Jan E. Kennedy

Preliminary findings of cortical thickness abnormalities in blast injured service members and their relationship to clinical findings.

Though cortical abnormalities have been demonstrated in moderate and severe traumatic brain injured (TBI) patients, there have been no studies examining cortical changes following blast related mild TBI (mTBI). The purpose of this study was to determine the effects and functional relevance of blast mTBI on cortical thickness in a small cohort of carefully screened blast injured US Service Members (SM). Twelve SM with mTBI acquired through blast injury were compared to 11 demographically matched control SM without TBI. Both mTBI and control participants were active duty and had completed a combat deployment. Subjects underwent MRI examination and the T1 weighted anatomic images were processed using the FreeSurfer suite of tools. Cortical thickness maps were compared between groups and examined for relationships with time since injury (TSI). Utilizing a large database of functional imaging results (BrainMap), significant regions of interest (ROI) were used to determine the behavioral profiles most consistently associated with the specific ROI. In addition, clinical variables were examined as part of post-hoc analysis of functional relevance. Group comparisons controlling for age demonstrated several significant clusters of cortical thinning for the blast injured SM. After multiple comparisons correction (False Discovery Rate (FDR)), two left hemisphere clusters remained significant (left superior temporal (STG) and frontal (SFG) gyri). No clusters were significantly correlated with TSI after FDR correction. Behavioral analysis for the STG and SFG clusters demonstrated three significant behavioral/cognitive sub-domains, each associated with audition and language. Blast injured SMs demonstrated distinct areas of cortical thinning in the STG and SFG. These areas have been previously shown to be associated with audition and language. Post-hoc analyses of clinical records demonstrated significant abnormal audiology reports for the blast injured SM suggesting that the thinning in these ROIs might be related to injury to the external auditory system rather than direct injury to the brain from the blast. It is clear that additional replication is needed in much larger cohorts. Importantly, the combination of imaging tools and methods in this study successfully demonstrated the potential to define unique ROIs and functional correlates that can be used to design future studies.

Treatment of persistent post-concussive symptoms after mild traumatic brain injury: a systematic review of cognitive rehabilitation and behavioral health interventions in military service members and veterans

Increased prevalence of traumatic brain injury (TBI) has been associated with service members and veterans who completed combat deployments in support of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF). Management of persistent post-concussive symptoms (PCS) has been a challenge to healthcare providers throughout the Military and Veterans Healthcare Systems, as well as civilian healthcare providers, due in part to the chronic nature of symptoms, co-occurrence of behavioral health disorders such as depression, Posttraumatic Stress Disorder (PTSD), and substance use disorders, and fear of a potential stigma associated with psychiatric diagnoses and behavioral health treatment(s). This systematic review examined non-pharmacologic behavioral health interventions and cognitive rehabilitation interventions for PCS in military service members and veterans with a history of mild TBI (mTBI). Six electronic databases were searched with specific term limitations, identifying 121 citations. Ultimately, 19 articles met criteria for inclusion in this systematic review. Studies were broadly categorized into four subtypes: psychoeducational interventions, cognitive rehabilitation, psychotherapeutic approaches, and integrated behavioral health interventions for PCS and PTSD. The review provides an update of the empirical evidence for these four types of interventions for PCS in active duty service members and veterans. Recommendations for future research are discussed, including the need to expand and improve the limited evidence basis on how to manage persistent post-concussive symptoms in this population.

Factors influencing postconcussion and posttraumatic stress symptom reporting following military-related concurrent polytrauma and traumatic brain injury.

