Development and Validation of the Veteran Military Occupational and Environmental Exposure Assessment Tool.

INTRODUCTION: Military exposures may present a cumulative load and increased individual susceptibility to negative health outcomes. Currently, there are no comprehensive and validated environmental exposure assessment tools covering the full spectrum of occupational and environmental exposures for Veterans. The Veterans Affairs (VA) War Related Illness and Injury Study Center in Washington, DC, developed the Veteran Military Occupational and Environmental Exposure Assessment Tool (VMOAT) to establish a structured, comprehensive self-report tool that captures military and non-military occupational and environmental exposures. The VMOAT is clinically insightful, modular, and flexible for adding novel exposures, meeting the needs of modern evolving threats and exposures in both clinical and research settings. This manuscript reviews the ongoing development and validation plans for the VMOAT. MATERIALS AND METHODS: The VMOAT is a self-reported structured questionnaire, and VMOAT 1.0 was developed to cover an individual's 3 life phases (pre, during, post-military service); 5 exposure domains (chemical, physical, biological, injuries including ergonomic, and psychological stress exposures, plus military preventive health measures); and 64 specific exposures nested within exposure categories. VMOAT 1.0 addresses exposure dose (frequency, duration, proximity, route), and can be administered online via VA approved Qualtrics survey software. VMOAT 1.0 to 2.0 updates began in December 2022 with changes focused on readability, streamlining the exposure history, refining the exposure metrics, and improving the skip logic embedded within the survey design. RESULTS: The initial VMOAT 1.0 development included face and construct validation with expert internal and external academic and military collaborators, undergoing an iterative 5-cycle review as well as sample testing among a small group of Veterans. The VMOAT 1.0 was used in Institutional Review Board (IRB)-approved longitudinal study, which has been examined preliminarily to compare the VMOAT 1.0 with other exposure assessments and to compare responses of Explosive Ordnance Disposal Veterans, a high occupational exposure cohort, to non-Explosive Ordnance Disposal Veterans. Ongoing VMOAT 2.0 updates will include integration of experiences from piloting the VMOAT 1.0 as well as additional face and content validation and survey cognitive testing with Veterans. VMOAT 2.0 data will improve the development of exposure-informed models using composite survey data to create scored- and scale-based exposure metrics for specific exposures and exposure domains. These data will highlight the effectiveness of the VMOAT as a structured comprehensive occupational and environmental exposure assessment instrument. CONCLUSIONS: VMOAT development supports the 2022 Promise to Address Comprehensive Toxics Act and fits into the existing VA exposure assessment approach as a standardized, comprehensive self-reported exposure assessment tool. It can be utilized as a stand-alone instrument or supplemented by clinician interviews in research or specialty evaluation programs. The collected VMOAT self-report information on military occupational and environmental exposures will allow direct evaluation with objective measures of exposure and health outcomes. These data outcomes have a high potential to guide the DoD and VA environmental exposure risk mitigation and risk communication efforts.

Linked Exposures Across Databases: an exposure common data elements aggregation framework to facilitate clinical exposure review.

Understanding the health outcomes of military exposures is of critical importance for Veterans, their health care team, and national leaders. Approximately 43% of Veterans report military exposure concerns to their VA providers. Understanding the causal influences of environmental exposures on health is a complex exposure science task and often requires interpreting multiple data sources; particularly when exposure pathways and multi-exposure interactions are ill-defined, as is the case for complex and emerging military service exposures. Thus, there is a need to standardize clinically meaningful exposure metrics from different data sources to guide clinicians and researchers with a consistent model for investigating and communicating exposure risk profiles. The Linked Exposures Across Databases (LEAD) framework provides a unifying model for characterizing exposures from different exposure databases with a focus on providing clinically relevant exposure metrics. Application of LEAD is demonstrated through comparison of different military exposure data sources: Veteran Military Occupational and Environmental Exposure Assessment Tool (VMOAT), Individual Longitudinal Exposure Record (ILER) database, and a military incident report database, the Explosive Ordnance Disposal Information Management System (EODIMS). This cohesive method for evaluating military exposures leverages established information with new sources of data and has the potential to influence how military exposure data is integrated into exposure health care and investigational models.

A regulatory pathway model of neuropsychological disruption in Havana syndrome.

