Contextual Effects of Traumatic Brain Injury on the Connectome: Differential Effects of Deployment- and Non-Deployment-Acquired Injuries.

OBJECTIVE: To identify differential effects of mild traumatic brain injury (TBI) occurring in a deployment or nondeployment setting on the functional brain connectome. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: In total, 181 combat-exposed veterans of the wars in Iraq and Afghanistan ( n = 74 with deployment-related mild TBI, average time since injury = 11.0 years, SD = 4.1). DESIGN: Cross-sectional observational study. MAIN MEASURES: Mid-Atlantic MIRECC (Mid-Atlantic Mental Illness Research, Education, and Clinical Center) Assessment of TBI, Clinician-Administered PTSD Scale, connectome metrics. RESULTS: Linear regression adjusting for relevant covariates demonstrates a significant ( P < .05 corrected) association between deployment mild TBI with reduced global efficiency (nonstandardized ß = -.011) and degree of the K-core (nonstandardized ß = -.79). Nondeployment mild TBI was significantly associated with a reduced number of modules within the connectome (nonstandardized ß = -2.32). Finally, the interaction between deployment and nondeployment mild TBIs was significantly ( P < .05 corrected) associated with increased mean (nonstandardized ß = 9.92) and mode (nonstandardized ß = 14.02) frequency at which connections occur. CONCLUSIONS: These results demonstrate distinct effects of mild TBI on the functional brain connectome when sustained in a deployment versus nondeployment context. This is consistent with findings demonstrating differential effects in other areas such as psychiatric diagnoses and severity, pain, sleep, and cognitive function. Furthermore, participants were an average of 11 years postinjury, suggesting these represent chronic effects of the injury. Overall, these findings add to the growing body of evidence, suggesting the effects of mild TBI acquired during deployment are different and potentially longer lasting than those of mild TBI acquired in a nondeployment context.

Factors associated with recovery from posttraumatic stress disorder in combat veterans: The role of deployment mild traumatic brain injury (mTBI).

OBJECTIVE: Examine factors associated with recovery from posttraumatic stress disorder (PTSD) and evaluate the role of deployment mild traumatic brain injury (mTBI) in the relationship between PTSD recovery and functional outcomes. METHOD: Post 9/11 combat veterans with lifetime history of PTSD (N = 124, 84.7% male) completed the Mid-Atlantic MIRECC Assessment of Traumatic Brain Injury (MMA-TBI), Salisbury Blast Interview (SBI), Clinician Administered PTSD scale (CAPS-5), cognitive assessment battery, and measures of depression, PTSD symptoms, neurobehavioral symptoms, sleep quality, pain interference, and quality of life. RESULTS: Analyses of variance (ANOVA) results revealed significant differences in most behavioral health outcomes based on PTSD recovery, with participants who have recovered from PTSD showing less severe neurobehavioral and depressive symptoms, better sleep quality, less functional pain interference, and higher quality of life. No differences were found in cognitive functioning between those who have recovered from PTSD and those who have not. History of deployment mTBI did not significantly moderate the relationship between PTSD recovery and most functional and cognitive outcomes with the exception of 2 measures of processing speed. Specifically, among participants with history of deployment mTBI, those who have recovered from PTSD displayed better cognitive functioning than those who have not. Additionally, participants who have not recovered from PTSD had higher levels of blast exposure during military service. CONCLUSIONS: PTSD recovery was associated with better psychological functioning and higher quality of life, but not with objective cognitive functioning. Deployment mTBI history moderated only the relationship between PTSD recovery status and tests of processing speed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Internalizing and externalizing comorbidity and symptom burden in a VA ADHD specialty evaluation clinic.

