Discriminating Mild Traumatic Brain Injury and Posttraumatic Stress Disorder Using Latent Neuroimaging and Neuropsychological Profiles in Active-Duty Military Service Members.

OBJECTIVE: Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) commonly occur among military Service Members and Veterans and have heterogenous, but also overlapping symptom presentations, which often complicate the diagnoses of underlying impairments and development of effective treatment plans. Thus, we sought to examine whether the combination of whole brain gray matter (GM) and white matter (WM) structural measures with neuropsychological performance can aid in the classification of military personnel with mTBI and PTSD. METHODS: Active-Duty US Service Members ( n = 156; 87.8% male) with a history of mTBI, PTSD, combined mTBI+PTSD, or orthopedic injury completed a neuropsychological battery and T1- and diffusion-weighted structural neuroimaging. Cortical, subcortical, ventricular, and WM volumes and whole brain fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were calculated. Latent profile analyses were performed to determine how the GM and WM indicators, together with neuropsychological indicators, classified individuals. RESULTS: For both GM and WM, respectively, a 4-profile model was the best fit. The GM model identified greater ventricular volumes in Service Members with cognitive symptoms, including those with a diagnosis of mTBI, either alone or with PTSD. The WM model identified reduced FA and elevated RD in those with psychological symptoms, including those with PTSD or mTBI and comorbid PTSD. However, contrary to expectation, a global neural signature unique to those with comorbid mTBI and PTSD was not identified. CONCLUSIONS: The findings demonstrate that neuropsychological performance alone is more robust in differentiating Active-Duty Service Members with mTBI and PTSD, whereas global neuroimaging measures do not reliably differentiate between these groups.

Research Letter: Long-Term Outcomes Following Cognitive Rehabilitation for Mild Traumatic Brain Injury: A 5-Year Follow-Up of a Cohort From the SCORE Randomized Clinical Trial.

OBJECTIVE: To examine the functioning of military service members 5 years after completing a randomized controlled trial (RCT) of cognitive rehabilitation for mild traumatic brain injury (mTBI). SETTING: Home-based telephonic interview and internet-based self-ratings. PARTICIPANTS: Sixty-nine of the 126 (55%) active-duty service members who were enrolled in a 4-arm RCT of cognitive rehabilitation 3 to 24 months after mTBI and were successfully contacted by phone 5 years later. Original and 5-year follow-up participants in each of 4 RCT treatment arms included: psychoeducation ( n = 32 original, n = 17 follow-up), computer ( n = 30 original, n = 11 follow-up), therapist-directed ( n = 30 original, n = 23 follow-up), integrated ( n = 34 original, n = 18 follow-up). DESIGN: Inception cohort evaluated 5 years after completion of an RCT of cognitive rehabilitation. MAIN MEASURES: Postconcussion symptoms (Neurobehavioral Symptom Inventory total score), psychological distress (Symptom Checklist-90-revised Global Severity Index score), and functional cognitive/behavioral symptoms (Key Behaviors Change Inventory total average score). RESULTS: Participants' postconcussive symptoms and psychological distress improved at the 5-year follow-up. Functional cognitive/behavioral symptoms were not significantly improved, but therapeutic gains were maintained across time, to 5 years after completing the RCT. CONCLUSION: In this sample of military personnel, postconcussive symptoms and psychological distress significantly improved from posttreatment to 5 years after cognitive rehabilitation, regardless of treatment arm. Functional cognitive/behavioral symptoms significantly improved with treatment while treatment gains were maintained at the 5-year follow-up. Replication of these results with a larger sample and interim data between 18 weeks and 5 years post-treatment is needed.

The impact of prior head injury on outcomes following group and individual cognitive processing therapy among military personnel.