Introduction: In 2016 diplomatic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurological symptoms consistent with brain injury. The etiology of these Anomalous Health Incidents (AHI) and subsequent symptoms remains unknown. This report investigates putative exposure-symptom pathology by assembling a network model of published bio-behavioral pathways and assessing how dysregulation of such pathways might explain loss of function in these subjects using data available in the published literature. Given similarities in presentation with mild traumatic brain injury (mTBI), we used the latter as a clinically relevant means of evaluating if the neuropsychological profiles observed in Havana Syndrome Havana Syndrome might be explained at least in part by a dysregulation of neurotransmission, neuro-inflammation, or both. Method: Automated text-mining of >9,000 publications produced a network consisting of 273 documented regulatory interactions linking 29 neuro-chemical markers with 9 neuropsychological constructs from the Brief Mood Survey, PTSD Checklist, and the Frontal Systems Behavior Scale. Analysis of information flow through this network produced a set of regulatory rules reconciling to within a 6% departure known mechanistic pathways with neuropsychological profiles in N = 6 subjects. Results: Predicted expression of neuro-chemical markers that jointly satisfy documented pathways and observed symptom profiles display characteristically elevated IL-1B, IL-10, NGF, and norepinephrine levels in the context of depressed BDNF, GDNF, IGF1, and glutamate expression (FDR < 5%). Elevations in CRH and IL-6 were also predicted unanimously across all subjects. Furthermore, simulations of neurological regulatory dynamics reveal subjects do not appear to be "locked in" persistent illness but rather appear to be engaged in a slow recovery trajectory. Discussion: This computational analysis of measured neuropsychological symptoms in Havana-based diplomats proposes that these AHI symptoms may be supported in part by disruption of known neuroimmune and neurotransmission regulatory mechanisms also associated with mTBI.

Randomized controlled trial protocol of health coaching for veterans with complex chronic pain.

BACKGROUND: Pain predominant multisymptom illness (pain-CMI) refers to symptom-based conditions where pain is a primary symptom. There is initial evidence that health coaching may be efficacious in treating pain-CMI because it can be tailored to the veteran's goals and emphasizes long-term behavior change, which may indirectly impact the maintaining factors of pain-CMI (e.g., catastrophizing, poor pain control, and limited activity). This paper describes the study protocol and rationale of a randomized controlled trial that will compare the efficacy of remote-delivered health coaching in reducing disability and pain impairment for veterans with pain-CMI to remote-delivered supportive psychotherapy. METHODS: This randomized controlled trial will consist of two treatment arms: remote-delivered health coaching and remote-delivered supportive psychotherapy, the active control. Each treatment condition will consist of twelve, weekly one-on-one meetings with a study provider. In addition to the baseline assessment, participants will also complete 6-week (mid-treatment), 12-week (post-treatment), and 24-week (follow-up) assessments that consist of questionnaires that can be completed remotely. The primary aims for this study are to determine whether health coaching reduces disability and pain impairment as compared to supportive psychotherapy. We will also examine whether health coaching reduces physical symptoms, catastrophizing, limiting activity, and increasing pain control as compared to supportive psychotherapy. DISCUSSION: This study will contribute to the existing literature on pain-CMI and report the effectiveness of a novel, remote-delivered behavioral intervention.

Mapping the network biology of metabolic response to stress in posttraumatic stress disorder and obesity.

The co-occurrence of stress-induced posttraumatic stress disorder (PTSD) and obesity is common, particularly among military personnel but the link between these conditions is unclear. Individuals with comorbid PTSD and obesity manifest other physical and psychological problems, which significantly diminish their quality of life. Current understanding of the pathways connecting stress to PTSD and obesity is focused largely on behavioral mediators alone with little consideration of the biological regulatory mechanisms that underlie their co-occurrence. In this work, we leverage prior knowledge to systematically highlight such bio-behavioral mechanisms and inform on the design of confirmatory pilot studies. We use natural language processing (NLP) to extract documented regulatory interactions involved in the metabolic response to stress and its impact on obesity and PTSD from over 8 million peer-reviewed papers. The resulting network describes the propagation of stress to PTSD and obesity through 34 metabolic mediators using 302 documented regulatory interactions supported by over 10,000 citations. Stress jointly affected both conditions through 21 distinct pathways involving only two intermediate metabolic mediators out of a total of 76 available paths through this network. Moreover, oxytocin (OXT), Neuropeptide-Y (NPY), and cortisol supported an almost direct propagation of stress to PTSD and obesity with different net effects. Although stress upregulated both NPY and cortisol, the downstream effects of both markers are reported to relieve PTSD severity but exacerbate obesity. The stress-mediated release of oxytocin, however, was found to concurrently downregulate the severity of both conditions. These findings highlight how a network-informed approach that leverages prior knowledge might be used effectively in identifying key mediators like OXT though experimental verification of signal transmission dynamics through each path will be needed to determine the actual likelihood and extent of each marker's participation.

