Military Operational Medicine Research Program Research Articles

Cold Habituation Does Not Alter Thermal Responses or Manual Dexterity During Prolonged Cold Air Exposure

Background: Habituation is a pattern of cold acclimatization characterized by attenuated cold defense responses, including a reduction in peripheral vasoconstriction and subsequent increase in skin temperature (TSk) as well as a decrease in shivering thermogenesis. Habituation is achieved through repeated reductions in TSk, rather than deep body core temperature (TC), via exposure to prolonged cold air or brief cold-water immersion. Due to improvements in TSk, enhanced manual dexterity and peripheral cold injury risk reduction are purported benefits of cold habituation. Warfighters frequently operate in cold climates and experience decrements in manual dexterity and strength. These functional losses can negatively impact mission critical tasks and training exercises; however, the effectiveness of cold habituation as a potential countermeasure to alleviate the deleterious effects of prolonged cold exposure on peripheral temperatures, thermal comfort, and hand function is unclear. Purpose: To evaluate the influence of eight consecutive cold air exposures on the thermal (TC and TSk), perceptual (thermal comfort and sensation), and functional (manual dexterity and strength) responses to cold air. We hypothesized that TSk would be higher and perceptual responses and manual dexterity improved, following repeated cold exposure. Methods: Eight young adults (6 M/1 F/1 FTM; 21 ± 2 years; %BF 24.5 ± 7.0) underwent a 2-h cold air exposure (8 °C, ~50% RH) on 8 consecutive days wearing minimal clothing. On Day 0 (baseline exposure ~1 week prior) and Days 1 and 8 of repeated exposure, TC was recorded continuously via a telemetry pill used as a rectal suppository. Extremity (Thand and Tfinger) and mean weighted TSk (MWTSk) from 8 skin sites were recorded continuously. Thermal comfort (TC) and thermal sensation (TS) were recorded at 20 min intervals. Expired gases were collected at 20 min intervals and used to calculate metabolic heat production (MHP). Manual dexterity was assessed using the Purdue Pegboard and Minnesota Manual Dexterity Test (MMDT), and hand strength were measured before and at the end of cold exposure. Results: TC changed across time ( p < 0.05) but did not differ between days ( p > 0.05). MWTSk, Thand, and Tfinger decreased across time ( p < 0.05) but also did not differ between days ( p > 0.05). Mean and minimum whole-body TS and TC were not different between days ( p > 0.05). MHP increased across time ( p < 0.05) but did not differ between days ( p > 0.05). Purdue Pegboard, MMDT task performance, and hand strength did not differ between days ( p > 0.05). Conclusion: Eight consecutive days of cold air exposure does not augment extremity skin temperature, thermal comfort, or manual performance during prolonged cold conditions. Supported by U.S. Army Medical Research and Development Command, Military Operational Medicine Research Program; author views not offcial US Army or DoD policy. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

NSAIDs do not influence exercise effects on muscle size in rats or muscle protein synthesis signaling in humans

BACKGROUND: The aim of this project was to determine the impact of non-steroidal anti-inflammatory drugs (NSAIDs) on skeletal muscle adaptations to exercise. NSAIDs possess analgesic and anti‐inflammatory properties that occur by blocking cyclooxygenase (COX) enzymes, thereby inhibiting the production of prostaglandins. In the first study, we determined if low-dose chronic NSAID use affects muscle size in rodents exercising for six weeks. In the second study, we determined if a single high dose of NSAIDs effects the muscle protein synthetic signaling response to a bout of plyometric exercise. Our hypotheses were that NSAIDs would reduce both muscle size and muscle protein synthesis (MPS) signaling. METHODS: Study 1: 9-wk-old male Wistar rats (n=80) were randomized to placebo (PLA), naproxen (NAP), ibuprofen (IBU), or flurbiprofen (FLU) with or without exercise (EX) for six weeks. Exercise consisted of treadmill running at 25 m/min, for 30 minutes per day, five days per week. Soleus muscle was stained for myosin heavy chain (MHC) I or MHC IIA then analyzed for cross sectional area (CSA) and fiber type percentage. Rodent data were analyzed using a one-way ANOVA. Study 2: In a randomized, counter-balanced order, 12 participants (2 females, 10 males), performed four independent plyometric exercise bouts consisting of 10 sets of 10 plyometric jumps at 40% of their 1RM, separated by a minimum of one week. Prior to each session, participants consumed a single dose of celecoxib (CEL 200 mg), IBU (800 mg), FLU (100 mg) or PLA. Muscle biopsies were collected before (PRE) and 3-hours post (POST) exercise. Muscle was analyzed via immunoblot for the following: phospho(p)-AKT(S473), total AKT, p-mTOR (S448), total mTOR, p-S6 (S235/236), total S6, p-4EBP1, and total 4EBP1. Fold changes were calculated from PRE to POST. Data were analyzed using a repeated measures ANOVA. All data are presented as mean ± SD. RESULTS: Study 1: There was no significant difference (p<0.05) in muscle CSA (PLA: 4060±517; PLA+EX: 3965±605; IBU: 3720±804; IBU+EX:4129±477; FLU: 3743±671; FLU+EX: 3649±541; NAP: 4157±1011; NAP+EX: 4123±586) or MHC IIA percentage (PLA: 10±7; PLA+EX: 10±5; IBU: 7±5; IBU+EX:9±3; FLU: 11±4; FLU+EX: 11±6; NAP: 11±4; NAP+EX: 12±3) between groups. Study 2: There was no significant difference (p<0.05) in fold-change between groups for p-AKT/total AKT (PLA: 1.23±0.4; IBU: 1.13±0.3; CEL: 1.26±0.4; FLU: 1.31±0.4), p-mTOR/total mTOR (PLA: 1.21±0.2; IBU: 1.21±0.3; CEL:1.34±0.2; FLU: 1.49±0.3), p-S6/total S6 (PLA: 11.48±10.6; IBU: 10.9±6.8; CEL: 6.01±2.98; FLU: 25.25±19.38), or p-4EBP1/total 4EBP1 (PLA: 1.71± 1.35; IBU: 1.23±0.98; CEL: 1.07 ±0.64; FLU: 2.03±1.49). CONCLUSION: Chronic low-dose NSAID consumption does not influence muscle size or MHC in exercising rodents. Similarly, an acute high dose of an NSAID does not affect the MPS signaling response in exercising humans. Funding was provided by the Military Operational Medicine Research Program. The opinions or assertions contained herein are the private views of the author(s) and are not to be construed as offcial or as reflecting the views of the Army or the Department of Defense. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