The purpose of this study was to evaluate psychiatric diagnosis and symptom comorbidity in veterans diagnosed with attention-deficit/hyperactivity disorder (ADHD). Study design was retrospective chart review from an ADHD evaluation clinic at a Veterans Affairs hospital. Participants were 227 military veterans who completed a standardized ADHD assessment and produced valid Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) profiles. There were no differences in rates of internalizing or externalizing psychiatric conditions diagnosed in inattentive compared to combined ADHD presentations. However, compared to a subsample with no psychiatric diagnoses, individuals diagnosed with ADHD endorsed significantly more internalizing symptom burden, with combined ADHD veterans also endorsing significantly greater levels of negative emotions and neuroticism. Base rates of comorbid classes of psychiatric diagnoses were not increased in individuals with ADHD, though higher rates of trauma disorders were seen in the combined group compared to the inattentive group. Multivariate base rates of MMPI-2-RF Restructured Clinical scales across various subgroups are presented. There was evidence for differential phenotypes of psychiatric symptoms across ADHD presentations in clinically referred veterans, predominantly related to higher rates of internalizing symptoms.

Alterations in the Topology of Functional Connectomes Are Associated with Post-Traumatic Stress Disorder and Blast-Related Mild Traumatic Brain Injury in Combat Veterans.

Post-traumatic stress disorder (PTSD) is a common condition in post-deployment service members (SM). SMs of the conflicts in Iraq and Afghanistan also frequently experience traumatic brain injury (TBI) and exposure to blasts during deployments. This study evaluated the effect of these conditions and experiences on functional brain connectomes in post-deployment, combat-exposed veterans. Functional brain connectomes were created using 5-min resting-state magnetoencephalography data. Well-established clinical interviews determined current PTSD diagnosis, as well as deployment-acquired mild TBI and history of exposure to blast. Linear regression examined the effect of these conditions on functional brain connectomes beyond covariates. There were significant interactions between blast-related mild TBI and PTSD after correction for multiple comparisons including number of nodes (non-standardized parameter estimate [PE] = -12.47), average degree (PE = 0.05), and connection strength (PE = 0.05). A main effect of blast-related mild TBI was observed on the threshold level. These results demonstrate a distinct functional connectome presentation associated with the presence of both blast-related mild TBI and PTSD. These findings suggest the possibility that blast-related mild TBI alterations in functional brain connectomes affect the presentation or progression of recovery from PTSD. The current results offer mixed support for hyper-connectivity in the chronic phase of deployment TBI.

Self-reported neurobehavioral symptoms in combat veterans: An examination of NSI with mBIAS symptom validity scales and potential effects of psychological distress.

This study evaluated symptom validity scales from the Neurobehavioral Symptom Inventory (NSI) and mild Brain Injury Atypical Symptom Scale (mBIAS) in a sample of 338 combat veterans. Classification statistics were computed using the Structured Inventory of Malingered Symptomatology (SIMS) as the validity criterion. Symptom distress was assessed with the Patient Health Questionnaire-9 and Posttraumatic Stress Disorder (PTSD) Checklist-5. At SIMS > 14, the NSI total score resulted in the highest area under the curve (AUC; .91), followed by Validity-10 (AUC = .88) and mBIAS (AUC = .67). At SIMS > 23, both NSI total and Validity-10 AUCs decreased to .88; in contrast, mBIAS AUC increased to .75. The NSI total score and Validity-10 were interpreted to reflect symptom magnification, whereas the mBIAS may reflect symptom fabrication. There was a subsample with elevated Patient Health Questionnaire-9 (PHQ-9) and PTSD Checklist-5 scores who were significantly distressed but not deemed invalid on the NSI; however, there appears to be an upper threshold on the NSI total score (>69) beyond which nobody produced an invalid score on the SIMS. A recommended approach is provided for using NSI-related validity measures. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Performance validity and symptom validity tests: Are they measuring different constructs?

