Neuroendocrine function and associated mental health outcomes following mild traumatic brain injury in OEF-deployed service members.

Mild traumatic brain injury (mTBI) has been linked to mental health disorders (MHDs) and pituitary function alterations. Due to the complex relationship of mTBI, the neuroendocrine system, and MHDs, we propose that neuroendocrine dysfunction (NED) may play a role in negative long-term health outcomes. The goal of this study was to determine if blast-concussed service members (SMs) have a stronger likelihood of developing NED. We hypothesized that NED either pre- or post-injury is associated with poor mental and physical health outcomes. Serum samples from the Armed Forces Health Surveillance Branch were obtained from concussed (n = 59) and non-concussed (n = 72) SMs treated at the Concussion Restoration Care Center (CRCC) in Afghanistan. Serum was collected within 2 years prior to deployment and one or two times within 3 years following their CRCC visit. Samples were analyzed for luteinizing hormone (LH), testosterone, human growth hormone, cortisol, and prolactin to assess post-injury neuroendocrine function. Results indicate that SMs who incurred an mTBI exhibited long-term LH and testosterone deficiencies 3 years following injury compared to controls. Specifically, 47.6% of head-injured SMs displayed hypofunction in at least one of five hormones at 3 years post-injury. Anxiety disorders were the most common MHD observed in concussed SMs with hypopituitarism, while there was also a trend for SMs with chronic pituitary dysfunction to have MHD diagnoses. Findings indicate blast-related mTBI may be associated with long-term health outcomes following a period of incubation. Neuroendocrine screenings may increase treatment opportunities, inform rehabilitation strategies, and improve overall quality of life for patients.

Dynamic motor tracking is sensitive to subacute mTBI.

Effective screening for mild traumatic brain injury (mTBI) is critical to accurate diagnosis, intervention, and improving outcomes. However, detecting mTBI using conventional clinical techniques is difficult, time intensive, and subject to observer bias. We examine the use of a simple visuomotor tracking task as a screening tool for mTBI. Thirty participants, 16 with clinically diagnosed mTBI (mean time since injury: 36.4 ± 20.9 days (95 % confidence interval); median = 20 days) were asked to squeeze a hand dynamometer and vary their grip force to match a visual, variable target force for 3 min. We found that controls outperformed individuals with mTBI; participants with mTBI moved with increased variability, as quantified by the standard deviation of the tracking error. We modeled participants' feedback response-how participants changed their grip force in response to errors in position and velocity-and used model parameters to classify mTBI with a sensitivity of 87 % and a specificity of 93 %, higher than several standard clinical scales. Our findings suggest that visuomotor tracking could be an effective supplement to conventional assessment tools to screen for mTBI and track mTBI symptoms during recovery.

Characterization of acute stress reaction following an IED blast-related mild traumatic brain injury.

PRIMARY OBJECTIVE: To characterize an acute stress reaction (ASR) following an improvised explosive device (IED) blast-related mild traumatic brain injury (mTBI). RESEARCH DESIGN: Participants were male, US military personnel treated in Afghanistan within 4 days following an IED-related mTBI event (n = 239). METHODS AND PROCEDURES: Demographics, diagnosis of ASR, injury history and self-reported mTBIs, blast exposures and psychological health histories were recorded. MAIN OUTCOMES AND RESULTS: In total, 12.5% of patients met ASR criteria. Patients with ASR were significantly younger and junior in rank (p < 0.05). Patients with ASR were more likely to experience the IED-blast while dismounted, report a loss of consciousness (LOC) and higher pain levels (p < 0.05). Adjusting for age and rank, multivariate logistic regression showed an association between mTBI history and ASR (AOR = 1.405; 95% CI = 1.105-1.786, p < 0.01). Adjusting for mechanism of injury (dismounted vs. mounted), LOC and pain, multivariate logistic regression showed an association between mTBI history and ASR (AOR = 1.453; 95% CI = 1.132-1.864, p < 0.01). Prior blast exposure and past psychological health issues were not associated with ASR. CONCLUSIONS: A history of multiple mTBIs is associated with increased risk of ASR. Future research is warranted.

Blast-related mild traumatic brain injury in the acute phase: acute stress reactions partially mediate the relationship between loss of consciousness and symptoms.

