBI. Notably, none of the participants with hyposmia had a clinical diagnosis of olfactory dysfunction or were receiving service-connected disability for loss of sense of smell at the time of their assessment.

Advanced brain age in deployment-related traumatic brain injury: A LIMBIC-CENC neuroimaging study.

OBJECTIVE: To determine if history of mild traumatic brain injury (mTBI) is associated with advanced or accelerated brain aging among the United States (US) military Service Members and Veterans. METHODS: Eight hundred and twenty-two participants (mean age = 40.4 years, 714 male/108 female) underwent MRI sessions at eight sites across the US. Two hundred and one participants completed a follow-up scan between five months and four years later. Predicted brain ages were calculated using T1-weighted MRIs and then compared with chronological ages to generate an Age Deviation Score for cross-sectional analyses and an Interval Deviation Score for longitudinal analyses. Participants also completed a neuropsychological battery, including measures of both cognitive functioning and psychological health. RESULT: In cross-sectional analyses, males with a history of deployment-related mTBI showed advanced brain age compared to those without (t(884) = 2.1, p = .038), while this association was not significant in females. In follow-up analyses of the male participants, severity of posttraumatic stress disorder (PTSD), depression symptoms, and alcohol misuse were also associated with advanced brain age. CONCLUSION: History of deployment-related mTBI, severity of PTSD and depression symptoms, and alcohol misuse are associated with advanced brain aging in male US military Service Members and Veterans.

Risk factors for decline in cognitive performance following deployment-related mild traumatic brain injury: A preliminary report.

Thorough identification of risk factors for delayed decline in cognitive performance following combat-related mild traumatic brain injury (mTBI) is important for guiding comprehensive post-deployment rehabilitation. In a sample of veterans who reported at least one deployment-related mTBI, preliminary results indicate that factors including a history of loss of consciousness over 1 min, current obesity and hypertension, and Black race were more prevalent in those with decreased scores on a measure of memory function. These factors should be considered by clinicians and researchers working with current and former military personnel.

Coordinating Global Multi-Site Studies of Military-Relevant Traumatic Brain Injury: Opportunities, Challenges, and Harmonization Guidelines.

Traumatic brain injury (TBI) is common among military personnel and the civilian population and is often followed by a heterogeneous array of clinical, cognitive, behavioral, mood, and neuroimaging changes. Unlike many neurological disorders that have a characteristic abnormal central neurologic area(s) of abnormality pathognomonic to the disorder, a sufficient head impact may cause focal, multifocal, diffuse or combination of injury to the brain. This inconsistent presentation makes it difficult to establish or validate biological and imaging markers that could help improve diagnostic and prognostic accuracy in this patient population. The purpose of this manuscript is to describe both the challenges and opportunities when conducting military-relevant TBI research and introduce the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Military Brain Injury working group. ENIGMA is a worldwide consortium focused on improving replicability and analytical power through data sharing and collaboration. In this paper, we discuss challenges affecting efforts to aggregate data in this patient group. In addition, we highlight how "big data" approaches might be used to understand better the role that each of these variables might play in the imaging and functional phenotypes of TBI in Service member and Veteran populations, and how data may be used to examine important military specific issues such as return to duty, the late effects of combat-related injury, and alteration of the natural aging processes.

Role of deployment-related mTBI and resilience in perceived participation limitations among Veterans.

Problems with social functioning are common following combat deployment, and these may be greater among individuals with a history of traumatic brain injury (TBI). The present investigation examined the impact of mild TBI (mTBI), deployment-related characteristics, and resilience on perceived participation limitations among combat Veterans. This was a cross-sectional study of 143 participants with a history of at least one deployment-related mTBI (TBI group) and 80 without a history of lifetime TBI (Comparison group). Self-report measures of participation, resilience, posttraumatic stress disorder (PTSD) symptoms, and combat exposure were administered. In addition, each participant completed a structured interview to assess lifetime TBI history. The groups did not differ in basic demographics, but significant differences were found for perceived limitations in participation, the presence of PTSD symptoms, and intensity of combat exposure. A stepwise model indicated a significant effect of resilience on reported limitations in participation (adjusted R2 = 0.61). Individuals with higher resiliency reported a higher degree of social participation, and this effect was stronger in the TBI group. Deployment-related characteristics, including intensity of combat exposure, did not have a significant effect (adjusted R2 = 0.28) on social participation. The role of resilience should be recognized within post-deployment transition and rehabilitation programs.

