Background:Both years of contact sport participation and years of military service are positively related to risk of sustaining multiple mild traumatic brain injuries (mTBIs). Little is known about the additive risk of mTBI exposure by combining premilitary contact sport participation with subsequent military service. Purpose:To assess the effect of premilitary contact sport participation on the odds of current and former military personnel sustaining mTBI(s) during their lifetime. Study Design:Cross-sectional study; Level of evidence, 3. Methods:This study analyzed data from 2651 individuals from the LIMBIC-PLS. The association between a history of contact sport participation and sustaining an mTBI pre-military service, during military service while not on deployment, or during deployment was estimated using odds ratios. The association between the total number of pre-military service, military service while not on deployment, and deployment-related mTBI events with history of contact sport participation (yes vs no) was estimated using incidence rate ratios (IRRs) and 95% confidence intervals. The authors adjusted those models for demographic factors and then repeated those analyses using years of contact sport exposure, categorized as 0 (referent), >0 to 5, >5 to 10, and >10 years. Results:In this cohort, 62% had a history of contact sport participation and 82% had a history mTBI. Individuals with a history of contact sport participation were more likely to have experienced an mTBI in their lifetime (OR, 1.26; 95% CI, 1.03-1.54; P = .023). This manifested only outside of military combat deployments. Specifically, a history of contact sport exposure was associated with a higher odds of an mTBI before military service (OR, 1.63; 95% CI, 1.39-1.91; P < .001) or a nondeployment mTBI (OR, 1.62; 95% CI, 1.37-1.91; P < .001) Moreover, a higher incidence rate of lifetime mTBI was observed as number of years of contact sport exposure increased. Conclusion:Similar to findings in civilians, these findings suggest that contact sport participation increases the likelihood of experiencing a single or multiple mTBI events among military personnel. These findings suggest that it would be appropriate to screen individuals' mTBI history before joining the military to identify individual potential risks for concerns associated with multiple lifetime mTBI events.

BACKGROUND AND OBJECTIVES:Traumatic brain injury (TBI) is heterogeneous, complicating efforts to develop standardized diagnostic and therapeutic approaches. Conventional group-based analyses often obscure individual differences by averaging across diverse injury patterns. By contrast, by comparing deviation from the expected distribution observed in healthy controls, normative modeling can capture patient-specific deviations from expected neuroanatomical norms. The aim of this research was to use normative modeling to capture individual variability in brain morphometry on individuals who have experienced a TBI. METHODS:In this study, we applied traditional case-control and a normative modeling approach to cortical and subcortical MRI. Data were analyzed from the Enhancing NeuroImaging Genetics through Meta-Analysis Consortium Adult Moderate-to-Severe TBI working group. Primary outcome measures were cortical thickness and subcortical volumes, derived from the Destrieux and Freesurfer subcortical atlases. Case-control tests were conducted using linear models controlling for age, sex, site, and intracranial volume. Normative modeling was carried out by accessing the Predictive Clinical Neuroscience Portal, estimating individual deviations using a model of Bayesian linear regression with likelihood warping. RESULTS:A total of 631 (407 patients with TBI, 224 healthy controls) MR images were processed. Conventional case-control analyses identified significant group differences in 153 regions of possible 178 cortical or subcortical regions. Normative modeling revealed far greater heterogeneity. No more than 23% of patients with TBI shared an extreme deviation (z-score >2 or z < -2) in the same region, but every region experienced at least 1 extreme positive or negative deviation across individuals. Stratifying by Glasgow Coma Scale (GCS) severity sustained this pattern; even within GCS 13-15, GCS 9-12, and GCS 3-8 subgroups, regional convergence did not exceed 34%. The median number of deviations increased with injury severity (GCS 13-15 = 9, GCS 9-12 = 19, GCS 3-8 = 22), demonstrating that group averages mask highly individualized morphologic abnormalities as injury severity increases. DISCUSSION:Normative modeling detects participant-specific cortical and subcortical abnormalities that conventional group comparisons overlook, better representing the true diversity of TBI-related morphologic changes. Generating individualized "morphologic fingerprints" may ultimately advance prognostic accuracy and lay the foundation for personalized interventions in research and clinical practice.