This study examined the impact of a history of head injury (HHI) on posttraumatic stress disorder (PTSD) and depression symptoms in active duty military personnel following group and individual cognitive processing therapy (CPT). Data for these secondary analyses were drawn from a clinical trial comparing group and individual CPT. Service members (N = 268, 91.0% male) were randomized to 12 sessions of group (n = 133) or individual (n = 135) CPT. Most participants (57.1%) endorsed a deployment-related HHI, 92.8% of whom reported currently experiencing symptoms (CES) related to the head injury (i.e., HHI/CES). Patients classified as non-HHI/CES demonstrated large, significant improvements in PTSD symptom severity in both individual and group therapy, ds = 1.1, p < .001. Patients with HHI/CES status showed similar significant improvements when randomized to individual CPT, d = 1.4, p < .001, but did not demonstrate significant improvements when randomized to group CPT, d = 0.4, p = .060. For participants classified as HHI/CES, individual CPT was significantly superior to group CPT, d = 0.98, p = .003. Symptoms of depression improved following treatment, with no significant differences by treatment delivery format or HHI/CES status. The findings of this clinical trial subgroup study demonstrate evidence that group CPT is less effective than individual CPT for service members classified as HHI/CES. The results suggest that HHI/CES status may be important to consider in selecting patients for group or individual CPT; additional research is needed to confirm the clinical implications of these findings.

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

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

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

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

Patient Attribution of Posttraumatic Symptoms to Brain Injury Versus PTSD in Military-Related Mild TBI.

OBJECTIVE: Persistent cognitive, somatic, and neuropsychiatric symptoms following mild traumatic brain injury (TBI) are influenced by posttraumatic stress disorder (PTSD), particularly in military patients. The authors evaluated the degree to which military service members with a history of mild TBI attributed posttraumatic symptoms to TBI versus PTSD. METHODS: Service members (N=372) with mild TBI were surveyed about the severity of posttraumatic symptoms across four symptom clusters (cognitive, affective, somatosensory, and vestibular) with the Neurobehavioral Symptom Inventory (NSI). Participants rated the degree to which they believed TBI, PTSD, or other conditions contributed to their symptoms. Differences in cognitive, affective, somatosensory, and vestibular symptom severity were evaluated across participants with TBI, PTSD, or combined TBI-PTSD attribution. Logistic regression was used to evaluate the association between symptom profiles and attribution. RESULTS: Participants attributed symptoms mostly to TBI, followed by insufficient sleep, PTSD, chronic pain, depression, and deployment-readjustment stress. PTSD and combined TBI-PTSD attribution were associated with higher total NSI scores (39.5 and 51.6, respectively), compared with TBI attribution only (31.4) (F=29.08, df=3, 358, p<0.01), as well as higher scores in every symptom category. More severe affective symptoms were associated with decreased odds of TBI attribution (odds ratio=0.90, 95% CI=0.83-0.97) and increased odds of PTSD attribution (odds ratio=1.14, 95% CI=1.03-1.26). A PTSD diagnosis was highly associated with PTSD attribution (odds ratio=2.44, 95% CI=1.07-5.58). CONCLUSIONS: The nature and severity of posttraumatic symptoms appear to play a role in patient beliefs about the causes of symptoms, whether from TBI or PTSD.

Self-efficacy predicts response to cognitive rehabilitation in military service members with post-concussive symptoms.

This study examined whether self-efficacy differentiated treatment responders from non-responders in a trial of cognitive rehabilitation (CR) for postconcussive symptoms. 126 service members with mild TBI seen on average 9.5 months since injury completed one of four cognitive rehabilitation treatments for 6 weeks. The four treatment arms were: (1) Psychoeducation control, (2) Self-administered computerized CR, (3) Interdisciplinary CR, and (4) Interdisciplinary CR integrated with CBT. Outcome was assessed across time (baseline, and 6, 12, and 18 weeks post-treatment) for three domains: psychological (Symptom Checklist-90-Revised; SCL-90-R), cognitive (Paced Auditory Serial Addition Test; PASAT), and functional/behavioural (Key Behaviors Change Inventory; KBCI). Mixed model ANOVAs tested for self-efficacy differences across time in treatment responders versus non-responders, as defined by reliable change indices. A significant interaction was found on the SCL-90 such that responders had increasing self-efficacy with respect to psychological symptoms across four time points, whereas non-responders' self-efficacy did not change. Perceived self-efficacy at the beginning of treatment was associated with treatment engagement within the psychological domain for responders only, suggesting a mediating role in treatment outcome. Overall, results suggest that increasing patients' level of self-efficacy may be important for successful treatment of psychological distress in those with remote concussion.

