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Introduction The hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes activate in response to stressors. Real-world exposure to stressors often co-occurs with total sleep deprivation (TSD). The SAM response to a single stressor appears unchanged by TSD, but salivary alpha-amylase (sAA) has shown that TSD blunts the SAM response to repeated stressor exposure. Using salivary cortisol concentration (SCC), we investigated the HPA response to repeated stressors under well-rested and TSD conditions. Methods N=10 healthy adults (ages 28.3±5.78; 5f) completed a 4-day/3-night in-laboratory study with 38h TSD preceded and followed by 10h sleep opportunities. On day 2 (well-rested) and day 3 (TSD), participants completed two stressor sessions in a high-fidelity shooting simulator, separated by 30min. Acting as police officers, civilian participants verbally interacted with emergency response scenarios and decided whether to use (simulated) deadly force. Seven saliva samples were collected each day: pre-stressor, and 0min, 15min, and 30min after each session. Samples were assayed for SCC and normalized against each day’s pre-stressor sample. Results Mixed-effects ANOVA showed a significant effect of sample time (F[5,99]=19.85, p< 0.001), with SCC peaking 15min after the first stressor session and steadily declining thereafter. The SCC peak was significantly blunted during TSD compared to well-rested (t[99]=2.84, p=0.006). Correlations with previously reported, simultaneously assessed sAA concentrations, which peaked right after the first stressor session, were not significant (p>0.2). Additionally, whereas sAA showed a second peak after the second stressor session when participants were well-rested, no second peak was found in SCC. Conclusion The SCC response after one stressor session with simulated emergency response scenarios was blunted during TSD, unlike the sAA response. However, while sAA peaked twice in response to repeated stressor exposure when participants were well-rested (though not during TSD), SCC continued to decline after the first stressor exposure, potentially indicating a HPA refractory mechanism or habituation. Also, over participants there was no significant relationship between the magnitude of the stressor response between SCC and sAA. Taken together, our results suggest fundamentally distinct SAM and HPA axis responsivity to repeated acute stressors, with differential impact of TSD. Support (if any) ONR N00014-13-1-0302, PRMRP W81XWH-20-1-0442.

Introduction Slow wave sleep (SWS) is thought to play a critical, if not unique, role in resilience and recovery of waking function. It has been posited that if SWS is preserved, the impact of sleep restriction on subsequent neurobehavioral functioning should be minimal. In this context, we investigated the effects of a delayed and restricted sleep opportunity on SWS and on neurobehavioral impairment during a subsequent period of total sleep deprivation (TSD). Methods N=21 healthy adults (21–38y, 9f) underwent three separate periods of 36h TSD, each preceded by one week of prior sleep extension to 12h time in bed (TIB) per night (PSE condition, twice), or prior sleep restriction to 6h TIB per night (PSR condition, once). The last night of each condition was spent inside the laboratory. TIB for the pre-TSD night was 22:00–10:00 (PSE) or 04:00–10:00 (PSR). During each 36h TSD period, subjects completed a neurobehavioral task battery every 2h including a digit-symbol substitution test (DSST) measuring cognitive throughput and the Karolinska Sleepiness Scale (KSS) measuring subjective sleepiness. Following TSD, subjects had a 12h sleep opportunity (22:00–10:00). Sleep was recorded polysomnographically during both pre- and post-TSD nights. Results The pre-TSD night in the PSR condition had less total sleep time, with significant reductions (p< 0.001) in N1, N2, and REM durations compared to the PSE condition. There were no significant differences between the PSE and PSR conditions in SWS duration (p=0.40). Moreover, in the post-TSD night, there were no significant differences (p>0.1) between the PSE and PSR conditions in any of the sleep stages, including SWS. Neurobehavioral functioning during TSD exhibited significant effects (p< 0.02) of prior sleep condition on DSST throughput and KSS sleepiness, with reduced throughput and increased sleepiness in the PSR condition relative to the PSE condition. Conclusion SWS was remarkably conserved in delayed, restricted sleep compared to extended sleep. However, this conservation of SWS did not prevent exacerbation of DSST throughput deficits or KSS sleepiness from prior sleep restriction during subsequent TSD. As such, other aspects of sleep besides SWS are also important in mediating sleep-induced resilience and recovery. Support (if any) NASA NAG9-1161, CDMRP W81XWH-20-1-0442, ARO W911NF2210223.

