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.

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.

Resting-State Correlations of Fatigue Following Military Deployment.

OBJECTIVE: Persistent fatigue is common among military servicemembers returning from deployment, especially those with a history of mild traumatic brain injury (mTBI). The purpose of this study was to characterize fatigue following deployment using the Multidimensional Fatigue Inventory (MFI), a multidimensional self-report instrument. The study was developed to test the hypothesis that if fatigue involves disrupted effort/reward processing, this should manifest as altered basal ganglia functional connectivity as observed in other amotivational states. METHODS: Twenty-eight current and former servicemembers were recruited and completed the MFI. All 28 participants had a history of at least one mTBI during deployment. Twenty-six participants underwent resting-state functional MRI. To test the hypothesis that fatigue was associated with basal ganglia functional connectivity, the investigators measured correlations between MFI subscale scores and the functional connectivity of the left and right caudate, the putamen, and the globus pallidus with the rest of the brain, adjusting for the presence of depression. RESULTS: The investigators found a significant correlation between functional connectivity of the left putamen and bilateral superior frontal gyri and mental fatigue scores. No correlations with the other MFI subscales survived multiple comparisons correction. CONCLUSIONS: This exploratory study suggests that mental fatigue in military servicemembers with a history of deployment with at least one mTBI may be related to increased striatal-prefrontal functional connectivity, independent of depression. A finding of effort/reward mismatch may guide future treatment approaches.

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.

Cingulo-Opercular and Frontoparietal Network Control of Effort and Fatigue in Mild Traumatic Brain Injury.

Neural substrates of fatigue in traumatic brain injury (TBI) are not well understood despite the considerable burden of fatigue on return to productivity. Fatigue is associated with diminishing performance under conditions of high cognitive demand, sense of effort, or need for motivation, all of which are associated with cognitive control brain network integrity. We hypothesize that the pathophysiology of TBI results in damage to diffuse cognitive control networks, disrupting coordination of moment-to-moment monitoring, prediction, and regulation of behavior. We investigate the cingulo-opercular (CO) and frontoparietal (FP) networks, which are engaged to sustain attention for task and maintain performance. A total of 61 individuals with mild TBI and 42 orthopedic control subjects participated in functional MRI during performance of a constant effort task requiring altering the amount of effort (25, 50, or 75% of maximum effort) utilized to manually squeeze a pneumostatic bulb across six 30-s trials. Network-based statistics assessed within-network organization and fluctuation with task manipulations by group. Results demonstrate small group differences in network organization, but considerable group differences in the evolution of task-related modulation of connectivity. The mild TBI group demonstrated elevated CO connectivity throughout the task with little variation in effort level or time on task (TOT), while CO connectivity diminished over time in controls. Several interregional CO connections were predictive of fatigue in the TBI group. In contrast, FP connectivity fluctuated with task manipulations and predicted fatigue in the controls, but connectivity fluctuations were delayed in the mild traumatic brain injury (mTBI) group and did not relate to fatigue. Thus, the mTBI group's hyper-connectivity of the CO irrespective of task demands, along with hypo-connectivity and delayed peak connectivity of the FP, may allow for attainment of task goals, but also contributes to fatigue. Findings are discussed in relation to performance monitoring of prediction error that relies on internal cues from sensorimotor feedback during task performance. Delay or inability to detect and respond to prediction errors in TBI, particularly evident in bilateral insula-temporal CO connectivity, corresponds to day-to-day fatigue and fatigue during task performance.

Testosterone and Resting State Connectivity of the Parahippocampal Gyrus in Men With History of Deployment-Related Mild Traumatic Brain Injury.

