Neuropsychological Performance and Functional Capacity Following Mild Traumatic Brain Injury in Veterans.

OBJECTIVE: To examine the relationship between neuropsychological functioning and performance-based functional capacity in veterans with a history of mild traumatic brain injury (mTBI), as well as the moderating effects of age and psychiatric symptoms on this relationship. SETTING: Three Veterans Affairs medical centers. PARTICIPANTS: One hundred nineteen Iraq/Afghanistan veterans with a history of mTBI and self-reported cognitive difficulties. DESIGN: Cross-sectional, secondary data analysis of baseline measures in a randomized controlled trial. MAIN MEASURES: The main outcome measure, functional capacity, was assessed using the objective and performance-based University of California San Diego Performance-based Skills Assessment-Brief. A global deficit score (GDS) was created as a composite score for performance on a battery of neuropsychological measures assessing domains of attention, processing speed, executive functioning, and verbal memory performance. Posttraumatic stress disorder (PTSD) symptom severity was assessed using the PTSD Checklist-Military Version, and depressive symptom severity was assessed using the Beck Depression Inventory, Second Edition. RESULTS: Bivariate analyses indicated that worse neuropsychological performance (ie, higher GDS) and greater PTSD symptom severity were associated with worse communication abilities and worse overall functional capacity. Multiple linear regressions demonstrated that GDS and PTSD symptom severity explained 9% of the variance in communication and 10% of the variance in overall functional capacity; however, GDS emerged as the only significant predictor in both regressions. Age, PTSD, and depressive symptom severity did not moderate the relationship between GDS and overall functional capacity. Performance in the verbal learning and memory domain emerged as the strongest neuropsychological predictor of communication and overall functional capacity. CONCLUSIONS: Worse neuropsychological functioning was moderately associated with worse performance-based functional capacity, even when accounting for PTSD symptom severity. Verbal learning and memory was the primary neuropsychological domain driving the relationship with functional capacity; improvement in verbal learning and memory may translate into improved functional capacity.

Repetitive blast mild traumatic brain injury increases ethanol sensitivity in male mice and risky drinking behavior in male combat veterans.

BACKGROUND: Mild traumatic brain injury (mTBI) is common in civilians and highly prevalent among military service members. mTBI can increase health risk behaviors (e.g., sensation seeking, impulsivity) and addiction risk (e.g., for alcohol use disorder (AUD)), but how mTBI and substance use might interact to promote addiction risk remains poorly understood. Likewise, potential differences in single vs. repetitive mTBI in relation to alcohol use/abuse have not been previously examined. METHODS: Here, we examined how a history of single (1×) or repetitive (3×) blast exposure (blast-mTBI) affects ethanol (EtOH)-induced behavioral and physiological outcomes using an established mouse model of blast-mTBI. To investigate potential translational relevance, we also examined self-report responses to the Alcohol Use Disorders Identification Test-Consumption questions (AUDIT-C), a widely used measure to identify potential hazardous drinking and AUD, and used a novel unsupervised machine learning approach to investigate whether a history of blast-mTBI affected drinking behaviors in Iraq/Afghanistan Veterans. RESULTS: Both single and repetitive blast-mTBI in mice increased the sedative properties of EtOH (with no change in tolerance or metabolism), but only repetitive blast potentiated EtOH-induced locomotor stimulation and shifted EtOH intake patterns. Specifically, mice exposed to repetitive blasts showed increased consumption "front-loading" (e.g., a higher rate of consumption during an initial 2-h acute phase of a 24-h alcohol access period and decreased total daily intake) during an intermittent 2-bottle choice condition. Examination of AUDIT-C scores in Iraq/Afghanistan Veterans revealed an optimal 3-cluster solution: "low" (low intake and low frequency), "frequent" (low intake and high frequency), and "risky" (high intake and high frequency), where Veterans with a history of blast-mTBI displayed a shift in cluster assignment from "frequent" to "risky," as compared to Veterans who were deployed to Iraq/Afghanistan but had no lifetime history of TBI. CONCLUSIONS: Together, these results offer new insight into how blast-mTBI may give increase AUD risk and highlight the increased potential for adverse health risk behaviors following repetitive blast-mTBI.

Change in Learning and Memory Partially Mediates Effects of Compensatory Cognitive Training on Self-Reported Cognitive Symptoms.

