Comorbid Mild Traumatic Brain Injury Research Articles

Factors influencing shared decision-making for insomnia and obstructive sleep apnea treatment among Veterans with mild traumatic brain injury.

We elicited perspectives of clinical stakeholders and Veterans regarding barriers and facilitators to implementing shared decision-making (SDM) for comorbid mild traumatic brain injury (mTBI) and sleep disorders in the Veterans Health Administration. We also compared the perspectives of clinical stakeholders and Veterans regarding determinants of SDM. Semistructured interviews were conducted with 29 clinical stakeholders and 20 Veterans (n = 49). Clinical stakeholders included Veterans Health Administration providers and policymakers involved in the management of mTBI and/or sleep disorders (insomnia disorder, obstructive sleep apnea). Veterans included those with a clinician-confirmed mTBI who received care for insomnia disorder and/or obstructive sleep apnea within the past year. Themes were identified using a descriptive and interpretive approach to qualitative analysis. We compared results across clinical stakeholders and Veterans. Barriers to implementing SDM were identified by both groups at the patient (eg, mTBI sequalae), provider (eg, deprioritization of Veteran preferences), encounter (eg, time constraints), and facility levels (eg, reduced care access). Similarly, both groups identified facilitators at the patient (eg, enhanced trust), provider (eg, effective communication), encounter (eg, decision support), and facility levels (eg, mitigating access barriers). Integrated services and provider discontinuity were factors identified by clinical stakeholders and Veterans alone, respectively. Our study revealed factors shaping the implementation of SDM at the levels of the patient, provider, encounter, and facility. Findings can inform the development of strategies aimed at implementing SDM for comorbid mTBI and sleep disorders, promoting patient-centered care and enhancing clinical outcomes. Kinney AR, Brenner LA, Nance M, etal. Factors influencing shared decision-making for insomnia and obstructive sleep apnea treatment among Veterans with mild traumatic brain injury. J Clin Sleep Med. 2024;20(5):801-812.

Relationship satisfaction among spouse caregivers of service members and veterans with comorbid mild traumatic brain injury and post-traumatic stress disorder.

This study examined relationship satisfaction and health-related quality of life (HRQOL) among spouse caregivers assisting service members and veterans (SMV) with comorbid uncomplicated mild traumatic brain injury (MTBI) and post-traumatic stress disorder (PTSD). Spouse caregivers (N=205) completed the Couples Satisfaction Index (CSI), 12 HRQOL measures, and the Mayo-Portland Adaptability Inventory 4th Edition (MPAI-4). T-scores were classified as "clinically elevated" using a cutoff of ≥60T. The sample was also classified into "Satisfied" (≥13.5, n=113, 55.0%) or "Dissatisfied" (<13.5, n=92, 44.0%) relationship categories. Using stepwise regression analysis, Anxiety, Family Disruption, Vigilance, Emotional Support, Feeling Trapped, and MPAI-4 Adjustment were identified as the strongest predictors of CSI total scores (p<0.001), accounting for 41.6% of the variance. Squared semi-partial correlations revealed that 18.1% of the variance was shared across all six measures, with 7.8% to 1.5% of unique variance accounted for by each measure separately. When comparing the number of clinically elevated measures simultaneously, the Dissatisfied group consistently had a higher number of clinically elevated scores compared to the Satisfied group (e.g., 3-or-more clinically elevated scores: Dissatisfied=40.2%, Satisfied=8.8%, OR=6.93, H=0.76). Caring for a SMV with comorbid TBI and PTSD can have a profound impact on the spouse caregiver's HRQOL, relationship satisfaction, and family functioning. The findings from the current study continue to support the need for family involvement in the SMV's treatment plan, but more effort is needed to integrate behavioral health treatment that focuses on the family member's own issues into military TBI and PTSD systems of care.

Altered Metabolic Interrelationships in the Cortico-Limbic Circuitry in Military Service Members with Persistent Post-Traumatic Stress Disorder Symptoms Following Mild Traumatic Brain Injury.