Introduction Repeated exposure to total sleep deprivation (TSD) within individuals has demonstrated task-specific, trait-like individual differences in cognitive impairment and subjective sleepiness. Research has suggested that introversion/extraversion may predict individual vulnerability to TSD. While previous analyses have found that extraversion does not reliably predict objective performance impairment on the psychomotor vigilance test (PVT) during TSD, it is not known whether extraversion may predict individuals’ subjective responses to TSD, including subjective ratings of sleepiness, fatigue, mood, performance, and effort. Methods N=21 healthy adults (aged 21-38; 9 women) completed three 4-day/3-night laboratory sessions – each including a baseline night, 36h TSD period, and recovery night –separated by at least 2 weeks each. Two of the sessions were preceded by a week of sleep extension (12h nightly sleep opportunities), while one session was preceded by a week of sleep restriction (6h nightly sleep opportunities), in randomized, counterbalanced order; only the sleep extension sessions are used here. Prior to the experiment, subjects filled out the Eysenck Personality Questionnaire (EPQ), which yielded an extraversion score; one subject did not complete the questionnaire and was excluded from analyses. Every 2h during TSD, subjects completed a 60min neurobehavioral test battery. At the beginning of the test battery, subjects completed the Karolinksa Sleepiness Scale (KSS) and visual analog scales of mood and fatigue (VAS-M and VAS-F). At the end of the test battery, subjects completed self-ratings of their performance (1–7 scale) and effort (1–4 scale). The relationship between extraversion and subjective scores after sleep deprivation (average over last 24h of 36h TSD period) relative to baseline (average over first 12h of TSD period) was analyzed using mixed-effects analysis of covariance, controlling for order, with a random effect over subjects on the intercept. Results No significant relationships were observed between extraversion and subjective estimates of sleepiness (KSS, p=0.45), fatigue (VAS-F, p=0.80), mood (VAS-M, p=0.14), performance (p=0.89), and effort (p=0.93). Conclusion These results indicate that extraversion is not a reliable predictor of trait-like individual differences in subjective vulnerability to 36h TSD. Support (if any) NASA grant NAG9-1161, CDMRP grant W81XWH-20-1-0442

Introduction Tasks requiring individuals to identify specific stimuli may create response/non-response conflict, which may impair performance depending on stimulus feature overlap. Whether sleep deprivation interacts with such impairment is unknown. We investigated the effects of total sleep deprivation (TSD) on stimulus identification in a continuous performance matching task (CPMT). Methods N=85 adults (ages 21–40; 50f) completed a 4-day laboratory study with 10h baseline sleep (22:00–08:00), a 38h acute TSD or 10h sleep opportunity (control condition), and 10h recovery sleep. The ~6min CPMT was administered every 2–4h during wakefulness. Participants completed 300 trials where a 3-digit number was flashed on the screen for 100ms. They were instructed to respond (mouse-click) within 900ms, but only if the number was the same as the preceding number (i.e., a repeat); for all other trials a response was to be withheld. The 5 daytime testing sessions (09:00–21:00) at baseline (day 2) and after TSD/control (day 3) were used for analysis. Trials were classified based on number of digits matching the preceding trial (stimulus feature overlap): none (180 trials), one (30 trials), two (near-repeat; 30 trials), or all (repeat; 60 trials). Hit and false alarm (FA) rates were analyzed with mixed-effects ANOVA for day, condition, trial type, and their interactions. Mean response time (MRT) was analyzed equivalently for repeat trials only. Results Hit rate declined from day 2 to day 3 in the TSD group (F[1,83]=0.15, p Conclusion Our results suggest that greater stimulus feature overlap on the CPMT was associated with greater costs required to resolve conflict. Sleep deprivation exacerbated these costs. Interpretation is limited however, because a response was not required for non-repeat trials. Implementing a two-alternative forced choice version of the task in future TSD studies would address this limitation. Support (If Any) PRMRP W81XWH-16-1-0319 and W81XWH-20-1-0442