Postconcussion Symptom Reporting After Mild Traumatic Brain Injury in Female Service Members: Impact of Gender, Posttraumatic Stress Disorder, Severity of Injury, and Associated Bodily Injuries.

OBJECTIVE: Examine effects of diagnostically relevant posttraumatic stress disorder (PTSD) symptoms, mild traumatic brain injury (TBI) severity, and associated bodily injury severity on postconcussion symptom reporting in female service members (SM) compared with a matched sample of male SM. SETTING: Six US military medical treatment facilities. PARTICIPANTS: A total of 158 SM (79 females, 79 males) evaluated within 30 months after mild TBI. Men and women were matched by age, days postinjury, PTSD symptom status, mild TBI severity, and bodily injury severity. All passed a measure of symptom validity. DESIGN: Compare reported postconcussion symptoms for men and women stratified by PTSD diagnostic symptoms (present/absent), mild TBI severity (alteration of consciousness/loss of consciousness), and bodily injury severity (mild/moderate-severe). MAIN MEASURES: Neurobehavioral Symptom Inventory, PTSD Checklist, Abbreviated Injury Scale. RESULTS: Overall postconcussion symptom reporting increased with PTSD but did not significantly differ based on severity of mild TBI or associated bodily injury. Females reported more somatosensory and/or vestibular symptoms than males under some circumstances. Females in the PTSD-Present group, Alteration of Consciousness Only group, and Moderate-Severe Bodily Injury group reported more somatosensory symptoms than males in those groups. Females in the Alteration of Consciousness Only group and Minor Bodily Injury group reported more vestibular symptoms than males in those groups. CONCLUSION: Diagnostically relevant PTSD symptoms, mild TBI severity, and bodily injury severity differentially impact somatosensory and vestibular postconcussion symptom reporting for male and female SM after mild TBI. Controlling for PTSD and symptom validity resulted in fewer gender-based differences in postconcussive symptoms than previously demonstrated in the literature.

Neuropsychological Performance and Subjective Symptom Reporting in Military Service Members With a History of Multiple Concussions: Comparison With a Single Concussion, Posttraumatic Stress Disorder, and Orthopedic Trauma.

OBJECTIVE: To examine differences in objective neurocognitive performance and subjective cognitive symptoms in individuals with a history of a single concussion, multiple concussions, orthopedic injuries, and posttraumatic stress disorder (PTSD). METHOD: Participants included 116 military service members who sustained a mild traumatic brain injury (mTBI) during combat deployment. Subjects were subdivided into groups based on concussion frequency: a single concussion (n = 42), 2 concussions (n = 21), and 3 or more concussions (n = 53). Eighty-one subjects sustained an orthopedic injury (n = 60) during deployment or were diagnosed with PTSD (n = 21), but had no history of mTBI. Subjects completed a battery of neuropsychological tests and self-report measures of postconcussive symptoms, PTSD symptoms, and psychopathology. RESULTS: No differences were found among the concussion groups on a composite neuropsychological measure. The PTSD group had the highest number of symptom complaints, with the 2-concussion and 3-plus-concussion groups being most similar to the PTSD group. The concussion groups showed a nonsignificant pattern of increasing distress with increasing number of concussions. CONCLUSIONS: The current findings are consistent with meta-analytic results showing no differential effect on neuropsychological functioning due to multiple concussions. Results also support the burden of adversity hypothesis suggesting increasing symptom levels with increasing psychological or physically traumatic exposures.

Relationships Between Subcortical Shape Measures and Subjective Symptom Reporting in US Service Members With Mild Traumatic Brain Injury.