Introduction: Comorbid mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) are common in military service members. The aim of this study is to investigate brain metabolic interrelationships in service members with and without persistent PTSD symptoms after mTBI by using 18F-fluorodeoxyglucose (FDG) positron emission tomography. Methods: Service members (n = 408) diagnosed with mTBI were studied retrospectively. Principal component analysis was applied to identify latent metabolic systems, and the associations between metabolic latent systems and self-report measures of post-concussive and PTSD symptoms were evaluated. Participants were divided into two groups based on DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, fourth edition-Text Revision) criteria for PTSD, and structural equation modeling was performed to test a priori hypotheses on metabolic interrelationships among the brain regions in the cortico-limbic circuitry responsible for top-down control and bottom-up emotional processing. The differences in metabolic interrelationships between age-matched PTSD-absent (n = 204) and PTSD-present (n = 204) groups were evaluated. Results: FDG uptake in the temporo-limbic system was positively correlated with post-concussive and hyperarousal symptoms. For the bottom-up emotional processing, the insula and amygdala-hippocampal complex in the PTSD-present group had stronger metabolic interrelationships with the bilateral rostral anterior cingulate, left lingual, right lateral occipital, and left superior temporal cortices, but a weaker relationship with the right precuneus cortex, compared with the PTSD-absent group. For the top-down control, the PTSD-present group had decreased metabolic engagements of the dorsolateral prefrontal cortex on the amygdala. Discussion: Our results suggest altered metabolic interrelationships in the cortico-limbic circuitry in mTBI subjects with persistent PTSD symptoms, which may underlie the pathophysiological mechanisms of comorbid mTBI and PTSD. Impact statement This is the first 18F-fluorodeoxyglucose positron emission tomography study to investigate brain metabolic interrelationships in service members with persistent post-traumatic stress disorder (PTSD) symptoms after mild traumatic brain injury (mTBI). We identified that the temporo-limbic metabolic system was associated with post-concussive and hyperarousal symptoms. Further, brain metabolic interrelationships in the cortico-limbic circuitry were altered in mTBI subjects with significant PTSD symptoms compared with those without them.

A-128 Intraindividual Neurocognitive Variability Is Associated with Poorer Prospective Memory in OEF/OIF/OND Veterans with Comorbid Mild Traumatic Brain Injury History and Current Posttraumatic Stress Disorder

Abstract Objective Mild Traumatic Brain Injury (mTBI) and Posttraumatic Stress Disorder (PTSD) frequently co-occur in service members, and each are associated with increased neurocognitive intraindividual variability (IIV), a proposed indicator of subtle disruptions in executive control, and prospective memory (PM), or “remembering to remember.” The current study sought to examine possible associations between IIV and PM performances among Veterans with comorbid mTBI and PTSD. Methods 46 OEF/OIF/OND Veterans with a history of mTBI and current PTSD enrolled in a VA research study of mTBI completed a standardized neurocognitive battery of 12 measures used to calculate the coefficient of variation (CoV) as an index of IIV, and the Memory for Intentions Screening Test (MIST) as a measure of PM. Veterans also completed clinical questionnaires (i.e., Patient Health Questionnaire-9, PTSD Checklist-Military), and a subset of the sample (n = 31) Veterans completed the Prospective and Retrospective Memory Questionnaire (PRMQ) as a measure of self-reported PM. Results Controlling for age and education, higher CoV was associated with time-based MIST scores (β = −0.02, p = 0.008, η2 = 0.16) and event-based MIST scores (β = −0.02, p = 0.031, η2 = 0.11). CoV was not associated with mood factors in the sample (ps &amp;gt;0.10). In a subset of the total sample, higher CoV was associated with elevated self-reported PM symptoms (r = −0.36, p = 0.046). Conclusions Among Veterans with a history of mTBI and current PTSD, elevated variability of performances across neurocognitive measures was associated with poorer performance-based PM and self-reported PM symptoms. Future studies are needed to examine IIV as a predictor of real-world PM performances (e.g., medication adherence).

Improvement in executive functioning after Goal-Oriented Attentional Self-Regulation training is associated with reduction in PTSD hyperarousal symptoms among veterans with comorbid PTSD and mild TBI