Introduction The Digit Symbol Substitution Test (DSST) has been used in sleep research to measure slowing of cognitive throughput. The task shows large aptitude differences in baseline performance and substantial inter-individual differences in vulnerability to performance deficits during total sleep deprivation (TSD). Fluid intelligence (Gf) is generally positively related to processing speed. However, DSST performance is typically found to be independent of Gf. The possible interaction of sleep loss with Gf on performance remains to be examined. Methods N=56 healthy adults (ages 22–37, 29 females) completed a 4-day/3-night in-laboratory study and were randomly assigned (2:1 ratio) to a TSD (n=37) or control (n=19) condition. Sleep opportunities were from 22:00–08:00 on the first (baseline) and last (recovery) night for the TSD group and on all three nights for the control group. Subjects completed a 4min, computerized DSST twice on day 2 (baseline) and twice on day 3 (TSD or control). At baseline, subjects also completed the Shipley Institute of Living Scale (SILS). The abstraction score was used to categorize fluid intelligence (Gf) as relatively high (≥34, n=36) or low ( Results As expected, DSST throughput was significantly reduced by TSD (day by condition interaction: F[1,166]=27.99, p Conclusion Our results indicate that the Gf measure from the SILS does not capture the aspects of cognition that are influenced by TSD and that lead to a decline in DSST throughput. This is consistent with findings that while the DSST has high sensitivity for cognitive dysfunction in clinical settings, it has low specificity in identifying components of cognition responsible for dysfunction. Support (If Any) ONR N00014-13-1-0302 and PRMRP W81XWH-20-1-0442.

Introduction Salivary α-amylase (sAA), a biomarker of autonomic nervous system (ANS) activity, is believed to reflect physiological responsiveness to stressors. Although exposure to stressors often co-occurs with sleep deprivation, little is known about their combined effects. We investigated the sAA response following repeated exposure to acute stressors at well-rested baseline and during total sleep deprivation (TSD). Methods As part of a larger study, N=8 healthy subjects (ages 29.0±6.6; 4 females) participated in a 4-day/3-night laboratory-based experiment. Subjects had 38h TSD preceded and followed by 10h sleep opportunities (22:00–08:00). On days 2 (baseline) and 3 (TSD), subjects completed two (A, B) deadly-force decision-making simulations in a high-fidelity shooting simulator with 30min rest between sessions. During each simulation, subjects (who were civilians) acted as police officers while viewing interactive videos depicting stressful law enforcement emergency response scenarios involving deadly-force decision-making. In these scenarios, subjects attempted to de-escalate the situations in the scenarios using verbal commands. If unsuccessful, they were to determine if the use of (simulated) deadly force was necessary and respond accordingly. Saliva samples were collected immediately before the first simulation of the baseline and TSD days, and immediately, 15min, and 30min after each simulation. Samples were assayed in duplicate using a sAA kinetic enzyme assay; results were normalized against the first pre-stressor sample of the baseline day. Results Post-simulation sAA values normalized to reference were analyzed with mixed-effects ANOVA with fixed effects of day and sample and their interaction and a random effect over subjects on the intercept. There was a significant effect of sample (F[5,76]=3.38, p=0.008) indicating that sAA spiked immediately after each deadly-force decision-making simulation. Planned comparisons revealed significantly blunted sAA during TSD compared to baseline immediately after the second simulation of the day (t[76]=2.09, p=0.040). Conclusion In our sample of civilian subjects, the deadly-force decision-making simulations elicited a sAA response, which was blunted after the second simulation on the day subjects were sleep-deprived, suggesting that TSD mediates the biological response to repeated exposure to acute stressors. Whether this result generalizes to police officers and military personnel trained in deadly-force decision-making remains to be determined. Support (If Any) ONR grant N00014-13-1-0302

