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Introduction During laboratory-based, voluntary exposure to total sleep deprivation (TSD), relatively large decreases in positive mood and relatively small increases in negative mood have been observed, with the magnitudes of change varying across individuals. People differ in their trait emotion reactivity, i.e., their sensitivity to emotion-evoking stimuli or events. As higher reactivity is associated with greater difficulty regulating emotion, we hypothesized this trait could moderate mood changes during TSD. Methods N=96 healthy adults (ages 21-38, 47% female) participated in one of three 4-day/3-night in-laboratory TSD studies. In each study, after 10h baseline sleep, participants were exposed to 38h TSD, followed by 10h recovery sleep. Participants completed the Emotion Reactivity Scale (ERS), and their self-reported affect was assessed every 2-4h during wake using the Positive and Negative Affect Schedule (PANAS). The 11 test bouts during TSD shared across studies were included in analyses (day 2: 09:00, 13:00, 21:00, 23:00; day 3: 01:00, 03:00, 05:00, 07:00, 09:00, 13:00, 21:00). Positive and negative affect ratings were analyzed with linear mixed-effects regression with fixed effects of test bout (categorical), ERS score (continuous), and their interaction, covariates for study, sex, and age, and a random intercept over participants. Results Participants showed the expected decrease in positive affect as a function of test bout (time awake and time of day, p< 0.001), and a smaller, non-significant increase in negative affect (p=0.17). Higher ERS scores were associated with increased negative affect during TSD (p=0.002), but this effect was small, and negative affect showed a floor effect. Emotion reactivity was not a significant predictor of decreased positive affect during TSD (p=0.97). Conclusion As hypothesized, emotion reactivity predicted individual variability in negative affect during TSD, but unexpectedly it did not predict the decrease in positive affect associated with TSD. This suggests that the trait measured by the ERS may be biased toward negative affect, and/or that positive affective changes may be more difficult to predict during the low arousal state induced by TSD. Studies inducing greater variability in negative affect during TSD (e.g., through exposure to a stressor) are needed to confirm our findings. Support (if any) NIH CA167691, ONR N00014-13-1-0302, and CDMRP W81XWH-16-1-0319 and W81XWH-20-1-0442.

Human Respiratory Syncytial Virus (RSV) infections pose a significant risk to human health worldwide, especially for young children. Whole genome sequencing (WGS) provides a useful tool for global surveillance to better understand the evolution and epidemiology of RSV and provide essential information that may impact on antibody treatments, antiviral drug sensitivity and vaccine effectiveness. Here we report the development of a rapid and simplified amplicon-based one-step multiplex reverse-transcription polymerase chain reaction (mRT-PCR) for WGS of both human RSV-A and RSV-B viruses. The method requires only two reactions for each sample, which significantly reduces the cost and time compared to other commonly used RSV WGS methods. In silico analysis and laboratory testing revealed that the primers used in the new method covered most of the currently circulating RSV-A and RSV-B. Amplicons generated were suitable for both Illumina and Oxford Nanopore Technologies (ONT) NGS platforms. This new method was tested on 200 clinical samples collected in Australia in 2020 and 2021 with RSV Ct values between 10 and 32. A success rate of 88% with a full coverage for the genome of 99 RSV-A and 77 RSV-B was achieved. This assay is simple to set up, robust, easily scalable in sample preparation and relatively inexpensive, and as such, provides a valuable addition to existing NGS RSV WGS methods.

Sleep deprivation consistently decreases vigilant attention, which can lead to difficulty in performing a variety of cognitive tasks. However, sleep-deprived individuals may be able to compensate for degraded vigilant attention by means of top-down attentional control. We employed a novel task to measure the degree to which individuals overcome impairments in vigilant attention by using top-down attentional control, the Flexible Attentional Control Task (FACT). The FACT is a two-choice task that has trials with valid, invalid, and neutral cues, along with an unexpected switch in the probability of cue validity about halfway in the task. The task provides indices that isolate performance components reflecting vigilant attention and top-down attentional control. Twelve healthy young adults completed an in-laboratory study. After a baseline day, the subjects underwent 39 hours of total sleep deprivation (TSD), followed by a recovery day. The FACT was administered at 03:00, 11:00, and 19:00 during sleep deprivation (TSD condition) and at 11:00 and 19:00 after baseline sleep and at 11:00 after recovery sleep (rested condition). When rested, the subjects demonstrated both facilitation and interference effects on cued trials. While sleep deprived, the subjects showed vigilant attention deficits on neutral cue trials, and an impaired ability to reduce these deficits by using predictive contextual cues. Our results indicate that the FACT can dissociate vigilant attention from top-down attentional control. Furthermore, they show that during sleep deprivation, contextual cues help individuals to compensate partially for impairments in vigilant attention, but the effectiveness of top-down attentional control is diminished.