OBJECTIVE: To evaluate the relationships among performance validity, symptom validity, symptom self-report, and objective cognitive testing. METHOD: Combat Veterans (N = 338) completed a neurocognitive assessment battery and several self-report symptom measures assessing depression, posttraumatic stress disorder (PTSD) symptoms, sleep quality, pain interference, and neurobehavioral complaints. All participants also completed two performance validity tests (PVTs) and one stand-alone symptom validity test (SVT) along with two embedded SVTs. RESULTS: Results of an exploratory factor analysis revealed a three-factor solution: performance validity, cognitive performance, and symptom report (SVTs loaded on the third factor). Results of t tests demonstrated that participants who failed PVTs displayed significantly more severe symptoms and significantly worse performance on most measures of neurocognitive functioning compared to those who passed. Participants who failed a stand-alone SVT also reported significantly more severe symptomatology on all symptom report measures, but the pattern of cognitive performance differed based on the selected SVT cutoff. Multiple linear regressions revealed that both SVT and PVT failure explained unique variance in symptom report, but only PVT failure significantly predicted cognitive performance. CONCLUSIONS: Performance and symptom validity tests measure distinct but related constructs. SVTs and PVTs are significantly related to both cognitive performance and symptom report; however, the relationship between symptom validity and symptom report is strongest. SVTs are also differentially related to cognitive performance and symptom report based on the utilized cutoff score. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Research Letter: Blast Exposure and Brain Volume.

OBJECTIVE: To determine whether blast exposure is associated with brain volume beyond posttraumatic stress disorder (PTSD) diagnosis and history of traumatic brain injury (TBI). SETTING: Veterans Affairs Medical Center. PARTICIPANTS: One hundred sixty-three Iraq and Afghanistan combat veterans, 86.5% male, and 68.10% with a history of blast exposure. Individuals with a history of moderate to severe TBI were excluded. MAIN MEASURES: Clinician-Administered PTSD Scale (CAPS-5), Mid-Atlantic MIRECC Assessment of TBI (MMA-TBI), Salisbury Blast Interview (SBI), and magnetic resonance imaging. Maximum blast pressure experienced from a blast event represented blast severity. METHODS: Hierarchical regression analysis evaluated effects of maximum pressure experienced from a blast event on bilateral volume of hippocampus, anterior cingulate cortex, amygdala, orbitofrontal cortex, precuneus, and insula. All analyses adjusted for effects of current and lifetime PTSD diagnosis, and a history of deployment mild TBI. RESULTS: Maximum blast pressure experienced was significantly associated with lower bilateral hippocampal volume (left: ΔR2 = 0.032, P < .001; right: ΔR2 = 0.030, P < .001) beyond PTSD diagnosis and deployment mild TBI history. Other characteristics of blast exposure (time since most recent exposure, distance from closest blast, and frequency of blast events) were not associated with evaluated volumes. CONCLUSION: Exposure to a blast is independently associated with hippocampal volume beyond PTSD and mild TBI; however, these effects are small. These results also demonstrate that blast exposure in and of itself may be less consequential than severity of the exposure as measured by the pressure gradient.

Sleep moderates symptom experience in combat veterans.

BACKGROUND: Though sleep disturbance has shown to negatively affect outcomes related to post-deployment conditions, it is unclear whether and how sleep disturbance affects mental health symptoms beyond these conditions. We evaluated the independent and moderating effects of sleep quality on posttraumatic stress disorder (PTSD), depressive, and neurobehavioral symptoms beyond mild traumatic brain injury (TBI) and PTSD diagnosis. METHODS: Participants were 274 US combat veterans who deployed after 9/11. All completed diagnostic TBI and PTSD interviews and self-report measures of sleep quality, as well as PTSD, depressive, and neurobehavioral symptoms. Only those who passed symptom validity were included in analyses. Hierarchical regression evaluated the contribution of sleep quality to outcomes beyond PTSD and mild TBI. Moderation analyses evaluated interactions between mild TBI, PTSD, and sleep quality on symptom outcomes. RESULTS: Mild TBI was only significantly associated with PTSD (p = .006) and neurobehavioral (p = .003) symptoms. PTSD diagnosis was associated with PTSD (p < .001), depressive (p < .001), and neurobehavioral symptoms (p < .001) beyond mild TBI. Sleep quality explained additional significant variance in all three outcome measures (p < .001), and also significantly moderated the effects of PTSD diagnosis on neurobehavioral symptoms (ΔR2 = .01, p = .023). LIMITATIONS: Sleep was evaluated subjectively and therefore must be interpreted in this context. CONCLUSIONS: These results provide support that sleep quality is an independent contributing factor to health outcomes in post-deployment veterans and should be considered in etiology of complaints.

