Blast exposure results in tau and neurofilament light chain changes in peripheral blood.

OBJECTIVES: To evaluate how blast exposure impacts peripheral biomarkers.in military personnel enrolled in 10-day blast training. METHODS: On day 7, 21 military personnel experienced peak overpressure <2 pounds per square inch (psi); while 29 military personnel experienced peak overpressure ≥5 psi. Blood samples were collected each day to measure changes in amyloid beta (Aß), neurofilament light chain (NFL), and tau concentrations. RESULTS: Within 24 hours following exposure ≥5 psi, the ≥5 psi group had lower Aß42 (p = .004) and NFL (p < .001) compared to the <2 psi group and lower Aß42 (9.35%) and NFL (22.01%) compared to baseline. Twenty-four hours after ≥5 psi exposure, the ≥5 psi group had lower tau (p < .001) and NFL (p < .001) compared to the <2 psi group and baseline. Seventy-two hours after exposure ≥5 psi, tau increased in the ≥5 psi group compared to the <2 psi group (p = .02) and baseline. The tau:Aß42 ratio 24 hours after blast (p = .012), and the Aß40:Aß42 ratio 48 hours after blast (p = .04) differed in the ≥5 psi group compared to the <2 psi group. CONCLUSIONS: These findings provide an initial report of acute alterations in biomarker concentrations following blast exposure.

Role of the hippocampus and orbitofrontal cortex during the disambiguation of social cues in working memory.

Human social interactions are complex behaviors requiring the concerted effort of multiple neural systems to track and monitor the individuals around us. Cognitively, adjusting our behavior on the basis of changing social cues such as facial expressions relies on working memory and the ability to disambiguate, or separate, the representations of overlapping stimuli resulting from viewing the same individual with different facial expressions. We conducted an fMRI experiment examining the brain regions contributing to the encoding, maintenance, and retrieval of overlapping identity information during working memory using a delayed match-to-sample task. In the overlapping condition, two faces from the same individual with different facial expressions were presented at sample. In the nonoverlapping condition, the two sample faces were from two different individuals with different expressions. fMRI activity was assessed by contrasting the overlapping and nonoverlapping conditions at sample, delay, and test. The lateral orbitofrontal cortex showed increased fMRI signal in the overlapping condition in all three phases of the delayed match-to-sample task and increased functional connectivity with the hippocampus when encoding overlapping stimuli. The hippocampus showed increased fMRI signal at test. These data suggest that lateral orbitofrontal cortex helps encode and maintain representations of overlapping stimuli in working memory, whereas the orbitofrontal cortex and hippocampus contribute to the successful retrieval of overlapping stimuli. We suggest that the lateral orbitofrontal cortex and hippocampus play a role in encoding, maintaining, and retrieving social cues, especially when multiple interactions with an individual need to be disambiguated in a rapidly changing social context in order to make appropriate social responses.

A Pilot Study of Whole-Blood Transcriptomic Analysis to Identify Genes Associated with Repetitive Low-Level Blast Exposure in Career Breachers.

Repetitive low-level blast exposure is one of the major occupational health concerns among US military service members and law enforcement. This study seeks to identify gene expression using microRNA and RNA sequencing in whole-blood samples from experienced breachers and unexposed controls. We performed experimental RNA sequencing using Illumina's HiSeq 2500 Sequencing System, and microRNA analysis using NanoString Technology nCounter miRNA expression panel in whole-blood total RNA samples from 15 experienced breachers and 14 age-, sex-, and race-matched unexposed controls. We identified 10 significantly dysregulated genes between experienced breachers and unexposed controls, with FDR corrected <0.05: One upregulated gene, LINC00996 (long intergenic non-protein coding RNA 996); and nine downregulated genes, IGLV3-16 (immunoglobulin lambda variable 3-16), CD200 (CD200 molecule), LILRB5 (leukocyte immunoglobulin-like receptor B5), ZNF667-AS1 (ZNF667 antisense RNA 1), LMOD1 (leiomodin 1), CNTNAP2 (contactin-associated protein 2), EVPL (envoplakin), DPF3 (double PHD fingers 3), and IGHV4-34 (immunoglobulin heavy variable 4-34). The dysregulated gene expressions reported here have been associated with chronic inflammation and immune response, suggesting that these pathways may relate to the risk of lasting neurological symptoms following high exposures to blast over a career.

Sleep leadership in the army: A group randomized trial.