OBJECTIVE: To assess interactions of subcortical structure with subjective symptom reporting associated with mild traumatic brain injury (mTBI), using advanced shape analysis derived from volumetric MRI. PARTICIPANTS: Seventy-six cognitively symptomatic individuals with mTBI and 59 service members sustaining only orthopedic injury. DESIGN: Descriptive cross-sectional study. MAIN MEASURES: Self-report symptom measures included the PTSD Checklist-Military, Neurobehavioral Symptom Inventory, and Symptom Checklist-90-Revised. High-dimensional measures of shape characteristics were generated from volumetric MRI for 7 subcortical structures in addition to standard volume measures. RESULTS: Several significant interactions between group status and symptom measures were observed across the various shape measures. These interactions were revealed in the right thalamus and globus pallidus for each of the shape measures, indicating differences in structure thickness and expansion/contraction for these regions. No relationships with volume were observed. CONCLUSION: Results provide evidence for the sensitivity of shape measures in differentiating symptomatic mTBI individuals from controls, while volumetric measures did not exhibit this same sensitivity. Disruptions to thalamic nuclei identified here highlight the role of the thalamus in the spectrum of symptoms associated with mTBI. Additional work is needed to prospectively, and longitudinally, assess these measures along with cognitive performance and advanced multimodal imaging methods to extend the utility of shape analysis in relation to functional outcomes in this population.

Diffusion Imaging Findings in US Service Members With Mild Traumatic Brain Injury and Posttraumatic Stress Disorder.

OBJECTIVE: Use diffusion tensor imaging to investigate white matter microstructure attributable to mild TBI (mTBI) and/or posttraumatic stress disorder (PTSD). PARTICIPANTS: Twenty-seven individuals with mTBI only, 16 with PTSD only, 42 with mTBI + PTSD, and 43 service members who sustained orthopedic injury. DESIGN: Descriptive cross-sectional study. MAIN MEASURES: Clinical diffusion tensor imaging sequence to assess fractional anisotropy, mean, axial, and radial diffusivity within selected regions of interest. RESULTS: Corrected analyses revealed a pattern of lower white matter integrity in the PTSD group for several scalar metrics. Regions affected included primarily right hemisphere areas of the internal capsule. These differences associated with the PTSD only cohort were observed in relation to all 3 comparison groups, while the mTBI + PTSD group did not exhibit any notable pattern of white matter abnormalities. CONCLUSION: Results suggest that lower resolution scan sequences are sensitive to post-acute abnormalities associated with PTSD, particularly in the right hemisphere. In addition, these findings suggest that ongoing PTSD symptoms are associated with differences in white matter diffusion that are more readily detected in a clinical scan sequence than mTBI abnormalities. Future studies are needed to prospectively assess service members prior to onset of injury to verify this pattern of results.

Cognitive Rehabilitation for Military Service Members With Mild Traumatic Brain Injury: A Randomized Clinical Trial.

OBJECTIVE: To compare cognitive rehabilitation (CR) interventions for mild traumatic brain injury (mTBI) with standard of care management, including psychoeducation and medical care for noncognitive symptoms. SETTING: Military medical center. PARTICIPANTS: A total of 126 service members who received mTBI from 3 to 24 months before baseline evaluation and reported ongoing cognitive difficulties. INTERVENTIONS: Randomized clinical trial with treatment outcomes assessed at baseline, 3-week, 6-week, 12-week, and 18-week follow-ups. Participants were randomly assigned to one of four 6-week treatment arms: (1) psychoeducation, (2) computer-based CR, (3) therapist-directed manualized CR, and (4) integrated therapist-directed CR combined with cognitive-behavioral psychotherapy (CBT). Treatment dosage was constant (10 h/wk) for intervention arms 2 to 4. MEASURES: Paced Auditory Serial Addition Test (PASAT); Symptom Checklist-90 Revised (SCL-90-R); Key Behaviors Change Inventory (KBCI). RESULTS: No differences were noted between treatment arms on demographics, injury-related characteristics, or psychiatric comorbidity apart from education, with participants assigned to the computer arm having less education. Using mixed-model analysis of variance, all 4 treatment groups showed a significant improvement over time on the 3 primary outcome measures. Treatment groups showed equivalent improvement on the PASAT. The therapist-directed CR and integrated CR treatment groups had better KBCI outcomes compared with the psychoeducation group. Improvements on primary outcome measures during treatment were maintained at follow-up with no differences among arms. CONCLUSIONS: Both therapist-directed CR and integrated CR with CBT reduced functional cognitive symptoms in service members after mTBI beyond psychoeducation and medical management alone.