Health Services Utilization, Health Care Costs, and Diagnoses by Mild Traumatic Brain Injury Exposure: A Chronic Effects of Neurotrauma Consortium Study.

OBJECTIVE: To compare Veterans Health Administration (VHA) diagnoses, health services utilization, and costs by mild traumatic brain injury (mTBI) group (blast-related [BR] mTBI vs non-blast-related [NBR] mTBI vs no mTBI) among Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF)/Operation New Dawn (OND) veterans in the Chronic Effects of Neurotrauma Consortium multicenter observational study. DESIGN: Prospective cohort study. SETTING: Four Veterans Affairs Medical Centers. PARTICIPANTS: OEF/OIF/OND veterans (N=472) who used Veterans Affairs Medical Centers services between 2002-2017. INTERVENTIONS: Not applicable. Lifetime mTBI history was assessed via semistructured interviews. MAIN OUTCOME MEASURES: VHA diagnoses, health services utilization, and costs. RESULTS: Relative to NBR mTBI and no mTBI, veterans with BR mTBI were more likely to be male, have greater combat, and have controlled and uncontrolled detonations exposures (median BR, 15.0 vs NBR, 3.0 vs no mTBI, 3.0). They also had higher prevalence of headache, posttraumatic stress disorder, and anxiety diagnoses. Veterans with BR had the highest site-adjusted mean annual VHA utilization (26.31 visits; 95% confidence interval [CI], 26.01-26.61) relative to NBR (20.43 visits; 95% CI, 20.15-20.71) and no mTBI (16.62 visits; 95% CI, 16.21-17.04) and highest site adjusted mean annual VHA outpatient costs ($6480; 95% CI, $5842-$7187) relative to NBR ($4901; 95% CI, $4392-$5468) and no mTBI ($4069; 95% CI, $3404-$4864). CONCLUSIONS: Veterans with BR mTBI had higher exposure to combat and detonation. BR was associated with greater prevalence of select diagnoses and higher health services utilization and costs relative to NBR and no mTBI. The role of health care needs from mTBI polytrauma, other deployment-related exposures, and VHA access warrants future research.

Obstructive Sleep Apnea Risk Is Associated with Cognitive Impairment after Controlling for Mild Traumatic Brain Injury History: A Chronic Effects of Neurotrauma Consortium Study.

The contribution of sleep disturbance to persistent cognitive symptoms following a mild traumatic brain injury (mTBI) remains unclear. Obstructive sleep apnea (OSA) is very common, yet its relationship between risk factors for developing OSA and cognitive performance in those with history of mTBI has not been investigated. The current study examined OSA risk levels and its association with cognitive performance in 391 combat-exposed, post-911 veterans and service members (median age = 37 years) enrolled in the Chronic Effects of Neurotrauma Consortium (CENC) prospective multi-center study. Participants included those with and without mTBI (n = 326 and 65, respectively). When using clinical cut-offs, those with history of mTBI were more likely to be categorized as high risk for OSA (mTBI positive = 65% vs. mTBI negative = 51%). After adjustment for TBI status and demographic variables, increased OSA risk was significantly associated with worse performance on measures of complex processing speed and executive functioning (Wechsler Adult Intelligence Scale Fourth Edition Coding, Trail Making Test, part B) and greater symptom burden (Neurobehavioral Symptom Inventory). Thus, OSA, a modifiable behavioral health factor, likely contributes to cognitive performance following mTBI. Accordingly, OSA serves as a potential point of intervention to improve clinical and cognitive outcomes after injury.

Methylphenidate Treatment of Cognitive Dysfunction in Adults After Mild to Moderate Traumatic Brain Injury: Rationale, Efficacy, and Neural Mechanisms.