0349 Contribution of Insomnia After Trauma to Depression and Posttraumatic Stress Disorder in Women Service Members

Abstract Introduction Trauma can lead to mental health disorders, such as posttraumatic stress disorder (PTSD) and depression. Historically, insomnia was thought of as a secondary symptom of these mental health disorders, but current research suggests insomnia can be an independent clinical disorder and can contribute to the development and severity of PTSD and depression among civilians. However, previous studies examining insomnia and mental health symptoms among service members are limited by cross-sectional designs, reliance on retrospective data, or inclusion of predominately male ­samples. We prospectively examined associations among trauma exposure, insomnia, and mental health symptoms in an exclusive sample of women service members and veterans. Methods We analyzed 2 waves of survey data (2011-2013, Time 1 [T1], and 2014-2016, Time 2 [T2]) from 26,443 current and former women service members from the Millennium Cohort Study. We assessed recent traumas (combat experience and sexual trauma) in the past 3 years, probable insomnia at T1, and probable PTSD and depression at T2. A longitudinal mediation model was used to quantify separate indirect effects of recent traumas on mental health outcomes through probable insomnia. Results Women who experienced recent sexual assault (odds ratio [OR] = 1.68; 95% CI, 1.24-2.10), sexual harassment (OR = 1.22; 95% CI, 1.05-1.41), or combat (OR = 1.34; 95% CI, 1.20-1.49) at T1 had greater risk of probable insomnia at T1 compared with women who had not recently experienced these events. Probable insomnia at T1, in turn, was associated with probable depression (OR = 2.66; 95% CI, 2.31-3.06) and PTSD (OR = 2.57; 95% CI, 2.27-2.90) at T2. Recent combat experience did not moderate the associations of recent sexual trauma with insomnia or mental health outcomes. Conclusion Insomnia contributes to subsequent mental health symptoms following trauma. The diagnosis and treatment of post-trauma insomnia during military service should be prioritized to mitigate the development of posttraumatic mental health symptoms. Sleep health in women service members remains an understudied area of research and should also be prioritized. Support (if any) Millennium Cohort Study: Military Operational Medicine Research Program, Defense Health Program, and Department of Veterans Affairs. VA HSR&D (RCS-20-191, Martin); NHLBI (K24HL143055, Martin).

0161 Structural Changes in Mood Domains During Sleep Deprivation and Recovery

Abstract Introduction Mood is known to vary as a function of sleep debt. Mood batteries often measure multiple, non-orthogonal domains. In the present study, the latent structure of the Automated Neuropsychological Assessment Metrics Mood (ANAM-mood) battery was assessed during five different states of alertness. We present a novel scheme to evaluate changes in the structure of such batteries across conditions. It was hypothesized that the structure would change, with the greatest changes manifest during sleep deprivation. Methods The present analyses were conducted on data from a prior sleep deprivation study (n = 25 healthy young adults). We used the identity property of MANOVA. Given correlation matrices Σi and Σj, structural invariance was defined as Σi Σj-1 ≈ I (Identity). MANOVA statistic m was the largest eigenvalue of Σi Σj-1. Resampling was used to generate m-distributions within and between the five different alertness conditions - Rested, Sleep Deprived (SD) days 1 and 2, and Recovery days 1 and 2. In addition, the relative number of mood dimensions was estimated by the odds (via resampling) of two dimensions explaining 80% of the variance of Σi compared to Σj. Results The pairwise MANOVA-statistic revealed significant structural variations across conditions (p< 0.001 for all comparisons). Significant differences included Rested vs SD1 and SD2. Recovery 1 showed the most pronounced differences to all conditions. Recovery 2 was like Recovery 1, but more like Rested than the prior day. The odds ratio of two-dimensions for Recovery 1 was much higher compared to all other conditions (OR: 2.4-245, p< 0.001). Conclusion Individuals respond differently to a mood survey across specific alertness conditions resulting in structural changes to the data. Wakefulness during recovery from severe sleep loss differs most significantly from all states, contrary to our hypothesis. This is important to consider when interpreting mood changes as measured by such batteries (including related Spielberger's State Anxiety Inventory and Beck Depression Inventory-II) during sleep studies. Follow up studies are needed to fully assess such effects and devise methods to account for them. Support (if any) This effort was fully supported by the Department of Defense Military Operational Medicine Research Program (MOMRP).