The relationship between Gulf War Illness symptom severity and heart rate variability: A pilot study.

INTRODUCTION: Gulf War Illness (GWI) is a chronic multisymptom illness affecting 250,000+ veterans of the '90-'91 Gulf War which remains under-explored in terms of its physiological characteristics. We investigated whether subjective GWI symptom severity scores were related to objective measures of autonomic nervous system activity. METHODS: We estimated activity in the two major branches of the autonomic nervous system (the parasympathetic nervous system [PNS] and the sympathetic nervous system [SNS]) via metrics of heart rate variability in a sample of Veterans who met established criteria for GWI with varying degrees of self-reported symptom severity. We hypothesized that subjective symptom severity scores would be inversely related to PNS activity and positively related to SNS activity. RESULTS: Significant negative relationships were observed between the root mean square of successive differences of beat-to-beat intervals (a measure of PNS activity) and symptom severity, both overall and across specific GWI symptom categories (sp. fatigue [r = -0.574], gastrointestinal [r = -0.544]). Furthermore, significant positive relationships were observed between the cardiac sympathetic index and symptom severity, both overall and across specific symptom categories (sp. cognitive [r = 0.721], fatigue [r = 0.560], gastrointestinal [r = 0.694], skin [r = 0.686]). CONCLUSIONS: Metrics of PNS activation revealed a negative relationship with self-reported symptom severity, while metrics of SNS activation revealed a positive relationship. The present results improve our understanding of the physiology of GWI and provide a new window from which to consider this medically unexplained illness.

Single-Trial Mechanisms Underlying Changes in Averaged P300 ERP Amplitude and Latency in Military Service Members After Combat Deployment.

Attenuation in P300 amplitude has been characterized in a wide range of neurological and psychiatric disorders such as dementia, schizophrenia, and posttraumatic stress disorder (PTSD). However, it is unclear whether the attenuation observed in the averaged event-related potential (ERP) is due to the reduction of neural resources available for cognitive processing, the decreased consistency of cognitive resource allocation, or the increased instability of cognitive processing speed. In this study, we investigated this problem by estimating single-trial P300 amplitude and latency using a modified Woody filter and examined the relation between amplitudes and latencies from the single-trial level to the averaged ERP level. ERPs were recorded from 30 military service members returning from combat deployment at two time points separated by 6 or 12 months. A conventional visual oddball task was used to elicit P300. We observed that the extent of changes in the within-subject average P300 amplitude over time was significantly correlated with the amount of change in three single-trial measures: (1) the latency variance of the single-trial P300 (r = -0.440, p = 0.0102); (2) the percentage of P300-absent trials (r = -0.488, p = 0.005); and (3) the consistent variation of the single-trial amplitude (r = 0.571, p = 0.0022). These findings suggest that there are multiple underlying mechanisms on the single-trial level that contribute to the changes in amplitudes seen at the averaged ERP level. The changes between the first and second assessments were quantified with the intraclass correlation coefficient, the standard error of measurement and the minimal detectable difference. The unique population, the small sample size and the large fraction of participants lost to follow up precludes generalizations of these measures of change to other populations.

Increased cognitive control and reduced emotional interference is associated with reduced PTSD symptom severity in a trauma-exposed sample: A preliminary longitudinal study.

