White Matter Organization and Cortical Thickness Differ Among Active Duty Service Members With Chronic Mild, Moderate, and Severe Traumatic Brain Injury.

Abstract This study compared findings from whole-brain diffusion tensor imaging (DTI) and volumetric magnetic resonance imaging (MRI) among 90 Active Duty Service Members with chronic mild traumatic brain injury (TBI; n = 52), chronic moderate-to-severe TBI (n = 17), and TBI-negative controls (n = 21). Data were collected on a Philips Ingenia 3T MRI with DTI in 32 directions. Results demonstrated that history of TBI was associated with differences in white matter microstructure, white matter volume, and cortical thickness in both mild TBI and moderate-to-severe TBI groups relative to controls. However, the presence, pattern, and distribution of these findings varied substantially depending on the injury severity. Spatially-defined forms of DTI fractional anisotropy (FA) analyses identified altered white matter organization within the chronic moderate-to-severe TBI group, but they did not provide clear evidence of abnormalities within the chronic mild TBI group. In contrast, DTI FA "pothole" analyses identified widely distributed areas of decreased FA throughout the white matter in both the chronic mild TBI and chronic moderate-to-severe TBI groups. Additionally, decreased white matter volume was found in several brain regions for the chronic moderate-to-severe TBI group compared with the other groups. Greater number of DTI FA potholes and reduced cortical thickness were also related to greater severity of self-reported symptoms. In sum, this study expands upon a growing body of literature using advanced imaging techniques to identify potential effects of brain injury in military Service Members. These findings may differ from work in other TBI populations due to varying mechanisms and frequency of injury, as well as a potentially higher level of functioning in the current sample related to the ability to maintain continued Active Duty status after injury. In conclusion, this study provides DTI and volumetric MRI findings across the spectrum of TBI severity. These results provide support for the use of DTI and volumetric MRI to identify differences in white matter microstructure and volume related to TBI. In particular, DTI FA pothole analysis may provide greater sensitivity for detecting subtle forms of white matter injury than conventional DTI FA analyses.

The Impact of Lifetime Traumatic Brain Injury (TBI) on Mental Health Symptoms among Service Members in Interdisciplinary TBI Programs.

INTRODUCTION: Traumatic brain injury (TBI) is highly prevalent among active duty service members (ADSMs) and imposes a significant health burden, particularly on mental health (e.g., post-traumatic stress disorder [PTSD] and depressive symptoms). Little is known about how TBI setting characteristics impact PTSD and depressive symptom expression in service members undergoing interdisciplinary TBI care. MATERIALS AND METHODS: The study included 455 patients enrolled in interdisciplinary, outpatient TBI programs within the military health system. Using Poisson regression with robust error variance, TBI injury setting characteristics (i.e., before military service, during military training, and during noncombat/combat deployment) were evaluated against clinically-elevated PTSD (PTSD Checklist, DSM-5 score ≥ 33) and depressive (Patient Health Questionnaire-8 score ≥ 15) symptoms. RESULTS: In adjusted models, TBI sustained before military service was associated with less likelihood for clinically-elevated PTSD symptoms at pretreatment (prevalence ratio [PR] = 0.76, confidence interval [CI] = 0.60-0.96) and post-treatment (PR = 0.67, CI = 0.52-0.87). TBI sustained during combat deployment, however, resulted in the greatest impact on clinically-elevated pretreatment PTSD (PR = 1.49, CI = 1.16-1.91) and depressive (PR = 1.47, CI = 1.06-2.03) symptoms. Null results were found between military training/noncombat deployment and mental health symptoms. Regardless of the TBI setting, following TBI treatment, there remained 37.5% (n = 180) and 24.8% (n = 108) with clinically-elevated PTSD and depressive symptoms, respectively. CONCLUSIONS: There was a differential impact of TBI settings, particularly between TBI sustained before military service and that from combat deployment among ADSMs enrolled in outpatient TBI programs. This may be indicative of differences in the characteristics of these environments (e.g., injury severity) or the impact of such an event during recovery from current TBIs. The large percentage of ADSMs who present with clinically-elevated mental health symptoms after treatment may suggest the need for additional resources to address mental health needs before, during, and after treatment in TBI programs.