Introduction Total sleep deprivation (TSD) impairs binding, i.e., the ability to form new associations. Unitization – when separate memory items are learned as a single unit (e.g., combining two words into a novel compound word) – reduces the need for binding. Unitization mitigates impaired memory for associations in amnesiacs, but whether it offsets binding problems from TSD is unknown. Methods N=23 healthy adults (ages 19-35, 8 women) participated in an ongoing, double-blind, 4-day/3-night in-laboratory study with a 10h baseline sleep opportunity, 38h TSD, and a 10h recovery sleep opportunity. During TSD, participants were randomized to four administrations of caffeine (200mg), modafinil (alternating between 200mg and 0mg), or placebo at 4h intervals beginning at 01:00. They completed a unitization task at 14:45 on day 2 (baseline, session 1), day 3 (TSD, session 2), and day 4 (recovery, session 3). The task began with a study phase where participants studied 60 pairs of words that were presented individually (e.g., “penny” and “tower”) or as new, unitized words (e.g., “pennytower”) (50% each). Afterward, in the test phase, participants indicated whether 60 presented pairs of individual words were old (presented together at study) or new (recombined into new pairs) (50% each). Results Repeated-measures ANOVA revealed significant effects of study pair type (individual or unitized), session (1–3), and their interaction (p Conclusion Across sessions, participants benefitted from practice on unitized word pairs, such that performance improved even during TSD. Although potentially partly attributable to drug condition (to which investigators are still blinded), no such practice effect was seen for word pairs studied individually. Whether this dissociation implies that unitization bypasses the need for binding and thus lessens the impact of TSD requires further investigation. Regardless, unitization may mitigate performance impairment from sleep loss in settings that require forming novel associations, such as eyewitness identifications. Support (If Any) USAMRDC W81XWH-18-1-0100 and CDMRP W81XWH-20-1-0442.

Introduction Military and law enforcement operators must make split-second decisions on whether to shoot during confrontations. Quick responses are crucial when force is necessary, but accurate decision-making is also imperative. Often, decisions are made while fatigued, which could impair speed and/or accuracy. Furthermore, the reliability of background information may impact performance. We investigated performance on a computerized shooting task during a total sleep deprivation (TSD) study. Methods N=86 healthy adults (39 males, age 21-38) completed a 4-day/3-night in-laboratory study, randomly assigned to a TSD (n=56) or control (n=28) condition. A custom task was administered after 32h or 8h of wakefulness (TSD and control groups). Participants were to shoot enemy robots (press spacebar) and not shoot friendly robots (no response) within 500ms of each robot being revealed inside shipping crates (1-5s inter-trial-interval). The task introduction described which crates would contain enemies, but the intel’s accuracy varied across four phases: 100% (20 trials), 80% (120 trials), and 20% (40 trials), then irrelevant in a new environment (60 trials). Reaction time (RT) and accuracy (hits and false alarms (FAs)) were analyzed using 2x4 mixed-effects ANOVAs to determine the effects of condition, phase, and their interaction. Results There was a significant effect of phase on RT (p Conclusion The results suggest a speed/accuracy tradeoff during TSD, where relative to the control group, RTs remained equivalent, but accuracy was worse. In both groups, the RT slowing from phase 1 to subsequent phases, suggests that participants initially used the intel to facilitate quicker decision-making, but disregarded it once it was not completely reliable. Support (If Any) CDMRP grants W81XWH-16-1-0319 and W81XWH-20-1-0442