Background and Objectives:Brain age is a global measure that compares structural brain MRI with large reference datasets. Predicted age deviation (PAD) is the deviation between predicted brain age and chronological age, with positive values indicating advanced aging. Identifying blood-based biomarkers that approximate brain PAD could provide an accessible and cost-effective measure of brain health as an alternative to MRI, but no blood-based biomarkers have yet been identified. This study aimed to investigate novel blood-based biomarkers associated with accelerated PAD using an unbiased proteomics approach to discover new biomarkers. Methods:This study is a secondary analysis with a cross-sectional case-control design using the LIMBIC-CENC dataset as a discovery approach to understand novel biomarker patterns. Brain age was estimated using brainageR in 137 participants aged ≤40 years with no substantial cognitive deficits or neurological disorders. Cases (n = 76) included individuals with brain age ≥5 years older than chronological age, whereas controls (n = 61) had brain age equal to or younger than chronological age (PAD range: -1.3 to 0; mean = -0.9) and were otherwise matched on demographics and clinical features. Unbiased proteomic profiling of ∼5,400 proteins was performed using the Olink Explore platform. Differential protein expression between groups was assessed using Wilcoxon tests with Benjamini-Hochberg correction. Receiver operating characteristic (ROC) analysis was performed on probabilities derived from generalized linear models (GLMs) to identify optimal protein combinations, prioritizing maximizing both sensitivity and negative predictive value. Results:Olink analyses identified 418 proteins that were significantly different between groups after multiple-comparison correction. Upregulated proteins in participants with PAD≥5 years included: component inhibitor-nuclear factor kappa-b kinase (CHUK), methenyltetrahydrofolate synthetase domain containing (MTHFSD), and epidermal growth factor (EGF), with log2 fold changes of 1.70-1.80. Insulin-like peptide 3 (INSL3) was the most downregulated protein (log2 fold change -2.27). Enriched pathways involved nuclear factor kappa-b (NF-κB), heat-shock protein, and Wingless/Integrated (Wnt) signaling. Models including 6-7 dysregulated proteins (e.g., CHUK and INSL3) achieved AUCs>0.9, with sensitivities >0.90 and specificities >0.70. Discussion:These discovery-based findings warrant validation in larger cohorts and suggest potential for blood-based protein panel detection of early, clinically silent, pre-pathological accelerated brain aging changes when interventions may be most effective.

The thalamus is a heterogeneous structure crucial for corticocortical communication, affective-perceptual integration, motor preparation, and memory-related functions. Posttraumatic stress disorder (PTSD) is characterized by various symptoms that likely relate to thalamic functions. Group-level and individual differential structural covariance (SC) analyses were conducted on intrathalamic, thalamocortical, and thalamosubcortical volumetric networks by segmenting structural MRI data from 2,784 subjects (PTSD n = 1,306; controls n = 1,478) into 25 thalamic nuclei per hemisphere. We found that PTSD was associated with stronger intrathalamic and thalamocortical network strength and stronger SC between the limbic thalamus and the somatomotor and auditory thalamus. PTSD severity was related to specific regional alterations in the intrathalamic network involving the lateral pulvinar. Comorbid depression severity positively correlated with global intrathalamic alterations, while avoidance symptoms positively correlated with global thalamosubcortical alterations. Hyperarousal symptoms related to altered SC in the thalamocortical network between the reuniens, central medial, paratenial, centromedian, and limitans-suprageniculate nuclei and lateral cortical regions spanning the occipital, temporal, and orbitofrontal cortices. Differential associations between avoidance, hyperarousal, and comorbid depression symptoms and thalamic SC in PTSD suggest that specific thalamic covariance patterns may be involved in unique facets of PTSD symptomatology.

