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ObjectiveDetermine the optimal combination of digital health intervention component settings that increase average sleep duration by ≥30 minutes per weeknight.MethodsOptimization trial using a 25factorial design. The trial included 2 week run-in, 7 week intervention, and 2 week follow-up periods. Typically developing children aged 9-12y, with weeknight sleep duration with their settings to which participants were randomized) were: 1) sleep goal (guideline-based or personalized); 2) screen time reduction messaging (inactive or active); 3) daily routine establishing messaging (inactive or active); 4) child-directed loss-framed financial incentive (inactive or active); and 5) caregiver-directed loss-framed financial incentive (inactive or active). The primary outcome was weeknight sleep duration (hours per night). The optimization criterion was: ≥30 minutes average increase in sleep duration on weeknights.ResultsAverage baseline sleep duration was 7.7 hours per night. The highest ranked combination included the core intervention plus the following intervention components: sleep goal (either setting was effective), caregiver-directed loss-framed incentive, messaging to reduce screen time, and messaging to establish daily routines. This combination increased weeknight sleep duration by an average of 39.6 (95% CI: 36.0, 43.1) minutes during the intervention period and by 33.2 (95% CI: 28.9, 37.4) minutes during the follow-up period.ConclusionsOptimal combinations of digital health intervention component settings were identified that effectively increased weeknight sleep duration. This could be a valuable remote patient monitoring approach to treat insufficient sleep in the pediatric setting.

Fatigue had classically been defined as a decrease in performance or performance capability as a function of time on task. This definition formed the basis for FAA duty time regulations for over 70 years, until January 2012, with the introduction of Part 117 Fatigue Risk Management (FRMP) regulations (FAA 14 CFR Part 117, 2013). Efforts to manage fatigue in aviation moved to science-based approaches that consider operational factors and experience. This resulted from a vast amount of scientific work over the past half century that established that human fatigue is dynamically influenced by now well-described neurobiological regulation of sleep need and endogenous circadian rhythms, which interact nonlinearly to produce changes in human alertness and cognitive performance over time. An international standard for defining fatigue has been established by the International Civil Aviation Organization (ICAO) and is the foundation of fatigue management approaches worldwide. ICAO defines fatigue as “a physiological state of reduced mental or physical performance capability resulting from: (1) sleep loss; (2) extended wakefulness; (3) circadian phase; and/or (4) workload (mental and/or physical activity) that can impair a person’s alertness and ability to perform safety-related operational duties (ICAO, 2015).

INTRODUCTION: Practice effects associated with the repeated administration of cognitive tests often confound true therapeutic or experimental effects. Alternate test forms help reduce practice effects, but generating stimulus sets with identical properties can be difficult. The main objective of this study was to disentangle practice and stimulus set effects for Cognition, a battery of 10 brief cognitive tests specifically designed for high-performing populations with 15 unique versions for repeated testing. A secondary objective was to investigate the effects of test-retest interval on practice effects. METHODS: The 15 versions of Cognition were administered in three groups of 15-16 subjects (total N=46, mean±SD age 32.5±7.2 years, range 25-54 years, 23 male) in a randomized but balanced fashion with administration intervals of ≥10 days, ≤5 days, or 4 times per day. Mixed effect models were used to investigate linear and logarithmic trends across repeated administrations in key speed and accuracy outcomes, whether these trends differed significantly between administration interval groups, and whether stimulus sets differed significantly in difficulty. RESULTS: Protracted, non-linear practice effects well beyond the second administration were observed for most of the 10 Cognition tests both in accuracy and speed, but test-retest administration interval significantly affected practice effects only for 3 out of the 10 tests and only in the speed domain. Stimulus set effects were observed for the 6 Cognition tests that use unique sets of stimuli. Factors were established that allow for correcting for both practice and stimulus set effects. CONCLUSIONS: Practice effects are pronounced and probably under-appreciated in cognitive testing. The correction factors established in this study are a unique feature of the Cognition battery that can help avoid masking practice effects, address noise generated by differences in stimulus set difficulty, and facilitate interpretation of results from studies with repeated assessments.

Sleep deprivation significantly impairs a range of cognitive and brain function, particularly episodic memory and the underlying hippocampal function. However, it remains controversial whether one or two nights of recovery sleep following sleep deprivation fully restores brain and cognitive function. In this study, we used functional magnetic resonance imaging (fMRI) and examined the effects of two consecutive nights (20-hour time-in-bed) of recovery sleep on resting-state hippocampal connectivity and episodic memory deficits following one night of total sleep deprivation (TSD) in 39 healthy adults in a controlled in-laboratory protocol. TSD significantly reduced memory performance in a scene recognition task, impaired hippocampal connectivity to multiple prefrontal and default mode network regions, and disrupted the relationships between memory performance and hippocampal connectivity. Following TSD, two nights of recovery sleep restored hippocampal connectivity to baseline levels, but did not fully restore memory performance nor its associations with hippocampal connectivity. These findings suggest that more than two nights of recovery sleep are needed to fully restore memory function and hippocampal-memory associations after one night of total sleep loss.