Introduction Changes in waking neurobehavioral functioning (NF) over time are governed by homeostatic and circadian processes. It has been reported that peak circadian timing varies inherently between tasks, such that the optimal timing for NF would be task-dependent. Here we investigated this idea with a simulated shift work study protocol followed by a 24h constant routine (CR) protocol to experimentally and statistically separate the circadian from the homeostatic process. Methods N=13 healthy adults (ages 25.5±3.2y; 9 men) completed a 7-day/6-night in-laboratory study. They were randomized to a 3-day simulated day shift condition (n=7) with nighttime sleep (22:00–06:00) or a 3-day simulated night shift condition (n=6) with daytime sleep (10:00–18:00). They then underwent a 24h CR protocol, during which they stayed awake under constant behavioral and environmental conditions and blood was collected at 1–3h intervals for the assessment of dim light melatonin onset (DLMO). During scheduled wakefulness, subjects completed three functionally distinct NF tasks at ~2h intervals: the Karolinska Sleepiness Scale (KSS), Digit Symbol Substitution Test (DSST), and Psychomotor Vigilance Test (PVT). Data from these tasks taken during the CR protocol were analyzed with non-linear mixed-effects regression to separate endogenous circadian effects from the homeostatic process. Results Following simulated night shift, compared to simulated day shift, on average there was a modest, 1.4h (±0.8h SE) delay in DLMO (F1,11=3.68, p=0.082). As such, the simulated night shift condition produced a 10.6h shift in alignment of the homeostatic process relative to the circadian process. Regardless of prior shift condition, the peak of the circadian rhythm effect on NF occurred post-DLMO by 16.8h (±1.0h) for KSS, 15.9h (±1.4h) for DSST, and 18.6h (±1.0h) for PVT, which was not significantly different (F2,9=1.55, p=0.26). Conclusion As proof of principle, we studied three distinct NF assays, and found only small, non-significant differences between them in the timing of underlying circadian rhythmicity. While a larger sample could have yielded statistical significance in our comparison of circadian peak times, the small magnitude of the observed difference does not support the idea of inherent task-dependent differences in the timing of the endogenous circadian rhythm’s influence on NF. Support (If Any) CDMRP W81XWH-16-1-0319 and W81XWH-20-1-0442

Introduction Total sleep deprivation (TSD) increases sleepiness and impairs vigilant attention. There are large individual differences in vulnerability to sleep loss, but individuals’ self-ratings of sleepiness often do not align with their objective performance impairment. Here we investigated whether the trait of social desirability – the desire to conform to social standards – plays a role. Methods N=39 healthy adults (ages 27.6±4.6y; 22 men) completed a 3-night/4-day in-laboratory study with 10h baseline and recovery sleep opportunities (22:00–08:00) preceding and following a 38h period of TSD. Every 2–4h during TSD, subjects completed the Karolinska Sleepiness Scale (KSS) and a 10min Psychomotor Vigilance Test (PVT) to assess subjective sleepiness and vigilant attention, respectively. Throughout the study, subjects were behaviorally monitored by the researchers. Prior to the study, subjects completed the Marlow-Crowne Social Desirability (MCSD) scale. Based on standard criteria, subjects were categorized post hoc into average (n=13) and high (n=26) social desirability groups (no subjects in the sample scored low on social desirability). Self-reported sleepiness scored on the KSS and lapses (reaction times ≥500ms) on the PVT were analyzed using mixed-effects ANOVA with fixed effects for time awake and MCSD group and their interaction. Results As expected, there was a main effect of time awake for KSS score (F[12,441]=31.48, p Conclusion Subjects high in social desirability reported less sleepiness during TSD than those with average social desirability yet their objective performance was equally degraded. This finding has implications for fatigue risk management because individuals with high social desirability may underreport their sleepiness. This may undermine the reliability of self-report assessments of sleepiness and ability to work safely. [ 1] Whether there is bias in self-reported sleepiness for individuals low in social desirability as well remains to be investigated. Support (If Any) Support: ONR N00014-13-1-0302 and PRMRP W81XWH-20-1-0442