Individuals with posttraumatic stress disorder (PTSD) show deficits in recruiting neural regions associated with cognitive control. In contrast, trauma exposed individuals (TEIs) show increased recruitment of these regions. While many individuals who experience a trauma exhibit some PTSD symptoms, relatively few develop PTSD. Despite this, no work has examined the relationship between changes in PTSD symptoms and changes in neural functioning in TEIs longitudinally. This study examined the neural correlates of changing PTSD symptom levels in TEIs. Twenty-one military service members completed the affective stroop task while undergoing fMRI within 2 months of returning from deployment and a second scan 6-12 months later. Participants with PTSD or depression at baseline were excluded. PTSD symptom improvement was associated with greater increase in response to incongruent relative to congruent negative stimuli in dorsal anterior cingulate cortex and inferior frontal gyrus/anterior insula and increased BOLD response over time to emotional relative to neutral stimuli in inferior parietal cortex. Improvement in PTSD symptoms were not associated with changes in amygdala responsiveness to emotional stimuli. In short, the current data indicate that TEIs who become more able to recruit regions implicated in cognitive control show greater reductions in PTSD symptom levels.

Utility of P300 ERP in monitoring post-trauma mental health: A longitudinal study in military personnel returning from combat deployment.

Military service members (SMs) returning from combat are at high risk of developing neuropsychiatric conditions such as posttraumatic stress disorder (PTSD) and major depression. Symptom dynamics following reintegration into civilian life may be magnified over time such that some SMs present with delayed onset and may not reach a diagnostic threshold for months to years. Monitoring the trajectory of mental health in the aftermath of combat trauma can therefore be particularly important in enhancing diagnosis. In this study, we investigated the possible utility of the P300 event-related potential (ERP) as an objective marker for monitoring post-trauma mental health. SMs recently returned from a combat deployment were recruited to undergo a baseline assessment, with subsequent follow-up assessment at 6 or 12 months later. At each assessment, ERPs were recorded using a conventional visual oddball task and a set of psychological scores assessing PTSD, depression, and psychosocial functioning were obtained. We observed that the individuals with overall improved psychological scores at follow-up had increased P300 amplitude and shortened P300 latency, and the individuals with overall worsened psychological scores at follow-up had prolonged P300 latency. The degree of change in aggregate psychological score was significantly correlated with the magnitude of change in P300 amplitude (r = -0.72, p < 0.0001) and latency (r = 0.42, p = 0.0201). These findings suggest that the P300 may be utilized as a quantitative biomarker for tracking the changes of mental health longitudinally. It may offer clinicians an objective tool for the assessment of the dynamics of mental health following trauma, and perhaps also for monitoring recovery during treatment.

Disrupted Gamma Synchrony after Mild Traumatic Brain Injury and Its Correlation with White Matter Abnormality.

Mild traumatic brain injury (mTBI) has been firmly associated with disrupted white matter integrity due to induced white matter damage and degeneration. However, comparatively less is known about the changes of the intrinsic functional connectivity mediated via neural synchronization in the brain after mTBI. Moreover, despite the presumed link between structural and functional connectivity, no existing studies in mTBI have demonstrated clear association between the structural abnormality of white matter axons and the disruption of neural synchronization. To investigate these questions, we recorded resting state EEG and diffusion tensor imaging (DTI) from a cohort of military service members. A newly developed synchronization measure, the weighted phase lag index was applied on the EEG data for estimating neural synchronization. Fractional anisotropy was computed from the DTI data for estimating white matter integrity. Fifteen service members with a history of mTBI within the past 3 years were compared to 22 demographically similar controls who reported no history of head injury. We observed that synchronization at low-gamma frequency band (25-40 Hz) across scalp regions was significantly decreased in mTBI cases compared with controls. The synchronization in theta (4-7 Hz), alpha (8-13 Hz), and beta (15-23 Hz) frequency bands were not significantly different between the two groups. In addition, we found that across mTBI cases, the disrupted synchronization at low-gamma frequency was significantly correlated with the white matter integrity of the inferior cerebellar peduncle, which was also significantly reduced in the mTBI group. These findings demonstrate an initial correlation between the impairment of white matter integrity and alterations in EEG synchronization in the brain after mTBI. The results also suggest that disruption of intrinsic neural synchronization at low-gamma frequency may be a characteristic functional pathology following mTBI and may prove useful for developing better methods of diagnosis and treatment.