OBJECTIVES: Examine impact of training military leaders in sleep health on leaders and unit members. DESIGN: Following a baseline survey, two-person platoon leadership teams were randomly assigned by company to a training or waitlist control condition. After training, leadership teams completed a post-training survey. Six weeks later, leaders and unit members completed a final survey. SETTING: Classroom-style areas on a US military base. PARTICIPANTS: US soldiers (76 leaders and 448 unit members) from 39 platoons across 14 companies in a brigade combat team. INTERVENTION: One-hour training in sleep leadership. MEASUREMENTS: Leaders were surveyed about sleep knowledge, sleep attitudes, sleep training, sleep quantity, sleep quality and sleep problems. Unit members were surveyed about sleep leadership behaviors, sleep hours, sleep quality and sleep problems. RESULTS: Leaders rated the training highly and most knowledge and some attitudes about sleep improved from the baseline to post-training survey. Fewer leaders in the training condition reported sleep problems at follow-up than those in the waitlist control condition; there were no differences in sleep hours or sleep quality. More unit members with leaders in the training condition reported that their leaders engaged in sleep leadership behaviors at least sometimes and reported sleeping at least 7 hours/24 hours period than did unit members in the waitlist control condition; sleep quality and sleep problems did not differ by condition. CONCLUSIONS: Results suggest a simple training intervention targeting leaders may be able to shift sleep health and the cultural perspective on sleep across an organization.

Chronic Effects of Breaching Blast Exposure on Sensory Organization and Postural Limits of Stability.

OBJECTIVE: The goal of this effort to investigate if experienced breachers, professionals with a career history of exposure to repeated low-level blasts, exhibited postural instability. METHODS: Postural data were examined using traditional tests of means and compared to normative data. RESULTS: Breachers had significantly lower NeuroCom Sensory Organization Test (SOT) visual scores (within normative limits), prolonged Limits of Stability (LOS) test reaction time (30% of breachers and 7% of controls testing abnormal), and slower LOS movement velocity (21% of breachers and 0% of controls testing abnormal) compared to controls. CONCLUSION: Our LOS test findings are like those previously reported for students in the military breacher training course and seem to indicate that while acute effects of blasts on sensory control of balance fade away, effects on postural LOS persist over time.

Neuronally-derived tau is increased in experienced breachers and is associated with neurobehavioral symptoms.

Military and law enforcement breachers are exposed to many low-level blasts during their training and occupational experiences in which they detonate explosives to force entry into secured structures. There is a concern that exposure to these repetitive blast events in career breachers could result in cumulative neurological effects. This study aimed to determine concentrations of neurofilament light (NF-L), tau, and amyloid-beta 42 (Aß42) in serum and in neuronal-derived extracellular vesicles (EVs) in an experienced breacher population, and to examine biomarker associations with neurobehavioral symptoms. Thirty-four participants enrolled in the study: 20 experienced breachers and 14 matched military or civilian law enforcement controls. EV tau concentrations were significantly elevated in experienced breachers (0.3301 ± 0.5225) compared to controls (-0.4279 ± 0.7557; F = 10.43, p = 0.003). No statistically significant changes were observed in EV levels of NF-L or Aß42 or in serum levels of NF-L, tau, or Aß42 (p's > 0.05). Elevated EV tau concentrations correlated with increased Neurobehavioral Symptom Inventory (NSI) score in experienced breachers (r = 0.596, p = 0.015) and predicted higher NSI score (F(1,14) = 7.702, p = 0.015, R2 = 0.355). These findings show that neuronal-derived EV concentrations of tau are significantly elevated and associated with neurobehavioral symptoms in this sample of experienced breachers who have a history of many low-level blast exposures.

Leader provided purpose: Military leadership behavior and its association with suicidal ideation.

Suicide in U.S. Army Soldiers is of major concern as it is estimated that over 100 Soldiers die by suicide each year. Examining risk and protective factors is essential to develop both an understanding of Soldier suicide as well as inform systemic interventions to reduce suicide. One potential systemic approach is to embed preventive mechanisms within the structure of the military rather than the typical administration of primary intervention through mandatory training. To examine potential mechanisms of leader-based interventions, several leadership behaviors were assessed in a cross-sectional sample of n = 1,096 active duty Soldiers. Soldiers completed self-report measures of interpersonal predictors of suicide, suicidal ideation (SI), leadership behaviors, and unit cohesion. Logistic regression was used to identify leadership behaviors related to SI. Only the leader behavior attempting to foster a sense of purpose predicted SI. Leader provided purpose (LPP) was then entered into indirect effect analyses to evaluate the mechanisms of this relationship. Analyses revealed that LPP predicted SI through unit cohesion, thwarted belongingness, and perceived burdensomeness. Results demonstrate that specific aspects of military leadership such as fostering Soldier purpose may enhance resilience and reduce risk for SI.