Introduction Visual search is important in many operational tasks, such as passive sonar monitoring in naval operations. Shift work can contribute to fatigue and task performance impairment; in particular, backward rotating shift schedules have been shown to impair vigilant attention performance. However, the impact on visual search performance, above and beyond impaired vigilant attention, is unknown. We investigated the effects of two distinct shift work schedules using a visual search task with properties of real-life visual search performance. Methods N=13 adult males (ages 18–39) completed a 6-day/5-night laboratory study with an acclimation day, four simulated shift days, and a recovery day. Shift days involved either a 5h-on/15h-off backward rotating schedule (n=8) or a 3h-on/9h-off fixed schedule (n=5). The visual search task was performed once per shift at varying time of day depending on shift. Participants viewed search arrays where stimuli consisted of colored letters of different shapes. Over three trial blocks of 24 trials each, participants determined if a target was present or absent among 1, 5, 15, or 30 distractors. Similarity between targets and distractors was manipulated between blocks, such that targets differed from distractors by color only, shape only, or either color or shape but not both. For each distinct target feature block, and separately for presence or absence of a target, slopes of response times regressed against number of stimuli were calculated to quantify visual search rates. Mixed-effects ANOVA was used to analyze visual search rates by shift schedule and shift day. Results There were no significant effects of shift schedule (all p>0.30), shift day (all p>0.13), or their interaction (all p>0.22) on visual search rates. Conclusion Previous work showed degraded vigilant attention in the shift schedules considered here, especially in the backward rotating schedule, which may compromise operational performance. However, while our sample may have been too small to have adequate statistical power, we failed to identify specific impairments in visual search with statistical significance. It remains to be determined whether greater levels of fatigue, such as could be induced by total sleep deprivation, would reveal significant visual search deficits. Support (if any) Naval Postgraduate School award N62271-13-M-1228

Introduction Sleep inertia (SI), the transient grogginess and disorientation that occurs upon awakening, may be particularly problematic in on-call operations that require safety-sensitive and time-critical action, such as healthcare and emergency response. The magnitude of SI is determined by multiple factors, including sleep history, and anecdotal evidence suggests individuals may differ considerably in susceptibility to impairment from SI. Methods As part of a larger study investigating individual differences in neurobehavioral impairment, N=21 healthy adults (aged 21–38y; 9 females) completed three laboratory-based neurobehavioral testing sessions, each preceded by baseline sleep. Baseline sleep and nightly at-home sleep opportunities during the week prior were either 12h (extended) or 6h (restricted); two sessions involved extension and one involved restriction in randomized, counterbalanced order. Baseline sleep opportunities ended at 10:00, whereupon subjects completed a 60min neurobehavioral test battery, which began with the Karolinska Sleepiness Scale (KSS). The test battery was repeated every 2h throughout the testing sessions. Results A nonlinear mixed-effects regression, controlling for prior sleep restriction/extension and session number, was used to estimate the subjective magnitude of SI immediately upon awakening from baseline sleep, as measured by KSS scores, and the exponential dissipation rate of the effect relative to KSS scores later in the day (12:00-20:00). Following prior sleep extension, SI was associated with a 1.82±0.59 KSS score increase (p=0.006), which subsequently dissipated from a level of 4.80±0.65 to 2.98±0.29 (p= Conclusion We observed sizeable, systematic individual differences in subjective sleepiness due to sleep inertia. To what degree these individual differences predict objective performance deficits remains to be investigated. Support (if any) NASA grant NAG9-1161 and CDMRP grant W81XWH-20-1-0442