Positive effects of methylphenidate (MPH) on attention and cognitive processing speed have been reported in studies of patients with moderate to severe traumatic brain injury (TBI). Studies which have acquired functional brain imaging before and while using MPH have also found alteration of brain activation while performing a cognitive task; in some studies, this alteration of activation in selective brain regions was also related to improved performance on cognitive tests administered outside of the scanning environment. Enhanced cognitive performance has been reported after single doses of MPH and after daily treatment over durations of up to and exceeding 1 month. Preclinical research and both positron emission tomography and single photon emission tomography of humans have shown that MPH increases extracellular dopamine and norepinephrine; the dose effects of MPH have an inverted U-shaped function where high doses may cause insomnia, nervousness, and increased heart rate among other symptoms and impair cognitive performance, whereas too low a dose fails to improve cognitive performance. In the past 5 years, small clinical trials, and experimental pilot studies have found therapeutic effects of single and repeated low doses of MPH in patients with mild TBI who reported cognitive dysfunction. This literature also suggests that MPH may interact with concurrent cognitive interventions to enhance their effects. This focused review will critically evaluate the recent literature on MPH effects on cognitive dysfunction after mild to moderate TBI. To elucidate the neural mechanisms of MPH effects, this review will also include recent imaging research, preclinical, and experimental human studies.

Detection of symptom over-reporting on the Neurobehavioral Symptom Inventory in OEF/OIF/OND veterans with history of mild TBI.

OBJECTIVE: As part of routine care at Veterans Affairs facilities, veterans with a service-related traumatic brain injury (TBI) are administered a self-report post-concussive symptom measure, the Neurobehavioral Symptom Inventory (NSI). Interpreting the NSI can be problematic given that over-reporting on self-report measures is often found in both civilian and military patient populations. This study investigates embedded scales on the NSI that identify possible and probable symptom exaggeration. METHOD: 183 veterans with a history of mild TBI were administered the Minnesota Multiphasic Personality Inventory, 2nd edition, Restructured Form (MMPI-2-RF) and the NSI. The participants were divided into symptom validity testing pass and fail groups based on their performance on the MMPI-2-RF symptom validity scales. Cut scores on the NSI Total and Validity-10 scores were then established and applied to two additional veteran populations. RESULTS: Sensitivity and specificity values were derived for all NSI Total and Validity-10 values. Optimal cut scores were determined based on specificity levels of ≥95%. The NSI Total cut score was ≥57 for possible and ≥67 for probable symptom exaggeration and the Validity-10 cut score was ≥22 for possible and ≥27 for probable symptom exaggeration, with sensitivity ranging from 27 to 43%. Applying these cut scores to a broader clinical and research sample resulted in lower rates of suspected exaggeration. CONCLUSIONS: Both the NSI Total and Validity-10 cut scores consistently identified potential symptom exaggeration across three mild TBI samples. Clinicians and researchers who use the NSI are encouraged to utilize either embedded validity measure in their practice.

ENIGMA MILITARY BRAIN INJURY: A COORDINATED META-ANALYSIS OF DIFFUSION MRI FROM MULTIPLE COHORTS.

Traumatic brain injury (TBI) is a significant cause of morbidity in military Veterans and Service Members. While most individuals recover fully from mild injuries within weeks, some continue to experience symptoms including headaches, disrupted sleep, and other cognitive, behavioral or physical symptoms. Diffusion magnetic resonance imaging (dMRI) shows promise in identifying areas of structural disruption and predicting outcomes. Although some studies suggest widespread structural disruption after brain injury, dMRI studies of military brain injury have yielded mixed results so far, perhaps due to the subtlety of mild injury, individual differences in injury location, severity and mechanism, and comorbidity with other disorders such as post-traumatic stress disorder (PTSD), depression, and substance abuse. We present preliminary dMRI results from the ENIGMA (Enhancing Neuroimaging Genetics through Meta-Analysis) military brain injury working group. We found higher fractional anisotropy (FA) in participants with a history of TBI. Understanding the injury and recovery process, along with factors that influence these, will lead to improved diagnosis and treatment.