Profile Analysis of the Neurobehavioral and Psychiatric Symptoms Following Combat-Related Mild Traumatic Brain Injury: Identification of Subtypes.

OBJECTIVE: To explore the taxonomy of combat-related mild traumatic brain injury (mTBI) based on symptom patterns. PARTICIPANTS: Up to 1341 military personnel who experienced a combat-related mTBI within 2 years of evaluation. MEASURES: Neurobehavioral Symptom Inventory and PTSD Checklist-Civilian Version (PCL-C). RESULTS: Cluster analysis revealed the following 4 subtypes: primarily psychiatric (posttraumatic stress disorder) group, a cognitive group, a mixed symptom group, and a good recovery group. The posttraumatic stress disorder cluster (21.9% of the sample) reported symptoms related to hyperarousal and dissociation/depression with few complaints related to cognition or headaches. The cognitive group (21.5% of the sample) had primarily cognitive and headache complaints with few mood symptoms. The mixed profile cluster included 18.6% of the sample and was characterized by a combination of mood complaints (hyperarousal and dissociation/depression), cognitive complaints, and headaches. The largest cluster (37.8% of the sample) had an overall low symptom profile and was labeled the "good recovery" group. CONCLUSIONS: The results support a unique taxonomy for combat-related mTBI. The clinical differences among these subtypes indicate a need for unique treatment resources and programs.

Screening for postdeployment conditions: development and cross-validation of an embedded validity scale in the neurobehavioral symptom inventory.

OBJECTIVE: To develop and cross-validate internal validity scales for the Neurobehavioral Symptom Inventory (NSI). PARTICIPANTS: Four existing data sets were used: (1) outpatient clinical traumatic brain injury (TBI)/neurorehabilitation database from a military site (n = 403), (2) National Department of Veterans Affairs TBI evaluation database (n = 48 175), (3) Florida National Guard nonclinical TBI survey database (n = 3098), and (4) a cross-validation outpatient clinical TBI/neurorehabilitation database combined across 2 military medical centers (n = 206). RESEARCH DESIGN: Secondary analysis of existing cohort data to develop (study 1) and cross-validate (study 2) internal validity scales for the NSI. MAIN MEASURES: The NSI, Mild Brain Injury Atypical Symptoms, and Personality Assessment Inventory scores. RESULTS: Study 1: Three NSI validity scales were developed, composed of 5 unusual items (Negative Impression Management [NIM5]), 6 low-frequency items (LOW6), and the combination of 10 nonoverlapping items (Validity-10). Cut scores maximizing sensitivity and specificity on these measures were determined, using a Mild Brain Injury Atypical Symptoms score of 8 or more as the criterion for invalidity. Study 2: The same validity scale cut scores again resulted in the highest classification accuracy and optimal balance between sensitivity and specificity in the cross-validation sample, using a Personality Assessment Inventory Negative Impression Management scale with a T score of 75 or higher as the criterion for invalidity. CONCLUSIONS: The NSI is widely used in the Department of Defense and Veterans Affairs as a symptom-severity assessment following TBI, but is subject to symptom overreporting or exaggeration. This study developed embedded NSI validity scales to facilitate the detection of invalid response styles. The NSI Validity-10 scale appears to hold considerable promise for validity assessment when the NSI is used as a population-screening tool.

Lifetime Blast Exposure Is Not Related to White Matter Integrity in Service Members and Veterans With and Without Uncomplicated Mild Traumatic Brain Injury.