Introduction Total sleep deprivation (TSD) has been shown to impair performance on a two-phase attentional control task, the AX-type continuous performance task with switch (AX-CPTs). Here we investigate whether the observed AX-CPTs impairments are a downstream consequence of TSD-induced non-specific effects (e.g., reduced vigilant attention) or reflect a distinct impact on attentional control. Methods N=55 healthy adults (aged 26.0±0.7y; 32 women) participated in a 4-day laboratory study with 10h baseline sleep (22:00-08:00) followed by 38h TSD and then 10h recovery sleep. At baseline (09:00 day 2) and after 25h and 30h TSD (09:00 and 14:00 day 3), subjects were tested on a 10min psychomotor vigilance test (PVT), an assay of vigilant attention, and on the AX-CPTs. The AX-CPTs required subjects to differentiate designated target from non-target cue-probe pairs. In phase 1, target trials occurred frequently, which promoted prepotent anticipatory responses; in phase 2, the target pair was switched. Accuracy of responses to various different AX-CPTs trial types was expressed relative to accuracy on phase 1 neutral (non-target cue and probe) trials, which should capture non-specific impairments on the task. For all three test sessions, these relative accuracy measures, along with accuracy on phase 1 neutral trials and lapses (RT>500ms) on the PVT, were subjected to principal component analysis (PCA). Results The PCA revealed three statistically independent factors. Following varimax rotation, factor 1 (36.3% variance explained) and factor 3 (14.8% variance explained) each had high loadings for relative accuracy on multiple AX-CPTs trial types from phases 1 and 2; whereas factor 2 (17.9% variance explained) had high loadings for accuracy on phase 1 neutral trials, relative accuracy on phase 1 target trials, and PVT lapses. Conclusion These results indicate a statistical separation between AX-CPTs phase 1 neutral trials and phase 1 target trials, in conjunction with PVT lapses, versus the various other AX-CPTs trial types. This suggests a dissociation between TSD-induced, non-specific impairments on the task—potentially related to reduced vigilant attention—and TSD-induced specific impairments related to attentional control. Thus, TSD-induced deficits in attentional control are unlikely to be a downstream consequence of non-specific impairments. Support (if any) CDMRP grant W81XWH-16-1-0319

Introduction When presented with a choice between sure gains or losses versus gambles, people tend to select sure gains over gambles, but gambles over sure losses. This pre-existing framing bias is embedded in the Framed Gambling Task (FGT), in which subjects choose between a sure option (gain or loss) and a gamble (card from one of two decks). For optimal performance, subjects need to recognize that one deck (‘good deck’) results in better average outcomes than the other deck (‘bad deck’) and select the gamble or sure option depending on the deck (good/bad) rather than the frame (sure loss/gain). A speeded version of the FGT, with 2s response deadlines to induce time pressure, was used in a laboratory total sleep deprivation (TSD) study to determine the impact of sleep loss on the ability to overcome pre-existing framing bias. Methods Eight-six subjects (ages 21–38; 47 females) were randomized (2:1 ratio) to a TSD condition (n=56) or control condition (n=30). They completed the speeded FGT at 11:00 on the baseline day (session 1), and again the following day (session 2) after 27h of wakefulness (TSD group) or 3h of wakefulness (control group). Performance accuracy was defined in terms of optimal task performance, i.e., gambling when the good deck was presented and not gambling when the bad deck was presented. Each test bout had 72 trials across three trial blocks. Results Accuracy improved across trial blocks (F1,84=20.44, p2s) was low ( Conclusion Sleep deprivation degraded FGT performance under time pressure, indicating reduced ability to overcome pre-existing framing bias. Support PRMRP award W81XWH-16-1-0319