Associations of mTBI and post-traumatic stress to amygdala structure and functional connectivity in military Service Members.

Introduction: Traumatic brain injury (TBI) is one of the highest public health priorities, especially among military personnel where comorbidity with post-traumatic stress symptoms and resulting consequences is high. Brain injury and post-traumatic stress symptoms are both characterized by dysfunctional brain networks, with the amygdala specifically implicated as a region with both structural and functional abnormalities. Methods: This study examined the structural volumetrics and resting state functional connectivity of 68 Active Duty Service Members with or without chronic mild TBI (mTBI) and comorbid symptoms of Post-Traumatic Stress (PTS). Results and discussion: Structural analysis of the amygdala revealed no significant differences in volume between mTBI and healthy comparison participants with and without post-traumatic stress symptoms. Resting state functional connectivity with bilateral amygdala revealed decreased anterior network connectivity and increased posterior network connectivity in the mTBI group compared to the healthy comparison group. Within the mTBI group, there were significant regions of correlation with amygdala that were modulated by PTS severity, including networks implicated in emotional processing and executive functioning. An examination of a priori regions of amygdala connectivity in the default mode network, task positive network, and subcortical structures showed interacting influences of TBI and PTS, only between right amygdala and right putamen. These results suggest that mTBI and PTS are associated with hypo-frontal and hyper-posterior amygdala connectivity. Additionally, comorbidity of these conditions appears to compound these neural activity patterns. PTS in mTBI may change neural resource recruitment for information processing between the amygdala and other brain regions and networks, not only during emotional processing, but also at rest.

Identifying Unique Symptom Groups Following Mild Traumatic Brain Injury Using the Neurobehavioral Symptom Inventory and PTSD Checklist-5 in Military Personnel: A Bifactor Analysis.

OBJECTIVE: To identify both shared and unique groups of posttraumatic stress and postconcussive symptoms using bifactor analysis. SETTING: Two large military outpatient traumatic brain injury (TBI) rehabilitation clinics in the Southwestern United States. PARTICIPANTS: A sample of 1476 Active Duty Service Members seeking treatment for a mild TBI sustained more than 30 days previously, without history of moderate or severe TBI, who completed measures of postconcussive and posttraumatic stress symptoms assessed at clinic intake. DESIGN: Observational, correlational study with data taken from an institutional review board-approved clinical registry study. MAIN MEASURES: Neurobehavioral Symptom Inventory (NSI) and Posttraumatic Stress Disorder (PTSD) Checklist for Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) ( DSM-V ) (PCL-5). Concurrent measures were Patient Health Questionnaire (PHQ-8), Pittsburgh Sleep Quality Index (PSQI), and Headache Impact Test (HIT-6). RESULTS: Results identified a bifactor model demonstrating unique posttraumatic stress, depressive, cognitive, and neurological/somatic symptom groups that were still evident after accounting for a universal factor representing general distress. These symptom groups were differentially related to concurrently measured clinical outcomes. CONCLUSION: Use of a bifactor structure may help derive clinically useful signals from self-reported symptoms among Active Duty Service Members seeking outpatient treatment for mild TBI.

Presenting symptoms as prognostic measures of mental health recovery among service members with concussion.

Background: Comorbid mental illness may negatively impact recovery from concussion. This study evaluated whether the level of symptom clusters at clinic intake contribute to poor mental health recovery in concussed patients during treatment, which may in turn serve as a target intervention. Objective: The objective of this study is to examine the association between the level of initial symptoms and mental health symptoms among service members with concussion. Methods: Data were obtained from 483 active duty service members treated in interdisciplinary treatment programs for traumatic brain injury, all of which were concussions. Pre-treatment symptom clusters included self-reported hyperarousal, dissociation/depression, cognitive dysfunction/headache and neurological symptoms. The outcomes, clinically-relevant decreases in depressive symptoms (assessed by the 8-item Patient Health Questionnaire, PHQ-8) and PTSD symptoms (assessed by the PTSD Checklist for DSM-5, PCL-5), were defined as a decrease in PHQ-8 > 5 and PCL-5 > 7, respectively. Poisson regression with robust error variance was used to evaluate the relationship between the level of each symptom cluster and clinically-relevant decrease in outcomes. Results: Participants with higher (vs. lower) levels of pre-treatment hyperarousal and dissociation/depression symptom cluster were less likely to improve in depressive and PTSD symptoms during treatment. The level of cognitive/headache and neurological symptom clusters were not significantly associated with any symptom changes. Conclusion: These findings support the need for individualized treatment for symptoms identified and treated after determining concussion history, with particular attention to high levels of hyperarousal and dissociation/depression prior to treatment.