Astronauts are required to maintain optimal neurobehavioral functioning despite chronic exposure to the stressors and challenges of spaceflight. Sleep of adequate quality and duration is fundamental to neurobehavioral functioning, however astronauts commonly experience short sleep durations in spaceflight (

Interindividual differences in the neurobehavioral response to sleep loss are largely unexplained and phenotypic in nature. Numerous factors have been examined as predictors of differential response to sleep loss, but none have yielded a comprehensive view of the phenomenon. The present study examines the impact of baseline factors, habitual sleep–wake patterns, and homeostatic response to sleep loss on accrued deficits in psychomotor vigilance during chronic partial sleep restriction (SR), in a total of 306 healthy adults that participated in one of three independent laboratory studies. Findings indicate no significant impact of personality, academic intelligence, subjective reports of chronotype, sleepiness and fatigue, performance on working memory, and demographic factors such as sex, ethnicity, and body mass index, on neurobehavioral vulnerability to the negative effects of sleep loss. Only superior baseline performance on the psychomotor vigilance test and ability to sustain wakefulness on the maintenance of wakefulness test were associated with relative resilience to decrements in vigilant attention during SR. Interindividual differences in vulnerability to the effects of sleep loss were not accounted for by prior sleep history, habitual sleep patterns outside of the laboratory, baseline sleep architecture, or homeostatic sleep response during chronic partial SR. A recent theoretical model proposed that sleep–wake modulation may be influenced by competing internal and external demands which may promote wakefulness despite homeostatic and circadian signals for sleep under the right circumstances. Further research is warranted to examine the possibility of interindividual differences in the ability to prioritize external demands for wakefulness in the face of mounting pressure to sleep.

Background Medical interns are at risk for sleep deprivation from long and often rotating work schedules. However, the effects of specific rotations on sleep are less clear. Objective To examine differences in sleep duration and alertness among internal medicine interns during inpatient intensive care unit (ICU) compared to general medicine (GM) rotations. Methods This secondary analysis compared interns during a GM or ICU rotation from a randomized trial (2015–2016) of 12 internal medicine residency programs assigned to different work hour limit policies (standard 16-hour shifts or no shift-length limits). The primary outcome was sleep duration/24-hour using continuous wrist actigraphy over a 13-day period. Secondary outcomes assessed each morning during the concomitant actigraphy period were sleepiness (Karolinska Sleepiness Scale [KSS]), alertness (number of Brief Psychomotor Vigilance Test [PVT-B] lapses), and self-report of excessive sleepiness over past 24 hours. Linear mixed-effect models with random program intercept determined associations between each outcome by rotation, controlling for age, sex, and work hour policy followed. Results Of 398 interns, 386 were included (n = 261 GM, n = 125 ICU). Average sleep duration was 7.00±0.08h and 6.84±0.10h, and number of PVT lapses were 5.5±0.5 and 5.7±0.7 for GM and ICU, respectively (all P > .05). KSS was 4.8±0.1 for both rotations. Compared to GM, ICU interns reported more days of excessive sleepiness from 12am–6am (2.6 vs 1.7, P < .001) and 6am–12pm (2.6 vs 1.9, P = .013) and had higher percent of days with sleep duration < 6 hours (27.6% vs 23.4%, P < .001). GM interns reported more days with no excessive sleepiness (5.3 vs 3.7, P < .001). Conclusions Despite ICU interns reporting more excessive sleepiness in morning hours and more days of insufficient sleep (

Effects of a Polar Expedition on the Brain Brain imaging in eight polar expeditioners before and after 14 months of isolation showed that the volume of the hippocampal dentate gyrus was lower than ...

OBJECTIVES: To compare sleep, work hours, and behavioral alertness in faculty and fellows during a randomized trial of nighttime in-hospital intensivist staffing compared to a standard daytime intensivist model. DESIGN: Prospective observational study. SETTING: Medical Intensive Care Unit (MICU) of a tertiary care academic medical center during a randomized controlled trial of in-hospital nighttime intensivist staffing. PATIENTS: 20 faculty and 13 fellows assigned to rotations in the MICU during 2012. INTERVENTIONS: As part of the parent study, there was weekly randomization of staffing model, stratified by 2-week faculty rotation. During the standard staffing model, there were in-hospital residents, with a fellow and faculty member available at nighttime by phone. In the intervention, there were in-hospital residents with an in-hospital nighttime intensivist. Fellows and faculty completed diaries detailing their sleep, work, and well-being; wore actigraphs; and performed psychomotor vigilance testing daily. MEASUREMENTS AND MAIN RESULTS: Daily sleep time (mean hours (standard deviation)) was increased for fellows and faculty in the intervention vs control—6.7 (0.3) vs 6.0 (0.2), p