OBJECTIVE: To examine associations among compensatory cognitive training (CCT), objective cognitive functioning, and self-reported cognitive symptoms. We examined whether change in objective cognitive functioning associated with participation in CCT at 10-week follow-up mediates change in self-reported cognitive symptoms associated with CCT at 15-week follow-up. SETTING: Three VA outpatient mental health clinics. PARTICIPANTS: Veterans with a history of mild traumatic brain injury who reported cognitive deficits. DESIGN: Randomized controlled trial post hoc causal mediation analysis. MAIN MEASURES: Self-reported cognitive symptoms were measured by the Prospective-Retrospective Memory Questionnaire and the Multiple Sclerosis Neuropsychological Screening Questionnaire. Objective cognitive functioning was measured using a battery of neuropsychological tests. RESULTS: Improvement on the Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall test mediated the association between participation in CCT and decrease in the Prospective-Retrospective Memory Questionnaire total score. Improvement on the HVLT-R Total Recall and HVLT-R Delayed Recall tests both meditated the association between participation in CCT and decrease in the Multiple Sclerosis Neuropsychological Screening Questionnaire total score. No other measures of objective cognitive functioning were significant mediators. CONCLUSION: Patients' perceptions of cognitive symptom improvement due to CCT are partially mediated by learning and memory, though these subjective improvements occur regardless of other changes in objective cognitive functioning associated with CCT.

Predictors of Intervention Adherence in Compensatory Cognitive Training for Veterans With a History of Mild Traumatic Brain Injury.

OBJECTIVE: The purpose of this study was to determine modifiable predictors of intervention adherence in a study of group-based Compensatory Cognitive Training (CCT) for Iraq/Afghanistan War veterans with a history of mild traumatic brain injury (mTBI). METHODS: One hundred twenty-three veterans enrolled in a randomized controlled trial of a 10-week CCT intervention (54 assigned to CCT) and were evaluated at baseline, 5 weeks, 10 weeks, and 15 weeks. CCT adherence was determined by the number of CCT sessions attended, with more sessions indicative of greater adherence. Baseline demographic and clinical characteristics, and subjective and objective neuropsychological performance, were examined in relation to CCT session attendance. RESULTS: Older age and worse attention performance at baseline were associated with higher CCT attendance rates. CONCLUSIONS: This study generates preliminary evidence for potential modifiable neuropsychological factors that may improve engagement in CCT interventions.

A multimodal investigation of cerebellar integrity associated with high-risk cannabis use.

With legalization efforts across the United States, cannabis use is becoming increasingly mainstream. Various studies have documented the effects of acute and chronic cannabis use on brain structure and cognitive performance, including within the frontal executive control network, but little attention has been given to the effects on the cerebellum. Recent evidence increasingly points to the role of the cerebellum in various nonmotor networks, and the cerebellum's expression of cannabinoid receptors may pose particular vulnerabilities to the consequences of cannabis use. Using a combined approach of resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), the present study aims to assess how cannabis use relates to the cerebellum's intrinsic functional connectivity and underlying white matter structure and whether these properties are associated with craving or severity of cannabis use. Resting-state fMRI and DTI data, as well as self-reports of substance use history, were analyzed from a sample of 26 adults at risk for cannabis use disorder (CUD) and an age- and sex-matched comparison group of 25 cannabis-naïve adults (control). Results demonstrated that individuals at risk for a CUD showed key differences in cerebellar functional connectivity, with specific impacts on the dorsal attention and default mode networks. In addition, group differences in white matter were localized to the middle cerebellar peduncle (MCP), with a relationship between lower MCP diffusivity and higher levels of self-reported craving. These findings lend further support to the cerebellum's role in key cognitive networks and potential consequences for substance use disorders.

Retrospective and Prospective Memory Among OEF/OIF/OND Veterans With a Self-Reported History of Blast-Related mTBI.