PRIMARY OBJECTIVE: The objective was to compare symptoms in service members diagnosed with a blast-related mTBI (mild traumatic brain injury) with a loss of consciousness (LOC) to those without LOC. RESEARCH DESIGN: Clinicians saw US military personnel within 72 hours of sustaining a blast-related mTBI and at a follow-up visit 48-72 hours later (n = 210). METHODS AND PROCEDURES: Demographics, post-concussive symptoms, diagnosis of acute stress reaction (ASR) and simple reaction time data from the Automated Neuropsychological Assessment Metric (ANAM) were collected. MAIN OUTCOMES AND RESULTS: ASRs were significantly more likely in patients reporting LOC versus patients reporting no LOC. At the first post-injury visit, LOC was associated with difficulty sleeping, hearing loss, memory problems and reporting more symptoms. A follow-up analysis explored if symptomatic differences were influenced by ASR. Adjusting for ASR, the statistical relationships between LOC and symptoms were weaker (i.e. reduced Odds Ratios). At the follow-up visit, difficulty sleeping was associated with LOC before and after adjusting for ASR. Patients with both ASR and LOC had the slowest simple reaction times. CONCLUSIONS: Results suggest ASR may partially mediate symptom presentation and cognitive dysfunction in the acute phase following blast-related mTBI. Future research is warranted.

High altitude headache and acute mountain sickness at moderate elevations in a military population during battalion-level training exercises.

Few studies have evaluated high altitude headache (HAH) and acute mountain sickness (AMS) in military populations training at moderate (1,500-2,500 m) to high altitudes (>2,500 m). In the current study, researchers interviewed active duty personnel training at Marine Corps Mountain Warfare Training Center. Participants were asked about HAH and AMS symptoms, potential risk factors, and medications used. In a sample of 192 U.S. Navy and Marine Corps personnel, 14.6% reported AMS (Lake Louise Criteria > or = 3) and 28.6% reported HAH. Dehydration and recent arrival at altitude (defined as data collected on days 2-3) were significantly associated with AMS; decreased sleep allowance was significantly associated with HAH. Although ibuprofen/Motrin users were more likely to screen positive for AMS, among AMS-positive participants, ibuprofen/Motrin users had decreased likelihood of reporting robust AMS relative to non-ibuprofen/Motrin users (p < 0.01). These results suggest that maintenance of hydration and adequate sleep allowance may be critical performance requirements at altitude. Further, ibuprofen/Motrin may be a reasonable treatment for the symptoms of AMS and HAH, although further study is warranted.

Automated Neuropsychological Assessment Metrics: repeated assessment with two military samples.

INTRODUCTION: U.S. military troops deploying to war zones are currently administered the Automated Neuropsychological Assessment Metrics (ANAM4) Traumatic Brain Injury (TBI) Battery to establish individual neurocognitive performance baselines. In part, the utility of the ANAM4 TBI Battery baseline measurement depends on test-retest reliability of this instrument. The purpose of this report was to evaluate performance following multiple administrations of the ANAM4 TBI Battery: does performance in a repeated measures paradigm constitute a stable, interpretable indication of baseline neurocognitive ability? METHODS: The data presented here are from the ANAM4 TBI Battery administered four times to a group of U.S. Marines in Study 1 and eight times to a group of New Zealand Defence Force personnel in Study 2. RESULTS: The results show practice effect in five of six performance subtests in both Study 1 and Study 2. DISCUSSION: Results are consistent with expectations that multiple test sessions are required to reach stable performance on some computerized tasks. These results have implications for taking ANAM4 TBI Battery practice effects into account in test administration and in data interpretation.

Virtual and augmented reality in a simulated naval engagement: Preliminary comparisons of simulator sickness and human performance.

The aim of this study was to compare simulator sickness symptoms while participants wore either a virtual reality (VR) or augmented reality (AR) headset. A secondary aim involved comparing how physical motion affects symptoms. During a simulation, participants wore VR and AR headsets while standing on a motion platform and firing at hostile ships under three motion conditions: No Physical Motion; Synchronous Motion, in which the physical and displayed motion were coupled; and Asynchronous Motion, in which the physical motion did not match the display. Symptoms increased over time but were not different with respect to headset or motion. The VR condition had higher accuracy and faster response time to the commence fire instruction. Further research is necessary to determine if this holds under more extreme motion. The use of VR or AR headsets for training under gentle motion conditions is practicable and should be permissible under normal conditions during deployment.

Affective profiling for anxiety-like behavior in a rodent model of mTBI.