Arterial spin labeled (ASL) perfusion magnetic resonance imaging (MRI) is increasingly used to assess regional brain activity and cerebrovascular function in both healthy and clinical populations. ASL perfusion imaging provides a quantitative measure of regional brain activity by determining absolute cerebral blood flow (CBF) values at a resting state or during task performance. However, the comparative reliability of these ASL measures is not well characterized. It is also unclear whether the test-retest reliability of absolute CBF or task-induced CBF change measures would be comparable to the reliability of task performance. In this study, fifteen healthy participants were scanned three times in a strictly controlled in-laboratory study while at rest and during performing a simple and reliable psychomotor vigilance test (PVT). The reliability of absolute CBF and task-induced CBF changes was evaluated using the intraclass correlation coefficient (ICC) and compared to that of task performance. Absolute CBF showed excellent test-retest reliability across the three scans for both resting and PVT scans. The reliability of regional absolute CBF was comparable to that of behavioral measures of PVT performance, and was slightly higher during PVT scans as compared with resting scans. Task-induced regional CBF changes demonstrated only poor to moderate reliability across three scans. These findings suggest that absolute CBF measures are more reliable than task-induced CBF changes for characterizing regional brain function, especially for longitudinal and clinical studies.

BACKGROUND: Concern persists that extended shifts in medical residency programs may adversely affect patient safety. METHODS: We conducted a cluster-randomized noninferiority trial in 63 internal-medicine residency programs during the 2015–2016 academic year. Programs underwent randomization to a group with standard duty hours, as adopted by the Accreditation Council for Graduate Medical Education (ACGME) in July 2011, or to a group with more flexible duty-hour rules that did not specify limits on shift length or mandatory time off between shifts. The primary outcome for each program was the change in unadjusted 30-day mortality from the pretrial year to the trial year, as ascertained from Medicare claims. We hypothesized that the change in 30-day mortality in the flexible programs would not be worse than the change in the standard programs (difference-in-difference analysis) by more than 1 percentage point (noninferiority margin). Secondary outcomes were changes in five other patient safety measures and risk-adjusted outcomes for all measures. RESULTS: The change in 30-day mortality (primary outcome) among the patients in the flexible programs (12.5% in the trial year vs. 12.6% in the pretrial year) was noninferior to that in the standard programs (12.2% in the trial year vs. 12.7% in the pretrial year). The test for noninferiority was significant (P = 0.03), with an estimate of the upper limit of the one-sided 95% confidence interval (0.93%) for a between-group difference in the change in mortality that was less than the prespecified noninferiority margin of 1 percentage point. Differences in changes between the flexible programs and the standard programs in the unadjusted rate of readmission at 7 days, patient safety indicators, and Medicare payments were also below 1 percentage point; the noninferiority criterion was not met for 30-day readmissions or prolonged length of hospital stay. Risk-adjusted measures generally showed similar findings. CONCLUSIONS: Allowing program directors flexibility in adjusting duty-hour schedules for trainees did not adversely affect 30-day mortality or several other measured outcomes of patient safety. (Funded by the National Heart, Lung, and Blood Institute and Accreditation Council for Graduate Medical Education; iCOMPARE ClinicalTrials.gov number, NCT02274818.)

BACKGROUND: A purpose of duty-hour regulations is to reduce sleep deprivation in medical trainees, but their effects on sleep, sleepiness, and alertness are largely unknown. METHODS: We randomly assigned 63 internal-medicine residency programs in the United States to follow either standard 2011 duty-hour policies or flexible policies that maintained an 80-hour workweek without limits on shift length or mandatory time off between shifts. Sleep duration and morning sleepiness and alertness were compared between the two groups by means of a noninferiority design, with outcome measures including sleep duration measured with actigraphy, the Karolinska Sleepiness Scale (with scores ranging from 1 [extremely alert] to 9 [extremely sleepy, fighting sleep]), and a brief computerized Psychomotor Vigilance Test (PVT-B), with long response times (lapses) indicating reduced alertness. RESULTS: Data were obtained over a period of 14 days for 205 interns at six flexible programs and 193 interns at six standard programs. The average sleep time per 24 hours was 6.85 hours (95% confidence interval [CI], 6.61 to 7.10) among those in flexible programs and 7.03 hours (95% CI, 6.78 to 7.27) among those in standard programs. Sleep duration in flexible programs was noninferior to that in standard programs (between-group difference, −0.17 hours per 24 hours; one-sided lower limit of the 95% confidence interval, −0.45 hours; noninferiority margin, −0.5 hours; P = 0.02 for noninferiority), as was the score on the Karolinska Sleepiness Scale (between-group difference, 0.12 points; one-sided upper limit of the 95% confidence interval, 0.31 points; non-inferiority margin, 1 point; P