OBJECTIVES: To evaluate prospective and retrospective memory abilities in Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) Veterans with and without a self-reported history of blast-related mild traumatic brain injury (mTBI). METHODS: Sixty-one OEF/OIF/OND Veterans, including Veterans with a self-reported history of blast-related mTBI (mTBI group; n=42) and Veterans without a self-reported history of TBI (control group; n=19) completed the Memory for Intentions Test, a measure of prospective memory (PM), and two measures of retrospective memory (RM), the California Verbal Learning Test-II and the Brief Visuospatial Memory Test-Revised. RESULTS: Veterans in the mTBI group exhibited significantly lower PM performance than the control group, but the groups did not differ in their performance on RM measures. Further analysis revealed that Veterans in the mTBI group with current PTSD (mTBI/PTSD+) demonstrated significantly lower performance on the PM measure than Veterans in the control group. PM performance by Veterans in the mTBI group without current PTSD (mTBI/PTSD-) was intermediate between the mTBI/PTSD+ and control groups, and results for the mTBI/PTSD- group were not significantly different from either of the other two groups. CONCLUSIONS: Results suggest that PM performance may be a sensitive marker of cognitive dysfunction among OEF/OIF/OND Veterans with a history of self-reported blast-related mTBI and comorbid PTSD. Reduced PM may account, in part, for complaints of cognitive difficulties in this Veteran cohort, even years post-injury. (JINS, 2018, 24, 324-334).

Untangling PTSD and TBI: Challenges and Strategies in Clinical Care and Research.

PURPOSE OF REVIEW: Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) can result from similar injuries and can result in similar symptoms, such as problems with sleep, concentration, memory, and mood. Although PTSD and persistent sequelae due to a TBI (PST) have generally been viewed as pragmatically confounded but conceptually separable entities, we examine emerging evidence emphasizing the breadth of overlap in both clinical presentation and underlying pathophysiology between PST and PTSD. RECENT FINDINGS: New evidence underscores the poor specificity of symptoms to etiology and emphasizes the potential, after both physical brain injury and traumatic stress, for changes in each of the three interacting systems that coordinate the body's response to the experience or expectation of major injury-the immune, endocrine, and neuromodulatory neurotransmitter systems. A view of PTSD and PST sharing common pathophysiologic elements related to the CNS response to acute injury or threat carries important implications for research and clinical care.

Mental Health Does Not Moderate Compensatory Cognitive Training Efficacy for Veterans With a History of Mild Traumatic Brain Injury.

OBJECTIVE: To examine the potential moderating effects of mental health symptoms on the efficacy of compensatory cognitive training (CCT) for Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans with a history of mild traumatic brain injury (mTBI). DESIGN: Secondary analysis of a randomized controlled trial of CCT. Posttraumatic stress disorder, depression, and substance dependence symptom severity were examined as potential moderators of CCT efficacy for subjective cognitive complaints, use of cognitive strategies, and objective neurocognitive performance. SETTING: Three Veterans Affairs medical centers. PARTICIPANTS: Participants included veterans with history of mTBI (N=119): 50 participated in CCT and 69 received usual care (UC). INTERVENTION: CCT is a 10-week group-based (90 minutes per session) manualized cognitive rehabilitation intervention. MAIN OUTCOME MEASURES: Objective (neuropsychological functioning) and subjective (self-report) cognitive functioning and use of cognitive strategies. RESULTS: Baseline mental health symptoms did not moderate CCT efficacy: veterans who received CCT reported significantly greater improvement in cognitive difficulties and use of cognitive strategies compared with the UC group, regardless of baseline mental health symptom severity. The CCT group also demonstrated significant improvements on neuropsychological measures of attention, learning, and executive functioning compared with the UC group, regardless of baseline mental health symptom severity. CONCLUSIONS: CCT is efficacious for improving objective cognitive functioning and compensatory strategy use for veterans with a history of mTBI, regardless of the severity of comorbid psychiatric symptoms.

Compensatory Cognitive Training for Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn Veterans With Mild Traumatic Brain Injury.

OBJECTIVE: The purpose of the study was to evaluate the efficacy of group-based compensatory cognitive training (CCT) for Operation Enduring Freedom (OEF)/Operation Iraqi Freedom(OIF)/Operation New Dawn (OND) Veterans with a history of mild traumatic brain injury. METHOD: One hundred nineteen OEF/OIF/OND Veterans with history of mild traumatic brain injury participated at 3 sites, and 50 of the Veterans were randomized to CCT group, while 69 Veterans were randomized to the usual care control group. The CCT group participated in 10 weeks of CCT. Both CCT and usual care groups were assessed at baseline, 5 weeks (midway through CCT), 10 weeks (immediately following CCT), and 15 weeks (5-week follow-up) on measures of subjective cognitive complaints, use of cognitive strategies, psychological functioning, and objective cognitive performance. RESULTS: Veterans who participated in CCT reported significantly fewer cognitive and memory difficulties and greater use of cognitive strategies. They also demonstrated significant improvements on neurocognitive tests of attention, learning, and executive functioning, which were 3 of the cognitive domains targeted in CCT. CONCLUSIONS: Findings indicate that training in compensatory cognitive strategies facilitates behavioral change (ie, use of cognitive strategies) as well as both subjective and objective improvements in targeted cognitive domains.