An App a Day Keeps the Doctor Away: Guided Education and Training via Smartphones in Subthreshold Post Traumatic Stress Disorder.

Post traumatic stress disorder (PTSD) symptoms are common in military service members (SMs), but stigma can impede treatment initiation. Smartphone applications (apps) are available anywhere, anytime, with the potential to both mitigate the impact of stigma and reduce PTSD symptom severity. We provided 144 SMs or family members, with subthreshold PTSD symptoms (PTSD Checklist [PCL] scores of 28-49), with apps promoting psychoeducation, social engagement, and relaxation and randomized them to 6 weeks of resilience enhancement (brief cognitive-behavioral session, followed by daily text messages directing app use) or a control group (daily text messages of inspirational quotes). Participants (54 percent males, 87 percent SMs) in both groups reported reductions in PTSD, anxiety, and depression symptoms during the 6-week intervention, which were sustained at 3 months, but exhibited partial rebound at 6-12 months. Our preliminary results suggest that app use, with or without specific direction, feasibly and effectively reduces symptom severity. Future studies should consider a longer intervention, enhanced compliance tracking, or boosters to sustain benefits.

Identifying Electrophysiological Prodromes of Post-traumatic Stress Disorder: Results from a Pilot Study.

The objective of this research project is the identification of a physiological prodrome of post-traumatic stress disorder (PTSD) that has a reliability that could justify preemptive treatment in the sub-syndromal state. Because abnormalities in event-related potentials (ERPs) have been observed in fully expressed PTSD, the possible utility of abnormal ERPs in predicting delayed-onset PTSD was investigated. ERPs were recorded from military service members recently returned from Iraq or Afghanistan who did not meet PTSD diagnostic criteria at the time of ERP acquisition. Participants (n = 65) were followed for up to 1 year, and 7.7% of the cohorts (n = 5) were PTSD-positive at follow-up. The initial analysis of the receiver operating characteristic (ROC) curve constructed using ERP metrics was encouraging. The average amplitude to target stimuli gave an area under the ROC curve of greater than 0.8. Classification based on the Youden index, which is determined from the ROC, gave positive results. Using average target amplitude at electrode Cz yielded Sensitivity = 0.80 and Specificity = 0.87. A more systematic statistical analysis of the ERP data indicated that the ROC results may simply represent a fortuitous consequence of small sample size. Predicted error rates based on the distribution of target ERP amplitudes approached those of random classification. A leave-one-out cross validation using a Gaussian likelihood classifier with Bayesian priors gave lower values of sensitivity and specificity. In contrast with the ROC results, the leave-one-out classification at Cz gave Sensitivity = 0.65 and Specificity = 0.60. A bootstrap calculation, again using the Gaussian likelihood classifier at Cz, gave Sensitivity = 0.59 and Specificity = 0.68. Two provisional conclusions can be offered. First, the results can only be considered preliminary due to the small sample size, and a much larger study will be required to assess definitively the utility of ERP prodromes of PTSD. Second, it may be necessary to combine ERPs with other biomarkers in a multivariate metric to produce a prodrome that can justify preemptive treatment.

Neural Efficiency in Expert Cognitive-Motor Performers During Affective Challenge.

Skilled individuals demonstrate a spatially localized or relatively lower response in brain activity characterized as neural efficiency when performing within their domain of expertise. Elite athletes are experts in their chosen sport and thus must be not only adept in the motor domain but must be resilient to performing under the stress of high-level competition. Such stability of performance suggests this population processes emotion and mental stress in an adaptive and efficient manner. This study sought to determine if athletes with a history of successful performance under circumstances of mental stress demonstrate neural efficiency during affective challenges compared to age-matched controls. Using functional magnetic resonance imaging, the blood-oxygen level-dependent response was recorded during emotional challenge induced by sport-specific and general unpleasant images. The athletes demonstrated neural efficiency in brain regions critical to emotion regulation (prefrontal cortex) and affect (insula) independently of their domain of expertise, suggesting adaptive processing of negative events and less emotional reactivity to unpleasant stimuli.

Psychophysiological Investigation of Combat Veterans with Subthreshold Post-traumatic Stress Disorder Symptoms.