Goal-Oriented Attentional Self-Regulation (GOALS) is a cognitive rehabilitation training program that combines mindfulness-based attention regulation with individualized goal management strategies to improve functioning in daily life after traumatic brain injury (TBI). While not a specific target of GOALS training, previous research has indicated improvements in emotional functioning following GOALS training, specifically symptoms related to depression and posttraumatic stress disorder (PTSD). The current study is based on the hypothesis that improvements in cognitive control processes related to executive functioning and attention after GOALS training generalize to improvements in emotional functioning, thereby resulting in reductions in emotional distress. The current study analyzed archival data from 33 Veteran participants with a confirmed diagnosis of PTSD and a history of mild TBI who received either GOALS training or a psychoeducational intervention matched for time, therapist attention, and participation format. Regression analysis was used to assess the strength of the relationship between improvements in Overall Attention/Executive Functioning and decreases in hyperarousal symptoms associated with PTSD. Results from the regression analysis revealed that improvements in Overall Attention/Executive Functioning after GOALS was significantly associated with reductions in hyperarousal symptoms associated with PTSD (R 2 = 0.26, F (1,15) = 5.01, β = −.51, p < .05). The current findings suggest that cognitive improvements after GOALS training may lead to changes in emotional functioning, resulting in decreased emotional distress. This is important, particularly in VA settings, because the results potentially highlight additional areas of research and focus on the treatment of comorbid mild TBI and PTSD among Veterans.

Brain Amygdala Volume Increases in Veterans and Active-Duty Military Personnel With Combat-Related Posttraumatic Stress Disorder and Mild Traumatic Brain Injury.

To identify amygdalar volumetric differences associated with posttraumatic stress disorder (PTSD) in individuals with comorbid mild traumatic brain injury (mTBI) compared with those with mTBI-only and to examine the effects of intracranial volume (ICV) on amygdala volumetric measures. Marine Corps Base and VA Healthcare System. A cohort of veterans and active-duty military personnel with combat-related mTBI (N = 89). Twenty-nine participants were identified with comorbid PTSD and mTBI. The remaining 60 formed the mTBI-only control group. Structural images of brains were obtained with a 1.5-T MRI scanner using a T1-weighted 3D-IR-FSPGR pulse sequence. Automatic segmentation was performed in Freesurfer. Amygdala volumes with/without normalizations to ICV. The comorbid mTBI/PTSD group had significantly larger amygdala volumes, when normalized to ICV, compared with the mTBI-only group. The right and left amygdala volumes after normalization to ICV were 0.122% ± 0.012% and 0.118% ± 0.011%, respectively, in the comorbid group compared with 0.115% ± 0.012% and 0.112% ± 0.009%, respectively, in the mTBI-only group (corrected P < .05). The ICV normalization analysis performed here may resolve previous literature discrepancies. This is an intriguing structural finding, given the role of the amygdala in the challenging neuroemotive symptoms witnessed in casualties of combat-related mTBI and PTSD.

Dynamics of Segregation and Integration in Directional Brain Networks: Illustration in Soldiers With PTSD and Neurotrauma.

Brain functioning relies on various segregated/specialized neural regions functioning as an integrated-interconnected network (i.e., metastability). Various psychiatric and neurologic disorders are associated with aberrant functioning of these brain networks. In this study, we present a novel framework integrating the strength and temporal variability of metastability in brain networks. We demonstrate that this approach provides novel mechanistic insights which enables better imaging-based predictions. Using whole-brain resting-state fMRI and a graph-theoretic framework, we integrated strength and temporal-variability of complex-network properties derived from effective connectivity networks, obtained from 87 U.S. Army soldiers consisting of healthy combat controls (n = 28), posttraumatic stress disorder (PTSD; n = 17), and PTSD with comorbid mild-traumatic brain injury (mTBI; n = 42). We identified prefrontal dysregulation of key subcortical and visual regions in PTSD/mTBI, with all network properties exhibiting lower variability over time, indicative of poorer flexibility. Larger impairment in the prefrontal-subcortical pathway but not prefrontal-visual pathway differentiated comorbid PTSD/mTBI from the PTSD group. Network properties of the prefrontal-subcortical pathway also had significant association (R2 = 0.56) with symptom severity and neurocognitive performance; and were also found to possess high predictive ability (81.4% accuracy in classifying the disorders, explaining 66–72% variance in symptoms), identified through machine learning. Our framework explained 13% more variance in behaviors compared to the conventional framework. These novel insights and better predictions were made possible by our novel framework using static and time-varying network properties in our three-group scenario, advancing the mechanistic understanding of PTSD and comorbid mTBI. Our contribution has wide-ranging applications for network-level characterization of healthy brains as well as mental disorders.

Non-invasive vagus nerve stimulation for the prevention/treatment of comorbid mild traumatic brain injury and PTSD

Non-invasive vagus nerve stimulation for the prevention/treatment of comorbid mild traumatic brain injury and PTSD

Neurocognitive and Information Processing Biases in Posttraumatic Stress Disorder.