Acute and Chronic Molecular Signatures and Associated Symptoms of Blast Exposure in Military Breachers.

Injuries from exposure to explosions rose dramatically during the Iraq and Afghanistan wars, which motivated investigations of blast-related neurotrauma and operational breaching. In this study, military "breachers" were exposed to controlled, low-level blast during a 10-day explosive breaching course. Using an omics approach, we assessed epigenetic, transcriptional, and inflammatory profile changes in blood from operational breaching trainees, with varying levels of lifetime blast exposure, along with daily self-reported symptoms (with tinnitus, headaches, and sleep disturbances as the most frequently reported). Although acute exposure to blast did not confer epigenetic changes, specifically in DNA methylation, differentially methylated regions (DMRs) with coordinated gene expression changes associated with lifetime cumulative blast exposures were identified. The accumulative effect of blast showed increased methylation of PAX8 antisense transcript with coordinated repression of gene expression, which has been associated with sleep disturbance. DNA methylation analyses conducted in conjunction with reported symptoms of tinnitus in the low versus high blast incidents groups identified DMRS in KCNE1 and CYP2E1 genes. KCNE1 and CYP2E1 showed the expected inverse correlation between DNA methylation and gene expression, which have been previously implicated in noise-related hearing loss. Although no significant transcriptional changes were observed in samples obtained at the onset of the training course relative to chronic cumulative blast, we identified a large number of transcriptional perturbations acutely pre- versus post-blast exposure. Acutely, 67 robustly differentially expressed genes (fold change ≥1.5), including UFC1 and YOD1 ubiquitin-related proteins, were identified. Inflammatory analyses of cytokines and chemokines revealed dysregulation of MCP-1, GCSF, HGF, MCSF, and RANTES acutely after blast exposure. These data show the importance of an omics approach, revealing that transcriptional and inflammatory biomarkers capture acute low-level blast overpressure exposure, whereas DNA methylation marks encapsulate chronic long-term symptoms.

Functional and Structural Neuroimaging Correlates of Repetitive Low-Level Blast Exposure in Career Breachers.

Combat military and civilian law enforcement personnel may be exposed to repetitive low-intensity blast events during training and operations. Persons who use explosives to gain entry (i.e., breach) into buildings are known as "breachers" or dynamic entry personnel. Breachers operate under the guidance of established safety protocols, but despite these precautions, breachers who are exposed to low-level blast throughout their careers frequently report performance deficits and symptoms to healthcare providers. Although little is known about the etiology linking blast exposure to clinical symptoms in humans, animal studies demonstrate network-level changes in brain function, alterations in brain morphology, vascular and inflammatory changes, hearing loss, and even alterations in gene expression after repeated blast exposure. To explore whether similar effects occur in humans, we collected a comprehensive data battery from 20 experienced breachers exposed to blast throughout their careers and 14 military and law enforcement controls. This battery included neuropsychological assessments, blood biomarkers, and magnetic resonance imaging measures, including cortical thickness, diffusion tensor imaging of white matter, functional connectivity, and perfusion. To better understand the relationship between repetitive low-level blast exposure and behavioral and imaging differences in humans, we analyzed the data using similarity-driven multi-view linear reconstruction (SiMLR). SiMLR is specifically designed for multiple modality statistical integration using dimensionality-reduction techniques for studies with high-dimensional, yet sparse, data (i.e., low number of subjects and many data per subject). We identify significant group effects in these data spanning brain structure, function, and blood biomarkers.

Hearing Loss and Irritability Reporting Without Vestibular Differences in Explosive Breaching Professionals.

Background: Blast exposure is a potential hazard in modern military operations and training, especially for some military occupations. Helmets, peripheral armor, hearing protection, and eye protection worn by military personnel provide some acute protection from blast effects but may not fully protect personnel against cumulative effects of repeated blast overpressure waves experienced over a career. The current study aimed to characterize the long-term outcomes of repeated exposure to primary blast overpressure in experienced career operators with an emphasis on the assessment of hearing and vestibular outcomes. Methods: Participants included experienced "breachers" (military and law enforcement explosives professionals who gain entry into structures through controlled detonation of charges) and similarly aged and experienced "non-breachers" (non-breaching military and law enforcement personnel). Responses to a clinical interview and performance on audiological and vestibular testing were compared. Results: Hearing loss, ringing in the ears, irritability, and sensitivity to light or noise were more common among breachers than non-breachers. Breachers reported more combat exposure than non-breachers, and subsequently, memory loss and difficulty concentrating were associated with both breaching and combat exposure. Vestibular and ocular motor outcomes were not different between breachers and non-breachers. Conclusion: Hearing-related, irritability, and sensitivity outcomes are associated with a career in breaching. Future studies examining long-term effects of blast exposure should take measures to control for combat exposure.