This study examines the impact of lifetime blast exposure on white matter integrity in service members and veterans (SMVs). Participants were 227 SMVs, including those with a history of mild traumatic brain injury (mTBI; n = 124), orthopedic injury controls (n = 58), and non-injured controls (n = 45), prospectively enrolled in a Defense and Veterans Brain Injury Center (DVBIC)/Traumatic Brain Injury Center of Excellence (TBICoE) study. Participants were divided into three groups based on number of self-reported lifetime blast exposures: none (n = 53); low (i.e., 1-9 blasts; n = 81); and high (i.e., ≥10 blasts; n = 93). All participants underwent diffusion tensor imaging (DTI) at least 11 months post-injury. Tract-of-interest (TOI) analysis was applied to investigate fractional anisotropy and mean, radial, and axial diffusivity (AD) in left and right total cerebral white matter as well as 24 tracts. Benjamini-Hochberg false discovery rate (FDR) correction was used. Regressions investigating blast exposure and mTBI on white matter integrity, controlling for age, revealed that the presence of mTBI history was associated with lower AD in the bilateral superior longitudinal fasciculus and arcuate fasciculus and left cingulum (ßs = -0.255 to -0.174; ps < 0.01); however, when non-injured controls were removed from the sample (but orthopedic injury controls remained), these relationships were attenuated and did not survive FDR correction. Regression models were rerun with modified post-traumatic stress disorder (PTSD) diagnosis added as a predictor. After FDR correction, PTSD was not significantly associated with white matter integrity in any of the models. Overall, there was no relationship between white matter integrity and self-reported lifetime blast exposure or PTSD.

Comparing resting-state connectivity of working memory networks in U.S. Service members with mild traumatic brain injury and posttraumatic stress disorder.

Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) are prevalent among military populations, and both have been associated with working memory (WM) impairments. Previous resting-state functional connectivity (rsFC) research conducted separately in PTSD and mTBI populations suggests that there may be similar and distinct abnormalities in WM-related networks. However, no studies have compared rsFC of WM brain regions in participants with mTBI versus PTSD. We used resting-state fMRI to investigate rsFC of WM networks in U.S. Service Members (n = 127; ages 18-59) with mTBI only (n = 46), PTSD only (n = 24), and an orthopedically injured (OI) control group (n = 57). We conducted voxelwise rsFC analyses with WM brain regions to test for differences in WM network connectivity in mTBI versus PTSD. Results revealed reduced rsFC between ventrolateral prefrontal cortex (vlPFC), lateral premotor cortex, and dorsolateral prefrontal cortex (dlPFC) WM regions and brain regions in the dorsal attention and somatomotor networks in both mTBI and PTSD groups versus controls. When compared to those with mTBI, individuals with PTSD had lower rsFC between both the lateral premotor WM seed region and middle occipital gyrus as well as between the dlPFC WM seed region and paracentral lobule. Interestingly, only vlPFC connectivity was significantly associated with WM performance across the samples. In conclusion, we found primarily overlapping patterns of reduced rsFC in WM brain regions in both mTBI and PTSD groups. Our finding of decreased vlPFC connectivity associated with WM is consistent with previous clinical and neuroimaging studies. Overall, these results provide support for shared neural substrates of WM in individuals with either mTBI or PTSD.

Association between combat stress and post-concussive symptom reporting in OEF/OIF service members with mild traumatic brain injuries.

OBJECTIVE: The relationship between combat stress and post-concussive symptoms in service members with mild traumatic brain injuries (mTBI) is poorly understood. It was hypothesized that the co-occurrence of combat stress would have a significant effect on the severity of post-concussive complaints, specifically on emotional and cognitive symptoms. METHODS: Four hundred and seventy-two combat-deployed service members with mTBI completed self-report inventories of post-traumatic stress and post-concussive symptoms. Two groups were formed based on post-traumatic stress symptoms (High Combat Stress and Low Combat Stress). RESULTS: A 3-8-fold increase in post-concussive symptoms was observed when comparing the High and Low Combat Stress Groups. Elevations in post-concussive symptom reporting were not limited to emotional and/or cognitive symptoms, but rather were inclusive of all measured post-concussive symptoms. CONCLUSIONS: The findings of the present study suggest that non-brain injury-related factors, such as high-levels of combat stress, may impact post-concussive symptom reporting in this population, further confounding the accuracy of the post-concussion syndrome (PCS) diagnosis. Considerable caution should be exercised in making the diagnosis of PCS in concussed service members with co-occurring combat-stress disorders.