We review recent research addressing neurocognitive and information processing abnormalities in posttraumatic stress disorder (PTSD), including studies informing direction of causality. We additionally consider neurocognition in the context of co-morbid mild traumatic brain injury (TBI) and psychosocial treatments for PTSD. Learning, memory, attention, inhibitory functions, and information processing biases frequently accompany PTSD, reflecting potential bi-directional relationships with PTSD. Although mild TBI is associated with increased risk of PTSD development and maintenance, TBI does not typically contribute significantly to sustained neurocognitive deficits in individuals with PTSD. Whereas better learning and memory is associated with mildly enhanced response to psychosocial interventions, such interventions may also improve neurocognitive performance and can be effectively provided to patients with TBI history. PTSD is associated with cognitive abnormalities in processing both emotionally relevant and emotionally neutral information and, although mild, may underlie some PTSD symptom expression.

A Clinical Evidence-Based Approach to Examine the Effects of mTBI and PTSD Symptoms on ANAM Performance in Recently Deployed Active Duty Soldiers: Results From the Warrior Strong Study.

Service members are frequently diagnosed with comorbid mild traumatic brain injury (mTBI) and posttraumatic stress disorder after returning from Afghanistan and Iraq. Little is known about how mTBI in the postacute and chronic phases combined with current posttraumatic stress disorder symptoms (PTS) affects performance on the Automated Neuropsychological Assessment Metrics, Version 4, Traumatic Brain Injury-Military (ANAM4) battery used by the US military. We examined postdeployment ANAM4 performance using conventional statistical methods, as well as rates of poor performance, below established cutoffs (<10th and ≤2nd percentile). A total of 868 soldiers were assessed for history of mTBI during the most recent deployment, as well as, lifetime mTBI, current PTS, and current pain-related symptoms. The ANAM4 was also administered. Soldiers with PTS and/or mTBI performed worse on ANAM4 relative to controls with those with both conditions performing worst. However, a nontrivial minority (∼10%-30%) of individuals with mTBI, PTS, or both had scores that were at or below the second percentile. Our results illustrate that a combination of mTBI and PTS is associated with worse ANAM4 performance than either condition alone. Furthermore, only a minority of soldiers with any, or both, of the conditions had ANAM deficits. The long-lasting impacts and unique contribution of each condition have yet to be determined.

The Deployment Trauma Phenotype and Employment Status in Veterans of the Wars in Iraq and Afghanistan.

To determine the prevalence of comorbid mild traumatic brain injury (mTBI), posttraumatic stress disorder (PTSD), and depression, termed the deployment trauma phenotype (DTP), and its constituent diagnoses' impact on unemployment status in a national cohort of veterans. Retrospective analysis of the comprehensive TBI evaluation, a Veterans Affairs-wide protocol for assessing TBI, employment status, and psychiatric impressions. The final data set consisted of 48 821 veterans. Frequency of mTBI, PTSD, and depression in isolation and combinations and their association with unemployment status. Age- and education-adjusted risk ratios (RRs) showed that the mTBI-only group was the least likely to be unemployed, RR = 0.65 (0.59-0.71). By contrast, the greatest likelihood of unemployment was associated with membership in the DTP group, RR = 1.45 (1.36-1.56), and the comorbid PTSD and depression group, RR = 1.39 (1.27-1.52). Furthermore, the DTP was nearly 3 times more prevalent (16.4%) in this sample compared with comorbid PTSD and depression (5.7%), indicating that the DTP conveys risk for unemployment to a significantly greater number of individuals. The comorbid and interactive conditions of PTSD, depression, and mTBI, rather than mTBI in isolation, were linked to significant risk for unemployment in this veteran cohort. These findings suggest that multifaceted assessments and interventions to improve postdeployment reintegration are needed.

Controlled Low-Pressure Blast-Wave Exposure Causes Distinct Behavioral and Morphological Responses Modelling Mild Traumatic Brain Injury, Post-Traumatic Stress Disorder, and Comorbid Mild Traumatic Brain Injury-Post-Traumatic Stress Disorder.