Working memory for social cues recruits orbitofrontal cortex and amygdala: a functional magnetic resonance imaging study of delayed matching to sample for emotional expressions.

During everyday interactions, we continuously monitor and maintain information about different individuals and their changing emotions in memory. Yet to date, working memory (WM) studies have primarily focused on mechanisms for maintaining face identity, but not emotional expression, and studies investigating the neural basis of emotion have focused on transient activity, not delay related activity. The goal of this functional magnetic resonance imaging study was to investigate WM for two critical social cues: identity and emotion. Subjects performed a delayed match-to-sample task that required them to match either the emotional expression or the identity of a face after a 10 s delay. Neuroanatomically, our predictions focused on the orbitofrontal cortex (OFC) and the amygdala, as these regions have previously been implicated in emotional processing and long-term memory, and studies have demonstrated sustained OFC and medial temporal lobe activity during visual WM. Consistent with previous studies, transient activity during the sample period representing emotion and identity was found in the superior temporal sulcus and inferior occipital cortex, respectively. Sustained delay-period activity was evident in OFC, amygdala, and hippocampus, for both emotion and identity trials. These results suggest that, although initial processing of emotion and identity is accomplished in anatomically segregated temporal and occipital regions, sustained delay related memory for these two critical features is held by the OFC, amygdala and hippocampus. These regions share rich connections, and have been shown previously to be necessary for binding features together in long-term memory. Our results suggest a role for these regions in active maintenance as well.

Sleep knowledge, goals, and habits in soldiers.

OBJECTIVES: The present study examines the link between these individual sleep knowledge, goals, and habits and self-reported sleep quantity in a military setting. METHODS: Survey data from active duty US soldiers were analyzed using a modified Poisson regression to provide relative risk ratios. RESULTS: Soldiers who had better sleep knowledge and endorsed healthy sleep goals and habits were more likely to report adequate sleep (7 or more hours of sleep per 24 hours) than those who did not. Specifically, soldiers who endorsed a goal of trying to get at least 7 hours of sleep per night had a 2.8 fold increase in the probability of reporting adequate sleep relative to short sleep (≤6 hours of sleep per 24 hours). CONCLUSIONS: These findings identify areas of focus for sleep education programs designed to target soldiers at-risk for insufficient sleep.

U.S. Soldiers and Foreign Language School: Stressors and Health.

INTRODUCTION: While previous studies have examined the stress of the military training environment, studies have not systematically examined the stress associated with attending the Defense Language Institute Foreign Language Center (DLIFLC). Service members assigned to DLIFLC endure intense academic pressure to succeed while meeting military requirements. Thus, not only are traditional academic stressors likely to be of concern but there are other academic and military-related stressors that have to managed by students. The goal of the present study was to characterize the stressors facing military students, document their mental health status and well-being, and identify mitigating factors such as coping, social support, time management, and the classroom environment. MATERIALS AND METHODS: Data were obtained from a cross-sectional survey administered in March of 2016. Study participants were 759 active-duty U.S. soldiers enrolled in DLIFLC, with a consent rate of 87.7%. Surveys were administered in classroom settings. Survey topics included demographics, student experience (e.g., classroom hours, stressors), mental health (e.g., depression, anxiety, hazardous alcohol use) and burnout, and mitigating factors (e.g., coping, social support, time management, classroom environment). Multiple logistic regressions were used to identify which variables in the predictor set were significantly associated with each of the five outcomes while controlling for the presence of all other variables. RESULTS: In terms of behavioral health, 7.2% met screening criteria for depression, 9.4% for anxiety, and 17.1% for hazardous alcohol use; 43.4% reported high/very high levels of burnout. About one-third of the sample who had taken a test failed at least one (32.2%). In terms of common stressors more than half reported high or very high-stress levels from meeting academic expectations, not getting enough sleep, and pressure to succeed from civilian language instructors. For depression and anxiety, regression results found that denial coping was a risk factor whereas positive social interaction and classroom climate were protective factors. For hazardous alcohol use, denial coping and higher rank were risk factors and acceptance and time management were protective factors. In terms of academic burnout, in-class and military work hours were risk factors, whereas time management and classroom climate were protective. Finally, lower educational attainment, time spent in the classroom and times spent on military duties predicted exam failure. CONCLUSION: Individual coping, social connection, and classroom climate are each associated with better DLIFLC student adjustment. Denial coping appears to impede individuals from assembling the personal resources needed to study a foreign language. In contrast, acceptance appears to support healthier adjustment, perhaps freeing individuals to focus on the task at hand rather than expend valuable energy resisting the demands being placed on them. Positive social interaction also appears to provide an important resource for students, and positive classroom climate is also associated with better mental health. These findings suggest that there are measures that individuals and the school can take to improve the DLIFLC experience and support students as they manage a myriad of stressors given the significance of their success to individual students and to the larger organization.