Objective:To examine associations between serum micronutrients and neurobehavioural function and the mediating role of sleep quality in early adolescents.Design:In this cross-sectional study, peripheral blood samples were analysed for Fe and Zn levels. The Pittsburgh Sleep Quality Index and Penn Computerized Neurocognitive Battery were used to assess sleep quality and neurobehavioural function, respectively. The logistic/linear regressions and generalised structural equation modelling were performed to estimate the associations.Setting:Jintan, ChinaParticipants:In total, 226 adolescents (106 females) from the Jintan Child Cohort study.Results:Adolescents with low Fe (P= 0·04) and low Zn (P< 0·001) were associated with increased odds for poor sleep quality. Adolescents with low Fe and Zn were associated with fast (Fe:β= –1353·71,P= 0·002, Zn:β= –2262·01,P= 0·02) but less-accurate (Fe:β= –0·97,P= 0·04; Zn:β= –1·76,P= 0·04) performance on non-verbal reasoning task and poor sleep quality partially mediated the associations between low Fe/Zn and non-verbal reasoning (P< 0·05). Additionally, low Fe was associated with a slower reaction on spatial processing task (β= 276·94,P= 0·04), and low Zn was associated with fast (β= –1781·83,P= 0·03), but error-prone performance (β= –1·79,P= 0·04) on spatial processing ability and slower reaction speed (β= 12·82,P= 0·03) on the attention task. We observed similar trends using a cut-off point of 75 μg/dl for low serum Zn, except for the association with attention task speed (P> 0·05).Conclusion:Fe and Zn deficiencies may possibly be associated with poor sleep and neurobehavioural function among early adolescents. Poor sleep may partially mediate the relationship between micronutrients and neurobehavioural function.

Biomathematical models of fatigue can be used to predict neurobehavioral deficits during sleep/wake or work/rest schedules. Current models make predictions for objective performance deficits and/or subjective sleepiness, but known differences in the temporal dynamics of objective versus subjective outcomes have not been addressed. We expanded a biomathematical model of fatigue previously developed to predict objective performance deficits as measured on the Psychomotor Vigilance Test (PVT) to also predict subjective sleepiness as self-reported on the Karolinska Sleepiness Scale (KSS). Four model parameters were re-estimated to capture the distinct dynamics of the KSS and account for the scale difference between KSS and PVT. Two separate ensembles of datasets – drawn from laboratory studies of sleep deprivation, sleep restriction, simulated night work, napping, and recovery sleep – were used for calibration and subsequent validation of the model for subjective sleepiness. The expanded model was found to exhibit high prediction accuracy for subjective sleepiness, while retaining high prediction accuracy for objective performance deficits. Application of the validated model to an example scenario based on cargo aviation operations revealed divergence between predictions for objective and subjective outcomes, with subjective sleepiness substantially underestimating accumulating objective impairment, which has important real-world implications. In safety-sensitive operations such as commercial aviation, where self-ratings of sleepiness are used as part of fatigue risk management, the systematic differences in the temporal dynamics of objective versus subjective measures of functional impairment point to a potentially significant risk evaluation sensitivity gap. The expanded biomathematical model of fatigue presented here provides a useful quantitative tool to bridge this previously unrecognized gap. Refereed/Peer-reviewed