0212 Insufficient Sleep and Behavioral Health in the Military: A 5-Nation Perspective

Abstract Introduction Insufficient sleep (< 7 hours per night) degrades both health and performance and constitutes a risk to military mission success. Accordingly, militaries across the globe are increasingly focusing on sleep management, including the role that leaders play in fostering and promoting a healthy sleep culture. In the present study, we assessed survey data from the militaries of five nations on: 1) sleep behavior, 2) the relationship between sleep behavior and mental health, and 3) the role leaders play in improving service member sleep. The goal was to determine the extent to which insufficient sleep, its link to behavioral health, and the role of leaders were relevant in militaries across allied English-speaking nations. Methods Data from five nations: Australia, Canada, New Zealand, the United Kingdom, and the United States were assessed. Each nation administered a survey to a military sample, including questions on sleep problems (e.g., Insomnia Severity Index) and mental health. In addition, some countries assessed how first-line leaders addressed sleep in their units using items from the sleep leadership scale. Each data collection differed in terms of scope, setting, and objective. Results Insufficient sleep (< 7 hours per night) was reported by 34.9%, 67.2% and 95.4% of survey respondents from the New Zealand Defence Force, Canadian Armed Forces, and the US Army, respectively. Those reporting shorter mean sleep durations also reported fewer sleep difficulties, likely reflecting higher sleep pressure from chronic sleep loss. Across all five nations, sleep problems (e.g., difficulty falling asleep) were positively correlated with behavioral health symptoms (e.g., depression and anxiety symptoms). Importantly, leader engagement in promoting healthy sleep was positively correlated with sleep duration and negatively correlated with sleep problems and behavioral health symptoms. Conclusion Insufficient sleep is pervasive in the militaries of the nations included in the present study – a finding that has serious implications for the behavioral health and resilience of service members, and more broadly for the overall effectiveness of these military forces. Across nations, militaries should attend to these risks and examine ways that first-line leaders can promote healthy sleep in their service members. Support (if any) Department of Defense Military Operational Medicine Research Program

0062 Slow Oscillatory Transcranial Direct Current Stimulation During Restricted Nighttime Sleep Enhances Memory Consolidation

Abstract Introduction Slow oscillatory transcranial direct current stimulation (SO-tDCS) during the first 30 min of nighttime sleep has been shown to improve memory consolidation of word pairs encoded immediately prior to sleep onset. We examined whether SO-tDCS administered during the second half of a restricted nighttime sleep opportunity likewise improves memory consolidation for previously encoded word pairs and mitigates subsequent performance deficits. Methods After three nights of baseline sleep in the laboratory, healthy subjects (ages 18-33, n=27, 17 females) were administered SO-tDCS (N=12) or SHAM (N=15) during the second hour of a 2h sleep period (between the hours of 23:00 and 03:00). Prior to this 2h sleep period, subjects were presented a series of 55 word-pairs. They were asked to recall 46 of the pairs immediately after learning (T0), and again at 20 min (T20) and 120 min (T120) post-awakening. Number of pairs recalled at T20 and T120 relative to T0 were analyzed with a mixed-effects ANOVA. Negative values indicate that subjects forgot pairs post-awakening relative to the initial learning recall. Results Subjects correctly recalled 35.0 ± 9.2 words (mean ± SD) at T0. Relative to T0, subjects in the SHAM condition correctly recalled significantly fewer words post-awakening than those in the SO-tDCS condition (SHAM: -0.8 ± 1.6 words; SO-tDCS: 0.3 ± 1.3 words; F=6.20, p=0.02), and fewer words at T20 than T120 (T20: -0.6 ± 1.5 words; T120: -0.1 ± 1.6 words; F=4.67, p=0.04). On average, subjects in the SHAM condition forgot words upon awakening relative to T0 (T20: -1.0 ± 1.4; T120: -0.6 ± 1.7 words), while those in the SO-tDCS condition forgot few to no words at T20 (0.0 ± 1.5 words) and actually recalled more words at T120 than T0 (0.6 ± 1.1 words). Conclusion Participants in the SHAM condition recalled fewer words after the restricted sleep period, whereas those in the SO-tDCS group increased recall following 2h of sleep. The present findings have important implications for the development of fatigue mitigation strategies during military operations, when sustaining performance in the face of insufficient sleep is critical. Support (if any) Department of Defense Military Operational Medicine Research Program (MOMRP)

0167 Influence of light exposure, exercise, caffeine intake, and nicotine use on sleep of U.S. Navy sailors during home port operations

Abstract Introduction Insufficient sleep is pervasive in U.S. Navy (USN) sailors and has been associated with increased risk of injury and mood disturbances. As such, monitoring sleep and identifying modifiable targets that influence sleep in this population is essential. We examined the sleep of USN sailors during 9-months in port and explored the influence of different lifestyle behaviors on sleep. Methods Sailors (n = 101, 31 ± 7 years old [mean ± SD], 21% female) wore a commercial wearable sleep-tracking device (Oura Ring, Gen2) during a 9-month home port maintenance period (September 2021 – May 2022). During the study, the sailors slept at home and had periods working on the ship (on-hull; higher demands) and off the ship (off-hull; lower demands). Participants also completed 5 self-report surveys that assessed sleep quality (Pittsburgh Sleep Quality Index; PSQI) and multiple lifestyle behaviors including: hours of natural light exposure, hours of moderate/vigorous physical activity, and intake of caffeine, nicotine, and alcohol. Sleep outcome measures from the wearable device included total sleep time (TST), standard deviation of TST (SD TST), and sleep efficiency (SE). Linear mixed models were used to examine the effects of lifestyle behaviors on sleep. Timepoint and on/off-hull condition were also included as fixed effects, while participant was included as a random effect. Results Participants slept 6.5 ± 0.7 hours a night (6.2 ± 0.9 on-hull; 6.4 ± 0.8 off-hull; p > .05) and had slightly elevated PSQI scores that were higher on-hull (8.3 ± 4.6) than off-hull (6.5 ± 3.5; B = 1.83, Std. Error = 0.71, p = .01). Lifestyle behaviors were not significant predictors of PSQI, TST, SD TST, or SE (p > .05). Conclusion Lifestyle behaviors had weak relationships with self-reported and objective sleep outcomes in this exploratory analysis. Therefore, modifying lifestyle behaviors may not significantly influence sleep in USN sailors during home port periods. Still, additional behavioral targets (e.g., diet), specific aspects of behavioral outcomes (e.g., light exposure timing, exercise intensity), and other work-related factors (e.g., workload, schedule) that can affect sleep should be explored in future efforts. Support (if any) Military Operational Medicine Research Program (work unit no. N2010).