IntroductionTraumatic Brain Injury is prevalent during military service and is associated with short- and long-term psychosocial and functional changes, though comprehensive longitudinal data on Veterans and active-duty service members (SMs) are lacking. To address this research gap, we utilized data from the Long-term Impact of Military-relevant Brain Injury Consortium (LIMBIC) and the Translational Research Center for TBI and Stress Disorders (TRACTS), two prospective longitudinal cohort studies of veterans and active duty SMs, each containing a wide range of symptom scales, objective assessments, and health-related outcomes.MethodsThis paper describes the innovative methods used to achieve the initial proof-of-concept harmonization for baseline psychosocial and physical health data from these two large cohort studies. To achieve harmonization, we gathered a multidisciplinary team with clinical and research expertise. We created a list of measures utilized by each study and organized them into larger clinically meaningful domains. When possible, we harmonized full measures, or single items directly, while others needed to be indirectly harmonized, by recoding, aligning categorical levels, and categorizing scales based on established cut scores. We calculated descriptive statistics to summarize and compare data. We then conducted Principal Component Analysis (PCA) for all continuous measures to assess whether site-level effects were observed in the shared variance.ResultsA total of 73 variables capturing psychosocial function, sensorimotor, pain, and clinical health factors were harmonized across the LIMBIC and TRACTS studies. There were no differences in sex or ethnicity distributions between the studies. Sensory, social health, and health related clinical data were broadly comparable across cohorts, while pain intensity and headache disability were higher in LIMBIC. PCA analysis suggests data is suitable for pooled analysis.DiscussionWe were able to directly harmonize multiple self-report measures of social well-being and indirectly harmonize other functional and demographic variables. While this initial effort focused on baseline data, the included principles can be employed to harmonize longitudinal data to increase the ability to detect clinical phenotypes to be applied in precision medicine approaches in future research.

Post 9/11-era veterans and service members are at high risk for posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) exposures. However, symptom overlap between these conditions presents challenges in differential diagnosis and discriminating the relative contributions of each when co-occurring. Neurological soft signs (NSS) represent a potential diagnostic tool given demonstrated associations with PTSD, but to date there is limited research assessing a possible association with mTBI history. The current study sought to identify whether NSS can discriminate between PTSD, mTBI, and their co-occurrence via a neuropsychological test of complex motor functioning, the Behavioral Dyscontrol Scale-II (BDS-II). The study sample included 241 post-9/11 veterans. After adjusting for symptom and performance validity, study results indicated that NSS as measured by the BDS-II did not discriminate between the mTBI, PTSD, and co-occurring mTBI+PTSD groups. Additionally, in contrast to previous research, no association was observed between NSS and PTSD symptoms. Findings do not support NSS insofar as their utility in discrimination between mTBI and PTSD.

BACKGROUND:Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group. METHODS:T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9). RESULTS:PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges' g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges' g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (p corrected  = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (p corrected  = .001). CONCLUSIONS:PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

ObjectivesTo explore associations of recent moderate-to-vigorous aerobic exercise (MVAE) participation and lifetime mild traumatic brain injury (mTBI) history with measures of brain gray matter volumes among military service members and Veterans (SMVs).MethodsParticipants (n = 1,340; aged 41.3 ± 10.3 years; 13% female) were SMV's who participated in the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium Prospective Longitudinal Study (LIMBIC-CENC PLS). MVAE participation was self-reported via the Behavioral Risk Factor Surveillance System and categorized according to current MVAE recommendations (Inactive, Insufficiently Active, Active, and Highly Active). Lifetime mTBI history was queried via validated structured interview and categorized as 0 mTBI, 1-2 mTBIs, 3 + mTBIs. Structural MRI (T1- and T2-weighted images) were used to measure gray matter volumetrics: ventricle-to-brain ratio (VBR); bilateral volumes of the frontal, parietal, temporal, occipital, cingulate, hippocampus, amygdala, and thalamus regions. Multivariable linear regression models were fit to test associations of MVAE participation, mTBI history, and their interaction on each of the volumetric outcomes while controlling for age, sex, education attainment, and PTSD symptoms. Effects were considered statistically significant if the corresponding unstandardized beta (B) and 95% CI did not include 0.ResultsRegarding main effects, participants in the Inactive MVAE group had significantly larger VBR values (worse outcome) than those in the Insufficiently Active group (B[95%CI] = -0.137[-0.260, -0.014]). Interaction effects showed participants with no lifetime mTBIs in the Highly Active group had larger VBR values (worse outcome) when compared to those in the Inactive and Insufficiently Active groups. SMVs with 3 + lifetime mTBIs who were Highly Active also had smaller VBR values (better outcome) when compared to Highly Active SMVs with fewer lifetime mTBIs. There were no other statistically significant differences for MVAE participation, mTBI history, or their interactions.ConclusionsHistory of one or more lifetime mTBIs was not associated with measures of brain gray matter volumes, suggesting that declines in structural brain health are not expected for the most SMVs with mTBI(s). Although MVAE may benefit brain health, a positive association between self-reported MVAE participation and gray matter volumes was not observed.