Perivascular Space Burden and Cerebrospinal Fluid Biomarkers in US Veterans With Blast-Related Mild Traumatic Brain Injury.

Blast-related mild traumatic brain injury (mTBI) is recognized as the "signature injury" of the Iraq and Afghanistan wars. Sleep disruption, mTBI, and neuroinflammation have been individually linked to cerebral perivascular space (PVS) dilatation. Dilated PVSs are putative markers of impaired cerebrospinal fluid (CSF) and interstitial fluid exchange, which plays an important role in removing cerebral waste. The aim of this cross-sectional, retrospective study was to define associations between biomarkers of inflammation and MRI-visible PVS (MV-PVS) burden in Veterans after blast-related mTBI (blast-mTBI) and controls. The CSF and plasma inflammatory biomarker concentrations were compared between blast-mTBI and control groups and correlated with MV-PVS volume and number per white matter cm3. Multiple regression analyses were performed with inflammatory biomarkers as predictors and MV-PVS burden as the outcome. Correction for multiple comparisons was performed using the Banjamini-Hochberg method with a false discovery rate of 0.05. There were no group-wise differences in MV-PVS burden between Veterans with blast-mTBI and controls. Greater MV-PVS burden was significantly associated with higher concentrations of several proinflammatory biomarkers from CSF (i.e., eotaxin, MCP-1, IL-6, IL-8) and plasma (i.e., MCP-4, IL-13) in the blast-mTBI group only. After controlling for sleep time and symptoms of post-traumatic stress disorder, temporal MV-PVS burden remained significantly associated with higher CSF markers of inflammation in the blast-mTBI group only. These data support an association between central, rather than peripheral, neuroinflammation and MV-PVS burden in Veterans with blast-mTBI independent of sleep. Future studies should continue to explore the role of blast-mTBI related central inflammation in MV-PVS development, as well as investigate the impact of subclinical exposures on MV-PVS burden.

CSF ß-Amyloid and Tau Biomarker Changes in Veterans With Mild Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Moderate-to-severe traumatic brain injuries (TBI) have been reported to increase the risk of Alzheimer disease (AD). Whether mild TBI (mTBI) in veterans confers a similar increased risk of AD is less known. This study investigated early AD changes using CSF biomarkers in veterans with blast mTBI. METHODS: This was a cross-sectional case-control study of veterans with mTBI and non-mTBI veterans and civilians from 2 study sources. Blast-mTBI veterans had at least 1 war zone blast or combined blast/impact mTBI meeting Veterans Affairs (VA) and Department of Defense (DoD) criteria for mTBI. Non-mTBI participants had no lifetime history of TBI. All participants underwent standardized clinical and neuropsychological assessments and lumbar puncture for collection of the CSF. CSF biomarkers were measured using MesoScale Discovery assays for Aß40 and Aß42 and INNOTEST ELISAs for phosphorylated tau181 (p-tau181) and total tau (t-tau). RESULTS: Our sample comprised 51 participants with mTBI and 85 non-mTBI participants with mean (SD) ages 34.0 (10.1) and 33.5 years (8.9), respectively. All participants but 1 (99%) were male. Differences in CSF AD biomarkers between mTBI and non-mTBI groups were age dependent and most pronounced at older ages (omnibus test p ≤ 0.08). At age 50 years, the mTBI group had lower mean [95% CI] CSF Aß42 and Aß40 than the non-mTBI group by 154 [-12 to 319] and 1864 [610-3,118] pg/mL, respectively. By contrast, CSF p-tau181 and t-tau mean levels remained relatively constant with age in participants with mTBI, while tending to be higher at older ages for the non-mTBI group. The mTBI group also demonstrated poorer cognitive performance at older ages (omnibus p < 0.08): at age 50 years, the mean TMT-B time was higher by 34 seconds [10-58] and the mean CVLT-II short-delay recall was lower by 4.2 points [1.9-6.6]. Poorer verbal memory and verbal fluency performance were associated with lower CSF Aß42 (p ≤ 0.05) in older participants. DISCUSSION: CSF Aß levels decreased in middle-aged veterans with blast-related mTBI. These data suggest that chronic neuropathologic processes associated with blast mTBI share properties in common with pathogenic processes known to portend AD onset, thus raising concern that veterans with blast-related mTBI may develop a dementing disorder later in life.