0013 Psychomotor Vigilance Test Performance Declines Related to Illness Severity, not Sleep

Abstract Introduction While the Psychomotor Vigilance Test (PVT) has been used extensively to track vigilance degradation following sleep loss, there is evidence that it may also track vigilance degradation related to illness. However, it is unclear how much performance decline is driven by sleep loss related to an illness or the illness itself independent of sleep loss. Here we assessed how sleep and acute infectious diarrhea impact vigilance performance in a controlled human infection model (CHIM) with enterotoxigenic Escherichia coli (ETEC). Methods During a CHIM assessing the efficacy of an immunoprophylactic targeting ETEC, we measured sleep via actigraphy over an 8-day inpatient period. A 10-minute PVT was also administered up to three times each day in the morning, afternoon, and evening. Participants ingested an oral immunoprophylaxis 3 times/day on days -2 and -1, and ingested ETEC on day 0. Participants were categorized as to whether or not they experienced the primary endpoint of moderate-severe diarrhea (MSD). Results Among 56 participants (aged 34.7±8.5 years, 64% male), 54% reached the primary endpoint of moderate-severe diarrhea following ETEC infection. Total sleep times across the study did not differ between those with and without MSD. While PVT minor lapses (i.e., not responding within 500 milliseconds) did increase following ETEC infection for all subjects as revealed by a mixed linear model [effect of day: f(7,657)=3.35, p=0.002], there was also a significant main effect of group [f(1,657)=5.85, p=0.016], where those participants who experienced MSD following ETEC infection had more minor lapses across the study than those who did not experience MSD (6.28±0.43 vs 4.88±0.38). Conclusion While the negative impact of sleep loss on performance has been well demonstrated, these are the first data to suggest that illness severity[KT1] , independent of sleep loss, also negatively impacts performance. In operational populations such as the military, special care should be taken to prevent illness and remove ill operators from the field, just as this care should be taken to prevent sleep loss and remove sleepy operators. By preventing and monitoring sleep loss and illness, these operations can avoid potentially costly performance errors. Support (If Any) The clinical trial from which these data were obtained was funded by the Congressionally Directed Medical Research Program through the Joint Warfighter Medical Research Program under Award No. W81XWH-15-C-0083 to the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. The U.S. Army Medical Research Acquisition Activity was the awarding and administering acquisition office. The study was also funded by a Collaborative Research and Development Agreement with PATH Enteric Vaccine Solutions (NCRADA-NMRC-15-9589), as well as by the Military Operational Medicine Research Program (MOMRP).

0229 Concerns about the future linked with poor sleep quality in U.S. Army Soldiers withdrawing from Afghanistan

Abstract Introduction A special operations unit of U.S. Soldiers rotated through Afghanistan from October, 2001 to the U.S. drawdown in 2020-2021. For these Soldiers, the drawdown has led to uncertainties about the future of the unit and their careers. Psychological stress resulting from these uncertainties could lead to sleep disturbances. This study assessed the relationship between attitudes about the Afghanistan drawdown and sleep. Methods A survey was broadly distributed in July-August 2021. To assess attitudes about the drawdown, participants were asked whether they felt changes in their personal readiness had occurred since the drawdown began. They were asked how they believed the unit should support Afghanistan in the future (remain in Afghanistan, support only through airstrikes, or no further support). Lastly, Soldiers were asked whether the drawdown made them more likely to switch to another unit, get out of the Army, or no change. Subjective sleep quality and duration from the month prior was assessed. Due to the abrupt fall of Kabul, the survey was discontinued earlier than planned, resulting in 35 participants. Results Soldiers were 32.80±5.99 years old. They had been in the unit for 8.89±5.71 years and had deployed to Afghanistan 5.14±3.14 times. The average sleep duration was 6.66±0.79 hours, and the average sleep quality was 63.39%±21.63%. There were no relationships between attitudes and sleep duration. However, regression analyses showed those who reported increased stress (B=18.16, p=.01), decreased morale (B=2.97, p=.006), and decreased motivation (B=2.69, p=.01) since the drawdown began had poorer sleep quality. ANOVA tests showed Soldiers who believed the unit should remain in Afghanistan had poorer sleep quality than those endorsing only air support or no involvement (F(2,29)=6.39, p=.005). Further, those who endorsed being more likely to make a career change had poorer sleep quality than those with no changes in career plans (F(2,29)=3.53, p=.04). Conclusion These results indicate that psychological distress resulting from the drawdown may be impacting sleep quality in this unit. Continuous monitoring of sleep quality may prove to be a sensitive indicator of elevated stress at the unit level. Support (If Any) Support for this study came from the Military Operational Medicine Research Program (MOMRP) of the United States Army Medical Research and Development Command (USAMRDC). Material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the authors, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense. The investigators have adhered to the policies for protection of human subjects as prescribed in AR 70–25. The authors have no conflicts of interest to disclose.

0292 Differential Utility of Psychomotor Vigilance Test vs. Sleep Latency Tests in Healthy Humans

Abstract Introduction The Psychomotor Vigilance Test (PVT), the Multiple Sleep Latency Test (MSLT), and the Maintenance of Wakefulness Test (MWT) are widely used in both sleep research and clinical settings. The PVT measures reaction time to a visual stimulus, whereas time to sleep onset is measured in both the MSLT and MWT, which differ primarily with respect to the instructions (i.e., whether to try to fall asleep vs. stay awake). Compared to sleep latency tests, the PVT is relatively inexpensive and easy to administer, so it is advisable to delimit the conditions under which its administration is most appropriate. Methods A comprehensive search of sleep studies on healthy adults revealed 30 studies in which both PVTs and sleep latency tests were administered – usually to assess the effects of various interventions on sleepiness and vigilance. Two reviewers compiled findings from each study and graded the levels of outcome agreement based on whether a test intervention produced similar effects on vigilance across tests. Results Of the 13 studies that included both PVT and MWT of studies, a high level of agreement (based on the presence and direction significant effect on vigilance) between test outcomes was evident in 8 (61.5%) of the studies. In contrast, a considerably lower percentage of studies in which both the PVT and MSLT were performed (6 of 17 studies; 35.3%) had high agreement between test outcomes. It was also found that the MSLT was more sensitive to interventions (e.g., caffeine, sleep loss, and cognitive workload) than the PVT in the majority of studies in which there was low agreement (5 of 6 studies; 83.3%). Conclusion There is generally more agreement between PVT and MWT measures than between PVT and MSLT measures in studies involving sleep loss. This is most likely because the PVT and MWT both require application of effort to resist sleepiness, whereas the MSLT involves the withdrawal of resistance to sleepiness. This suggests that the PVT is potentially more useful in operational environments (where ability to sustain performance is the primary concern) than in clinical settings (where the focus is on determining the severity of sleepiness). Support (If Any) Department of Defense Military Operational Medicine Research Program (MOMRP)