Besides degrading vigilant attention, total sleep deprivation (TSD) impairs reversal learning performance and blunts affective reactions to feedback. Whether these effects are downstream consequences of information acquisition failures from degraded vigilant attention, or distinct from degraded vigilant attention, is unclear. In well-rested individuals we simulated information acquisition failures by masking a portion of trial information in a go/no-go reversal learning task with four conditions: stimulus masking, feedback masking, alternating stimulus/feedback masking, and no-masking control. No condition reproduced the previously documented pattern of TSD effects, suggesting that information acquisition failures cannot fully account for impaired reversal learning and blunted affective reactions during TSD.

PURPOSE: Our study examined psychosocial risk and protective features affecting cardiovascular and mortality disparities in American Indians, including stress, anger, cynicism, trauma, depression, quality of life, and social support. METHODS: The Strong Heart Family Study cohort recruited American Indian adults from 12 communities over 3 regions in 2001–2003 (N = 2786). Psychosocial measures included Cohen Perceived Stress, Spielberger Anger Expression, Cook-Medley cynicism subscale, symptoms of post-traumatic stress disorder, Centers for Epidemiologic Studies Depression scale, Short Form 12-a quality of life scale, and the Social Support and Social Undermining scale. Cardiovascular events and all-cause mortality were evaluated by surveillance and physician adjudication through 2017. RESULTS: Participants were middle-aged, 40% male, with mean 12 years formal education. Depression symptoms were correlated with anger, cynicism, poor quality of life, isolation, criticism; better social support was correlated with lower cynicism, anger, and trauma. Adjusted time-to-event regressions found that depression, (poor) quality of life, and social isolation scores formed higher risk for mortality and cardiovascular events, and social support was associated with lower risk. Social support partially explained risk associations in causal mediation analyses. CONCLUSION: Altogether, our findings suggest that social support is associated with better mood and quality of life; and lower cynicism, stress, and disease risk—even when said risk may be increased by comorbidities. Future research should examine whether enhancing social support can prospectively reduce risk, as an efficient, cost-effective intervention opportunity that may be enacted at the community level.

Canine distemper virus (CDV) causes a highly contagious systemic infection in an array of animal species. In this study we report an outbreak of distemper in ferrets in two research facilities in Australia, caused by a novel lineage of CDV. While the CDV strain caused mainly mild symptoms in ferrets, histopathology results presented a typical profile of distemper pathology, with multi-system virus replication. Through the development of a discriminatory PCR, paired with full genome sequencing, we revealed that the outbreak was caused by a novel lineage of CDV. The novel CDV lineage was highly divergent, with less than 93% similarity across the H gene to other described lineages, including the vaccine strain, and diverged approximately 140-400 years ago. Enhanced surveillance to determine the prevalence of CDV in ferrets, dogs and other at-risk species is critical to better understand the presence and diversity of CDV in Australia currently.

Sleep loss is reported to influence affective processing, causing changes in overall mood and altering emotion regulation. These aspects of affective processing are seldom investigated together, making it difficult to determine whether total sleep deprivation has a global effect on how affective stimuli and emotions are processed, or whether specific components of affective processing are affected selectively. Sixty healthy adults were recruited for an in-laboratory study and, after a monitored night of sleep and laboratory acclimation, randomly assigned to either a total sleep deprivation condition (n = 40) or a rested control condition (n = 20). Measurements of mood, vigilant attention to affective stimuli, affective working memory, affective categorization, and emotion regulation were taken for both groups. With one exception, measures of interest were administered twice: once at baseline and again 24 hours later, after the sleep deprived group had spent a night awake (working memory was assessed only after total sleep deprivation). Sleep deprived individuals experienced an overall reduction in positive affect with no significant change in negative affect. Despite the substantial decline in positive affect, there was no evidence that processing affectively valenced information was biased under total sleep deprivation. Sleep deprived subjects did not rate affective stimuli differently from rested subjects, nor did they show sleep deprivation-specific effects of affect type on vigilant attention, working memory, and categorization tasks. However, sleep deprived subjects showed less effective regulation of negative emotion. Overall, we found no evidence that total sleep deprivation biased the processing of affective stimuli in general. By contrast, total sleep deprivation appeared to reduce controlled processing required for emotion regulation.

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.