OBJECTIVE:Those who served on active duty after September 11, 2001 (Post-9/11) are screened for deployment-related mild traumatic brain injury (mTBI) when initiating Veterans Health Administration (VHA) clinical services. Positive screeners are offered a referral to a Comprehensive TBI Evaluation (CTBIE) by a TBI specialist to further determine deployment-related mTBI history and access interdisciplinary care if indicated. This study examined whether Post-9/11 veterans who screened positive and also participated in a prospective longitudinal study (PLS) differed in characteristics and outcomes depending on their clinical VHA CTBIE completion status and mTBI positive (+) or negative (-) determinations (CTBIE = mTBI+, CTBIE = mTBI-, No CTBIE). SETTING:Veterans Health Administration (VHA) clinical and research settings. PARTICIPANTS:658 Post-9/11 veterans. DESIGN:Secondary analysis of the PLS using a retrospective cohort design. MAIN MEASURES:Primary outcomes were associations of VHA CTBIE completion/determination with competitive employment and service-connected disability ratings obtained at time of PLS completion. Secondary outcomes included a range of PLS demographic, military, potential concussive event, health, functional, and quality-of-life measures. RESULTS:Based on their PLS research data, relative to the No CTBIE group, the CTBIE = mTBI+ group had lower adjusted odds ratios (aOR) of competitive employment (aOR = .51, 95% confidence interval [CI] = 0.31-0.83, P = .008) and higher odds of having a ≥50% service-connected disability rating (aOR = 2.02, 95% CI = 0.31-0.83, P = .01). The CTBIE = mTBI+ group also reported higher neurobehavioral and posttraumatic stress disorder symptom severity, and poorer outcomes on quality-of-life measures than the No CTBIE group. Generally, few differences were detected between the CTBIE = mTBI- and either of the CTBIE = mTBI+ and No CTBIE groups. CONCLUSIONS:This study leveraged the unique ability to combine VHA clinical and comprehensive research data to examine outcomes not routinely collected as part of standard VHA clinical care. These research data can inform VHA TBI leadership about long-term health and functional status of veterans who screen positive for TBI.

Community reintegration serves an integral role to enhance veterans' quality of life as they transition to civilian life. Unsuccessful reintegration after military separation may contribute to the relative increase in adverse outcomes such as homelessness and suicide in this population. Mild traumatic brain injury (TBI) has been linked to poor mental health, which, in turn, may compromise community reintegration; however, little is known about how the characteristics of mild TBI may impact community reintegration either directly or indirectly. The objectives of this study are to: (1) evaluate the association of the characteristics of mild TBI, including blast versus nonblast mechanism and combat versus noncombat deployment (i.e., outside of combat deployment) setting on community reintegration; (2) determine whether this association varies by the level of perceived social support; and (3) explore the potential mediation effect of mental health symptom levels. This cross-sectional analysis used data from the Long-term Impact of Military-relevant Brain Injury Consortium Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) Prospective Longitudinal Study on 2,177 service members and veterans (SMVs) who were registered for clinical care at a Department of Defense and/or Veterans' Affairs Medical Facility. The exposure of interest was the characteristics of each mild TBI, including from blast/nonblast mechanism, combat deployment/noncombat deployment setting, or lack of any lifetime mild TBI. The outcome was community reintegration measured by the Community Reintegration of Injured Service Members survey. Perceived social support was measured using the Deployment Risk & Resilience Inventory-2 Post-deployment Social Support Scale. Mental health symptoms (post-traumatic stress and depressive) were evaluated using the post-traumatic stress disorder checklist, DSM-5, and the Patient Health Questionnaire-9, respectively. Community reintegration among SMVs who sustained mild TBI(s) only with a nonblast mechanism outside of a combat deployment was better compared with those sustaining mild TBI(s) during a combat deployment or by blast mechanism. Those with no mild TBI history had a similar level of community reintegration as those who sustained nonblast mild TBI(s) outside of combat deployment. The level of perceived social support did not significantly alter these relationships; however, inclusion of variables to account for mental health symptoms in the models attenuated the results to nonsignificance, supporting potential mediation by mental health symptoms. This study found mild TBI sustained during combat deployment (either blast or nonblast mechanism) may be a risk factor for poor community reintegration. These results support clinical care processes that include identifying SMs with sustained mild TBI during combat deployment (particularly those with blast mechanism) for targeted interventions that may facilitate transition into the community. Future studies are needed to evaluate the mechanism through which mild TBI sustained during combat deployment for both blast and nonblast type injuries may impact community reintegration.