Tianxin Mao,1,2 David Dinges,3 Yao Deng,1,2 Ke Zhao,2 Zijing Yang,2,4 Hui Lei,2 Zhuo Fang,2 Fan Nils Yang,2 Olga Galli,3 Namni Goel,5 Mathias Basner,3 Hengyi Rao1– 3 1Key Laboratory of Applied Brain and Cognitive Sciences, School of Business and Management, Shanghai International Studies University, Shanghai, People’s Republic of China; 2Center for Functional Neuroimaging, Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA; 3Division of Sleep and Chronobiology, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA; 4School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 5Biological Rhythms Research Laboratory, Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, IL, USACorrespondence: Hengyi RaoCenter for Functional Neuroimaging & Department of Neurology, University of Pennsylvania Perelman School of Medicine, Room D502, Richards Medical Research Building, 3700 Hamilton Walk, Philadelphia, PA, 19104-4202, USATel +1 215-746-2470Email hengyi@pennmedicine.upenn.eduPurpose: Sleep loss impairs a range of neurobehavioral functions, particularly vigilant attention and arousal. However, the detrimental effects of sleep deprivation on inhibition control and its relationship to vigilant attention impairments remain unclear. This study examined the extent to which vigilant attention deficits contribute to inhibition control performance after one night of total sleep deprivation (TSD) and two nights of partial sleep restriction (PSR).Participants and Methods: We analyzed data from N = 49 participants in a one-night of TSD experiment, N=16 participants in a control experiment without sleep loss, and N = 16 participants in a two-nights of PSR experiment (time in bed, TIB = 6 h for each night). Throughout waking periods in each condition, participants completed the psychomotor vigilance test (PVT), which measures vigilant attention, and the Go/No-Go task, which measures inhibition control.Results: After TSD and PSR, participants displayed significantly slower reaction times (RT) and more lapses in PVT performance, as well as slower Go RT and more errors of omission during the Go/No-Go task. PVT deficits accounted for 18.0% of the change in Go RT and 12.4% of the change in errors of omission in the TSD study, and 23.7% of the change in Go RT and 20.3% of the change in errors of omission in the PSR study.Conclusion: Both TSD and PSR impaired inhibition control during the Go/No-Go task, which can be partly accounted for by vigilant attention deficits during the PVT. These findings support the key role of vigilant attention in maintaining overall neurobehavioral function after sleep loss.Keywords: total sleep deprivation, partial sleep restriction, vigilant attention, inhibition control

Microgravity and elevated CO(2) levels are two important environmental spaceflight stressors that can adversely affect astronaut cognitive performance and jeopardize mission success. This study investigated the effects of 6° head-down tilt bed rest (HDBR) with (n = 11 participants, 30-day HDBR) and without (n = 8 participants, 60-day HDBR) elevated ambient (3.73 mmHg) CO(2) concentrations on cognitive performance. Participants of both groups performed all 10 tests of NASA’s Cognition battery and a brief alertness and mood survey repeatedly before, during, and after the HDBR period. Test scores were adjusted for practice and stimulus set effects. Concentrating on the first 30 days of HDBR, a modest but statistically significant slowing across a range of cognitive domains was found in both groups (controls: −0.37 SD; 95% CI −0.48, −0.27; adjusted P < 0.0001; CO(2): −0.25 SD; 95% CI −0.34, −0.16; adjusted P < 0.001), most prominently for sensorimotor speed. These changes were observed early during HDBR and did not further deteriorate or improve with increasing time in HDBR. The study found similar cognitive effects of HDBR irrespective of CO(2) levels, suggesting that elevated CO(2) neither ameliorated nor worsened the HDBR effects. In both groups, cognitive performance after 15 days of recovery was statistically indistinguishable from pre-HDBR performance. However, subjects undergoing 60 days of HDBR rated themselves as feeling more sleepy, tired, physically exhausted, stressed, and unhealthy during recovery compared to their 30-day counterparts. NEW AND NOTEWORTHY This study investigated the effects of prolonged head-down tilt bed rest with and without elevated (3.73 mmHg) levels of ambient CO(2) on cognitive performance across a range of cognitive domains and is one of the few studies investigating combined effects of environmental stressors prevalent in spaceflight. The study showed moderate declines in cognitive speed induced by head-down tilt bed rest and suggests that exposure to elevated levels of ambient CO(2) did not modify this effect.

INTRODUCTION: Environmental and operational stressors commonly encountered in spaceflight can affect astronaut cognitive performance. It is currently unclear how performance decrements on test batteries that assess individual cognitive domains translate to complex operational performance.METHODS: N 30 healthy adults (mean SD age 33.5 7.1 yr, range 2548 yr; 16 men) with demographic characteristics similar to astronauts performed all 10 tests of the Cognition test battery as well as a simulated 6 degrees-of-freedom (6df) spacecraft docking task 15 times. Performance on 60 Cognition outcome variables was rank-correlated with 6df docking performance individually as well as in models containing up to 12 predictors after accounting for sex, age, and study design effects.RESULTS: Average response time on the Digit Symbol Substitution Test (DSST)a measure of processing speed requiring complex scanning, visual tracking, and working memorywas the best individual predictor of 6df docking performance (unadjusted r 0.550; semipartial cross-validated R2 0.244). Furthermore, higher levels of spatial orientation efficiency and vigilant attention, lower levels of impulsivity, and faster response speed were associated with higher 6df performance, while sensorimotor speed, memory, and risk decision making were less relevant. After semipartial cross-validation, a model with three Cognition outcomes (DSST average response time, Abstract Matching accuracy, and conservative response bias on the Fractal 2-Back test) explained 30% of the variance in 6df performance.CONCLUSIONS: This study demonstrates direct links between performance on tests designed to assess specific cognitive domains and complex operational docking performance.Basner M, Moore TM, Hermosillo E, Nasrini J, Dinges DF, Gur RC, Johannes B. Cognition test battery performance is associated with simulated 6df spacecraft docking performance. Aerosp Med Hum Perform. 2020; 91(11):861867.