The purpose of this study was to identify factors that are predictive of, or associated with, high endorsement of postconcussion and posttraumatic stress symptoms following military-related traumatic brain injury (TBI). Participants were 1,600 U.S. service members (age: M = 27.1, SD = 7.1; 95.4% male) who had sustained a mild-to-moderate TBI and who had been evaluated by the Defense and Veterans Brain Injury Center at one of six military medical centers. Twenty-two factors were examined that included demographic, injury circumstances/severity, treatment/evaluation, and psychological/physical variables. Four factors were statistically and meaningfully associated with clinically elevated postconcussion symptoms: (i) low bodily injury severity, (ii) posttraumatic stress, (iii) depression, and (iv) military operation where wounded (p < .001, 43.2% variance). The combination of depression and posttraumatic stress symptoms accounted for the vast majority of unique variance (41.5%) and were strongly associated with, and predictive of, clinically elevated postconcussion symptoms [range: odds ratios (OR) = 4.24-7.75; relative risk (RR) = 2.28-2.51]. Five factors were statistically and meaningfully associated with clinically elevated posttraumatic stress symptoms: (i) low bodily injury severity, (ii) depression, (iii) a longer time from injury to evaluation, (iv) military operation where wounded, and (v) current auditory deficits (p < .001; 65.6% variance accounted for). Depression alone accounted for the vast majority of unique variance (60.0%) and was strongly associated with, and predictive of, clinically elevated posttraumatic stress symptoms (OR = 38.78; RR = 4.63). There was a very clear, strong, and clinically meaningful association between depression, posttraumatic stress, and postconcussion symptoms in this sample. Brain injury severity, however, was not associated with symptom reporting following TBI.

The suppression of brain activation in post-deployment military personnel with posttraumatic stress symptoms

Previous research using cognitive paradigms has found task-related activation that includes prefrontal brain structures and that is attenuated in association with posttraumatic stress symptoms (PTSS). The present investigation used a cognitive control paradigm, the Arrows Task, to study subjects who had not sustained a traumatic brain injury during deployment and who had a wide range of scores on the Posttraumatic Stress Disorder Checklist (PCL). During the Arrows Task there was no significant activation within the full sample of 15 subjects, but deactivation was found within areas that are likely to be involved in cognitive control, including the dorsal anterior cingulate gyrus and parietal cortex. Exploratory analyses were also conducted to compare subjects with relatively high PTSS (HIGH PTSS, nu2009=u20097) to those with lower severity or no symptoms (LOW PTSS, nu2009=u20098). LOW PTSS subjects exhibited activation in nonfrontal brain areas and their activation was greater relative to the HIGH PTSS subjects. In contrast, the HIGH PTSS group had extensive deactivation and there was a negative relationship between activation and PCL scores within subcortical structures, the cerebellum, and higher-order cortical association areas. For the HIGH PTSS group there was also a positive relationship between PCL scores and activation within basic sensory and motor areas, as well as structures thought to have a role in emotion and the regulation of internal bodily states. These findings are consistent with widespread neural dysfunction in subjects with greater PTSS, including changes similar to those reported to occur with acute stress and elevated noradrenergic activity.

Adversity and Resilience are Associated with Outcome Following Mild Traumatic Brain Injury in Military Service Members

The objective of this study was to assess the associations between resilience, adversity, post-concussion symptoms, and post-traumatic stress symptom reporting after mild traumatic brain injury (mTBI). We hypothesized that resilience would be associated with less symptom reporting, and adversity would be associated with greater symptom reporting. This was a cross-sectional study of retrospective data collected for an ongoing TBI repository. United States military service members who screened positive for mTBI during a primary care visit completed the Trauma History Screen (THS), Connor-Davidson Resilience Scale (CD-RISC), Neurobehavioral Symptom Inventory (NSI), and post-traumatic stress disorder (PTSD) Checklist-Civilian Version (PCL-C). Data collected from February 2015 to August 2016 were used for the present study. Only participants with complete data for the above measures were included, yielding a sample size of 165 participants. Adversity (THS) and resilience (CD-RISC) scores were each correlated significantly with post-concussion (NSI) and traumatic stress (PCL-C) total and subscale scores in the hypothesized direction. Interactions between adversity and resilience were absent for all measures except the NSI sensory subscale. Four traumatic event types were significantly associated positively with most NSI and PCL-C total and subscale scores, but the age at which traumatic events were first experienced showed few and mixed significant associations. In conclusion, resilience and adversity were significantly associated with symptom endorsement after mTBI. Screening for cumulative adversity may identify individuals at greater risk of developing persistent post-concussion symptoms and/or PTSD, and interventions that increase resilience may reduce symptom severity.