Disparities in mental health symptoms recovery across race/ethnicity and education level following mild traumatic brain injury.

Purpose: The purpose of this study was to investigate the relationship between race/ethnicity and post-concussive mental health (i.e., depressive, post-traumatic stress disorder [PTSD]) and neurobehavioral symptoms among service members, and whether this association differed by education level. Methods: The study sample consisted of 524 patients from a multidisciplinary US military outpatient treatment facility for post-concussive symptoms. Poisson regression with robust error variance was utilized to investigate outcome (i.e., clinically-elevated depressive [Patient Health Questionnaire-8 ≥15], PTSD [PTSD Checklist, DSM 5 ≥38] and neurobehavioral [Neurobehavioral Symptom Inventory >75th percentile] symptoms at admission and last follow-up in this cohort study. Modification by education level (low [no college degree] vs. high [associate's degree or higher]) was additionally evaluated. Results: The relationship between race/ethnicity and mental health/neurobehavioral symptoms varied by education level (p-interaction: depressive symptoms = 0.002, PTSD symptoms = 0.035, neurobehavioral symptoms = 0.040). Specifically, non-Whites were at a significantly higher prevalence for clinically-elevated depressive symptoms post-treatment than Whites, but only among those with higher education level (PR = 2.22, CI = 1.37-3.59). A similar trend was demonstrated for PTSD and neurobehavioral symptoms. Conclusion: Military healthcare may need to increase depression-focused treatment options that are acceptable for racial/ethnic minority patients, particularly those with higher education, while they are recovering from comorbid traumatic brain injury.

Impact of Prior Brain Injury on Concussion Recovery in Military Personnel: Evaluation of Timing Between Concussions.

OBJECTIVE: To evaluate the potential impact of timing between the current and the most recent previous concussions on symptom severity among acutely concussed active duty military Service members (SMs). SETTING: Three military installations. PARTICIPANTS: Eighty-four SMs aged 18 to 44 years who sustained a concussion within 72 hours of enrollment. No previous concussion within 1 year preenrollment. DESIGN: Longitudinal study with enrollment within 72 hours of injury, and follow-up at 1 week and 1 month postinjury. MAIN MEASURES: Lifetime concussion history (yes/no) and recency of the latest concussion (no history, relatively more recent [1 to <6 years ago], and more remote [6+ years ago]) from the current concussion using the Ohio State University Traumatic Brain Injury Identification Method-Interview Form. Symptom severity (total and by categories: cognitive, affective, somatosensory, vestibular) at all time points using the Neurobehavioral Symptoms Inventory. RESULTS: Concussion history assessed as having any previous concussion was not found significantly related to symptom severity (total or by categories) following a current concussion. However, when timing between concussion was taken into account, time since previous concussion was significantly related to symptomatology, whereby those with relatively more recent previous concussion had greater total symptoms within 72 hours of injury and at 1 week postinjury (though not at 1 month) than those with more remote previous concussion (≤72 hours: difference = 15.4, 95% CI = 1.8 to 29.1; 1 week: difference = 15.2, 95% CI = 1.2 to 29.2) or no history (≤72 hours: difference = 11.6, 95% CI = 0.4 to 22.8; 1 week: difference = 13.9, 95% CI = 2.4 to 25.4). When evaluated by symptom category, this relationship was particularly important on affective and somatosensory symptoms. CONCLUSION: In recently concussed active duty SMs, the timing between the current and previous concussions may be an important factor in determining prognosis. Clinical assessment of concussion history that accounts for the timing of the most recent event may be necessary to identify patients who may require a more conservative plan of care and more gradual return to activity in the acute recovery stage.