Increased [18F]Fluorodeoxyglucose Uptake in the Left Pallidum in Military Veterans with Blast-Related Mild Traumatic Brain Injury: Potential as an Imaging Biomarker and Mediation with Executive Dysfunction and Cognitive Impairment.

Blast-related mild traumatic brain injury (blast-mTBI) can result in a spectrum of persistent symptoms leading to substantial functional impairment and reduced quality of life. Clinical evaluation and discernment from other conditions common to military service can be challenging and subject to patient recall bias and the limitations of available assessment measures. The need for objective biomarkers to facilitate accurate diagnosis, not just for symptom management and rehabilitation but for prognostication and disability compensation purposes is clear. Toward this end, we compared regional brain [18F]fluorodeoxyglucose-positron emission tomography ([18F]FDG-PET) intensity-scaled uptake measurements and motor, neuropsychological, and behavioral assessments in 79 combat Veterans with retrospectively recalled blast-mTBI with 41 control participants having no lifetime history of TBI. Using an agnostic and unbiased approach, we found significantly increased left pallidum [18F]FDG-uptake in Veterans with blast-mTBI versus control participants, p < 0.0001; q = 3.29 × 10-9 [Cohen's d, 1.38, 95% confidence interval (0.96, 1.79)]. The degree of left pallidum [18F]FDG-uptake correlated with the number of self-reported blast-mTBIs, r2 = 0.22; p < 0.0001. Greater [18F]FDG-uptake in the left pallidum provided excellent discrimination between Veterans with blast-mTBI and controls, with a receiver operator characteristic area under the curve of 0.859 (p < 0.0001) and likelihood ratio of 21.19 (threshold:SUVR ≥ 0.895). Deficits in executive function assessed using the Behavior Rating Inventory of Executive Function-Adult Global Executive Composite T-score were identified in Veterans with blast-mTBI compared with controls, p < 0.0001. Regression-based mediation analyses determined that in Veterans with blast-mTBI, increased [18F]FDG-uptake in the left pallidum-mediated executive function impairments, adjusted causal mediation estimate p = 0.021; total effect estimate, p = 0.039. Measures of working and prospective memory (Auditory Consonant Trigrams test and Memory for Intentions Test, respectively) were negatively correlated with left pallidum [18F]FDG-uptake, p < 0.0001, with mTBI as a covariate. Increased left pallidum [18F]FDG-uptake in Veterans with blast-mTBI compared with controls did not covary with dominant handedness or with motor activity assessed using the Unified Parkinson's Disease Rating Scale. Localized increased [18F]FDG-uptake in the left pallidum may reflect a compensatory response to functional deficits following blast-mTBI. Limited imaging resolution does not allow us to distinguish subregions of the pallidum; however, the significant correlation of our data with behavioral but not motor outcomes suggests involvement of the ventral pallidum, which is known to regulate motivation, behavior, and emotions through basal ganglia-thalamo-cortical circuits. Increased [18F]FDG-uptake in the left pallidum in blast-mTBI versus control participants was consistently identified using two different PET scanners, supporting the generalizability of this finding. Although confirmation of our results by single-subject-to-cohort analyses will be required before clinical deployment, this study provides proof of concept that [18F]FDG-PET bears promise as a readily available noninvasive biomarker for blast-mTBI. Further, our findings support a causative relationship between executive dysfunction and increased [18F]FDG-uptake in the left pallidum.

Poorer prospective memory performance is associated with reduced time monitoring among OEF/OIF/OND Veterans with a history of blast-related mild traumatic brain injury.