BACKGROUND:Previous investigations of whole thalamus and thalamic nuclei volumes in posttrauma psychopathology have been sparse and limited in scope and have yielded inconsistent results. To address this, volumetric estimates of whole thalamus and thalamic nuclei were obtained from structural brain magnetic resonance imaging scans from 2058 participants across 20 worldwide sites in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Posttraumatic Stress Disorder (PTSD) working group. METHODS:Thalamic volumes were compared in trauma-exposed participants with PTSD (n = 238), major depressive disorder (MDD) (n = 184), and comorbid PTSD+MDD (n = 618) and in trauma-exposed control participants (n = 1018). PTSD and MDD symptom severity, PTSD symptom clusters, and childhood trauma were similarly examined for associations with thalamic volume. RESULTS:Participants with PTSD had smaller sensorimotor thalamic nuclei, while participants with MDD or comorbid PTSD+MDD had smaller mediodorsal (MD) thalamus volumes relative to control participants. Severity of PTSD and MDD symptoms negatively correlated with MD volume. A significant interaction between PTSD and MDD severity was found, such that MDD severity was positively associated with whole thalamus volume only among individuals with high PTSD severity. We observed both positive and negative volumetric associations for specific PTSD symptom clusters and childhood trauma subtypes. CONCLUSIONS:Whole thalamus volume and volumes of the sensorimotor and limbic thalamus may play an important role in the development of PTSD and MDD in the aftermath of trauma exposure. The interaction between PTSD and MDD symptoms and contrasting effects across PTSD symptom clusters and types of childhood adversity suggest that multiple neurobiological mechanisms are involved in shaping thalamic volume posttrauma.

OBJECTIVES:To (1) evaluate differences in psychological health outcomes between US female service members and veterans (FSMVs) with and without mild traumatic brain injury (mTBI) history, and (2) examine the associations between psychological health and lifetime mTBI history, time since last mTBI, blast-mTBI history, and combat-mTBI history. SETTING:Ten military and veteran health care study sites nationwide. PARTICIPANTS:FSMV enrolled in the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) study. We used 2:1 propensity score matching to match FSMVs with a prior mTBI (n = 148; age: 40.0 ± 8.7 years; time since last mTBI: 11.6 ± 9.4 years) to those without mTBI history (n = 74) on demographic and health-history confounders. DESIGN:Prospective, longitudinal study design with current cross-sectional analysis. MAIN MEASURES:FSMVs completed thorough health history evaluations and standardized assessments consisting of the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL5), Patient Health Questionnaire-9 (PHQ-9), Neurobehavioral Symptom Inventory (NSI), Satisfaction With Life Scale (SWLS), and the Traumatic Brain Injury-Quality of Life (TBI-QoL) anxiety and emotional-behavioral dyscontrol modules. RESULTS:Compared to the no mTBI group, FSMVs with any lifetime mTBI displayed worse PCL-5, PHQ-9, NSI, and TBI-QoL Anxiety total scores ( P ≤ .002), but not SWLS or TBI-QoL emotional-behavioral dyscontrol. Combat mTBI history demonstrated worse PCL-5, SWLS, and TBI-QoL Anxiety total scores ( P ≤ .047). Greater SWLS scores were observed for each year since their last mTBI ( P = .048). No significant differences for cumulative mTBI history or any blast-mTBI history were observed across outcomes ( P ≥ .146). CONCLUSIONS:FSMVs with ≥1 mTBI history reported greater psychological symptoms than those without. Among FSMVs with lifetime mTBI history, combat-mTBI history was associated with worse PTSD, life satisfaction, and anxiety symptoms. Our findings indicate that a single mTBI, notably combat-related, may adversely impact psychological health, but future research is necessary for longitudinal, comprehensive FSMV health understanding across the lifespan post-mTBI.