OBJECTIVE: Military service members (SMs) with subthreshold combat-related post-traumatic stress disorder (PTSD) symptoms often have clinically significant functional impairment, even though they do not meet full PTSD criteria. We therefore assessed the psychophysical responses of SMs, upon their return from Afghanistan or Iraq, to a fear conditioning paradigm to better understand the biological underpinnings of symptom severity. METHODS: Heart rate (HR), skin conductance, electromyography startle, and respiratory rate (RR) were monitored throughout three distinct phases of the paradigm-fear acquisition, fear inhibition, and fear extinction-while plasma catecholamines (epinephrine, norepinephrine, and dopamine) were measured at the end of fear inhibition. RESULTS: Those with higher PTSD symptom severity demonstrated elevations in HR and startle response to danger cues; elevated self-reported depression and anxiety; impaired functional status; poor skin conductance discrimination between danger and safety; and increases in HR and RR during fear extinction. Moreover, an inverse relationship was seen between plasma dopamine and HR during fear inhibition for those with high symptoms. CONCLUSION: Overall, the physiological responses we observed in our subthreshold PTSD population parallel what has been previously observed in full PTSD, making a case for addressing subthreshold PTSD symptoms in combat veterans.

White matter microstructure of the uncinate fasciculus is associated with subthreshold posttraumatic stress disorder symptoms and fear potentiated startle during early extinction in recently deployed Service Members.

Early intervention following combat deployment has the potential to prevent posttraumatic stress disorder (PTSD), but there is a need for greater understanding of the factors that contribute to PTSD symptom progression. This study investigated: (1) fear-potentiated startle during a fear extinction, (2) white matter microstructure, and (3) PTSD symptom severity, in 48 recently deployed service members (SMs) who did not have sufficient PTSD symptoms to meet criteria for a clinical diagnosis. Electromyography startle during a conditional discrimination paradigm, diffusion tensor imaging, and the Clinician Administered PTSD Scale were assessed in a cohort of SMs within 2 months after their return from Iraq or Afghanistan. Significant correlations were found between left uncinate fasciculus (UF) white matter tract integrity and total PTSD symptoms, r=-0.343, p=0.018; the left UF and hyperarousal symptoms, r=-0.29, p=0.047; right UF integrity and total PTSD symptoms r=-0.3371, p=0.01; right UF integrity and hyperarousal symptoms r=-0.332, p=0.023; left UF and startle during early extinction, r=.31, p=0.033. Our results indicate that compromise of UF tract frontal-limbic connections are associated with greater PTSD symptom severity and lower startle response during extinction. In a subthreshold population, such a relationship between brain structure, physiological reactivity, and behavioral expression may reveal vulnerabilities that could have significant implications for PTSD symptom development.

Functional neuroimaging correlates of thinking flexibility and knowledge structure in memory: Exploring the relationships between clinical reasoning and diagnostic thinking.

BACKGROUND: Diagnostic reasoning involves the thinking steps up to and including arrival at a diagnosis. Dual process theory posits that a physician's thinking is based on both non-analytic or fast, subconscious thinking and analytic thinking that is slower, more conscious, effortful and characterized by comparing and contrasting alternatives. Expertise in clinical reasoning may relate to the two dimensions measured by the diagnostic thinking inventory (DTI): memory structure and flexibility in thinking. AIM: Explored the functional magnetic resonance imaging (fMRI) correlates of these two aspects of the DTI: memory structure and flexibility of thinking. METHODS: Participants answered and reflected upon multiple-choice questions (MCQs) during fMRI. A DTI was completed shortly after the scan. The brain processes associated with the two dimensions of the DTI were correlated with fMRI phases - assessing flexibility in thinking during analytical clinical reasoning, memory structure during non-analytical clinical reasoning and the total DTI during both non-analytical and analytical reasoning in experienced physicians. RESULTS: Each DTI component was associated with distinct functional neuroanatomic activation patterns, particularly in the prefrontal cortex. CONCLUSION: Our findings support diagnostic thinking conceptual models and indicate mechanisms through which cognitive demands may induce functional adaptation within the prefrontal cortex. This provides additional objective validity evidence for the use of the DTI in medical education and practice settings.

Predictors of Neurocognitive Syndromes in Combat Veterans.