Objective:Prospective memory (PM) or "remembering to remember" has been shown to be reduced in Veterans with histories of mild traumatic brain injury (mTBI), particularly on tasks with high strategic demands such as recalling time-based information in the absence of external cues. This study examined whether time monitoring during a PM task was reduced in Veterans with a history of mTBI and was associated with time-based PM performance. Method:Veterans with a history of mTBI (n = 49) and Veterans without a history of TBI (n = 16) completed the Memory for Intentions Screening Test (MIST) as a measure of PM during which their time monitoring (i.e. number of clock checks) was recorded. Results:Adjusting for age, education, depression, and PTSD symptoms, negative binomial regression revealed that the mTBI group checked the clock less frequently compared to the control group (Cohen's d = 0.84, p = 0.005). Within the mTBI group, less frequent time monitoring across the entire MIST task was associated with poorer time-based MIST performance (rs = .57, p < 0.001), but not with event-based MIST (rs = .04, p = 0.768). Conclusions:Veterans with a history of mTBI evidenced significantly reduced time monitoring during a PM task compared to Veterans without a history mTBI, which was associated with strategically-demanding PM. Current findings provide that mTBI-associated difficulties with strategic aspects of PM may be due to reduced time monitoring. Future studies are needed to determine if reduced time monitoring also contributes to mTBI-associated PM difficulties in the real-world (e.g. medication non-adherence).

The relative contribution of COVID-19 infection versus COVID-19 related occupational stressors to insomnia in healthcare workers.

Objective/Background: Healthcare workers have experienced high rates of psychiatric symptom burden and occupational attrition during the COVID-19 pandemic. Identifying contributory factors can inform prevention and mitigation measures. Here, we explore the potential contributions of occupational stressors vs COVID-19 infection to insomnia symptoms in US healthcare workers.Patients/Methods: An online self-report survey was collected between September 2020 and July 2022 from N = 594 US healthcare workers, with longitudinal follow-up up to 9 months. Assessments included the Insomnia Severity Index (ISI), the PTSD Checklist for DSM-5 (PCL-5), and a 13-item scale assessing COVID-19 related occupational stressors. Results: Insomnia was common (45% of participants reported at least moderate and 9.2% reported severe symptoms at one or more timepoint) and significantly associated with difficulty completing work-related tasks, increased likelihood of occupational attrition, and thoughts of suicide or self-harm (all p<.0001). In multivariable regression with age, gender, and family COVID-19 history as covariates, past two-week COVID-related occupational stressors, peak COVID-related occupational stressors, and personal history of COVID-19 infection were all significantly related to past two-week ISI scores (ß = 1.7 ± 0.14SE, ß = 0.08 ± 0.03, and ß = 0.69 ± 0.22 respectively). Although similar results were found for the PCL-5, when ISI and PCL-5 items were separated by factor, COVID-19 infection was significantly related only to the factor consisting of sleep-related items. Conclusions: Both recent occupational stress and personal history of COVID-19 infection were significantly associated with insomnia in healthcare workers. These results suggest that both addressing occupational stressors and reducing rate of COVID-19 infection are important to protect healthcare workers and the healthcare workforce.

Neuropsychological Correlates of PTSD and Depressive Symptom Improvement in Compensatory Cognitive Training for Veterans With a History of Mild Traumatic Brain Injury.

INTRODUCTION: Mild traumatic brain injury (mTBI), depression, and PTSD are highly prevalent in post-9/11 veterans. With the comorbidity of depression and PTSD in post-9/11 veterans with mTBI histories and their role in exacerbating cognitive and emotional dysfunction, interventions addressing cognitive and psychiatric functioning are critical. Compensatory Cognitive Training (CCT) is associated with improvements in prospective memory, attention, and executive functioning and has also yielded small-to-medium treatment effects on PTSD and depressive symptom severity. We sought to examine neuropsychological correlates of PTSD and depressive symptom improvement in veterans with a history of mTBI who received CCT. MATERIALS AND METHODS: Thirty-seven post-9/11 veterans with mTBI histories and cognitive complaints received 10 weekly 120-minute CCT group sessions. Participants completed a baseline neuropsychological assessment, including tests of premorbid functioning, attention/working memory, processing speed, verbal learning/memory, and executive functioning, and completed psychiatric symptom measures (PTSD and depression) at baseline, post-treatment, and a 5-week follow-up. Paired samples t-tests were used to examine statistically significant changes in PTSD (total and symptom cluster scores) and depressive symptom scores over time. Pearson's correlations were calculated between neuropsychological scores and PTSD and depressive symptom change scores at post-treatment and follow-up. Neuropsychological measures identified as significantly correlated with psychiatric symptom change scores were entered as independent variables in multivariable regression analyses to examine their association with symptom change at post-treatment and follow-up. RESULTS: Over 50% of CCT participants had clinically meaningful improvement in depressive symptoms (≥17.5% score reduction), and over 20% had clinically meaningful improvement in PTSD symptoms (≥10-point improvement) at post-treatment and follow-up. Examination of PTSD symptom cluster scores revealed a statistically significant improvement in avoidance/numbing at follow-up. Bivariate correlations indicated that worse baseline performance on Category Fluency was moderately associated with PTSD symptom improvement at post-treatment. Worse performance on both Category Fluency and Category Switching Accuracy was associated with improvement in depressive symptoms at post-treatment and follow-up. Worse performance on Trail-Making Number-Letter Switching was also associated with improvement in depressive symptoms at follow-up. Subsequent regression analyses revealed that worse processing speed and worse aspects of executive functioning at baseline were associated with depressive symptom improvement at post-treatment and follow-up. CONCLUSIONS: Worse baseline performances on tests of processing speed and aspects of executive functioning were significantly associated with improvements in PTSD and depressive symptoms during the trial. Our results suggest that cognitive training may bolster skills that are helpful for PTSD and depressive symptom reduction and that those with worse baseline functioning may benefit more from treatment because they have more room to improve.