Chronic sleep loss is associated with escalating declines in vigilant attention across days of sleep restriction. However, studies exceeding 2 weeks of chronic sleep loss are scarce, and the cognitive performance outcomes assessed are limited. We assessed the effects of 6 weeks of chronic sleep restriction on a range of cognitive domains in 15 high-performing individuals (38.5 ± 8.2 years, 6 women) confined to small space in groups of 4. Sleep opportunities were limited to 5 h on weekdays and 8 h on weekends. Individual sleep–wake patterns were recorded with actigraphy. Neurobehavioral performance was assessed in evenings with Cognition, a computerized battery of ten tests assessing a range of cognitive domains. There were some small to moderate effects of increasing sleep debt relative to pre-mission baseline, with decreases in accuracy across cognitive domains (standardized β = –0.121, p = 0.001), specifically on tests of spatial orientation (β = –0.289, p = 0.011) and vigilant attention (β = –0.688, p < 0.001), which were not restored by two nights of weekend recovery sleep. Cognitive and subjective decrements occurred despite occasional daytime napping in breach of study protocol, evening testing around the circadian peak, and access to caffeine before 14:00. Sensorimotor speed, spatial learning and memory, working memory, abstraction and mental flexibility, emotion identification, abstract reasoning, cognitive throughput, and risk decision making were not significantly affected by sleep debt. Taken together with modest lower subjective ratings of happiness and healthiness, these findings underline the importance of sufficient sleep, on both an acute and chronic basis, for performance in selected cognitive domains and subjective wellbeing in operationally relevant environments.

Study Objectives Over 75% of US high school students obtain insufficient sleep, placing them at risk for adverse health outcomes. Identification of modifiable determinants of adolescent sleep is needed to inform prevention strategies, yet little is known about the influence of the built environment on adolescent sleep. Methods In this prospective study, actigraphy was used to assess sleep outcomes among 110 adolescents for 14 days each in eighth and ninth grades: duration (hours/night), onset and offset, and sleeping ≥8 hours. Home addresses were linked to built environment exposures: sound levels, tree canopy cover, street density, intersection density, population density, and housing density. Mixed-effects regression estimated associations of built environment measures with sleep outcomes, adjusting for sex, race, parent education, household income, household size, grade, weeknight status, and neighborhood poverty. Results A 1-standard deviation (SD) increase in neighborhood sound was associated with 16 minutes later sleep onset (β = 0.28; 95% confidence interval (CI): 0.06, 0.49) and 25% lower odds of sleeping for ≥8 hours (odds ratio (OR) = 0.75, 95% CI: 0.59, 0.96). A 1-SD increase in neighborhood tree canopy was associated with 18 minutes earlier sleep onset (β = −0.31, 95% CI: −0.49, −0.13) and 10 minutes earlier sleep offset (β= −0.17, 95% CI: −0.28, −0.05). No associations were observed for density-based exposures. Conclusions Higher neighborhood sound level was associated with lower odds of sufficient sleep, while higher tree canopy cover was associated with more favorable sleep timing. Neighborhood sound levels and tree canopy cover are potential targets for policies and interventions to support healthier sleep among adolescents.

Study Objectives The psychomotor vigilance test (PVT) is frequently used to measure behavioral alertness in sleep research on various software and hardware platforms. In contrast to many other cognitive tests, PVT response time (RT) shifts of a few milliseconds can be meaningful. It is, therefore, important to use calibrated systems, but calibration standards are currently missing. This study investigated the influence of system latency bias and its variability on two frequently used PVT performance metrics, attentional lapses (RTs ≥500 ms) and response speed, in sleep-deprived and alert participants. Methods PVT data from one acute total (N = 31 participants) and one chronic partial (N = 43 participants) sleep deprivation protocol were the basis for simulations in which response bias (±15 ms) and its variability (0–50 ms) were systematically varied and transgressions of predefined thresholds (i.e. ±1 for lapses, ±0.1/s for response speed) recorded. Results Both increasing bias and its variability caused deviations from true scores that were higher for the number of lapses in sleep-deprived participants and for response speed in alert participants. Threshold transgressions were typically rare (i.e. Conclusions A bias of ±5 ms with a standard deviation of ≤10 ms could be considered maximally allowable margins for calibrating PVT systems for timing accuracy. Future studies should report the average system latency and its standard deviation in addition to adhering to published standards for administering and analyzing the PVT.