Introduction:Prior research suggests that olfactory dysfunction may occur following a traumatic brain injury (TBI) due to structural injury to the olfactory peripheral or central networks. Olfaction may also be affected in posttraumatic stress disorder (PTSD) due to traumatic re-experiencing. Given the relevance of both TBI and PTSD to the military and veteran populations, the purpose of this study was to evaluate whether the University of Pennsylvania Smell Identification Test (UPSIT) would be useful in differentiating TBI from significant PTSD symptom burden in a sample of post-deployed active-duty military and veterans. Methods:A sample of 276 participants with UPSIT data and passing scores on validity measures completed a larger study on neurocognition of predominantly post-deployed veterans of the wars in Afghanistan and Iraq. TBI history was ascertained by medical records or a self-report questionnaire; PTSD symptoms were measured using the PTSD Checklist-Military version (PCL-M) and the Traumatic Stress scale (ARD-T) of the Personality Assessment Inventory. Those with a history of TBI (+TBI) were compared with those without (-TBI) on total UPSIT score; severity of injury and number of injuries were also evaluated. Furthermore, those with and without significant PTSD symptoms (+PTSD and -PTSD) were compared on UPSIT total scores. Finally, group comparisons were conducted to assess whether PTSD demonstrated a significant effect above and beyond TBI. Results:History of TBI was associated with lower UPSIT scores (-TBI M = 34.02, +TBI M = 32.76, z = -2.38, p = 0.017, r = 0.14); however, the effect size was small and driven by the difference between moderate/severe TBI and -TBI (moderate/severe M = 31.78). Number of mild TBIs was not associated with UPSIT scores: The presence of PTSD symptoms and symptom clusters were not significantly associated with UPSIT scores. PTSD symptoms showed no additional effects on poorer olfaction scores above and beyond TBI. Discussion:Olfactory identification was significantly reduced in those with a history of TBI, suggesting that olfaction may be useful in the assessment of these individuals for potential treatment needs. Veterans with significant PTSD symptoms, however, did not display different olfactory ability compared with those without, regardless of TBI status.

Objective: Define and characterize extreme phenotypes of pain catastrophizing for persons with chronic pain following mild to severe traumatic brain injury (TBI) requiring inpatient rehabilitation. Setting: 18 TBI Model System (TBIMS) centers. Participants: 1762 TBIMS participants 1 to 30 years post-injury reporting chronic pain. Design: Cross-sectional, secondary analyses. Primary Measures: Catastrophizing, sociodemographic, injury, functional outcome, pain, and treatment characteristics. Results: Participants were male predominantly (73%), White (76%), middle-aged (mean 46.5 years), injured in motor vehicle accidents (53%) or falls (20%). Extreme phenotypes were identified based on upper and lower 25 th percentiles to create low catastrophizing (N = 434) and high catastrophizing (N = 458) groups. Bivariate comparisons found significant differences ( P < .001) on all measures of concurrent function and pain interference with those in the low catastrophizing phenotype experiencing better function and lower pain interference than those in the high catastrophizing phenotype. Combination Lasso and logistic regression identified multivariable predictors of phenotypes. Increased odds of high versus low catastrophizing extreme phenotypes were associated being younger (odds ratio [OR] = 1.24 for a 10-unit decrease), less than a college level of education (OR = 1.70-2.53), no military history (OR = 3.25), lower FIM motor (OR = 1.20 for a 5-unit decrease) and cognitive (OR = 1.53 for a 5-unit decrease) scores, increased pain intensity (OR = 1.22 for a 1 unit increase) and pain interference (OR = 1.93 for a 1-unit increase), neuropathic type pain (OR = 1.82-1.86), and migraine type pain versus no head pain (OR = 1.65). Conclusion: High pain catastrophizing phenotypes were associated with a greater degree of pain and functional disability and higher likelihood of neuropathic pain and migraine headache. Given pain catastrophizing’s contribution to pain-related disability and treatment outcomes, additional research is necessary to investigate its role in adjustment to chronic pain among individuals with TBI. Adapting evidence-based interventions for this population that specifically targets pain catastrophizing is warranted.