Correlates of sleep disturbance in Veterans with traumatic brain injury and chronic pain: A cross-sectional study.

BACKGROUND: Few studies have investigated sleep in Veterans with comorbid traumatic brain injury (TBI) and chronic pain. OBJECTIVE: To describe mood and cognitive correlates with sleep disturbance in a sample of Veterans with both TBI and chronic pain. RESEARCH METHOD: Cross-sectional, correlational analyses were completed using baseline data from a randomized controlled trial comparing psychosocial treatments for pain in Veterans with TBI. Enrollment occurred between July 2015 and January 2017. Self-report measures of hours slept, insomnia severity, depression and PTSD symptoms were collected along with a brief neuropsychological assessment. RESULTS: Participants (n = 221) were an average age of 37.2 years (SD = 8.2) and mostly male (89%). Participants reported sleeping an average of 4.9 h a night (SD = 1.4) with an average Insomnia Severity Index (ISI) score of 17.4 (SD = 5.4) suggesting moderate insomnia symptoms. Fewer hours slept was associated with higher depression scores (r = -0.28, p < 0.001) and slower processing speed (r = 0.23, p < 0.001). Increasing insomnia severity was associated with greater depression (r = 0.57, p < 0.001) and PTSD symptoms (r = 0.44, p < 0.001), and slower processing speed (r = -0.22, p < 0.001). CONCLUSIONS: The average ISI score was above the clinical cut off for insomnia diagnosis. Results suggest that those with more severe insomnia symptoms report higher depression and PTSD symptoms as well as exhibit slower processing speed. Improving sleep in this population may be important for improving outcome following TBI.

Self-perceived irritability among OEF/OIF/OND veterans with a history of deployment-related mTBI: Associations with prospective memory and quality of life.

Objective: Examine relationships between self-perceived irritability, prospective memory, and quality of life (QOL) following mild traumatic brain injury (mTBI). Methods: 75 OEF/OIF/OND-era Veterans (56 deployment-related mTBI; 19 no history of TBI), were administered a battery of neuropsychological tests and self-report measures of mood and QOL. Self-perceived irritability was measured using the Neurobehavioral Symptom Inventory. Prospective memory (PM) was measured using the Memory for Intentions Test (MIST). Results: Self-perceived irritability was significantly higher for Veterans with, versus without, a history of deployment-related mTBI. Among Veterans with a history of mTBI, self-perceived irritability was inversely associated with PM performance, even after adjusting for PTSD severity. Greater self-perceived irritability was also associated with higher depressive symptoms and reduced QOL for perceived physical health, psychological health, social support, and environmental factors; however, only social support remained significant after adjusting for PTSD severity. Depression symptom severity was not significantly associated with PM, suggesting that PM may be uniquely related to self-perceived irritability rather than mood dysregulation more generally. Conclusions: Findings provide preliminary evidence of a relationship between PM and self-perceived irritability in Veterans with a history of mTBI. PM and irritability may be related via their mutual reliance on high-level cognitive control. Results illustrate possible cognitive and affective factors contributing to psychological and interpersonal challenges for this population. Future investigations with larger and more diverse samples are needed to replicate findings and explore potential mechanisms linking irritability and PM following mTBI.