Pain interference and quality of life in combat veterans: Examining the roles of posttraumatic stress disorder, traumatic brain injury, and sleep quality.

OBJECTIVE: The goal of this study was to examine the associations among posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), sleep quality, pain interference, and quality of life in combat veterans. METHOD: Veterans (N = 289, 86.51% male) completed the Mid-Atlantic MIRECC Assessment of Traumatic Brain Injury, the Clinician-Administered PTSD Scale for DSM-5, and measures of sleep quality, pain interference, and quality of life. RESULTS: Hierarchical linear regressions evaluated associations between PTSD severity, deployment TBI severity, sleep quality, and the outcomes of pain interference and quality of life after adjusting for demographic variables and the number of nondeployment TBIs. PTSD severity, B = 0.15, SE B = 0.04, deployment TBI severity, B = 3.98, SE B = 1.01, and sleep quality, B = 0.74, SE B = 0.13, were significantly associated with pain interference, p < .001. PTSD severity, B = -0.57, SE B = 0.07, and pain interference, B = -0.45, SE B = 0.11, were significantly, independently associated with quality of life, p < .001. However, pain interference, B = -0.24, SE B = 0.11, was no longer significantly associated with quality of life when sleep quality, B = -1.56, SE B = 0.25, was included in the model. There was no significant association between deployment TBI severity and quality of life. Interactions among the studied variables were not significant for either of the outcome variables. CONCLUSIONS: PTSD symptom severity, deployment TBI history, and sleep quality may be important to consider in treatment planning for veterans experiencing pain-related functional interference. For veterans with numerous conditions comorbid with pain, treatment plans may include interventions targeting sleep and PTSD to maximize quality of life improvements. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Differential effects of deployment and nondeployment mild TBI on neuropsychological outcomes.

Objective: Mild traumatic brain injury (TBI) that occurs in a deployment environment is characteristically different from mild TBI that occurs outside of deployment. This study evaluated differential and interaction effects of deployment and nondeployment mild TBI on cognitive and behavioral health outcomes. Research Method: Combat veterans (N = 293) who passed performance-validity measures completed the Mid-Atlantic MIRECC Assessment of TBI (MMA-TBI), Clinician-Administered Posttraumatic Stress Disorder (PTSD) Scale (CAPS-5), a neuropsychological assessment battery, and self-report questionnaires. A 2 × 2 × 2 analysis of variance (ANOVA) was conducted to evaluate the main and interaction effects across mild TBI groups and PTSD diagnosis. Results: Deployment TBI was associated with poorer outcomes on several cognitive tests: Wechsler Adult Intelligence Scale, 4th edition (WAIS-IV); Working Memory Index (WMI; p = .018); Trail Making Test A (TMT-A; p < .001); and Trail Making Test B (TMT-B; p = .002). Deployment TBI and PTSD were also associated with increased PTSD, depressive, and neurobehavioral symptoms; pain interference; and poorer sleep quality. Nondeployment TBI had no effect on cognitive performance and was associated only with poorer sleep quality. PTSD had the strongest associations with symptom measures and deployment TBI with cognitive outcomes. There were no significant interaction effects after adjusting for multiple comparisons. Conclusions: Remote outcomes associated with mild deployment TBI are different from those associated with nondeployment mild TBI and are robust beyond PTSD. This suggests that the environment surrounding a TBI event influences cognitive and symptom sequelae. Veterans who experience mild TBI during deployment may report changes in cognition, but most will continue to function within the expected range. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Test of Premorbid Functioning: You're Doing It Wrong, but Does It Matter?