0094 Oscillatory Theta-Band Activity as a Sleep Stage Independent Measure of REM-like Activity throughout Sleep

Abstract Introduction The importance of human cortical theta-band power during REM is suggested by its association with aspects of emotional processing. Currently, this is measured first by visual-inspection of polysomnography to define REM-sleep (scored-REM) and then summing the total theta power within. However, activity attributed to scored-REM has been hypothesized to occur during some scored-NREM (“covert REM”) and total theta conflates different theta-band sources. Oscillatory theta-band activity (OTA) in the hippocampus and associated regions is the hallmark of REM-like sleep in invasive animal studies. We posit that an EEG assessment specifically targeting all-night OTA is a more accurate biomarker of theta-dependent REM functions than current methods. As a first step towards testing this hypothesis, we developed a sleep stage independent approach to isolate REM-like OTA from scalp-EEG. For validation, we compared this measure to conventional-staging and high-frequency activity. Methods Our method uses Irregular-Resampling Auto-Spectral Analysis to remove the aperiodic spectrum (a major source of theta-band power), followed by low-band power normalization to derive the relative oscillatory-theta activity (OTA). Covert REM-containing epochs were calculated based on OTA exceeding a threshold. We combined data from two in-laboratory studies resulting in a sample size of 42 healthy young adult subjects. Analyses used non-sleep restricted overnight EEG recordings from a frontal channel. Results A clear oscillatory-theta peak was observed after processing. Using all sleep stages, we found separation of OTA from total theta-band power evidenced by conventional staging (OTA: scored-REM>scored-NREM, p=0.003 vs total theta: scored-REM<scored-NREM, p<0.001) and correlation with beta-band activity (OTA: r=0.2, p<0.001 vs total theta: p=0.4). Supporting “covert REM”, OTA was present during scored-NREM (p<0.001). On average during a single sleep episode, covert REM was found in 28% of scored- NREM epochs (range=2-85%). Conclusion We developed a novel automated method for measuring REM-like oscillatory-theta activity, independent of conventional sleep staging methods. This method was used to measure REM-like activity across all sleep stages and, as reported in a companion abstract, test the hypothesis that this constitutes a better predictor of REM-dependent behavioral effects than current conventions. Support (If Any) This effort was fully supported by the Department of Defense Military Operational Medicine Research Program (MOMRP).

0163 The Differential Relationship Between Berthing Habitability, Job Stress, and Workload on Self-Reported Sleep Deficiency in a Representative Sample of Sailors Attached to U.S. Navy Warships

Abstract Introduction Berthing habitability factors (e.g., noise, temperature, lighting) and workload are known to negatively impact sleep for Sailors serving onboard United States (U.S.) Navy warships. However, it is unknown what factors have the strongest relationship with sleep outcomes. Using data from a representative sample of warships, the relationships between berthing habitability, job stress, and workload on sleep were explored. Methods Participants (N = 3,313; 84% ≤ 35 yrs, 55% white) from 33 warships voluntarily completed an online survey. Using structural equation modeling, latent factors of workload, job stress, and berthing habitability were modeled to test relationships with self-reported sleep deficiency. Sleep deficiency was calculated by dividing the sleep obtained on their ship (“How many hours of sleep (to include naps) per day do you get when sleeping onboard your current ship?”) by their required sleep amount (“How many hours of sleep do you require to feel well-rested?”). Job stress was modeled with three scores from questions related to job stress (1=strongly disagree, 5=strongly agree). Habitability was modeled by the degree in which environmental factors disturbed sleep (1=not at all, 5=extremely). Workload was modeled by the hours completed performing job-related tasks (e.g., work center, watch team, training, meetings). Results On average, participants reported shorter sleep durations on their ship than they require (Ship: 5.2±1.4 hrs; Required: 7.0±1.3 hrs, mean±SD). Overall, habitability, job stress, and workload were negatively related to sleep deficiency (standardized βs=-0.16 to -0.26, ps < 0.001, CFI/TLI > 0.90, RMSEA=0.056). Among all latent constructs, larger coefficients were found for the direct path from workload to sleep deficiency than those from habitability (β1=-0.16 vs β2=-0.12). Additionally, watch team duties loaded most heavily onto the construct of workload, suggesting that it contributed most to the relationship of workload with sleep deficiency. Conclusion These results confirm that workload and berthing habitability are related to sleep deficiency in Sailors while serving onboard U.S. Navy Ships. Additionally, greater workload may have a stronger relationship with sleep deficiency than other factors such as habitability. Future research should utilize objective measures of sleep and workload to better estimate their relationships with sleep. Support (If Any) Military Operational Medicine Research Program (MOMRP) under work unit no. N2010.