Traumatic brain injury, depression and posttraumatic stress disorder (PTSD) are neurocognitive syndromes often associated with impairment of physical and mental health, as well as functional status. These syndromes are also frequent in military service members (SMs) after combat, although their presentation is often delayed until months after their return. The objective of this prospective cohort study was the identification of independent predictors of neurocognitive syndromes upon return from deployment could facilitate early intervention to prevent disability. We completed a comprehensive baseline assessment, followed by serial evaluations at three, six, and 12 months, to assess for new-onset PTSD, depression, or postconcussive syndrome (PCS) in order to identify baseline factors most strongly associated with subsequent neurocognitive syndromes. On serial follow-up, seven participants developed at least one neurocognitive syndrome: five with PTSD, one with depression and PTSD, and one with PCS. On univariate analysis, 60 items were associated with syndrome development at p < 0.15. Decision trees and ensemble tree multivariate models yielded four common independent predictors of PTSD: right superior longitudinal fasciculus tract volume on MRI; resting state connectivity between the right amygdala and left superior temporal gyrus (BA41/42) on functional MRI; and single nucleotide polymorphisms in the genes coding for myelin basic protein as well as brain-derived neurotrophic factor. Our findings require follow-up studies with greater sample size and suggest that neuroimaging and molecular biomarkers may help distinguish those at high risk for post-deployment neurocognitive syndromes.

Catecholamine responses to virtual combat: implications for post-traumatic stress and dimensions of functioning.

Posttraumatic stress disorder (PTSD) symptoms can result in functional impairment among service members (SMs), even in those without a clinical diagnosis. The variability in outcomes may be related to underlying catecholamine mechanisms. Individuals with PTSD tend to have elevated basal catecholamine levels, though less is known regarding catecholamine responses to trauma-related stimuli. We assessed whether catecholamine responses to a virtual combat environment impact the relationship between PTSD symptom clusters and elements of functioning. Eighty-seven clinically healthy SMs, within 2 months after deployment to Iraq or Afghanistan, completed self-report measures, viewed virtual-reality (VR) combat sequences, and had sequential blood draws. Norepinephrine responses to VR combat exposure moderated the relationship between avoidance symptoms and scales of functioning including physical functioning, physical-role functioning, and vitality. Among those with high levels of avoidance, norepinephrine change was inversely associated with functional status, whereas a positive correlation was observed for those with low levels of avoidance. Our findings represent a novel use of a virtual environment to display combat-related stimuli to returning SMs to elucidate mind-body connections inherent in their responses. The insight gained improves our understanding of post-deployment symptoms and quality of life in SMs and may facilitate enhancements in treatment. Further research is needed to validate these findings in other populations and to define the implications for treatment effectiveness.

Relationship of neuroimaging to typical sleep times during a clinical reasoning task: a pilot study.

BACKGROUND: Sleep deprivation and fatigue have been associated with medical errors, clinical performance decrements, and reduced quality of life for both practicing physicians and medical students. Greater understanding of the impact of sleep quantity on clinical reasoning could improve patient care. The purpose of our pilot study was to examine relationships between clinical reasoning (assessed by functional magnetic resonance imaging) and sleep time (measured in different ways by actigraphy) while answering multiple-choice questions (MCQs) from licensing agencies. METHODS: Residents and faculty were administered a clinical reasoning exercise (MCQs from licensing bodies) during functional magnetic resonance imaging. Usual sleep patterns were sampled with actigraphy. Covariate analysis was used to examine the relationship between sleep duration (mean sleep, minimum sleep, maximum sleep) and brain activity during clinical reasoning (solving MCQs from licensing bodies). RESULTS: The mean sleep time over the duration of monitoring for the group was 7.19 hours (SD 0.66) with a range of 6.1 to 8.1 hours (internal medicine faculty 7.1 hours, SD 0.41; internal medicine residents 7.27 hours, SD 0.92). There was a negative relationship between activation in the prefrontal cortex and minimum sleep time while reflecting on MCQs. CONCLUSION: Our findings provide evidence that the quantity of sleep can modulate brain activity while completing a clinically meaningful task that should be confirmed in larger studies. Our findings suggest that the construct of sleepiness may be more complex than appreciated by many and that the most important of these sleep measures in terms of outcomes remains to be determined.