Profile Analyses of the Personality Assessment Inventory Following Military-Related Traumatic Brain Injury

Personality Assessment Inventory (PAI) profiles were examined in 160 U.S. service members (SMs) following mild-severe traumatic brain injury (TBI). Participants who sustained a mild TBI had significantly higher PAI scores than those with moderate-severe TBI on eight of the nine clinical scales examined. A two-step cluster analysis identified four PAI profiles, heuristically labeled High Distress, Moderate Distress, Somatic Distress, and No Distress. Postconcussive and posttraumatic stress symptom severity was highest for the High Distress group, followed by the Somatic and Moderate Distress groups, and the No Distress group. Profile groups differed in age, ethnicity, rank, and TBI severity. Findings indicate that meaningful patterns of behavioral and personality characteristics can be detected in active duty military SMs following TBI, which may prove useful in selecting the most efficacious rehabilitation strategies.

Subcortical shape and neuropsychological function among U.S. service members with mild traumatic brain injury

In a recent manuscript, our group demonstrated shape differences in the thalamus, nucleus accumbens, and amygdala in a cohort of U.S. Service Members with mild traumatic brain injury (mTBI). Given the significant role these structures play in cognitive function, this study directly examined the relationship between shape metrics and neuropsychological performance. The imaging and neuropsychological data from 135 post-deployed United States Service Members from two groups (mTBI and orthopedic injured) were examined. Two shape features modeling local deformations in thickness (RD) and surface area (JD) were defined vertex-wise on parametric mesh-representations of 7 bilateral subcortical gray matter structures. Linear regression was used to model associations between subcortical morphometry and neuropsychological performance as a function of either TBI status or, among TBI patients, subjective reporting of initial concussion severity (CS). Results demonstrated several significant group-by-cognition relationships with shape metrics across multiple cognitive domains including processing speed, memory, and executive function. Higher processing speed was robustly associated with more dilation of caudate surface area among patients with mTBI who reported more than one CS variables (loss of consciousness (LOC), alteration of consciousness (AOC), and/or post-traumatic amnesia (PTA)). These significant patterns indicate the importance of subcortical structures in cognitive performance and support a growing functional neuroanatomical literature in TBI and other neurologic disorders. However, prospective research will be required before exact directional evolution and progression of shape can be understood and utilized in predicting or tracking cognitive outcomes in this patient population.

Long-Term Outcomes and Needs of Military Service Members After Noncombat-Related Traumatic Brain Injury

OBJECTIVESnAssess the prevalence of self-identified unmet service needs in a military sample an average of 5 years following noncombat traumatic brain injury (TBI). Examine relationships between unmet needs and background, injury-related and outcome variables.nnnMETHODSnThe study sample consisted of 89 veterans and service members who sustained non-combat TBI between 1999 and 2003, selected from enrollees in the Defense and Veterans Brain Injury Center TBI registry. Semistructured telephone interview was used to collect information about participants self-reported unmet service needs, symptoms, and functional status.nnnRESULTSnMost participants (65%) reported having at least one unmet service need. The most prevalent needs were getting information about available post-TBI services (47%) and improving memory and attention (45%). Unmet needs were associated with cognitive difficulties, physical and emotional symptoms, mental health diagnosis/treatment, and poorer functional status.nnnCONCLUSIONSnNeeds for services following TBI are associated with poor symptomatic and functional outcomes and may persist for years after injury in military service members and veterans. The study suggests service members needs post TBI for improved cognition, support for emotional issues, and resources for vocational skills. Information about available services should be made accessible to those recovering from TBI to reduce the incidence of long-term unmet needs.