OBJECTIVE:The aim of the study was to identify the impact of mild traumatic brain injury history and current emotional status on olfactory functioning.DESIGN:This was a cross-sectional study of 49 predominantly male, military veterans, reservists, and active duty service members with Operations Enduring Freedom, Iraqi Freedom, and New Dawn deployments and varying mild traumatic brain injury histories.RESULTS:Those with a positive history of mild traumatic brain injury (n = 32) endorsed significantly higher rates of self-reported olfactory disturbance. However, there were no differences between the mild traumatic brain injury and no mild traumatic brain injury groups for rates of objective odor identification dysfunction (none vs. microsmia or more severe) or overall accuracy of odor identification. In keeping with this, self-reported olfactory disturbance also failed to associate with odor identification dysfunction. In both groups, those self-reporting olfactory disturbance reported significantly greater emotional distress, severity of posttraumatic stress symptoms, and attentional impulsivity. However, self-reported olfactory disturbance was not associated with other behavioral factors frequently attributed to TBI, such as aggression, motor impulsiveness, poor planning, and cognitive flexibility.CONCLUSIONS:These findings indicate mild traumatic brain injury is not a risk factor for postacute microsomia among Operations Enduring Freedom, Iraqi Freedom, and New Dawn military veterans. Higher observed rates of self-reported olfactory disturbance in patients with mild traumatic brain injury may be a function of emotional distress rather than organic brain injury.

OBJECTIVE:To examine the impact of low-level blast (LLB) exposure on cognitive functioning in combat-exposed service members and Veterans (SM/Vs), and its interaction with posttraumatic stress disorder (PTSD) and deployment-related mild traumatic brain injury (TBI). SETTING:Multi-site Department of Defense and Veterans Affairs research centers participating in the LIMBIC-CENC Prospective Longitudinal Study. PARTICIPANTS:1036 SM/Vs who deployed in support of combat operations and completed comprehensive baseline assessments between 2015 and 2023. DESIGN:Cross-sectional observational study using multivariate linear regression and interaction models to evaluate associations between LLB, PTSD, deployment-related mild TBI, and cognitive outcomes. MAIN MEASURES:LLB exposure was assessed using the generalized blast exposure value from the Blast Exposure Threshold Survey. Cognitive functioning was evaluated using neuropsychological tests assessing memory, attention, processing speed, executive function, and global performance. PTSD was assessed using the PTSD Checklist for DSM-5. RESULTS:LLB was not independently associated with poorer cognitive performance. However, LLB moderated the relationship between PTSD and memory outcomes, with significantly worse visual memory in those with PTSD and high LLB exposure. Significant interaction effects were also observed between PTSD and deployment-related TBI on verbal memory, working memory, and processing speed. PTSD demonstrated the most consistent independent associations across cognitive domains. CONCLUSIONS:Although LLB exposure alone was not associated with cognitive deficits, it interacted with PTSD and TBI to influence cognitive performance. These findings support the need for integrated assessments of blast exposure, PTSD, and TBI history in evaluating cognitive health among SM/Vs.

