Jeffrey D. Lewis

Posttraumatic stress symptoms in OIF/OEF service members with blast-related and non-blast-related mild TBI

PURPOSE To examine the proportion and severity of stress-related symptoms in U.S. service members with mild traumatic brain injuries (mTBI) received during deployment to Operation Iraqi Freedom (OIF) or Operation Enduring Freedom (OEF). Stress-related symptoms reported by service members with mTBI from explosive munitions are compared to symptoms reported by those with mTBI received from other mechanisms (i.e. falls, motor vehicle accidents). METHODS Posttraumatic stress, as measured by scores on the Posttraumatic Stress Disorder Checklist (PCL-C), for a sample of 586 OIF/OEF service members with blast-related mTBI was compared to a sample of 138 OIF/OEF service members with non-blast mTBI selected from retrospective review of research records. RESULTS Re-experiencing symptoms such as flashbacks and nightmares were higher for the blast mTBI group than for the non-blast mTBI group. Symptoms on other PTSD clusters and total score did not significantly differ between groups. Equivalent proportions of the blast and non-blast groups endorsed severe PTSD symptoms, with total PCL-C scores greater than or equal to 50. CONCLUSIONS Consistent with prior reports, high levels of posttraumatic stress symptoms occur in a substantial proportion of service members who experienced deployment-related blast and non-blast mTBI. Results suggest that the psychological rehabilitation of OIF/OEF service members with mTBI from explosive blast should include particular attention to addressing re-experiencing symptoms.

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.

Central sensitization as a component of post-deployment syndrome

Many service members and veterans report chronic unexplained symptoms such as pain, fatigue and memory complaints, which have most recently been characterized as post-deployment syndrome (PDS). Chronic widespread pain is a component of this syndrome, producing significant disability and considerable health care costs. The similarity between the nature of these complaints and other medically unexplained illnesses such as fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome suggest that they may share a common mechanism. Here, we provide support for PDS as a consequence of pain and sensory amplification secondary to neuroplastic changes within the central nervous system, a phenomenon often termed central sensitization. We also discuss how factors such as stress and genetics may promote chronic widespread pain in veterans and service members who develop PDS.

Factors associated with neurocognitive performance in OIF/OEF servicemembers with postconcussive complaints in postdeployment clinical settings.

Cognitive difficulties are frequently reported by Operation Enduring Freedom /Operation Iraqi Freedom military personnel who sustained mild traumatic brain injuries (TBIs). The current study examined several potential factors that may contribute to self-reported cognitive difficulties in postdeployment clinical settings. Eighty-four subjects who sustained a mild or moderate TBI and reported cognitive difficulties underwent neurocognitive testing. Multiple regression analyses were used to determine the amount of variance in neurocognitive performance accounted for by the predictor variables (demographic, mechanism of injury, time since injury, headache severity, combat stress, postconcussive complaints, and effort/performance validity). The predictor variables collectively accounted for 51.7% of the variance in cognitive performance (F (8,72) = 11/99, p < 0.001). The most potent predictor of cognitive functioning was performance validity/effort, which uniquely accounted for 16.3% of the variance (p < 0.01). Self-reported symptom severity, including postconcussive complaints, combat stress, and headache intensity, accounted for 7.2% of the variance (p < 0.05). Demographic factors and injury characteristics, such as time since injury and mechanism of injury, were not significant predictive factors of cognitive performance. The findings of the current study underscore the need to include measurement of effort as part of neurocognitive evaluation in postdeployment settings when evaluating cognitive complaints associated with mild TBI.

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.

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.

Anhedonia in combat veterans with penetrating head injury

Anhedonia is a common symptom following traumatic brain injury. The neural basis of anhedonia is poorly understood, but believed to involve disturbed reward processing, rather than the loss of sense of pleasure. This analysis was undertaken to determine if injury to specific regions of prefrontal cortex (PFC) result in anhedonia. A CT-based lesion analysis was undertaken in 192 participants of the Vietnam Head Injury Study, most with penetrating head injury. Participants were divided into left and right ventrolateral prefrontal, bilateral ventromedial prefrontal, and other injury locations. Anhedonia was measured by self-report in each group using the four-item anhedonia subscale score of the Beck Depression Inventory-II. Individuals with right ventrolateral injury reported greater severity of anhedonia compared to those with injury in the left ventrolateral region. These findings support an association between injury in the right ventrolateral PFC and anhedonia.

MRI in Management of Mild TBI/Concussion in the Deployed Setting

Magnetic resonance imaging (MRI) has specific limitations in theater and has unique requirements for its safe use with patients which require additional technician training and strict adherence to MRI-specific safety protocols. Neuroimaging is recommended for the evaluation of service members with clinical red flags new onset or persistent or worsening symptoms, and individuals whose recovery is not progressing as anticipated. This article is a brief discussion of when MRI is appropriate.

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.

Examination of corticothalamic fiber projections in United States service members with mild traumatic brain injury

Mild traumatic brain injury (mTBI) is characterized clinically by a closed head injury involving differential or rotational movement of the brain inside the skull. Over 3 million mTBIs occur annually in the United States alone. Many of the individuals who sustain an mTBI go on to recover fully, but around 20% experience persistent symptoms. These symptoms often last for many weeks to several months. The thalamus, a structure known to serve as a global networking or relay system for the rest of the brain, may play a critical role in neurorehabiliation and its integrity and connectivity after injury may also affect cognitive outcomes. To examine the thalamus, conventional tractography methods to map corticothalamic pathways with diffusion-weighted MRI (DWI) lead to sparse reconstructions that may contain false positive fibers that are anatomically inaccurate. Using a specialized method to zero in on corticothalamic pathways with greater robustness, we noninvasively examined corticothalamic fiber projections using DWI, in 68 service members. We found significantly lower fractional anisotropy (FA), a measure of white matter microstructural integrity, in pathways projecting to the left pre- and postcentral gyri – consistent with sensorimotor deficits often found post-mTBI. Mapping of neural circuitry in mTBI may help to further our understanding of mechanisms underlying recovery post-TBI.