Multimodal Neurocognitive Screening of Military Personnel With a History of Mild Traumatic Brain Injury Using the Bethesda Eye & Attention Measure.

OBJECTIVE: To evaluate a neurocognitive eye tracking task, the Bethesda Eye & Attention Measure (BEAM), for use in cognitive screening of patients with a history of mild traumatic brain injury (TBI). SETTING: US military TBI rehabilitation clinic. DESIGN/PARTICIPANTS: Cross-sectional study of 191 military personnel receiving outpatient services related to history of mild TBI. Main measures: BEAM; neuropsychological screening measures of attention, processing speed, executive function, and memory. RESULTS: Medium effect sizes were found for partial correlations (controlling for age) between key BEAM metrics and neuropsychological screening tests. Linear regression analyses demonstrated that BEAM saccadic eye movements and manual (button press) metrics each provided complementary value in measurement of cognitive performance, above and beyond effects of demographic factors and clinical characteristics. CONCLUSION: This study provides initial support for the use of BEAM neurocognitive eye tracking in cognitive screening of adults with a history of mild TBI. BEAM saccadic metrics appear to be particularly well-suited for the assessment of visual attention. Study findings also highlight opportunities for greater cognitive sensitivity or testing efficiency that may be missed by tests measuring only one response modality at a time.

Recent cocaine use and memory impairment in HIV.

Both Human Immunodeficiency Virus (HIV) and cocaine use have been associated with impairment in neuropsychological functioning. The high comorbidity between HIV and cocaine use highlights the importance of ascertaining whether there is a compounding effect of cocaine use in individuals with HIV. Among neuropsychological domains impacted by HIV, verbal memory deficits have received substantial attention partly because they have been associated with declines in functional status in HIV positive individuals. We collected California Verbal Learning Test-II data from HIV participants who met lifetime diagnostic criteria of cocaine abuse and/or dependence (HIV/CocDx+, N = 80 & HIV/CocDx-, N = 30, respectively) and those with and without recent cocaine use, which was confirmed by toxicology analysis (HIV/Coc+, N = 56 & HIV/Coc-, N = 57, respectively). The Item Specific Deficit Approach (ISDA) was employed to determine any additional cocaine-associated deficits in encoding, consolidation, and retrieval, which attempts to control for potential confounding factors of memory such as attention. Using conventional methods of evaluating memory profiles, we found that the HIV/Coc + group demonstrated worse learning, immediate and delayed free recall, and recognition in contrast to the HIV/Coc - group; although using the ISDA, we found that encoding was the only significant difference between HIV/Coc + and HIV/Coc-participant, with HIV/Coc - performing better. Our data suggest that for individuals with HIV, cocaine use is associated with a temporary decline in verbal memory, is characterized by greater encoding deficits, and these effects may reduce with abstinence. Clinically, our findings suggest that reduced encoding is the likely contributor to verbal memory decline in HIV/Coc + and these effects are partially reversible-at least to the level of their HIV/Coc - counterparts.

Brain bases of recovery following cognitive rehabilitation for traumatic brain injury: a preliminary study.

Many patients with traumatic brain injury (TBI) have persistent cognitive deficits, including decreased attention and working memory. This preliminary study examined fMRI data from a clinical trial implementing a 4-week virtual reality driving intervention to assess how sustained training can improve deficits related to traumatic brain injury. Previously-reported behavioral findings showed improvements in working memory and processing speed in those who received the intervention; this report explores the brain bases of these effects by comparing neural activity related to working memory (n-back task) and resting state connectivity before and after the intervention. In the baseline visit (n = 24), working memory activity was prominent in bilateral DLPFC and prefrontal cortex, anterior insula, medial superior frontal gyrus, left thalamus, bilateral supramarginal / angular gyrus, precuneus, and left posterior middle temporal gyrus. Following intervention, participants showed less global activation on the n-back task, with regions of activity only in the bilateral middle frontal cortex, posterior middle frontal gyrus, and supramarginal gyrus. Activity related to working memory load was reduced for the group that went through the intervention (n = 7) compared to the waitlist control group (n = 4). These results suggest that successful cognitive rehabilitation of working memory in TBI may be associated with increased efficiency of brain networks, evidenced by reduced activation of brain activity during cognitive processing. These results highlight the importance of examining brain activity related to cognitive rehabilitation of attention and working memory after brain injury.