Number of Concussions Does Not Affect Treatment Response to Cognitive Rehabilitation Interventions Following Mild TBI in Military Service Members.

OBJECTIVE: The study objective was to determine whether number of concussions would affect symptom improvement following cognitive rehabilitation (CR) interventions. METHOD: Service members (N = 126) with concussion history completed a 6-week randomized control trial of CR interventions. Participants were stratified based on self-reported lifetime concussion frequency. Outcome measures included the Paced Auditory Serial Addition Test (PASAT), the Global Severity Index (GSI) from the Symptom Checklist-90-Revised, and the Key Behaviors Change Inventory (KBCI). RESULTS: Mixed-model analyses of variance revealed a significant main effect for time on cognitive, psychological, and neurobehavioral functioning. A significant main effect for the number of concussions was observed for GSI and KBCI, but not PASAT. Interactions between the number of concussions and time were not significant for any of the outcome variables. CONCLUSIONS: Over the 6-week interval, improvements were found for all participants across all outcome measures. Number of concussions did not affect improvements over time.

Distinct patterns of resting-state connectivity in U.S. service members with mild traumatic brain injury versus posttraumatic stress disorder.

Mild traumatic brain injury (mTBI) is highly prevalent in military populations, with many service members suffering from long-term symptoms. Posttraumatic stress disorder (PTSD) often co-occurs with mTBI and predicts worse clinical outcomes. Functional neuroimaging research suggests there are both overlapping and distinct patterns of resting-state functional connectivity (rsFC) in mTBI versus PTSD. However, few studies have directly compared rsFC of cortical networks in military service members with these two conditions. In the present study, U.S. service members (n = 137; ages 19-59; 120 male) underwent resting-state fMRI scans. Participants were divided into three study groups: mTBI only, PTSD only, and orthopedically injured (OI) controls. Analyses investigated group differences in rsFC for cortical networks: default mode (DMN), frontoparietal (FPN), salience, somatosensory, motor, auditory, and visual. Analyses were family-wise error (FWE) cluster-corrected and Bonferroni-corrected for number of network seeds regions at the whole brain level (pFWE < 0.002). Both mTBI and PTSD groups had reduced rsFC for DMN and FPN regions compared with OI controls. These group differences were largely driven by diminished connectivity in the PTSD group. rsFC with the middle frontal gyrus of the FPN was increased in mTBI, but decreased in PTSD. Overall, these results suggest that PTSD symptoms may have a more consistent signal than mTBI. Our novel findings of opposite patterns of connectivity with lateral prefrontal cortex highlight a potential biomarker that could be used to differentiate between these conditions.

Single-Item Versus Multiple-Item Headache Ratings in Service Members Seeking Treatment for Brain Injury.

INTRODUCTION: Headaches are the most common complaint after traumatic brain injury (TBI) and a significant cause of morbidity and disability among military personnel. Currently, there are a several measures which can assess headache disability, but there is a significant burden to assess each individual symptom given this heterogeneous polymorbid population. The objective of this proposed study was to validate the single headache item from the Neurobehavioral Symptom Inventory (NSI) compared to the 6-item Headache Impact Test (HIT-6). MATERIALS AND METHODS: Participants included consecutive treatment-seeking outpatients at the Brain Injury Rehabilitation Service at the Brooke Army Medical Center from August 2007 to January 2010 who were administered a battery of assessment measures at initial intake, as part of usual care. Archival record review was conducted using procedures approved by the local Institutional Review Board. Inclusionary criteria included completion of both the HIT-6 and NSI. Participants with a cut-off score of >22 on the NSI Validity-10 were excluded in a post hoc analysis to validate findings among those who passed validity screen. RESULTS: The Pearson correlation between the single-item NSI headache measure and the HIT-6 revealed at least 64% shared variance in this military sample (r = 0.8, p < 0.001), indication a high association between the two measures. CONCLUSION: The NSI single-item headache measure adequately captured headache severity in this military cohort. Use of the single-item NSI headache measure may minimize survey burden on participants whose primary complaint is not headaches, or who present with multiple symptoms. Future studies are needed to validate the single-item headache measure in other samples.