Using actigraphy feedback to improve sleep in soldiers: an exploratory trial.

OBJECTIVES: The objective of this study was to assess the impact of wearing an actigraph and receiving personalized feedback on the sleep of a high-risk occupational group: United States soldiers recently returned from a combat deployment. DESIGN: Following a baseline survey with a full sample, a subsample of soldiers wore an actigraph, received feedback, and completed a brief survey. Two months later, the full sample completed a follow-up survey. The actigraph intervention involved wearing an actigraph for 3 weeks and then receiving a personalized report about sleep patterns and an algorithm-based estimate of cognitive functioning derived from individual sleep patterns. RESULTS: Propensity score matching with a genetic search algorithm revealed that subjects in the actigraph condition (n=43) reported fewer sleep problems (t value = -2.55, P<.01) and getting more sleep hours (t value =1.97, P<.05) at follow-up than those in a matched comparison condition (n=43, weighted). There were no significant differences in functioning, somatic symptoms, and mental health outcomes (posttraumatic stress disorder symptoms and depression). A significant interaction indicated that the actigraph had a more beneficial effect on those with more somatic symptoms at baseline but not those with more sleep problems. Most participants rated the personalized report as helpful. CONCLUSION: Actigraphs combined with personalized reports may offer a useful, simple intervention to improve the sleep patterns of large, high-risk occupational groups.

Scopolamine reduces persistent activity related to long-term encoding in the parahippocampal gyrus during delayed matching in humans.

Recent computational modeling and slice physiology studies have suggested that long-term encoding may depend on sustained spiking during brief memory delays in parahippocampal neurons, and that this persistent spiking activity is modulated by effects of acetylcholine at muscarinic receptors. Our recent functional magnetic resonance imaging (fMRI) study has shown that sustained parahippocampal delay period activity during delayed match-to-sample performance in healthy young individuals predicted subsequent memory of visual stimuli on a recognition memory assessment 20 min later (Schon et al., 2004). The current study combined this fMRI paradigm with a pharmacological manipulation to test whether this long-term encoding-related delay activity is reduced in subjects who receive the muscarinic cholinergic antagonist scopolamine before fMRI scanning. Subsequent memory was predicted by sustained activity during brief memory delays bilaterally in the perirhinal/entorhinal cortex, in the right posterior parahippocampal and mid-fusiform gyri, and in the hippocampal body in healthy young individuals without a scopolamine challenge. This activity was reduced in subjects receiving scopolamine. The results are consistent with computational modeling data and behavioral pharmacological studies, suggesting that long-term encoding-related activity may be reduced if cholinergic receptors are blocked by scopolamine.

Persistence of parahippocampal representation in the absence of stimulus input enhances long-term encoding: a functional magnetic resonance imaging study of subsequent memory after a delayed match-to-sample task.

Recent theoretical models based on cellular processes in parahippocampal structures show that persistent neuronal spiking in the absence of stimulus input is important for encoding. The goal of this study was to examine in humans how sustained activity in the parahippocampal gyrus may underlie long-term encoding as well as active maintenance of novel information. The relationship between long-term encoding and active maintenance of novel information during brief memory delays was studied using functional magnetic resonance imaging (fMRI) in humans performing a delayed matching-to-sample (DMS) task and a post-scan subsequent recognition memory task of items encountered during DMS task performance. Multiple regression analyses revealed fMRI activity in parahippocampal structures associated with the active maintenance of trial-unique visual information during a brief memory delay. In addition to a role in active maintenance, we found that the subsequent memory for the sample stimuli as measured by the post-scan subsequent recognition memory task correlated with activity in the parahippocampal gyrus during the delay period. The results provide direct evidence that encoding mechanisms are engaged during brief memory delays when novel information is actively maintained. The relationship between active maintenance during the delay period and long-term subsequent memory is consistent with current theoretical models and experimental data that suggest that long-term encoding is enhanced by sustained parahippocampal activity.