Intracranial Abnormalities Are Associated With Fewer Self-Reported Symptoms in Military Service Members Following Moderate-to-Severe Traumatic Brain Injury.

OBJECTIVE: This study examined the relationship between intracranial abnormalities (ICAs) and self-reported neurobehavioral and posttraumatic stress (PTS) symptoms in members of the military with moderate-to-severe traumatic brain injury (msTBI). METHOD: Participants included 539 members of the US military with nonpenetrating msTBI. Self-reported neurobehavioral and PTS symptoms were assessed using the Neurobehavioral Symptom Inventory and the PTSD Checklist-Civilian Version. ICAs were categorized as present/absent (by subtype) based upon medical record review. Spearman rank-order correlations and stepwise multiple regression analyses examined univariate and combined predictive relationships between ICAs and self-reported symptoms. RESULTS: The presence of any ICA was associated with reduced self-reported neurobehavioral and PTS symptoms. ICA-associated reductions were largest for PTS, followed by affective and cognitive neurobehavioral symptoms, and relatively weak for somatic/sensory and vestibular symptoms. Effects of different types of ICAs were comparable. Greater time since injury was related to greater symptom report, whereas duration of loss of consciousness and posttraumatic amnesia were not consistently related to self-reported symptoms. CONCLUSIONS: Results suggest that ICAs are associated with suppression of reported PTS and neurobehavioral symptoms-potentially via reduction in self-awareness. These findings support comprehensive, objective evaluation to identify impairments in self-awareness and functioning in msTBI patients.

Best Practices for Progressive Return to Activity after Concussion: Lessons Learned from a Prospective Study of U.S. Military Service Members.

Primary care providers can play a crucial role in the clinical management of concussion. However, many providers lack up-to-date information about best practices for rest and return to activity after these injuries. Most research on this topic has been conducted in athletes, and so less is known about how to assist patients with returning to activity in other settings and populations. This article provides a review of best practices for management of progressive return to activity after concussion, with an emphasis on "lessons learned" from the Defense and Veterans Brain Injury Center (DVBIC) Progressive Return to Activity (PRA) study, a multi-site longitudinal research project conducted to evaluate concussion management practices and the effectiveness of provider training on DVBIC clinical recommendations (CRs). Provider clinical practices and patient outcomes were examined at three U.S. military treatment facilities before and after providers completed a standardized training on DVBIC PRA CRs. In summary, research findings provide additional support that concussion recovery can be influenced by patients' activity levels after injury. Patients with concussion may experience poorer outcomes if they return to pre-injury levels of activity too rapidly, but they may also be at risk for prolonged symptoms if they fail to increase activity levels over time after an initial period of rest. Additionally, training primary care providers in return to activity guidelines can result in more effective patient education and better clinical outcomes. This knowledge can be used to inform best practices for progressive return to activity in both civilian and military settings.

Beliefs About the Influence of Rest During Concussion Recovery May Predict Activity and Symptom Progression Within an Active Duty Military Population.