In around-the-clock operations, reduced alertness due to circadian misalignment and sleep loss causes performance impairment, which can lead to catastrophic errors and accidents. There is mounting evidence that performance on different tasks is differentially affected, but the general principles underlying this differentiation are not well understood. One factor that may be particularly relevant is the degree to which tasks require executive control, that is, control over the initiation, monitoring, and termination of actions in order to achieve goals. A key aspect of this is cognitive flexibility, i.e., the deployment of cognitive control resources to adapt to changes in events. Loss of cognitive flexibility due to sleep deprivation has been attributed to “feedback blunting,” meaning that feedback on behavioral outcomes has reduced salience - and that feedback is therefore less effective at driving behavior modification under changing circumstances. The cognitive mechanisms underlying feedback blunting are as yet unknown. Here we present data from an experiment that investigated the effects of sleep deprivation on performance after an unexpected reversal of stimulus-response mappings, requiring cognitive flexibility to maintain good performance. Nineteen healthy young adults completed a 4-day in-laboratory study. Subjects were randomized to either a total sleep deprivation condition (n = 11) or a control condition (n = 8). Athree-phase reversal learning decision task was administered at baseline, and again after 30.5 h of sleep deprivation, or matching well-rested control. The task was based on a go/no go task paradigm, in which stimuli were assigned to either a go (response) set or a no go (no response) set. Each phase of the task included four stimuli (two in the go set and two in the no go set). After each stimulus presentation, subjects could make a response within 750 ms or withhold their response. They were then shown feedback on the accuracy of their response. In phase 1 of the task, subjects were explicitly told which stimuli were assigned to the go and no go sets. In phases 2 and 3, new stimuli were used that were different from those used in phase 1. Subjects were not explicitly told the go/no go mappings and were instead required to use accuracy feedback to learn which stimuli were in the go and nogo sets. Phase 3 continued directly from phase 2 and retained the same stimuli as in phase 2, but there was an unannounced reversal of the stimulus-response mappings. Task results confirmed that sleep deprivation resulted in loss of cognitive flexibility through feedback blunting, and that this effect was not produced solely by (1) general performance impairment because of overwhelming sleep drive; (2) reduced working memory resources available to perform the task; (3) incomplete learning of stimulus-response mappings before the unannounced reversal; or (4) interference with stimulus identification through lapses in vigilant attention. Overall, the results suggest that sleep deprivation causes a fundamental problem with dynamic attentional control. This element of performance impairment due to sleep deprivation appears to be distinct from vigilant attention deficits, and represents a particularly significant challenge for fatigue risk management.

A naturalistic experiment was conducted to test the hypothesis that synchronous computer-mediated communication (CMC) can indirectly improve L2 oral proficiency by developing the same cognitive mechanisms underlying spontaneous conversational speech. The theoretical framework guiding this inquiry consists of Levelt's (1989) model of language production augmented by concepts from Working Memory theory. The findings show a significant difference between the experimental and control groups oral proficiency development with participants in the experimental condition (two of four contact hours per week were in a chatroom) scoring higher than participants in the control condition. Implications for language instruction and the second language oral proficiency development for different types of learners are discussed.

Prospective memory pervades our daily lives and failures can have detrimental consequences. This ability to execute delayed intentions may be impacted by stress, yet few studies have examined these effects. Moreover, as many cannabis users report using cannabis to cope with stress, it is important to understand how stress impacts memory in cannabis users. We assessed the effects of acute and chronic stress on prospective memory to examine whether stress differentially impacts prospective memory in cannabis users vs. non-users. Forty cannabis users and 42 non-users were assigned an episodic and a habitual prospective memory test before completing either the stress or no stress condition of the Maastricht Acute Stress Test (MAST). Participants were instructed to execute the habitual test during the MAST and the episodic test shortly after the MAST. Chronic stress was measured using the Perceived Stress Scale, and acute stress was measured using subjective ratings and cortisol. There was a main effect of acute stress indicating that stress detrimentally impacted habitual prospective memory performance. Although there was not a significant stress x cannabis interaction, further planned comparisons indicated the habitual prospective memory impairment was selective to cannabis users. There were also significant negative correlations between (i) episodic prospective memory and both subjective stress as well as chronic stress, and (ii) habitual prospective memory and change in subjective stress. This study is the first to reveal detrimental effects of acute stress on prospective memory performance, which may be exacerbated in cannabis users.