0293 The Effect of Sleep Loss on Divergent Thinking using a Remote Associates Task

Abstract Introduction Sleep loss-induced neurobehavioral deficits are a recognized threat to health, safety, and performance. Sleep loss has previously been shown to differentially impact distinct types of cognitive function, although less is known about the higher-order cognitive function, divergent thinking. Understanding the influence of sleep on divergent thinking can assist in developing targeted strategies to mitigate specific cognitive function impairments. Methods Eight participants (3M/5F), mean age 27.875y (± 5.5y SD) were studied over the course of 40 days in a crossover design. Participants were randomly assigned to one of two study schedules, with 4 participants in each that alternated the order of sleep restriction and total sleep deprivation. The schedules consisted of a baseline assessment and 6 study phases [sleep extension prior to sleep restriction (10h Time in Bed (TIB)), sleep restriction (6h TIB), recovery following sleep restriction, sleep extension prior to total sleep deprivation (10h TIB), total sleep deprivation (62h), and recovery following sleep restriction. The Remote Associates Task (RAT), a task to assess divergent thinking by presenting a triad of apparently unrelated words with the goal of identifying a unifying 4th word, was administered the evening of the last day of every phase. RAT performance metrics included number of triads attempted, correct responses, repeated trials, and mean correct and incorrect reaction times. Results No differences were found in total number of word triads attempted by participants (p=0.18). The number of correct responses during baseline was lower than during sleep restriction, recovery from sleep restriction, and total sleep restriction (p=0.00691), most likely reflecting a steep learning curve. No significant main effect of phase was found for any RAT metric. Conclusion These preliminary findings suggest divergent thought as measured by the RAT is conserved across a differential amounts of sleep. More studies are needed to better characterize the impact of sleep loss on divergent thinking as well as possible mediating effects of other higher-order cognitive functions. Support (If Any) Department of Defense Military Operational Medicine Research Program (MOMRP)

0248 The Influence of Circadian Shifts on Post Mission Event Subjective Fatigue during a 72H Live-Fire Mission Simulation

Abstract Introduction Circadian misalignment from sustained 24/7 operations and sleep loss are common occurrences in military operations, and operational demands can often lead to high levels of fatigue. Although the relationship between the circadian system and fatigue is well characterized, the relationship between magnitude of the circadian shift and fatigue during operational mission events has not been widely explored. Methods Twenty-one male participants aged 23.3±3.9 years (mean±SD) were recruited from a sample of active-duty Soldiers. The study consisted of a single day baseline data collection and then a month later the Soldiers participated in a sustained live-fire mission simulation consisting of a pre-mission day, the 72-hour live-fire exercise, and post-mission day. During the simulation, Soldiers completed the following mission events: Tactical Stress Marksmanship Assessment (TSMA), Individual Shooter Scenario (ISS), Small Unit Performance Analytics (SUPRA), Reconnaissance (RECON), infiltration and extraction ruck-march (INFIL/EXFIL RUCK), and RAID, to model actual combat or operational activities. Subjective fatigue was assessed using a Visual Analog Scale (VAS) after each mission event. Circadian phase was measured by salivary dim light melatonin onset (DLMO) at baseline and then again following the post-mission day. Half-hourly saliva samples were collected under dim light (<10lux) sedentary conditions. The circadian phase shift was calculated as the difference between the two DLMO collections. Results Twenty of the twenty-one participants advanced their circadian rhythm with a total mean shift of 0.91±0.88 SD hours. Of the six mission events, significant correlations were found between the magnitude of the phase shift and subjective fatigue for three of the events. The magnitude of the circadian phase shift was negatively correlated with fatigue for RECON r=-0.59 (p=0.008), RAID r=-0.55 (p=0.01), and EXFIL RUCK r=-0.44 (p=0.046). The amount of sleep in the 24 hours prior to each of these events had no significant correlation. Conclusion For the RECON, RAID, and RUCK, we found that the greater the magnitude of the phase shift, the less fatigue individuals endorsed. Yet, there was no significant relationship with sleep prior to the events. This suggests a potential greater need to consider the impact of the circadian system on military operations, especially with regard to circadian effects on fatigue. Support (If Any) Department of Defense Military Operational Medicine Research Program (MOMRP); DEVCOM SC

0140 Operationalizing Sleep for the Military: Advancing an Infrastructure for Fatigue Risk Management with Wearable Technology

Abstract Introduction A recent investigation on fatigue within United States (US) Naval Surface Force by the Government Accountability Office recommended that the US Navy incorporate methods to empirically monitor and manage fatigue-related threats. In response, a feasibility effort was undertaken to assess two commercial wearable devices previously evaluated against polysomnography by our group for potential use within a novel fatigue monitoring system onboard US warships. Methods 501 Sailors from three warships (415 men, 85 women, 1 response missing; 29.1±7.4 years, mean±SD) were included in analyses. During multi-day missions at sea, participants were instructed to continuously wear a wrist-worn Fatigue Science Readiband and an Oura Ring. Participants met with the research team daily to sync wearable devices and complete self-ratings of sleep and fatigue on a tablet. While returning to port, participants completed a user experience questionnaire that included 5-point scales for device comfort and interference with daily activities (larger values indicate greater comfort or interference). Results There were no overall differences in total sleep time (TST) and sleep efficiency (SE) between devices (TST: Ring=352.23±87.1, Readiband=353.89±97.79; p=0.45, d=-0.01; SE: Ring=84.59±7.08, Readiband=84.20±10.24; p=0.06, d=0.04). There were 9 days for TST and 4 days for SE (of 66 total days) that resulted in effect sizes >0.50 between devices (for >0.20: TST, 39/66; SE, 29/66). Preliminary analyses between TST and self-reported exhaustion and inability to function suggest predictive relationships with the wearables (Ring: r=-0.20; Readiband: r=-0.21), with no relationship with SE across devices (both r<0.01). Average comfort ratings for Ring (3.74) exceeded Readiband (3.59), but this difference was small (p=0.04, d=0.12). Interference with daily activities was also similar between devices (Ring=2.10, Readiband=2.20; p=0.14, d=0.08). Conclusion Both commercial wearables performed similarly for their TST and SE assessments, and TST was associated with self-rated fatigue within this operational environment. While the ring form factor was selected more for comfort than the wrist form factor, the difference was small. Collectively, findings indicate that both devices show promise for operational use within fatigue monitoring systems. Further testing is being conducted to better understand the strengths and limitations of wearable devices for monitoring sleep in warship environments. Support (If Any) Military Operational Medicine Research Program