ObjectivePosttraumatic stress (PTS) symptoms and problematic alcohol use (e.g., binge drinking and alcohol-related problems; ARP) commonly co-occur following stressors and traumatic events. Ecological momentary assessment methods can clarify the functional relationships between these conditions.MethodsTwenty-five trauma-exposed combat veterans with pre-pandemic heavy drinking histories completed three daily smartphone surveys for four weeks, assessing binge drinking, ARP, PTS symptoms, and positive and negative affect. Within-person multi-level models assessed PTS and alcohol relationships, covarying for affect and demographics.ResultsWithin-person variation in PTS was inversely associated with binge drinking but not associated with ARP after adjustment for interindividual heterogeneity. Within-person variation in ARP was not associated with PTS after adjustment for interindividual heterogeneity. The covariate of negative affect was positively associated with ARP and PTS.ConclusionsFindings suggest negative affect, rather than PTS, has the strongest association with variation in ARP symptoms in this at-risk sample. There was also evidence of individual differences in the strength and direction of effects.

To examine the association between environmental barriers and unmet rehabilitation needs during chronic recovery from traumatic brain injury (TBI) in persons discharged from inpatient rehabilitation. Five Veterans Affairs Polytrauma Rehabilitation Centers. Cohort study of Veterans Affairs TBI Model Systems study participants who completed a 10 or 15 year follow up (N = 474). Craig Hospital Inventory of Environmental Factors, Short Form (CHIEF-SF); TBI Rehabilitation Needs Survey (RNS). RNS scores ranged from 0 to 42 with an average score of 6.9 (SD = 7.7). The most frequent unmet needs endorsed included the need to improve memory, solve problems, and control physical symptoms. In the adjusted model, unmet rehabilitation needs (RNS total) was associated with overall environmental barriers (CHIEF-SF Total Score) and three of five CHIEF-SF subscales: Policy barriers, Attitudes/Support barriers, and Services/Assistance barriers. Results from this study suggest that rehabilitation needs persist for at least a decade after TBI and occur in areas that may be modifiable with intervention. Health care providers shoulder consider periodic screening for unmet needs and consider potential treatments to address them as medically indicated Also, results support the growing recognition of TBI as a dynamic and lifelong condition necessitating a chronic disease management model. Despite significant investment in healthcare infrastructure for Veterans and Service Members, knowledge gaps remain regarding understanding and addressing their long-term rehabilitation needs, as well as and how environmental barriers impact the ability to address those needs. Unmet needs among women and minority groups; as well as evaluation of systems interventions to ameliorate environmental barriers they face are important foci of future research.

BACKGROUND:Mild traumatic brain injury (mTBI) is common among military service members. Moderate-to-vigorous aerobic exercise (MVAE) is a modifiable behavior with potential benefits for individuals following mTBI but is poorly understood for long-term mTBI health. OBJECTIVE:To explore the associations between mTBI history and MVAE participation and appreciate their association with health-related quality of life (HR-QOL) among service members and Veterans. METHODS:Data from a larger study were used in these secondary cross-sectional analyses. Lifetime mTBI history (0, 1-2, 3+) was captured via validated structured interviews. Self-reported weekly MVAE (none, below, meeting, or ≥2 times the recommendation) was recorded from the Behavioral Risk Factor Surveillance System questionnaire. Participants' HR-QOL was self-reported via Traumatic Brain Injury-Quality of Life instrument and the Patient Health Questionnaire-9 (depression symptoms). Univariate mTBI history and MVAE associations were assessed via Pearson's chi-square and Kendall's Tau. Multivariable linear regression models with unstandardized beta values and 95% confidence intervals were fit for each HR-QOL questionnaire outcome, with current age, sex, and posttraumatic stress disorder symptoms as covariates (α = .05). RESULTS:Among the 1995 participants (87.7% male; aged 41.7 ± 10.1 years), those meeting or exceeding (≥2 times) MVAE recommendations had significantly higher HR-QOL for fatigue, executive function, pain interference, resilience, social participation, and depression than the inactive MVAE group. Exceeding MVAE recommendations by ≥2 times was also significantly associated with better self-reported cognition - general concerns. Those who participated in exercise but didn't meet the MVAE recommendations had higher pain interference, social participation, and depression scores compared to the inactive group. More lifetime mTBIs were associated with worse HR-QOL across all domains. Level of MVAE participation was not dependent on mTBI history. CONCLUSIONS:More MVAE was associated with better TBI-related HR-QOL regardless of mTBI history. MVAE is recommended for service members and Veterans due to these findings and previously reported health benefits.