Introduction Health experts recommend that adults should sleep between 7 to 9 hours in a 24-hour period, with data indicating higher mortality risks both above and below these thresholds. However, no study to date has examined the association between sleep duration and mortality risk across racial/ethnic groups. Methods Data from the linked mortality files of the 2004-2015 National Health Interview Survey (NHIS) were used to examine the association between sleep duration and all-cause mortality among U.S. adults. Of 278,103 adults aged 25+, 22,347 individuals died over the follow-up period. Sleep duration was coded as: 9 hours. Race/ethnicity was categorized as: non-Hispanic (NH) White, NH Black, NH American Indian/Alaska Native, NH Asian, NH multiple races, and Hispanic. Cox Proportional Hazard models were used to estimate associations between sleep duration, race/ethnicity, and mortality. All results are reported as relative risk ratios (RRR). Results Across the sample, we replicated previous research, finding increased mortality risk for those sleeping 9 hours in a 24-hour period. Relative to NH Whites, after adjustments for sociodemographic and socioeconomic variables, mortality risk for NH Blacks and NH multiracial individuals was statistically indistinguishable while NH Asians (RRR= 0.79; p 9 hours experienced 1.82 times higher (p Conclusion The association between sleep duration and all-cause mortality risk varies by race/ethnicity. While sleeping 9 hours is associated with a higher mortality risk, but more so for NH Whites than other groups. More research on sleep duration and mortality that takes race/ethnic specific risk factors into account is needed to identify causal mechanisms. Support (If Any) Health Equity Research Center (HERC) at Washington State University

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.

Binding information to its context in long-term memory is critical for many tasks, including memory tasks and decision making. Failure to associate information to its context could be an important aspect of sleep deprivation effects on cognition, but little is known about binding problems from being sleep-deprived at the time of encoding. We studied how sleep deprivation affects binding using a well-established paradigm testing the ability to remember auditorily presented words (items) and their speakers (source context). In a laboratory study, 68 healthy young adults were randomly assigned to total sleep deprivation or a well-rested control condition. Participants completed an affective item and source memory task twice: once after 7-hour awake during baseline and again 24 hours later, after nearly 31 hours awake in the total sleep deprivation condition or 7 hours awake in the control condition. Participants listened to negative, positive, and neutral words presented by a male or female speaker and were immediately tested for recognition of the words and their respective speakers. Recognition of items declined during sleep deprivation, but even when items were recognized accurately, recognition of their associated sources also declined. Negative items were less bound with their sources than positive or neutral items, but sleep deprivation did not significantly affect this pattern. Our findings indicate that learning while sleep-deprived disrupts the binding of information to its context independent of item valence. Such binding failures may contribute to sleep deprivation effects on tasks requiring the ability to bind new information together in memory.

Total sleep deprivation (TSD) is known to impair sustained attention. However, previously reported effects of TSD on response inhibition are mixed. We administered a "stop-signal" variation of the psychomotor vigilance test, which included 25% of trials requiring withholding of a response to assess response inhibition alongside sustained attention. Participants completed the task at baseline and after 34.5 h of wakefulness. Accuracy was not reduced during TSD. However, response times were significantly slower. A speed/accuracy trade-off allowed participants to effectively withhold responses on inhibition trials and conferred resilience of inhibitory control during TSD under conditions of relatively low time pressure.

Adaptive decision making is profoundly impaired by total sleep deprivation (TSD). This suggests that TSD impacts fronto-striatal pathways involved in cognitive control, where dopamine is a key neuromodulator. In the prefrontal cortex (PFC), dopamine is catabolized by the enzyme catechol-O-methyltransferase (COMT). A functional polymorphism (Val158Met) influences COMT's enzymatic activity, resulting in markedly different levels of prefrontal dopamine. We investigated the effect of this polymorphism on adaptive decision making during TSD. Sixty-six healthy young adults participated in one of two in-laboratory studies. After a baseline day, subjects were randomized to either a TSD group (n = 32) with 38 h or 62 h of extended wakefulness or a well-rested control group (n = 34) with 10 h nighttime sleep opportunities. Subjects performed a go/no-go reversal learning (GNGr) task at well-rested baseline and again during TSD or equivalent control. During the task, subjects were required to learn stimulus–response relationships from accuracy feedback. The stimulus–response relationships were reversed halfway through the task, which required subjects to learn the new stimulus–response relationships from accuracy feedback. Performance on the GNGr task was quantified by discriminability (d′) between go and no-go stimuli before and after the stimulus–response reversal. GNGr performance did not differ between COMT genotypes when subjects were well-rested. However, TSD exposed a significant vulnerability to adaptive decision making impairment in subjects with the Val allele. Our results indicate that sleep deprivation degrades cognitive control through a fronto-striatal, dopaminergic mechanism.