Mild traumatic brain injury is a common outcome of blast exposure, and current literature indicates high rates of comorbid posttraumatic stress disorder (PTSD) in military personnel. Blast-exposed rats display PTSD-like behavior, suggesting relationships may exist between PTSD and blast exposure. Other studies demonstrate the roles of stathmin and corticosterone associated with fear- and anxiety-like behaviors in rodent models. Furthermore, studies have observed ranges of responses to both physical and psychological trauma in animal populations (Elder 2012, Ritov 2016). This study exposed rodents to repeated blast overpressure (BOP) and analyzed behavioral responses and molecular variables at 3 weeks and 6 months after exposure. We applied a modified version of a previously reported behavioral profiling approach that separates "affected" and "unaffected" rats based on the presence of anxiety-like behaviors (Ritov, 2016). We report that "affected" 3 week animals showed higher plasma corticosterone and amygdalar stathmin levels, while "affected" 6 month animals had lower prefrontal cortex stathmin. Higher corticosterone also paralleled anxiety behavior in "affected" 3 week animals, which was not observed in 6 month animals, indicating possible negative feedback loop mechanisms. Elevated levels of amygdalar stathmin correlated with anxiety behaviors in "affected" 3 week and 6 month animals, indicating sustained molecular changes. We conclude that this unique analysis may provide more information about response to blast. This type of analysis should also be considered when treating clinical populations, since individual differences may affect behavioral and long-term outcomes. Future studies should elucidate relationships of stress and fear responses in the context of BOP.

Trial-selective effects of U50,488H, a kappa-opioid receptor agonist, on consummatory successive negative contrast.

A series of experiments studied the effects of the kappa-opioid receptor agonist U50,488H on consummatory successive negative contrast (cSNC) in rats. In cSNC, previous experience with a 32% sucrose solution leads to greater rejection of 4% sucrose than exclusive experience with 4% sucrose. Experiments 1 and 2 revealed that U50,488H failed to influence cSNC when administered before the first downshifted trial, but either attenuated (1mg/kg) or enhanced (3 and 10mg/kg) cSNC when administered before the second downshift trial. Experiment 3 showed that U50,488H administered immediately after the first downshift trial had no effect on cSNC at the 1mg/kg dose, but tended to increase cSNC at the 3mg/kg dose. However, Experiment 4 suggested that the apparent enhancement of cSNC after 3mg/kg U50 administered posttrial 11 may have reflected the development of a conditioned taste aversion. The trial-selective attenuating effect of the low dose may reflect an anxiolytic-like property of U50,488H.

Recovery from Mild Traumatic Brain Injury Following Uncomplicated Mounted and Dismounted Blast: A Natural History Approach.

Objective: The purpose of this study is to utilize a natural history approach to describe and understand symptom recovery in personnel diagnosed with a blast-related mild traumatic brain injury (mTBI) resulting from an improvised explosive device blast. Participants and Design: The population included military personnel who experienced a blast mTBI while mounted (vehicle; n = 176) or dismounted (on foot; n = 37) (N = 213). Patients had no co-morbid psychiatric or muscle-skeletal issues and were treated within 72 h of injury. Prevalence and duration of self-reported symptoms were separately analyzed by injury context (mounted vs dismounted). Results: Headache was prominently reported in both mounted (85%) and dismounted (75%) populations. The mean time from injury to return to full duty was between 7.8 d (mounted) and 8.5 d (dismounted). The dismounted population reported visual changes that lasted 0.74 d longer. Conclusion: Our analysis implicates that headache is a common and acutely persistent symptom in mTBI regardless of injury context. Additionally, patients in mounted vs dismounted injury did not report significant differences in symptom prevalence. Although knowing the injury context (i.e., dismounted vs mounted) may be beneficial for providers to understand symptom presentations and deliver accurate anticipatory guidance for patients with blast-related mTBI, no significant differences were observed in this population. This may be due to the population characteristic as the trajectory of recovery may vary for patients who were not able to return to full duty within 30 d or required higher levels of care.

Applications of Transductive Spectral Clustering Methods in a Military Medical Concussion Database.

Traumatic brain injury (TBI) is one of the most common forms of neurotrauma that has affected more than 250,000 military service members over the last decade alone. While in battle, service members who experience TBI are at significant risk for the development of normal TBI symptoms, as well as risk for the development of psychological disorders such as Post-Traumatic Stress Disorder (PTSD). As such, these service members often require intense bouts of medication and therapy in order to resume full return-to-duty status. The primary aim of this study is to identify the relationship between the administration of specific medications and reductions in symptomology such as headaches, dizziness, or light-headedness. Service members diagnosed with mTBI and seen at the Concussion Restoration Care Center (CRCC) in Afghanistan were analyzed according to prescribed medications and symptomology. Here, we demonstrate that in such situations with sparse labels and small feature sets, classic analytic techniques such as logistic regression, support vector machines, naïve Bayes, random forest, decision trees, and k-nearest neighbor are not well suited for the prediction of outcomes. We attribute our findings to several issues inherent to this problem setting and discuss several advantages of spectral graph methods.

