Matthew W. Reid

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.

A Multisite Study of the Relationships between Blast Exposures and Symptom Reporting in a Post-Deployment Active Duty Military Population with Mild Traumatic Brain Injury

Explosive devices have been the most frequent cause of traumatic brain injury (TBI) among deployed contemporary U.S. service members. The purpose of this study was to examine the influence of previous cumulative blast exposures (that did or did not result in TBI) on later post-concussion and post-traumatic symptom reporting after sustaining a mild TBI (MTBI). Participants were 573 service members who sustained MTBI divided into four groups by number of blast exposures (1, 2, 3, and 4-10) and a nonblast control group. Post-concussion symptoms were measured using the Neurobehavioral Symptom Inventory (NSI) and post-traumatic stress disorder (PTSD) symptoms using the Post-traumatic Checklist-Civilian version (PCL-C). Results show groups significantly differed on total NSI scores (p<0.001), where symptom endorsement increased as number of reported blast exposures increased. Total NSI scores were significantly higher for the 3- and 4-10 blast groups compared with the 1- and 2-blast groups with effect sizes ranging from small to moderate (d=0.31 to 0.63). After controlling for PTSD symptoms using the PCL-C total score, NSI total score differences remained between the 4-10-blast group and the 1- and 2-blast groups, but were less pronounced (d=0.35 and d=0.24, respectively). Analyses of NSI subscale scores using PCL-C scores as a covariate revealed significant between-blast group differences on cognitive, sensory, and somatic, but not affective symptoms. Regression analyses revealed that cumulative blast exposures accounted for a small but significant amount of the variance in total NSI scores (4.8%; p=0.009) and total PCL-C scores (2.3%; p<0.001). Among service members exposed to blast, post-concussion symptom reporting increased as a function of cumulative blast exposures. Future research will need to determine the relationship between cumulative blast exposures, symptom reporting, and neuropathological changes.

Susceptibility Weighted Imaging and White Matter Abnormality Findings in Service Members With Persistent Cognitive Symptoms Following Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is a major health concern among active duty service members and Veterans returning from combat operations, and it can result in variable clinical and cognitive outcomes. Identifying biomarkers that can improve diagnosis and prognostication has been at the forefront of recent research efforts. The purpose of this study was to compare the sensitivity and specificity of abnormalities identified using more traditional magnetic resonance imaging (MRI) sequences such as fluid attenuation inversion recovery (FLAIR) to more advanced MRI sequences such as susceptibility weighted imaging (SWI) among a cohort of active duty service members experiencing persistent cognitive symptoms after mTBI. One-hundred and fifty-two active duty service members (77 mTBI, 58 orthopedically injured [OI] only, 17 post-traumatic stress disorder [PTSD] only) underwent MRI and neuropsychological evaluation at a large military treatment facility. Results demonstrated that FLAIR white matter hyperintensities (WMHs) were present in all three groups at statistically similar rates (41% mTBI, 49% OI, and 29% PTSD). With the exception of a single OI participant showing a small discrete SWI lesion, SWI abnormalities were overwhelmingly present in mTBI patients (22% mTBI, 1% OI, and 0% PTSD). Functionally, mTBI participants with and without SWI abnormalities did not differ in demographics, symptom reporting, or cognitive performance. However, mTBI participants with and without WMH did differ for on measures of working memory with the mTBI participants with WMH having worse cognitive performance. No other significant differences were noted for those participants with and without imaging abnormalities for either the OI or PTSD only cohorts. These results appear to illustrate the sensitivity and specificity of SWI findings though these results did not have any significant functional impact in this cohort. In contrast, WMHs noted on FLAIR imaging were not sensitive or specific findings, but functionally relevant among mTBI participants. These findings emphasize the complexity of injury and functional outcome in mTBI patients that requires additional examination.

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.

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.

Comparing Two Processing Pipelines to Measure Subcortical and Cortical Volumes in Patients with and without Mild Traumatic Brain Injury

To compare volumetric results from NeuroQuant® and FreeSurfer in a service member setting. Since the advent of medical imaging, quantification of brain anatomy has been a major research and clinical effort. Rapid advancement of methods to automate quantification and to deploy this information into clinical practice has surfaced in recent years. NeuroQuant® is one such tool that has recently been used in clinical settings. Accurate volumetric data are useful in many clinical indications; therefore, it is important to assess the intermethod reliability and concurrent validity of similar volume quantifying tools.

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.

Symptom Reporting Patterns of US Military Service Members with a History of Concussion According to Duty Status

Objective To compare symptom reporting patterns of service members with a history of concussion based on work status: full duty, limited duty, or in the Medical Evaluation Board (MEB)/disability process. Methods Retrospective analysis of 181 service members with a history of concussion (MEB n = 56; limited duty n = 62; full duty n = 63). Neurobehavioral Symptom Inventory (NSI) Validity-10 cutoff (>22) and Mild Brain Injury Atypical Symptoms Scale (mBIAS) cutoffs (≥10 and ≥8) were used to evaluate potential over-reporting of symptoms. Results The MEB group displayed significantly higher NSI scores and significantly higher proportion scored above the mBIAS ≥10 cutoff (MEB = 15%; limited duty = 3%; full duty = 5%). Validity-10 cutoff did not distinguish between groups. Conclusions MEB but not limited duty status was associated with increased risk of over-reporting symptoms in service members with a history of concussion. Results support the use of screening measures for over-reporting in the MEB/disability samples.