Sleep deprivation impairs performance on cognitive tasks, but it is unclear which cognitive processes it degrades. We administered a semantic matching task with variable stimulus onset asynchrony (SOA) and both speeded and self-paced trial blocks. The task was administered at the baseline and 24 hours later after 30.8 hours of total sleep deprivation (TSD) or matching well-rested control. After sleep deprivation, the 20% slowest response times (RTs) were significantly increased. However, the semantic encoding time component of the RTs remained at baseline level. Thus, the performance impairment induced by sleep deprivation on this task occurred in cognitive processes downstream of semantic encoding.

Background Cannabis use has increased rapidly in recent decades. The increase in cannabis use makes it important to understand the potential influence of chronic use on attentional control and other executive functions (EFs). Because cannabis is often used to reduce stress, and because stress can constrain attentional control and EFs, the primary goal of this study was to determine the joint effect of acute stress and chronic cannabis use on specific EFs. Methods Thirty-nine cannabis users and 40 non-users were assigned to either a stress or no stress version of the Maastricht Acute Stress Test. Participants then completed two cognitive tasks that involve EFs: (1) task switching, and (2) a novel Flexible Attentional Control Task. These two tasks provided assessments of vigilant attention, inhibitory control, top-down attentional control, and cognitive flexibility. Salivary cortisol was assessed throughout the study. Results Reaction time indices showed an interaction between stress and cannabis use on top-down attentional control (p = 0.036, np2 = 0.059). Follow-up tests showed that cannabis users relied less on top-down attentional control than did non-users in the no stress version. Despite not relying on top-down control, the cannabis users showed no overall performance deficits on the tasks. Conclusions Chronic cannabis users performed cognitive tasks involving EFs as well as non-users while not employing cognitive control processes that are typical for such tasks. These results indicate alterations in cognitive processing in cannabis users, but such alterations do not necessarily lead to global performance deficits.

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 Effective memory often requires recall of both specific information and the context in which the information was encountered. Total sleep deprivation (TSD) is known to impair memory for information items (e.g., words on a studied list), but the impact of TSD on binding, or associative linking, between items and context is not clear. Methods N=68 healthy adults (ages 22–40; 35 females) completed a 4-day (3-night) in-laboratory study. After a baseline night with 10h nighttime sleep opportunity, participants were randomly assigned to either 38h TSD (n=38) or a well-rested control (WRC) condition with 10h nighttime sleep opportunity (n=30). Both study arms concluded with a 10h nighttime recovery sleep opportunity. Participants completed a standardized recognition memory task at 14:50 on day 2 (baseline, session 1) and again 24h later (session 2). The memory task consisted of a study phase in which words with negative, positive, and neutral affective valence were spoken by a female or male speaker (50% each); followed immediately by a test phase, in which subjects made recognition judgments for the items (words) and their source (speaker). Results Mixed-effects ANOVA revealed significant interactions of session by condition for both word and speaker recognition (p Conclusion TSD impaired memory for items, but more importantly, also impaired memory for the context in which items were presented, even if the items were themselves correctly recognized, and regardless of their affective valence. These results indicate that TSD may disrupt binding of information to its context, which could explain TSD deficits in decision-making tasks that require novel associative linking. Furthermore, our findings are important in real-world situations such as eyewitness accounts and perseveration of the influence of misinformation. Support (if any) NIH grant R21 CA167691 and CDMRP award 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 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

The cognitive effects of sleep loss are often attributed to compromised functioning of the prefrontal cortex (PFC). However, compromised PFC functioning does not account for well-known effects of sleep deprivation on vigilance. Furthermore, the executive attentional control functions associated with the PFC show considerable variability in the effects of sleep deprivation. Evidence from neuroimaging suggests that sleep deprived people are sometimes able to maintain performance on cognitive tasks by increasing PFC activation of task-relevant circuits and by recruiting new circuits not typically involved in a particular cognitive operation. Still, little is known about how such compensatory processes work on a functional level, or what tradeoffs in processing they may entail. We propose a dynamic attentional control framework to bridge the gap between the evidence on sleep deprived neural circuits and cognitive task performance. We review evidence that shows that the pattern of preserved and compromised task performance can be understood in terms of sleep deprivation's influence on frontostriatal circuitry such that the ability to maintain task-relevant information in the focus of attention is relatively spared but the ability to update task-relevant information in response to changing circumstances is more negatively affected. This framework helps account for why some tasks are more affected by SD than others, and why individual differences in the effects of sleep deprivation are task-specific.