OBJECTIVES: To evaluate relationships between beliefs about the impact of rest and the level of activities and symptoms over time among active duty Service members sustaining concussion, and whether these relationships vary by provision of concussion education. DESIGN: Longitudinal study using multilevel modeling to assess the relationship between beliefs about rest within 72 hours of concussion and change in activity and symptom level over time, as well as interaction by concussion education at the initial clinic visit. SETTING: Three military treatment facilities. PARTICIPANTS: Study participants included active duty Service members diagnosed with a concussion (N=111; median age, 24 y). Individuals with previous history of concussion within 12 months of study enrollment were excluded. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Activity questionnaire and the Neurobehavioral Symptom Inventory assessed within 72 hours of concussion; at 1 week; and at 1, 3, and 6 month(s) postinjury. RESULTS: Receipt of concussion education from providers was significantly associated with greater belief that rest influences concussion recovery. Greater belief that rest influences symptom recovery at the acute stage of concussion was associated with a greater increase in activities over time, but only among those who received education from their provider. Additionally, greater belief about the influence of rest was related to a more rapid decrease in symptoms over time. CONCLUSIONS: Concussed Service members who underestimate the influence of rest during acute recovery may be at risk for poorer recovery. Treatment of Service members with postconcussive symptoms should consider patient knowledge and/or beliefs about rest and recovery, which may influence prognosis. Our results support the provider's use of concussion education to correct potential misconceptions that may negatively impact symptom recovery.

Clinical validation of an optimized multimodal neurocognitive assessment of chronic mild TBI.

OBJECTIVE: Previous laboratory-based studies have shown that neurocognitive eye-tracking metrics are sensitive to chronic effects of mild traumatic brain injury (mTBI), even in individuals with normal performance on traditional neuropsychological measures. In this study, we sought to replicate and extend these findings in a military medical environment. We expected that metrics from the multimodal Fusion n-Back test would successfully distinguish chronic mTBI participants from controls, particularly eye movement metrics from the more cognitively challenging "1-Back" subtest. METHODS: We compared performance of participants with chronic mTBI (n = 46) and controls (n = 33) on the Fusion n-Back test and a battery of conventional neuropsychological tests. Additionally, we examined test reliability and the impact of potential confounds to neurocognitive assessment. RESULTS: Our results supported hypotheses; Fusion 1-Back metrics were successful in multimodal (saccadic and manual) classification of chronic mTBI versus control. In contrast, conventional neuropsychological measures could not distinguish these groups. Additional findings demonstrated the reliability of Fusion n-Back test metrics and provided evidence that saccadic metrics are resistant to confounding influences of age, intelligence, and psychiatric symptoms. INTERPRETATION: The Fusion n-Back test could provide advantages in differential diagnosis for complex brain injury populations. Additionally, the rapid administration of this test could be valuable for screening patients in clinical settings where longer test batteries are not feasible.

"Return to duty" as an outcome metric in military concussion research: Problems, pitfalls, and potential solutions.

OBJECTIVE: "Return to duty" (RTD) is often used as an outcome metric in military concussion research, but is inconsistently defined across studies and presents several key problems to researchers. Using results from the Defense and Veterans Brain Injury Center's (DVBIC) Progressive Return to Activity (PRA) study, we highlight problems with RTD, and suggest solutions to inform future efforts. METHOD: 116 service members (SMs) were enrolled in one of two groups (pre-implementation and post-implementation of the PRA Clinical Recommendation [CR]). Data, including the Neurobehavioral Symptom Inventory (NSI-22), was collected within 72-hours of injury (baseline), and at 1-week, 1-month, 3-months, and 6-months post-injury. Our analyses focused on three time points: baseline, approximate RTD date, and post-RTD follow-up, with RTD data captured via self-report and electronic medical record (EMR). Secondary analyses included comparisons across PRA-CR implementation groups. RESULTS: Of those SMs (<50% of the sample) with both self-reported and EMR RTD dates, dates largely did not match (range 1 to 36 days). RTD (either date) also did not indicate symptom recovery, with >50% of SMs reporting "abnormally high" symptom levels (i.e., NSI-22 total ≥75th percentile) at RTD, and over 50% of SMs reporting at least one significant symptom (i.e., any NSI-22 item ≥ 2) after RTD. CONCLUSIONS: Our data demonstrate challenges encountered with a RTD outcome metric. Military concussion researchers should strive to use a well-defined RTD outcome metric. We propose defining RTD as a return to deployment readiness. Further, researchers should utilize Department of Defense definitions of Individual Medical Readiness and Deployment Limiting conditions to increase specificity of a RTD outcome metric. Improving the way RTD is captured will improve confidence that tools used after a SM sustains concussion are adequately informing RTD decisions.