0004 Sleep, Team and Social Processes, and Health, Performance, and Safety in Naval Operational Environments

Abstract Introduction Sleep disruption and teamwork are inherent features of 24/7 operational environments, yet little is known about how sleep and team/social processes interact to affect crew readiness and endurance. Methods We analyzed data of 3,434 active duty US sailors (80% male) from the Afloat Safety Climate Assessment Survey. Using structural equation modeling, we specified latent factors of Sleep Health (typical hours of sleep per day and sleep disturbances in shipboard environment); crew team and social factors of Team Transition Processes, Team Action Processes, Team Interpersonal Processes, Unit Cohesion, Psychological Safety, and Social Support; and operational outcome risks of Physical Health (no. days in previous 30 with physical illness or injury), Mental Health (no. days with stress, depression, or emotional problems), Performance (frequency of fatigue-induced functional impairments on duty), and Safety (individual and crew noncompliance, and rate of observed near misses). Results Higher Sleep Health reduced impairments in Physical Health, Mental Health, Performance, and Safety (standardized βs = −0.096 to −0.542, ps < 0.0001, CFI/TLI > 0.980, RMSEA = 0.033). Higher Sleep Health improved Team Transition, Action, and Interpersonal Processes, Unit Cohesion, Psychological Safety, and Social Support (βs = 0.178 to 0.380, ps < 0.0001, CFI/TLI > 0.982, RMSEA = 0.029). Social Support reduced risks to Physical Health, Mental Health, and Performance; Team Interpersonal Processes reduced Metal Health risk; Psychological Safety reduced Performance and Safety risks; Unit Cohesion reduced Safety risk (βs = −0.053 to −0.709, ps < 0.05, CFI/TLI > 0.979, RMSEA = 0.027). Mediation models indicated good Sleep Health enhances Social Support’s beneficial impact on Physical Health, Mental Health, and Performance; Psychological Safety’s impact on Performance and Safety; Team Interpersonal Processes’ impact on Physical Health; and Unit Cohesion’s impact on Safety (indirect effect βs = −0.032 to −0.127, ps < 0.0001, CFI/TLI > 0.967, RMSEAs < 0.051). Conclusion Sleep health improves team/social functioning, which serves an additive protective function and enhancement to crew operational health, performance, and safety. Future work should closely examine these interrelationships to identify mechanisms as targets for policy and procedures to help optimize crew readiness and endurance. Support (If Any) Military Operational Medicine Research Program under work unit N2010.

0142 From Shore to Shipboard: Severity of Sleep Disturbance and Sleep-Related Impairment of Sailors Aboard US Navy Warships

Abstract Introduction Sleep quality is known to be negatively impacted during military operations at sea. Yet, there are limited naval studies that explore measures of sleep disturbances and sleep-related impairment, especially in relation to different warship classes. This analysis compares sleep disturbances and sleep-related impairment across two warship classes during similar at-sea periods. Methods 432 sailors (77.6% male; 27.4±7.1 years) participated in a training evolution aboard either a destroyer (DDG; n=194) or an amphibious class ship (LHD; n=238). Participants completed a 7-day recall questionnaire assessing their sleep and health behavior prior to getting underway (baseline) and 1–2 days prior to completing a 2-week underway (underway). Primary outcomes included the PROMIS Sleep-Related Impairment scale (P-SRI) and the PROMIS Sleep Disturbance scale (P-SD). While underway, participants self-reported their diet quality, daily caffeine and nicotine intake, overall health, and daily time spent exercising; these factors were included as covariates in all analyses. Linear mixed effects models were used to explore the within-subject effect of baseline vs. underway sleep and a between-subjects effect by ship class (i.e., DDG or LHD). Independent t tests and chi-square tests were used to compare ship groups at baseline. Results Participants within ship class had a similar age, time in military service, and sex (p≥.06). Across both ship classes, there were increases in severity of sleep-related daytime impairment and sleep disturbances between baseline and underway (P-SRI: B=5.2±0.6; P-SD: B=3.4±0.5; p<.001). Additionally, DDG participants had a significantly greater increase in sleep-related impairment between baseline and underway compared with their LHD-class counterparts (Group*Time interaction effect: B=4.3±0.9, p<.001; LHD: 54.5±0.6 [baseline] vs. 54.5±0.5 [underway], DDG: 54.9±0.6 [baseline] vs. 60.2±0.6 [underway]). Conclusion These results suggest sleep-related impairment and sleep disturbances are greater while underway compared with an in-port environment. Although preliminary, these results suggest that differential impacts on sleep-related impairment may occur across ship classes, even when undergoing similar underway events. Further research is needed to understand how insufficient sleep and its consequences change in shipboard environments and how these effects may vary between ship classes so as to better inform targeted naval-focused sleep health improvement strategies. Support (If Any) Military Operational Medicine Research Program under work unit no. N2010.