Corticotropin releasing hormone type 2 receptors in the dorsal raphe nucleus mediate the behavioral consequences of uncontrollable stress.

Uncontrollable shock produces a constellation of behavioral changes that are not observed after equivalent escapable shock. These include interference with escape and potentiation of fear conditioning. The activation of corticotropin-releasing hormone (CRH) receptors within the caudal dorsal raphe nucleus (DRN) during inescapable tailshock (IS) has been shown to be critical for the development of these behavioral changes. CRH binds to two receptor subtypes, both of which are found in the DRN. The present set of studies examined which CRH receptor subtype mediates the effects of IS. Intra-DRN administration of the CRH(2) receptor antagonist anti-sauvagine-30 before IS dose-dependently blocked IS-induced behavioral changes; the CRH(1) receptor antagonist 2-methyl-4-(N-propyl-N-cycloproanemethylamino)-5-chloro-6-(2,4,6-trichloranilino)pyrimidine (NBI27914), administered in the same manner, did not. Moreover, the highly selective CRH(2) receptor agonist urocortin II (Ucn II) dose-dependently caused behavioral changes associated with IS in the absence of shock. Ucn II was effective at doses 100-fold lower than those previously required for CRH. The relationship between CRH(2) receptors and DRN 5-HT is discussed.

The role of corticotropin-releasing hormone in the dorsal raphe nucleus in mediating the behavioral consequences of uncontrollable stress.

Inescapable shock (IS) produces subsequent interference with escape behavior and increased fear conditioning that has been linked to increased activity and release of serotonin (5-HT) from neurons within the caudal dorsal raphe nucleus (DRN) both at the time of IS and later behavioral testing. Extrahypothalamic corticotropin-releasing hormone (CRH) has been implicated in many stress-related phenomena and has recently been shown to increase DRN 5-HT activity in the same caudal DRN area at which IS increases 5-HT activity. The current set of studies therefore examined the role of CRH in mediating the behavioral sequelae of IS. Intra-DRN microinjection of the nonselective CRH receptor antagonist d-Phe CRH (12-41) blocked the IS-induced behavioral changes when administered before IS but not when administered before later behavioral testing. Furthermore, intra-DRN administration of CRH in the absence of IS dose-dependently mimicked the effects of IS and interfered with escape behavior and increased fear conditioning 24 hr later. This effect was specific to injection of CRH into the caudal DRN and was not produced by microinjection into the rostral DRN. Intracerebroventricular CRH produced escape deficits and potentiated fear conditioning 24 hr later at only much higher doses, further confirming the site specificity of the effects. The potential role of the caudal DRN in states of anxiety is discussed.

Ubiquitin carboxy-terminal hydrolase-l1 as a serum neurotrauma biomarker for exposure to occupational low-level blast.

Repeated exposure to low-level blast is a characteristic of a few select occupations and there is concern that such occupational exposures present risk for traumatic brain injury. These occupations include specialized military and law enforcement units that employ controlled detonation of explosive charges for the purpose of tactical entry into secured structures. The concern for negative effects from blast exposure is based on rates of operator self-reported headache, sleep disturbance, working memory impairment, and other concussion-like symptoms. A challenge in research on this topic has been the need for improved assessment tools to empirically evaluate the risk associated with repeated exposure to blast overpressure levels commonly considered to be too low in magnitude to cause acute injury. Evaluation of serum-based neurotrauma biomarkers provides an objective measure that is logistically feasible for use in field training environments. Among candidate biomarkers, ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) has some empirical support and was evaluated in this study. We used daily blood draws to examine acute change in UCH-L1 among 108 healthy military personnel who were exposed to repeated low-level blast across a 2-week period. These research volunteers also wore pressure sensors to record blast exposures, wrist actigraphs to monitor sleep patterns, and completed daily behavioral assessments of symptomology, postural stability, and neurocognitive function. UCH-L1 levels were elevated as a function of participating in the 2-week training with explosives, but the correlation of UCH-L1 elevation and blast magnitude was weak and inconsistent. Also, UCH-L1 elevations did not correlate with deficits in behavioral measures. These results provide some support for including UCH-L1 as a measure of central nervous system effects from exposure to low-level blast. However, the weak relation observed suggests that additional indicators of blast effect are needed.