Introduction Total sleep deprivation (TSD) causes profound vigilant attention deficits, with large, trait-like individual differences, as evidenced convincingly by response lapses on the psychomotor vigilance test (PVT). There is debate, however, about the role of vigilant attention deficits in the effects of TSD on other speeded performance tasks besides the PVT. We addressed this issue by testing whether PVT response lapses are related to delays in responding to stimuli under strict deadlines in two decision making tasks. Methods N=54 healthy adults (aged 21-38y; 31 females) completed an in-laboratory TSD study. Following a 10h baseline sleep opportunity, cognitive testing occurred after 25h and 29h of TSD (09:00 and 13:00). Testing included an AX continuous performance task with switch (AX-CPTs), which is a dynamic decision making task requiring subjects to respond to a frequently occurring cue-probe combination; an identical pairs continuous performance task (CPT-IP), which is a 1-back go/no-go task; and a 10min PVT. Lapses (RTs>500ms) on the PVT and target accuracy on the AX-CPTs and CPT-IP were calculated as indices of vigilant attention. Intraclass correlation coefficients (ICCs) were used to quantify the stability of individual differences, and absolute rank-order correlation (|ρ|) was used to compare the three indices. Results The stability of individual differences ranged from fair to substantial (PVT: ICC=0.44; AX-CPTs: ICC=0.73; CPT-IP: ICC=0.31). The rank-order correlation between the AX-CPTs and CPT-IP vigilant attention indices was relatively high (|ρ|=0.44), whereas correlations with PVT lapses were much lower (AX-CPTs: |ρ|=0.14; CPT-IP: |ρ|=0.04). Conclusion Individual differences during TSD were moderately stable for each index of vigilant attention, but the relationships between PVT lapses and the other indices were weak. This suggests that any or all of the indices considered here are not pure measures of vigilant attention, or that vigilant attention may constitute multiple, distinct constructs. Support CDMRP grant W81XWH-16-1-0319

Introduction There are substantial, phenotypical individual differences in the adverse impact of total sleep deprivation (TSD) on vigilant attention performance. Dopaminergic genotypes have been found to contribute to these phenotypical differences. Here we investigated the association between a single nucleotide polymorphism (SNP) of the dopamine receptor D2 (DRD2) gene, C957T (rs6277), on vigilant attention performance measured with the psychomotor vigilance test (PVT) in a laboratory TSD study. Methods N=46 healthy adults (ages 26.0±5.3y; 25 females) completed a 4-day in-laboratory study with a baseline day (10h time in bed: 22:00-08:00), a 38h TSD period, and a recovery day (10h time in bed: 22:00-08:00). DNA isolated from whole blood was assayed for DRD2 C957T genotype using real-time polymerase chain reaction. PVT performance was measured during TSD at 2-4h intervals, and analyzed for genotype using mixed-effects analysis of covariance of lapses of attention (RTs>500ms). Results The genotype distribution in this sample - 28.3% C/C, 50.0% C/T, 21.7% T/T - was found to be in Hardy-Weinberg Equilibrium (X21=0.0008, p=0.98). As expected, there was a significant effect of time awake on PVT performance (F14,602=26.67, p Conclusion Subjects homozygous for the T allele of DRD2 C957T were considerably more vulnerable to TSD-induced PVT performance impairment than carriers of the C allele. A recent study showed that DRD2 C957T influences PVT performance in interaction with a SNP of the DAT1 gene. Here, DRD2 genotype was by itself also associated with PVT performance impairment during TSD. Support CDMRP awards W81XWH-16-1-0319 and W81XWH-18-1-0100.

Introduction Stimuli with an emotional valence tend to produce better recognition from memory than neutral stimuli. Sleep loss is believed to increase reactivity to negative stimuli, as compared to positive stimuli, which may comparatively enhance subsequent recognition from memory for negative stimuli. We investigated the impact of total sleep deprivation (TSD) on recognition accuracy for words with different emotional valence using the Affective Item Source Memory Task (AISM). Methods N=14 adults (ages 21–39; 7 females) completed a 4-day in-laboratory study with 9h baseline sleep (22:00-07:00), 39h acute TSD, and 9h recovery sleep. The AISM was administered at 16:30 during baseline and after 34h TSD. During a 5min study phase, participants heard a list, twice, of 20 positive, 20 negative, and 20 neutral words spoken with a male or female voice. During an immediately subsequent 8min recognition phase, participants heard 120 words (50% new) and judged whether each word had been presented in the study list (item memory). For words judged to have been presented previously, participants indicated whether those were presented by a female or male speaker (source memory). Results Mixed-effects ANOVA showed effects of session (p Conclusion Sleep deprivation reduced item memory for words of all valence types. However, there was no comparatively greater impact on item or source memory for negative words nor any differential effect of TSD for different valences. Whether our results would hold with longer time intervals between task phases or an intervening sleep period remains to be determined. Support Jazz Pharmaceuticals