Activity Level During Acute Concussion May Predict Symptom Recovery Within an Active Duty Military Population.

OBJECTIVE: To evaluate the impact on symptom resolution of activity acutely following a concussion and the role of acute-phase symptoms on this relationship among active duty service members (SMs). SETTING: Three military installations. PARTICIPANTS: Sixty-two SMs aged 18 to 44 years who sustained a concussion within 72 hours of enrollment. DESIGN: Longitudinal design with data collected within 72 hours of injury (baseline, n = 62) and at 1 week (n = 57), 1 month (n = 50), 3 months (n = 41), and 6 months (n = 40) postinjury. MAIN MEASURES: Baseline activity level using a 60-item Activity Questionnaire. Symptom level at baseline and during follow-up using Neurobehavioral Symptoms Inventory. RESULTS: Significant interaction (Pi < .05) was found, with significant main effects (P < .05) limited to SMs with elevated baseline symptomatology. Among these participants, greater baseline total activity was significantly related to greater vestibular symptoms at 1, 3, and 6 months (ß = .61, .63, and .59, respectively). Significant associations were also found for particular types of baseline activity (eg, physical; vestibular/balance; military-specific) and symptoms at 1, 3, and/or 6 months postinjury. CONCLUSION: These results provide support for clinical guidance that symptomatic SMs, particularly those with high levels of acute symptoms, may need to avoid excessive activity acutely following concussion.

Use of the Progressive Return to Activity Guidelines May Expedite Symptom Resolution After Concussion for Active Duty Military.

BACKGROUND: Clinical recommendations for concussion management encourage reduced cognitive and physical activities immediately after injury, with graded increases in activity as symptoms resolve. Empirical support for the effectiveness of such recommendations is needed. PURPOSE: To examine whether training medical providers on the Defense and Veterans Brain Injury Center's Progressive Return to Activity Clinical Recommendation (PRA-CR) for acute concussion improves patient outcomes. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: This study was conducted from 2016 to 2018 and compared patient outcomes before and after medical providers received an educational intervention (ie, provider training). Patients, recruited either before or after intervention, were assessed at ≤72 hours, 1 week, 1 month, 3 months, and 6 months after a concussion. The participant population included 38 military medical providers and 106 military servicemembers with a diagnosed concussion and treated by one of the military medical providers: 58 patient participants received care before the intervention (ie, provider training) and 48 received care after intervention. The primary outcome measure was the Neurobehavioral Symptom Inventory. RESULTS: The patients seen before and after the intervention were predominantly male (89.7% and 93.8%, respectively) of military age (mean ± SD, 26.62 ± 6.29 years and 25.08 ± 6.85 years, respectively) and a mean ± SD of 1.92 ± 0.88 days from injury. Compared with patients receiving care before intervention, patients receiving care after intervention had smaller increases in physical activities (difference in mean change; 95% CI, 0.39 to 6.79) and vestibular/balance activities (95% CI, 0.79 to 7.5) during the first week of recovery. Although groups did not differ in symptoms at ≤72 hours of injury (d = 0.22; 95% CI, -2.21 to 8.07), the postintervention group reported fewer symptoms at 1 week (d = 0.61; 95% CI, 0.52 to 10.92). Postintervention patients who completed the 6-month study had improved recovery both at 1 month (d = 1.55; 95% CI, 5.33 to 15.39) and 3 months after injury (d = 1.10; 95% CI, 2.36 to 11.55), but not at 6 months (d = 0.35; 95% CI, 5.34 to 7.59). CONCLUSION: Training medical providers on the PRA-CR for management of concussion resulted in expedited recovery of patients.

Neurocognitive Driving Rehabilitation in Virtual Environments (NeuroDRIVE): A pilot clinical trial for chronic traumatic brain injury.