Associations between Intra-Individual Neurocognitive Variability and Prospective Memory in Veterans with Mild Traumatic Brain Injury History and Posttraumatic Stress Disorder.

OBJECTIVE: Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) frequently co-occur and are associated with neurocognitive intra-individual variability (IIV) and difficulty with prospective memory (PM). The current study aimed to examine associations between IIV and PM in this comorbid group. METHOD: Fifty veterans with a history of blast mTBI and current comorbid PTSD completed a standardized neurocognitive battery to measure IIV, and the Memory for Intentions Screening Test measuring PM. RESULTS: Adjusting for age, education, and race, higher IIV was associated with poorer time-based PM (p < .001, f2 = .34), but not event-based PM. In a subset of the sample with self-report data, higher IIV was associated with poorer self-reported retrospective memory, but not PM. CONCLUSIONS: Cognitive variability on a standardized neuropsychological battery was associated with strategically demanding PM, which is an ecologically relevant ability and highlights the possible connection between subtle cognitive difficulties in-clinic and those experienced in daily life.

The relative contribution of COVID-19 infection versus COVID-19 related occupational stressors to insomnia in healthcare workers.

Objective/Background: Healthcare workers have experienced high rates of psychiatric symptom burden and occupational attrition during the COVID-19 pandemic. Identifying contributory factors can inform prevention and mitigation measures. Here, we explore the potential contributions of occupational stressors vs COVID-19 infection to insomnia symptoms in US healthcare workers. Patients/Methods: An online self-report survey was collected between September 2020 and July 2022 from N=594 US healthcare workers, with longitudinal follow-up up to 9 months. Assessments included the Insomnia Severity Index (ISI), the PTSD Checklist for DSM-5 (PCL-5), and a 13-item scale assessing COVID-19 related occupational stressors. Results: Insomnia was common (45% of participants reported at least moderate and 9.2% reported severe symptoms at one or more timepoint) and significantly associated with difficulty completing work-related tasks, increased likelihood of occupational attrition, and thoughts of suicide or self-harm (all p<.0001). In multivariable regression with age, gender, and family COVID-19 history as covariates, past two-week COVID-related occupational stressors, peak COVID-related occupational stressors, and personal history of COVID-19 infection were all significantly related to past two-week ISI scores (ß=1.7±0.14SE, ß=0.08±0.03, and ß=0.69±0.22 respectively). Although similar results were found for the PCL-5, when ISI and PCL-5 items were separated by factor, COVID-19 infection was significantly related only to the factor consisting of sleep-related items. Conclusions: Both recent occupational stress and personal history of COVID-19 infection were significantly associated with insomnia in healthcare workers. These results suggest that both addressing occupational stressors and reducing rates of COVID-19 infection are important to protect healthcare workers and the healthcare workforce.

Cerebrocerebellar hypometabolism associated with repetitive blast exposure mild traumatic brain injury in 12 Iraq war Veterans with persistent post-concussive symptoms.

Disagreement exists regarding the extent to which persistent post-concussive symptoms (PCS) reported by Iraq combat Veterans with repeated episodes of mild traumatic brain injury (mTBI) from explosive blasts represent structural or functional brain damage or an epiphenomenon of comorbid depression or posttraumatic stress disorder (PTSD). Objective assessment of brain function in this population may clarify the issue. To this end, twelve Iraq war Veterans (32.0 ± 8.5 [mean ± standard deviation (SD)] years of age) reporting one or more blast exposures meeting American Congress of Rehabilitation Medicine criteria for mTBI and persistent PCS and 12 cognitively normal community volunteers (53.0 ± 4.6 years of age) without history of head trauma underwent brain fluorodeoxyglucose positron emission tomography (FDG-PET) and neuropsychological assessments and completed PCS and psychiatric symptom rating scales. Compared to controls, Veterans with mTBI (with or without PTSD) exhibited decreased cerebral metabolic rate of glucose in the cerebellum, vermis, pons, and medial temporal lobe. They also exhibited subtle impairments in verbal fluency, cognitive processing speed, attention, and working memory, similar to those reported in the literature for patients with cerebellar lesions. These FDG-PET imaging findings suggest that regional brain hypometabolism may constitute a neurobiological substrate for chronic PCS in Iraq combat Veterans with repetitive blast-trauma mTBI. Given the potential public health implications of these findings, further investigation of brain function in these Veterans appears warranted.