Maintaining optimal cognitive performance in astronauts during spaceflight is critical to crewmember safety and mission success. To investigate the combined effects of confinement, isolation, and sleep deprivation on cognitive performance during spaceflight, we administered the computerized neurobehavioral test battery "Cognition" to crew members of simulated spaceflight missions as part of NASA's ground-based Human Exploration Research Analog project. Cognition was administered to N = 32 astronaut-like subjects in four 1-week missions (campaign 1) and four 2 weeks missions (campaign 2), with four crewmembers per mission. In both campaigns, subjects performed significantly faster on Cognition tasks across time in mission without sacrificing accuracy, which is indicative of a learning effect. On an alertness and affect survey, subjects self-reported significant improvement in several affective domains with time in mission. During the sleep restriction challenge, subjects in campaign 1 were significantly less accurate on a facial emotion identification task during a night of partial sleep restriction. Subjects in campaign 2 were significantly slower and less accurate on psychomotor vigilance, and slower on cognitive throughput and motor praxis tasks during a night of total sleep deprivation. On the survey, subjects reported significantly worsening mood during the sleep loss challenge on several affective domains. These findings suggest that confinement and relative isolation of up to 2 weeks in this environment do not induce a significant negative impact on cognitive performance in any of the domains examined by Cognition, although the concurrent practice effect may have masked some of the mission's effects. Conversely, a night of total sleep deprivation significantly decreased psychomotor vigilance and cognitive throughput performance in astronaut-like subjects. This underscores the importance of using cognitive tests designed specifically for the astronaut population, and that survey a range of cognitive domains to detect the differential effects of the wide range of stressors common to the spaceflight environment.

BACKGROUND: Cognition is a neurocognitive test battery created at the University of Pennsylvania and adapted by the National Aeronautics and Space Administration (NASA). It comprises 10 neurocognitive tests that examine multiple domains, and has been validated in a normative sample of STEM-educated adults and compared to NASA’s WinSCAT battery.METHODS: The purpose of this study was to follow the original sample to assess Cognition and WinSCAT’s test-retest reliability and age, sex, and test-retest interval effects on performance.RESULTS: Performance on both Cognition and WinSCAT decreased with age but improved with repeated administration due to practice effects, and men had higher scores than women on tasks that required vigilant attention, spatial reasoning, and risk-taking behaviors. Assessment of test-retest reliability showed intraclass coefficients for efficiency ranging from 0.417 to 0.810, reflecting the broad nature of constructs assessed by Cognition.DISCUSSION: Results largely matched predictions, with some counter-intuitive results for test-retest reliability interval.Lee G, Moore TM, Basner M, Nasrini J, Roalf DR, Ruparel K, Port AM, Dinges DF, Gur RC. Age, sex, and repeated measures effects on NASA’s “Cognition” Test Battery in STEM educated adults. Aerosp Med Hum Perform. 2020; 91(1):18–25.

Background Concern persists that inflexible duty-hour rules in medical residency programs may adversely affect the training of physicians. Methods We randomly assigned 63 internal medicine residency programs in the United States to be governed by standard duty-hour policies of the 2011 Accreditation Council for Graduate Medical Education (ACGME) or by more flexible policies that did not specify limits on shift length or mandatory time off between shifts. Measures of educational experience included observations of the activities of interns (first-year residents), surveys of trainees (both interns and residents) and faculty, and intern examination scores. Results There were no significant between-group differences in the mean percentages of time that interns spent in direct patient care and education nor in trainees’ perceptions of an appropriate balance between clinical demands and education (primary outcome for trainee satisfaction with education; response rate, 91%) or in the assessments by prog...

Microgravity and elevated levels of CO2 are two common environmental stressors in spaceflight that may affect cognitive performance of astronauts. In this randomized, double-blind, crossover trial (SPACECOT), 6 healthy males (mean ± SD age: 41 ± 5 yr) were exposed to 0.04% (ambient air) and 0.5% CO2 concentrations during 26.5-h periods of −12° head-down tilt (HDT) bed rest with a 1-wk washout period between exposures. Subjects performed the 10 tests of the Cognition Test Battery before and on average 0.1, 5.2, and 21.0 h after the initiation of HDT bed rest. HDT in ambient air induced a change in response strategy, with increased response speed (+0.19 SD; P = 0.0254) at the expense of accuracy (−0.19 SD; P = 0.2867), resulting in comparable cognitive efficiency. The observed effects were small and statistically significant for cognitive speed only. However, even small declines in accuracy can potentially cause errors during mission-critical tasks in spaceflight. Unexpectedly, exposure to 0.5% CO2 reversed the response strategy changes observed under HDT in ambient air. This was possibly related to hypercapnia-induced cerebrovascular reactivity that favors cortical regions in general and the frontal cortex in particular, or to the CNS arousing properties of mildly to moderately increased CO2 levels. There were no statistically significant time-in-CO2 effects for any cognitive outcome. The small sample size and the small effect sizes are major limitations of this study and its findings. The results should not be generalized beyond the group of investigated subjects until they are confirmed by adequately powered follow-up studies. NEW & NOTEWORTHY Simulating microgravity with exposure to 21 h of −12° head-down tilt bed rest caused a change in response strategy on a range of cognitive tests, with a statistically significant increase in response speed at the expense of accuracy. Cognitive efficiency was not affected. The observed speed-accuracy tradeoff was small but may nevertheless be important for mission-critical tasks in spaceflight. Importantly, the change in response strategy was reversed by increasing CO2 concentrations to 0.5%.