Sensitivity of the Balance Error Scoring System and the Sensory Organization Test in the Combat Environment.

This study evaluated the utility of the Balance Error Scoring System (BESS) and the Sensory Organization Test (SOT) as tools for the screening and monitoring of Service members (SMs) with mild traumatic brain injury (mTBI) in a deployed setting during the acute and subacute phases of recovery. Patient records (N = 699) were reviewed for a cohort of SMs who sustained a blast-related mTBI while deployed to Afghanistan and were treated at the Concussion Restoration Care Center (CRCC) at Camp Leatherneck. On initial intake into the CRCC, participants completed two assessments of postural control, the BESS, and SOT. SMs with mTBI performed significantly worse on the BESS and SOT when compared with comparative samples. When the SOT data were further examined using sensory ratios, the results indicated that postural instability was primarily a result of vestibular and visual integration dysfunction (r > 0.62). The main finding of this study was that the sensitivity of the SOT composite score (50-58%) during the acute phase was higher than previous sensitivities found in the sports medicine literature for impact-related trauma.

ANAM4 TBI reaction time-based tests have prognostic utility for acute concussion.

The Concussion Restoration Care Center has used the Automated Neuropsychological Assessment Metrics version 4 Traumatic Brain Injury (ANAM4 TBI) battery in clinical assessment of concussion. The study's aim is to evaluate the prognostic utility of the ANAM4 TBI. In 165 concussed active duty personnel (all ultimately returned to duty) seen and tested on the ANAM4 TBI on days 3 and 5 (median times) from their injury, Spearman's ρ statistics showed that all performance subtests (at day 5) were associated with fewer days return-to-duty (RTD) time, whereas concussion history or age did not. Kruskal-Wallis statistics showed that ANAM4 TBI, loss of consciousness, and post-traumatic amnesia were associated with increased RTD time; ANAM4 TBI reaction time-based subtests, collectively, showed the largest effect sizes. A survival analysis using a Kaplan-Meier plot showed that the lowest 25% on the reaction time-based subtests had a median RTD time of 19 days, whereas those in the upper 25% had a median RTD time of approximately 7 days. Results indicate that until validated neurocognitive testing is introduced, the ANAM4 TBI battery, especially reaction time-based tests, has prognostic utility.

Posttrial d-cycloserine enhances the emotional memory of an incentive downshift event.

The present research was designed to determine whether an incentive downshift event induces an emotional memory that can be modulated by d-cycloserine (DCS), a partial agonist at the glycine site of N-methyl-d-aspartate receptor (NMDAR). DCS has been reported to have memory-enhancing properties in other training situations. Experiments 1 and 2 involved a consummatory successive negative contrast (cSNC) situation in which animals are exposed to an incentive downshift involving sucrose solutions of different concentrations. DCS administration (30 mg/kg, ip) immediately after the first 32-to-4% sucrose downshift trial (Experiment 1) retarded recovery of consummatory behavior, but immediately after the first 32-to-6% sucrose downshift trial (Experiment 2) did not affect recovery. There was no evidence that DCS affected consummatory behavior in the absence of an incentive downshift in a manner analogous to a conditioned taste aversion (Experiment 3). These results suggest that activation of NMDARs via the glycine modulatory site enhances the emotional memory triggered by exposure to an incentive downshift event.

Naloxone facilitates appetitive extinction and eliminates escape from frustration.

Two experiments tested the effects of opioid receptor blockage on behavior. In Experiment 1, rats reinforced for lever pressing with either sucrose or food pellets received treatment with saline, 2, and 10 mg/kg naloxone, i.p. (within-subject design). Naloxone 10 mg/kg increased response latency, but 2 mg/kg had no effect. When shifted to extinction (between-group design), naloxone (2 and 10 mg/kg) facilitated extinction relative to saline animals, after reinforcement with either sucrose or food pellets. In Experiment 2, after 10 sessions of access to 32% sucrose or an empty tube (between-group design), all rats were exposed to the empty tube while allowing them to jump over a barrier into a different compartment. Escape latencies were shorter for downshifted saline than for saline rats always given access to the empty tube. This escape-from-frustration effect was eliminated by naloxone (2 mg/kg, i.p.). Opioid blockage appears to reduce the value of alternative incentives.