INTRODUCTION: The purpose of this study was to explore the effect of low testosterone level on whole-brain resting state (RS) connectivity in male veterans with symptoms such as sleep disturbance, fatiguability, pain, anxiety, irritability, or aggressiveness persisting after mild traumatic brain injury (mTBI). Follow-up analyses were performed to determine if sleep scores affected the results. MATERIALS AND METHODS: In our cross-sectional design study, RS magnetic resonance imaging scans on 28 veterans were performed, and testosterone, sleep quality, mood, and post-traumatic stress symptoms were measured. For each participant, we computed the average correlation of each voxel's time-series with the rest of the voxels in the brain, then used AFNI's 3dttest++ on the group data to determine whether the effects of testosterone level on whole-brain connectivity were significant. We then performed follow-up region of interest-based RS analyses of testosterone, with and without sleep quality as a covariate. The study protocol was approved by the National Institute of Health's Combined Neuroscience Institutional Review Board. RESULTS: Sixteen participants reported repeated blast exposure in theater, leading to symptoms; the rest reported exposure to a single blast or a nonblast TBI. Thirty-three percent had testosterone levels <300 ng/dL. Testosterone level was lower in participants who screened positive for post-traumatic stress disorder compared to those who screened negative, but it did not reach statistical significance. Whole-brain connectivity and testosterone level were positively correlated in the left parahippocampal gyrus (LPhG), especially in its connectivity with frontal areas, the lingual gyrus, cingulate, insula, caudate, and right parahippocampal gyrus. Further analysis revealed that the effect of testosterone on LPhG connectivity is only partially mediated by sleep quality. Sleep quality by itself had an effect on connectivity of the thalamus, cerebellum, precuneus, and posterior cingulate. CONCLUSION: Lower testosterone levels were correlated with lower connectivity of the LPhG. Weaknesses of this study include a retrospective design based on self-report of mTBI and the lack of a control group without TBI. Without a control group or pre-injury testosterone measures, we were not able to attribute the rate of low testosterone in our participants to TBI per se. Also testosterone levels were checked only once. The high rate of low testosterone level that we found suggests there may be an association between low testosterone level and greater post-traumatic stress disorder symptoms following deployment, but the causality of the relationships between TBI and deployment stress, testosterone level, behavioral symptomatology, and LPhG connectivity remains to be determined. Our study on men with persistent symptoms postdeployment and post-mTBI may help us understand the role of low testosterone and sleep quality in persistent symptoms and may be important in developing therapeutic interventions. Our results highlight the role of the LPhG, as we found that whole-brain connectivity in that region was positively associated with testosterone level, with only a limited portion of that effect attributable to sleep quality.

Barriers and facilitators to implementation of epilepsy self-management programs: a systematic review using qualitative evidence synthesis methods.

BACKGROUND: Epilepsy affects nearly 50 million people worldwide. Self-management is critical for individuals with epilepsy in order to maintain optimal physical, cognitive, and emotional health. Implementing and adopting a self-management program requires considering many factors at the person, program, and systems levels. We conducted a systematic review of qualitative and mixed-methods studies to identify facilitators and barriers that impact implementation and adoption of self-management programs for adults with epilepsy. METHODS: We used established systematic review methodologies for qualitative and mixed-methods studies. We included studies addressing facilitators (i.e., factors that aided) or barriers (i.e., factors that impeded) to implementation and adoption of self-management interventions for adults with epilepsy. We conducted a narrative thematic synthesis to identify facilitators and barriers. RESULTS: The literature search identified 2700 citations; 13 studies met eligibility criteria. Our synthesis identified five themes that categorize facilitators and barriers to successful implementation epilepsy self-management: (1) relevance, intervention content that facilitates acquisition of self-management skills; (2) personalization, intervention components that account for the individual's social, physical, and environmental characteristics; (3) intervention components, components and dosing of the intervention; (4) technology considerations, considerations that account for individual's use, familiarity with, and ownership of technology; and (5) clinician interventionist, role and preparation of the individual who leads intervention. We identified facilitators in 11 of the 13 studies and barriers in 11 of the 13 studies and classified these by social-ecological level (i.e., patient/caregiver, program, site/system). CONCLUSION: Identification of facilitators and barriers at multiple levels provides insight into disease-specific factors that influence implementation and adoption of self-management programs for individuals with epilepsy. Our findings indicate that involving individuals with epilepsy and their caregivers in intervention development, and then tailoring intervention content during the intervention, can help ensure the content is relevant to intervention participants. Our findings also indicate the role of the clinician (i.e., the individual who provides self-management education) is important to intervention implementation, and key issues with clinicians were identified as barriers and opportunities for improvement. Overall, our findings have practical value for those seeking to implement and adopt self-management interventions for epilepsy and other chronic illnesses. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number is CRD42018098604.

Self-management of Epilepsy: A Systematic Review.