The intense focus in the clinical literature on the mental and neurocognitive sequelae of explosive blast-wave exposure, especially when comorbid with post-traumatic stress-related disorders (PTSD) is justified, and warrants the design of translationally valid animal studies to provide valid complementary basic data. We employed a controlled experimental blast-wave paradigm in which unanesthetized animals were exposed to visual, auditory, olfactory, and tactile effects of an explosive blast-wave produced by exploding a thin copper wire. By combining cognitive-behavioral paradigms and ex vivo brain MRI to assess mild traumatic brain injury (mTBI) phenotype with a validated behavioral model for PTSD, complemented by morphological assessments, this study sought to examine our ability to evaluate the biobehavioral effects of low-intensity blast overpressure on rats, in a translationally valid manner. There were no significant differences between blast- and sham-exposed rats on motor coordination and strength, or sensory function. Whereas most male rats exposed to the blast-wave displayed normal behavioral and cognitive responses, 23.6% of the rats displayed a significant retardation of spatial learning acquisition, fulfilling criteria for mTBI-like responses. In addition, 5.4% of the blast-exposed animals displayed an extreme response in the behavioral tasks used to define PTSD-like criteria, whereas 10.9% of the rats developed both long-lasting and progressively worsening behavioral and cognitive "symptoms," suggesting comorbid PTSD-mTBI-like behavioral and cognitive response patterns. Neither group displayed changes on MRI. Exposure to experimental blast-wave elicited distinct behavioral and morphological responses modelling mTBI-like, PTSD-like, and comorbid mTBI-PTSD-like responses. This experimental animal model can be a useful tool for elucidating neurobiological mechanisms underlying the effects of blast-wave-induced mTBI and PTSD and comorbid mTBI-PTSD.

Three Scoring Approaches to the Neurobehavioral Symptom Inventory for Measuring Clinical Change in Service Members Receiving Intensive Treatment for Combat-Related mTBI.

To examine the use of the Neurobehavioral Symptom Inventory to measure clinical changes over time in a population of US service members undergoing treatment of mild traumatic brain injury and comorbid psychological health conditions. A 4-week, 8-hour per day, intensive, outpatient, interdisciplinary, comprehensive treatment program at the National Intrepid Center of Excellence in Bethesda, Maryland. Three hundred fourteen active-duty service members being treated for combat-related comorbid mild traumatic brain injury and psychological health conditions. Repeated-measures, retrospective analysis of a single-group using a pretest-posttest treatment design. Three Neurobehavioral Symptom Inventory scoring methods: (1) a total summated score, (2) the 3-factor method, and (3) the 4-factor method (with and without orphan items). All 3 scoring methods yielded statistically significant within-subject changes between admission and discharge. The evaluation of effect sizes indicated that the 3 different Neurobehavioral Symptom Inventory scoring methods were comparable. Findings indicate that the different scoring methods all have potential for assessing clinical changes in symptoms for groups of patients undergoing treatment, with no clear advantage with any one method.

Neurobehavioral, neuropathological and biochemical profiles in a novel mouse model of co-morbid post-traumatic stress disorder and mild traumatic brain injury.

Co-morbid mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) has become the signature disorder for returning combat veterans. The clinical heterogeneity and overlapping symptomatology of mTBI and PTSD underscore the need to develop a preclinical model that will enable the characterization of unique and overlapping features and allow discrimination between both disorders. This study details the development and implementation of a novel experimental paradigm for PTSD and combined PTSD-mTBI. The PTSD paradigm involved exposure to a danger-related predator odor under repeated restraint over a 21 day period and a physical trauma (inescapable footshock). We administered this paradigm alone, or in combination with a previously established mTBI model. We report outcomes of behavioral, pathological and biochemical profiles at an acute timepoint. PTSD animals demonstrated recall of traumatic memories, anxiety and an impaired social behavior. In both mTBI and combination groups there was a pattern of disinhibitory like behavior. mTBI abrogated both contextual fear and impairments in social behavior seen in PTSD animals. No major impairment in spatial memory was observed in any group. Examination of neuroendocrine and neuroimmune responses in plasma revealed a trend toward increase in corticosterone in PTSD and combination groups, and an apparent increase in Th1 and Th17 proinflammatory cytokine(s) in the PTSD only and mTBI only groups respectively. In the brain there were no gross neuropathological changes in any groups. We observed that mTBI on a background of repeated trauma exposure resulted in an augmentation of axonal injury and inflammatory markers, neurofilament L and ICAM-1 respectively. Our observations thus far suggest that this novel stress-trauma-related paradigm may be a useful model for investigating further the overlapping and distinct spatio-temporal and behavioral/biochemical relationship between mTBI and PTSD experienced by combat veterans.