OBJECTIVE: Clarify procedures to correctly score Test of Premorbid Functioning (TOPF) and assess the accuracy of TOPF scores in the estimation of premorbid intellectual functioning. METHOD: In this cross-sectional study, post-9/11 veterans (N = 233, 84.12% male) completed the TOPF, the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV), and performance validity measures. RESULTS: All TOPF scores were significantly correlated with WAIS-IV FSIQ scores (range r = 0.56-.73). The degree of discrepancy between TOPF scores and FSIQ varied with 10%-17% of TOPF scores deviating from FSIQ scores by one SD or more. CONCLUSIONS: Proper TOPF scoring procedures are presented. The TOPF Actual and Predicted scores were related to FSIQ. However, a higher percentage of Actual and Predicted scores were discrepant from FSIQ compared with the other three TOPF estimates, arguing against their use as independent premorbid estimates. Use of the TOPF as was designed is recommended.

Initial Validation of the Mid-Atlantic Mental Illness Research, Education, and Clinical Center Assessment of Traumatic Brain Injury.

With the increasing prevalence of traumatic brain injury (TBI), the need for reliable and valid methods to evaluate TBI has also increased. The purpose of this study was to establish the validity and reliability of a new comprehensive assessment of TBI, the Mid-Atlantic Mental Illness Research, Education, and Clinical Center (MIRECC) Assessment of TBI (MMA-TBI). The participants in this study were post-deployment, combat exposed veterans. First, MMA-TBI outcomes were compared with those of independently conducted clinical TBI assessments. Next, MMA-TBI outcomes were compared with those of a different validated TBI measure (the Ohio State University TBI Identification method [OSU-TBI-ID]). Next, four TBI subject matter experts independently evaluated 64 potential TBI events based on both clinical judgment and Veterans Administration/Department of Defense (VA/DoD) Clinical Practice Guidelines. Results of the MMA-TBI algorithm (based on VA/DoD clinical guideline) were compared with those of the subject matter experts. Diagnostic correspondence with independently conducted expert clinical evaluation was 96% for lifetime TBI and 92% for deployment-acquired TBI. Consistency between the MMA-TBI and the OSU-TBI-ID was high (κ = 0.90; Kendall Tau = 0.94). Comparison of MMA-TBI algorithm results with those of subject matter experts was high (κ = 0.97-1.00). The MMA-TBI is the first TBI interview to be validated against an independently conducted clinical TBI assessment. Overall, results demonstrate the MMA-TBI is a highly valid and reliable instrument for determining TBI based on VA/DoD clinical guidelines. These results support the need for application of standardized TBI criteria across all diagnostic contexts.

Brain Volume in Veterans: Relationship to Posttraumatic Stress Disorder and Mild Traumatic Brain Injury.

OBJECTIVE: Clarify associations between diagnosis of posttraumatic stress disorder (PTSD) and deployment traumatic brain injury (TBI) on salient regional brain volumes in returning combat veterans. PARTICIPANTS: Iraq and Afghanistan era combat veterans, N = 163, 86.5% male. MAIN MEASURES: Clinician-administered PTSD Scale (CAPS-5), Mid-Atlantic MIRECC Assessment of TBI (MMA-TBI), magnetic resonance imaging. METHODS: Hierarchical regression analyses evaluated associations and interactions between current and lifetime PTSD diagnosis, deployment TBI, and bilateral volume of hippocampus, anterior cingulate cortex, amygdala, orbitofrontal cortex, precuneus, and insula. RESULTS: Deployment TBI was associated with lower bilateral hippocampal volume (P = .007-.032) and right medial orbitofrontal cortex volume (P = .006). Neither current nor lifetime PTSD diagnosis was associated with volumetric outcomes beyond covariates and deployment TBI. CONCLUSION: History of deployment TBI is independently associated with lower volumes in hippocampus and medial orbitofrontal cortex. These results support TBI as a potential contributing factor to consider in reduced cortical volume in PTSD.

Sequelae of Blast Events in Iraq and Afghanistan War Veterans using the Salisbury Blast Interview: A CENC Study.