Background: Although self-management is recommended for persons with epilepsy, its optimal strategies and effects are uncertain. Purpose: To evaluate the components and efficacy of self-management interventions in the treatment of epilepsy in community-dwelling persons. Data Sources: English-language searches of MEDLINE, Cochrane Central Register of Controlled Trials, PsycINFO, and CINAHL in April 2018; the MEDLINE search was updated in March 2019. Study Selection: Randomized and nonrandomized comparative studies of self-management interventions for adults with epilepsy. Data Extraction: An investigator assessed study characteristics; intervention details, including 6 components of self-management; and outcomes, which were verified by a second reviewer. Risk of bias (ROB) was assessed independently by 2 investigators. Data Synthesis: 13 randomized and 2 nonrandomized studies (2514 patients) evaluated self-management interventions. Interventions were delivered primarily in group settings, used a median of 4 components, and followed 2 general strategies: 1 based on education and the other on psychosocial therapy. Education-based approaches improved self-management behaviors (standardized mean difference, 0.52 [95% CI, 0.0 to 1.04]), and psychosocial therapy-based approaches improved quality of life (mean difference, 6.64 [CI, 2.51 to 10.77]). Overall, self-management interventions did not reduce seizure rates, but 1 educational intervention decreased a composite of seizures, emergency department visits, and hospitalizations. Limitation: High ROB in most studies, incomplete intervention descriptions, and studies limited to English-language publications. Conclusion: There is limited evidence that self-management strategies modestly improve some patient outcomes that are important to persons with epilepsy. Overall, self-management research in epilepsy is limited by the range of interventions tested, the small number of studies using self-monitoring technology, and uncertainty about components and strategies associated with benefit. Primary Funding Source: U.S. Department of Veterans Affairs. (PROSPERO: CRD42018098604).

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.

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.

Effort and Fatigue-Related Functional Connectivity in Mild Traumatic Brain Injury.

Mental fatigue in healthy individuals is typically observed under conditions of high cognitive demand, particularly when effort is required to perform a task for a long period of time-thus the concepts of fatigue and effort are closely related. In brain injured individuals, mental fatigue can be a persistent and debilitating symptom. Presence of fatigue after brain injury is prognostic for return to work/school and engagement in activities of daily life. As such, it should be a high priority for treatment in this population, but because there is little understanding of its behavioral and neural underpinnings, the target for such treatment is unknown. Here, the neural underpinnings of fatigue and effort are investigated in active duty military service members with mild traumatic brain injury (mTBI) and demographically-matched orthopedic controls. Participants performed a Constant Effort task for which they were to hold a pre-defined effort level constant for long durations during fMRI scanning. The task allowed for investigation of the neural systems underlying fatigue and their relationship with sense of effort. While brain activation associated with effort and fatigue did not differentiate the mTBI and controls, functional connectivity amongst active brain regions did. The mTBI group demonstrated immediate hyper-connectivity that increased with effort level but diminished quickly when there was a need to maintain effort. Controls, in contrast, demonstrated a similar pattern of hyper-connectivity, but only when maintaining effort over time. Connectivity, particularly between the left anterior insula, rostral anterior cingulate cortex, and right-sided inferior frontal regions, correlated with effort-level and state fatigue in mTBI participants. These connections also correlated with effort level in the Control group, but only the connection between the left insula and superior medial frontal gyrus correlated with fatigue, suggesting a differing pattern of connectivity. These findings align, in part, with the dopamine imbalance, and neural efficiency hypotheses that pose key roles for medial frontal connections with insular or striatal regions in motivating or optimizing performance. Sense of effort and fatigue are closely related. As people fatigue, sense of effort increases systematically. The data propose a complex link between sense of effort, fatigue, and mTBI that is centered in what may be an inefficient neural system due to brain trauma that warrants further investigation.

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.

PURPOSE: 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. METHODS: Volumetric data from 148 U.S. service members across three different experimental groups participating in a study of mild traumatic brain injury (mTBI) were examined. Groups included mTBI (n = 71), posttraumatic stress disorder (n = 22), or a noncranial orthopedic injury (n = 55). Correlation coefficients and nonparametric group mean comparisons were used to assess reliability and concurrent validity, respectively. RESULTS: Comparison of these methods across our entire sample demonstrates generally fair to excellent reliability as evidenced by large intraclass correlation coefficients (ICC = .4 to .99), but little concurrent validity as evidenced by significantly different Mann-Whitney U comparisons for 26 of 30 brain structures measured. CONCLUSION: While reliability between the two segmenting tools is fair to excellent, volumetric outcomes are statistically different between the two methods. As suggested by both developers, structure segmentation should be visually verified prior to clinical use and rigor should be used when interpreting results generated by either method.

Volumetric and shape analyses of subcortical structures in United States service members with mild traumatic brain injury.