Neuropsychological functioning of combat veterans with posttraumatic stress disorder and mild traumatic brain injury

This study examined the neuropsychological performance of 125 outpatient Operation Enduring Freedom/Operation Iraqi Freedom combat veterans with posttraumatic stress disorder (PTSD) and nonacute mild traumatic brain injury (TBI) (n = 66) and PTSD (n = 59) across multiple cognitive domains to determine whether mild TBI results in greater impairment among those with PTSD. Profile analyses revealed that veterans with PTSD and mild TBI did not differ significantly from those with just PTSD across domains, suggesting that comorbid mild TBI does not result in an additive effect. A norms-based comparison also revealed that neither group demonstrated impaired performance on any of the objective neuropsychological measures examined. However, both groups endorsed moderately elevated symptoms of depression and anxiety, indicating that comorbid psychopathology may contribute to subjective cognitive complaints.

Relationship Between Processing Speed and Executive Functioning Performance Among OEF/OIF Veterans

Comorbid mild traumatic brain injury (mTBI) with posttraumatic stress disorder (PTSD) is a common clinical presentation among troops returning from Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF). This study examined processing speed and executive functioning in a sample of OEF/OIF veterans who had sustained mTBI, a subset of whom also had comorbid PTSD. Fifty-three OEF/OIF veterans with a history of mTBI completed Wechsler Adult Intelligence Scale-III Symbol Search and Digit Symbol-Coding subscales, Stroop Word, color and color-word trials, and Trail Making Test, Parts A and B as part of a comprehensive neuropsychological test battery. Excluding from analysis those who scored poorly on effort testing, multiple regression showed that measures of processing speed accounted for 43% of the variance in performance on the Trail Making Test, Part B and 50% of the variance in performance on the Stroop task. Significant differences in processing speed and executive functioning were found on the basis of presence of comorbid PTSD. Stroop Color (F = 9.27, df = 52, P < .004) and Stroop Color Word (F = 7.19, df = 52, P < .01) scores differed significantly between the groups. Those having comorbid PTSD (+TBI/+PTSD) scored significantly poorer than the mTBI-only group (+TBI/-PTSD). Implications for treatment of the comorbid conditions are discussed.

Traumatic brain injury research state-of-the-art conference

Joel Kupersmith, MD; Alex K. Ommaya, ScD; Michael E. Selzer, MD, PhD, FRCP; Robert L. Ruff, MD, PhD; Henry L. Lew, MD, PhD The Department of Veterans Affairs (VA), treating more than 5.5 million veterans annually [1], manages the largest integrated healthcare system in the nation and is committed to providing veterans with the highest quality healthcare. Conflicts in Iraq and Afghanistan (Operation Iraqi Freedom/Operation Enduring Freedom [OIF/OEF]) have resulted in an influx of new veterans to the VA health system. From 2002 to 2008, 945,423 OIF/OEF veterans left active duty, with 42 percent (400,304) obtaining VA healthcare [2]. The challenge that this trend presents to the maintenance of the VA’s high standard of care is compounded by the fact that many are returning home with complex injuries, such as traumatic brain injury (TBI), frequently referred to as the signature injury of modern warfare. Many knowledge gaps exist regarding TBI. Accordingly, in late April 2008, the VA’s Office of Research and Development (ORD) sponsored a state-of-theart (SOTA) conference to advance the knowledge base in TBI. This SOTA conference identified what we know and what we need to know about TBI, from the basic science to diagnosis, evidence-based treatment, acute management, and long-term rehabilitation for TBI. The goal was to recommend for all stakeholders further research on the development of clinical practice guidelines, policies, or processes that would improve quality and outcomes of TBI care. ORD assembled a prestigious planning committee. The planning committee developed the objectives for the SOTA conference and commissioned background articles to stimulate discussions among the 100 invited experts at the conference. Subject matter experts wrote the background articles and submitted them for peer review. Of those articles, 17 passed the rigorous review process and are published here in this special issue of Journal Rehabilitation Research and Development (JRRD). The articles cover various aspects of TBI and its comorbidities. Topics include— 1. Acute clinical care for TBI: Continuation of care from the battlefield to the Department of Defense (DOD) and the VA. 2. Pathology of blast-related brain injury. 3. Infectious complications in OIF/OEF veterans with TBI. 4. Posttraumatic epilepsy. 5. Prevalence of chronic pain, posttraumatic stress disorder (PTSD), and persistent postconcussive symptoms in OIF/OEF veterans: The polytrauma clinical triad. 6. Treating veterans with comorbid mild TBI (mTBI) and PTSD. 7. Advances in neuroimaging of TBI and PTSD. 8. Approaches to war-related mild to moderate TBI.