Objective: To comprehensively characterize blast exposure across the lifespan and relationship to TBI.Participants: Post-deployment veterans and service members (N = 287).Design: Prospective cohort recruitment.Main Measures: Salisbury Blast Interview (SBI).Results: 94.4% of participants reported at least one blast event, 75% reported a pressure gradient during a blast event. Participants reported an average of 337.7 (SD = 984.0) blast events (range 0-4857), 64.8% occurring during combat. Across participants, 19.7% reported experiencing a traumatic brain injury (TBI) during a blast event. Subjective ratings of blast characteristics (wind, debris, ground shaking, pressure, temperature, sound) were significantly higher when TBI was experienced and significantly lower when behind cover. Pressure had the strongest association with resulting TBI (AUC = 0.751). Pressure rating of 3 had the best sensitivity (.54)/specificity (.87) with TBI. Logistic regression demonstrated pressure, temperature and distance were the best predictors of TBI, and pressure was the best predictor of primary blast TBI.Conclusion: Results demonstrate the ubiquitous nature of blast events and provide insight into blast characteristics most associated with resulting TBI (pressure, temperature, distance). The SBI provides comprehensive characterization of blast events across the lifespan including the environment, protective factors, blast characteristics and estimates of distance and munition.

Distress Tolerance and Symptom Severity as Mediators of Symptom Validity Failure in Veterans With PTSD.

OBJECTIVE: Performance validity tests (PVTs) and symptom validity tests (SVTs) are necessary in clinical and research contexts. The extent to which psychiatric distress contributes to failure on these tests is unclear. The authors hypothesized that the relation between posttraumatic stress disorder (PTSD) and validity would be serially mediated by distress tolerance and symptom severity. METHODS: Participants included 306 veterans, 110 of whom met full criteria for current PTSD. PVTs included the Medical Symptom Validity Test (MSVT) and b Test. The Structured Inventory of Malingered Symptomatology (SIMS) was used to measure symptom validity. RESULTS: MSVT failure was significantly and directly associated with PTSD severity (B=0.05, CI=0.01, 0.08) but not distress tolerance or PTSD diagnosis. b Test performance was not significantly related to any variable. SIMS failure was significantly associated with PTSD diagnosis (B=0.71, CI=0.05, 1.37), distress tolerance (B=-0.04, CI=-0.07, -0.01), and symptom severity (B=0.07, CI=0.04, 0.09). The serial mediation model significantly predicted all SIMS subscales. CONCLUSIONS: PTSD severity was associated with failing a memory-based PVT but not an attention-based PVT. Neither PVT was associated with distress tolerance or PTSD diagnosis. SVT failure was associated with PTSD diagnosis, poor distress tolerance, and high symptomatology. For veterans with PTSD, difficulty managing negative emotional states may contribute to symptom overreporting. This may reflect exaggeration or an inability to tolerate stronger negative affect, rather than a "cry for help."

Digit Span embedded validity indicators in neurologically-intact veterans.

Objective: Embedded validity measures are useful in neuropsychological evaluations but should be updated with new test versions and validated across various samples. This study evaluated Wechsler Adult Intelligence Scale, 4th edition (WAIS-IV) Digit Span validity indicators in post-deployment veterans.Method: Neurologically-intact veterans completed structured diagnostic interviews, the WAIS-IV, the Medical Symptom Validity Test (MSVT), and the b Test as part of a larger study. The Noncredible group included individuals who failed either the MSVT or the b Test. Of the total sample (N = 275), 21.09% failed the MSVT and/or b Test. Diagnostic accuracy was calculated predicting group status across cutoff scores on two Digit Span variables, four Reliable Digit Span (RDS) variables, and two Vocabulary minus Digit Span variables.Results: Digit Span age-corrected scaled score (ACSS) had the highest AUC (.648) of all measures assessed; however, sensitivity at the best cutoff of <7 was only 0.17. Of RDS measures, the Working Memory RDS resulted in the highest AUC (.629), but Enhanced RDS and Alternate RDS produced the highest sensitivities (0.22). Overall, cutoff scores were consistent with other studies, but sensitivities were lower. Vocabulary minus Digit Span measures were not significant.Conclusions: Digit Span ACSS was the strongest predictor of noncredible performance, and outperformed traditional RDS variants. Sensitivity across all validity indicators was low in this research sample, though cutoff scores were congruent with previous research. Although embedded Digit Span validity indicators may be useful, they are not sufficient to replace standalone performance validity tests.