Mild traumatic brain injury (mTBI) is a significant health concern. The majority who sustain mTBI recover, although ~20 % continue to experience symptoms that can interfere with quality of life. Accordingly, there is a critical need to improve diagnosis, prognostic accuracy, and monitoring (recovery trajectory over time) of mTBI. Volumetric magnetic resonance imaging (MRI) has been successfully utilized to examine TBI. One promising improvement over standard volumetric approaches is to analyze high-dimensional shape characteristics of brain structures. In this study, subcortical shape and volume in 76 Service Members with mTBI was compared to 59 Service Members with orthopedic injury (OI) and 17 with post-traumatic stress disorder (PTSD) only. FreeSurfer was used to quantify structures from T1-weighted 3 T MRI data. Radial distance (RD) and Jacobian determinant (JD) were defined vertex-wise on parametric mesh-representations of subcortical structures. Linear regression was used to model associations between morphometry (volume and shape), TBI status, and time since injury (TSI) correcting for age, sex, intracranial volume, and level of education. Volumetric data was not significantly different between the groups. JD was significantly increased in the accumbens and caudate and significantly reduced in the thalamus of mTBI participants. Additional significant associations were noted between RD of the amygdala and TSI. Positive trend-level associations between TSI and the amygdala and accumbens were observed, while a negative association was observed for third ventricle. Our findings may aid in the initial diagnosis of mTBI, provide biological targets for functional examination, and elucidate regions that may continue remodeling after injury.

Staying at the Cutting Edge: Partnership With a Level 1 Trauma Center Improves Clinical Currency and Wartime Readiness for Military Surgeons.

INTRODUCTION: Surgical currency is a critical component of medical corps readiness. We report a review of surgeons embedded into a civilian institution and analyze whether this improves surgical currency and wartime readiness. METHODS: Patient management and operative volume were acquired from four surgeons embedded at a civilian institution and compared to operative case loads of surgeons based at a military treatment facility (MTF). RESULTS: The surgeons embedded in the civilian institution had a mean of 49.3 cases compared to a mean of 8.3 cases for surgeons at the MTF over this 6-month period. In addition, the embedded surgeons obtained 44.4 to 94.7% of these cases during their civilian experience as opposed to cases done at the MTF. The cases performed by the embedded orthopedic surgeon (n = 247) was over 20 times the mean number of cases (mean = 12) performed at the MTF. Over a 6-month period, the trauma surgeon and general surgeon each evaluated 150 and 170 new trauma patients, respectively. In addition, the trauma/critical care surgeon cared for 250 critical care patients over this same 6-month period. CONCLUSION: This study demonstrates that embedding surgeons into a civilian institution allows them to maintain skill sets critical for currency and wartime readiness.

Online feedback enhances early consolidation of motor sequence learning and reverses recall deficit from transcranial stimulation of motor cortex.

Feedback and monetary reward can enhance motor skill learning, suggesting reward system involvement. Continuous theta burst (cTBS) transcranial magnetic stimulation (TMS) of the primary motor area (M1) disrupts processing, reduces excitability and impairs motor learning. To see whether feedback and reward can overcome the learning impairment associated with M1 cTBS, we delivered real or sham stimulation to two groups of participants before they performed a motor sequence learning task with and without feedback. Participants were trained on two intermixed sequences, one occurring 85% of the time (the "probable" sequence) and the other 15% of the time (the "improbable" sequence). We measured sequence learning as the difference in reaction time (RT) and error rate between probable and improbable trials (RT and error difference scores). Participants were also tested for sequence recall with the same indices of learning 60 min after cTBS. Real stimulation impaired initial sequence learning and sequence knowledge recall as measured by error difference scores and impaired sequence knowledge recall as measured by RT difference score. Relative to non-feedback learning, the introduction of feedback during sequence learning improved subsequent sequence knowledge recall indexed by RT difference score, in both real and sham stimulation groups and feedback reversed the RT difference score based sequence knowledge recall impairment from real cTBS that we observed in the non-feedback learning condition. Only the real cTBS group in the non-feedback condition showed no evidence of explicit sequence knowledge when tested at the end of the study. Feedback improves recall of implicit and explicit motor sequence knowledge and can protect sequence knowledge against the effect of M1 inhibition. Adding feedback and monetary reward/punishment to motor skill learning may help overcome retention impairments or accelerate training in clinical and other settings.

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.

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.

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.