BACKGROUND: Virtual reality (VR) technology may provide an effective means to integrate cognitive and functional approaches to TBI rehabilitation. However, little is known about the effectiveness of VR rehabilitation for TBI-related cognitive deficits. In response to these clinical and research gaps, we developed Neurocognitive Driving Rehabilitation in Virtual Environments (NeuroDRIVE), an intervention designed to improve cognitive performance, driving safety, and neurobehavioral symptoms. OBJECTIVE: This pilot clinical trial was conducted to examine feasibility and preliminary efficacy of NeuroDRIVE for rehabilitation of chronic TBI. METHODS: Eleven participants who received the intervention were compared to six wait-listed participants on driving abilities, cognitive performance, and neurobehavioral symptoms. RESULTS: The NeuroDRIVE intervention was associated with significant improvements in working memory and visual search/selective attention- two cognitive skills that represented a primary focus of the intervention. By comparison, no significant changes were observed in untrained cognitive areas, neurobehavioral symptoms, or driving skills. CONCLUSIONS: Results suggest that immersive virtual environments can provide a valuable and engaging means to achieve some cognitive rehabilitation goals, particularly when these goals are closely matched to the VR training exercises. However, additional research is needed to augment our understanding of rehabilitation for driving skills, cognitive performance, and neurobehavioral symptoms in chronic TBI.

Activity Level and Type During Post-acute Stages of Concussion May Play an Important Role in Improving Symptoms Among an Active Duty Military Population.

Background: Previous research demonstrates that early rest and gradual increases in activity after concussion can improve symptoms; however, little is known about the intensity and type of activity during post-acute time periods-specifically months post-injury-that may promote optimal recovery in an active duty service member (SM) population. Objective: The objectives of this study were to investigate how activity level and type at the post-acute stages of concussion (at 1 and 3 month[s] post-injury) impact subsequent symptoms among SMs, and how this relationship might differ by the level of symptoms at the time of injury. Methods: Participants included 39 SMs ages 19-44 years from 3 military installations who were enrolled within 72 h after sustaining a concussion. Linear regression was used to evaluate whether the association between activity level at 1 or 3 month(s) post-injury (as measured by a multi-domain Activity Questionnaire) and subsequent symptoms at 3 and/or 6 months (as measured by the Neurobehavioral Symptom Inventory) varied by the level of symptoms at acute stages of concussion. Partial correlation was used to evaluate relationships that did not differ by acute symptom level. Symptoms at the time of activity assessment (1 or 3 month[s]) were accounted for in all models, as well as activity level at acute stages of concussion. Results: Greater physical and vestibular/balance activity at 1 month were significantly correlated with lower symptoms at 3 months, but not at 6 months post-injury. There were no significant associations found between activity (total or by type) at 3 months and symptoms at 6 months. The association between activity level at either 1 or 3 months and subsequent symptoms at 3 and/or 6 months did not differ by the level of acute symptoms. Conclusion: The intensity and type of activities in which SMs engage at post-acute stages of concussion may impact symptom recovery. Although low levels of activity have been previously shown to be beneficial during the acute stage of injury, higher levels of activity may provide benefit at later stages. These findings provide support for the importance of monitoring and managing activity level beyond the acute stage of concussion.

Insights into cognitive pupillometry: Evaluation of the utility of pupillary metrics for assessing cognitive load in normative and clinical samples.

Despite increasing use of pupillometry to understand cognitive deficits in clinical populations, there is no consensus on what pupillary metrics are most useful. In this study, we compare the reliability, sensitivity to mild traumatic brain injury (TBI) and cognitive load differences, and the likelihood of replication between various pupillary metrics. Raw pupil diameter was recorded from 15 patients with chronic mild TBI and 23 uninjured controls while they performed a cognitive task with three levels of cognitive load. Several pupillary metrics were quantified from the pupillary data and submitted to tests of internal consistency, group ∗ cognitive load repeated measures ANOVAs, and bootstrapping analyses of effect size. Most pupillary metrics demonstrated acceptable, good, or excellent reliability. Metrics differed in sensitivity to group, cognitive load, and their interaction. Bootstrapping analyses revealed that peak-based metrics are more likely to replicate than means- or ratio-based metrics. Several pupillary metrics were determined to have great utility for measuring cognitive load in clinical or normative samples. This study directly addresses a known methodological gap in the cognitive pupillometry literature.