0095 Sleep Enhancement Technology in 2021: An Updated Survey of Apps

Abstract Introduction Commercially available smartphone apps that claim to improve sleep quantity and/or quality represent an ever-evolving and fast-growing market. Although a large body of work has validated the performance of sleep tracking technologies, there is little information regarding potential sleep enhancement technologies. Our study systematically surveyed currently available commercial sleep enhancement smartphone apps to provide details to inform both providers and patients alike, in addition to the healthy consumer market. Methods We systematically searched the Google Play Store (Android) on 30 JUN 2021 and the App Store (Apple) on 30 JUN 2021 and 26 JUL 2021 in the US using the keyword “sleep.” The Android search was conducted via the Google Play Store website. The Apple search was conducted via third-party websites linked to the App Store due to restrictions on searching the App Store online. This survey was conducted using Google Chrome web browsers and is inclusive of all smartphone applications found. Results We identified 550 apps: 59.5% on Android (N=327) and 40.5% on Apple (N=223). Ninety-four percent of apps offered a free version. The majority of sleep apps were intended for use during wake (72.7% exclusively during wake; 25.1% during both wake and sleep), with only 2.2% intended to be used during sleep alone. Most apps purport to enhance rather than measure sleep (87.8% versus 0.5%). The vast majority of apps claim to enhance sleep via reductions in sleep latency (92.9%). Reduced sleep latency is primarily achieved using auditory stimuli (74.5%). Conclusion Most current sleep apps are designed to be used while awake, prior to sleep, and focus on the enhancement of sleep, rather than measurement, by targeting sleep latency. Given the evidence that supports sleep latency as an important target for sleep promoting interventions and the multitude of available sleep enhancement apps across both Android and Apple platforms, sleep apps could be considered a possible strategy for patients and consumers to improve their sleep, although validation of these apps is required. Support (If Any) Department of Defense Military Operational Medicine Research Program (MOMRP)

0097 REM-like Neural Activity Is Superior to NREM Parameters for Predicting Non-sleep Restricted Vigilance

Abstract Introduction Currently unknown is whether REM-like neural activity reverses, incurs, or is neutral with respect to its effect on sleep pressure independent from NREM recovery. We investigated the relationship between a novel scalp-EEG measure of REM-like neural activity and next-day performance on the Psychomotor Vigilance Task (PVT) – a sensitive measure of sleep debt. Our EEG measure reflects the oscillatory-theta activity (OTA) that is the hallmark of REM sleep in animal studies. This method preserves amplitude information, isolates OTA from aperiodic theta-band power, and accounts for REM-like activity thought to occur outside of conventionally scored-REM epochs. We compared the PVT-association of OTA, traditionally measured EEG REM-theta, and traditional sleep parameters. To assess REM-like independent effects, we controlled for traditional parameters using a multivariate model. Methods Our method uses Irregular-Resampling Auto-Spectral Analysis to remove the aperiodic spectrum, followed by low-band power normalization to derive the relative oscillatory-theta activity (OTA). The average OTA was then used to predict next-day performance on the PVT. Traditional sleep parameters (sleep efficiency, total sleep time, %NREM, %N3, and delta-band power) were also examined. We combined data from two previously reported in-laboratory studies resulting in a sample size of 42 healthy young adult subjects. Analyses used non-sleep restricted overnight EEG recordings from a frontal channel. Results There was a substantial PVT-OTA association (OTA positively correlated with response-time and thus with reduced vigilance) during scored-REM epochs (r=0.44, p=0.003). This was stable irrespective of conventional sleep staging when using all sleep epochs (r=0.48, p=0.001), and OTA during scored-NREM (r=0.35, p=0.02). The effect was also stable after controlling for total sleep time, %NREM, and N3 delta-band power in a multivariate model (all-sleep PVT-OTA: r=0.5, p=0.004). Traditional sleep parameters were not significantly correlated with PVT performance. Conclusion OTA was a superior quantitative predictor of reduced next-day vigilance than traditional sleep parameters, and this persisted after controlling for NREM parameters. These findings are consistent with the hypothesis that periods of high REM-like activity are less restorative than other periods and may actually increase homeostatic sleep pressure. Support (If Any) This effort was supported by the Department of Defense Military Operational Medicine Research Program.

0014 Insufficient sleep is related to poor infantry battle drill performance in special operations Soldiers

Abstract Introduction Although multiple studies have documented the impact of insufficient sleep on Soldier performance, most studies have done so using artificial measures of performance (e.g., tablet or simulator tests). The current study sought to test the relationship between sleep and Soldier performance during infantry battle drill training, a more naturalistic measure of performance. Methods Fifteen junior special operations infantry Soldiers participated in the study. Soldiers wore Phillips Actiwatch Spectrum and reported their subjective sleep duration and quality during the week prior to Close Quarters Battle (CQB) drills. CQB training emphasizes close quarter combat tactics and requires a diverse range of cognitive skills (e.g., memory, decision-making, scanning). Each team of Soldiers performed six iterations of CQB – three using Ultimate Training Munitions (UTM; non-lethal rounds of munition) and three with live ammunition. Experienced leaders monitored each iteration and recorded errors on scorecards that are regularly used by the unit during CQB trainings. Results Participating Soldiers were all male and were 24.3 ± 3.82 years old. Soldiers slept an average of 6.6 hours per night leading up to the exercise and had an average sleep efficiency of 82/100%. The average number of errors committed during the UTM trials was 2.5 ± 1.9, and the average number of errors during the live ammunition trials was 1.1 ± 1.1. The number of errors committed during the live ammunition iterations was negatively correlated with subjective number of hours slept (r = -.67, p = .006) and subjective sleep efficiency/quality (r = -.55, p = .03). A t-test showed those with subjective sleep duration ≥ 7 hours had a significantly lower number of errors than Soldiers with subjective sleep duration < 7 hours (t(14) = 2.26, p = .04). Conclusion Enhancing infantry battle drill performance during training may directly translate to greater success in combat scenarios. These data preliminarily suggest that sleep quality and duration may influence subsequent performance on infantry battle drill training, particularly for Soldiers with limited experience in battle drill conduction who have not yet perfected battle drill techniques. Future studies should enact sleep augmentation to determine the causal influence of sleep on performance in this setting. Support (If Any) Support for this study came from the Military Operational Medicine Research Program (MOMRP) of the United States Army Medical Research and Development Command (USAMRDC). Material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the authors, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense. The investigators have adhered to the policies for protection of human subjects as prescribed in AR 70–25. The authors have no conflicts of interest to disclose.