Introduction The global pandemic due to the novel coronavirus (COVID-19) has had unprecedented effects on society, in particular for those who are also working with children in the household. The aim of this analysis was to evaluate sleep amount and sleep quality during the COVID-19 pandemic compared to before COVID-19 for those working from home with minor household dependents. Methods We developed the “Anonymous Survey on Confinement during the COVID-19 Pandemic”, a national survey for individuals ≥18 years of age hosted on the Penn Medicine Clinical Research website from May 16th to November 11th, 2020. This 200 question survey captured demographics and multiple dimensions of health and well-being, including stress, sleep, eating behaviors, and coping activities. Respondents who indicated they were working from home were stratified by whether they were living with ≥1 minor dependent vs no dependents. Separate ordinal logistic regression models were used to evaluate associations between living with a minor dependent and sleep amount (less, same, more) and disturbed quality (none, less, same, more) during, compared to before, COVID-19 controlled for age, sex, ethnicity, and annual income. Results A total of 232 respondents (n=182 no dependents, n=50 dependents, 84.9% Caucasian) reported working from home, the majority of which had been in confinement (95.7%). Respondents with dependents were younger (mean age 38.9±13.5 vs 47.4±18.0, p=0.002) and mostly female (86% vs 76.9%, p=0.03). On average, reported days worked/week (3.5±2.4 days) and hours worked/day (5.5±4.17 hours) were similar regardless of dependents. Comparing those without to those with minor dependents, there were no significant differences in log odds of getting enough sleep (β=-0.38, p=0.25) or worse sleep quality (β=0.41, p=0.22) during the COVID-19 pandemic compared to before COVID-19. Respondents with dependents reported a higher log odds of taking longer to fall asleep during COVID-19 (β=0.71, p=0.045), and higher stress (β=-0.65, p=0.04). Conclusion In this mostly Caucasian female sample of people working from home, having minor dependents in the household did not significantly impact sleep amount or quality compared to no minor household dependents. However, respondents with dependents reported longer time to fall asleep and were more stressed. Support (if any) MC/CJ are supported by NHLBI (T32 HL007713).

Objective To provide a quantitative meta-analysis of the antidepressant effects of sleep deprivation to complement qualitative reviews addressing response rates. Data sources English-language studies from 1974 to 2016 using the keywords sleep deprivation and depression searched through PubMed and PsycINFO databases. Study selection A total of 66 independent studies met criteria for inclusion: conducted experimental sleep deprivation, reported the percentage of the sample that responded to sleep deprivation, provided a priori definition of antidepressant response, and did not seamlessly combine sleep deprivation with other therapies (eg, chronotherapeutics, repetitive transcranial magnetic stimulation). Data extraction Data extracted included percentage of responders, type of sample (eg, bipolar, unipolar), type of sleep deprivation (eg, total, partial), demographics, medication use, type of outcome measure used, and definition of response (eg, 30% reduction in depression ratings). Data were analyzed with meta-analysis of proportions and a Poisson mixed-effects regression model. Results The overall response rate to sleep deprivation was 45% among studies that utilized a randomized control group and 50% among studies that did not. The response to sleep deprivation was not affected significantly by the type of sleep deprivation performed, the nature of the clinical sample, medication status, the definition of response used, or age and gender of the sample. Conclusions These findings support a significant effect of sleep deprivation and suggest the need for future studies on the phenotypic nature of the antidepressant response to sleep deprivation, on the neurobiological mechanisms of action, and on moderators of the sleep deprivation treatment response in depression.

Insufficient sleep increasingly characterizes modern society, contributing to a host of serious medical problems. Loss of sleep is associated with metabolic diseases such as obesity and diabetes, cardiovascular disorders, and neurological and cognitive impairments. Shifts in gut microbiome composition have also been associated with the same pathologies; therefore, we hypothesized that sleep restriction may perturb the gut microbiome to contribute to a disease state. In this study, we examined the fecal microbiome by using a cross-species approach in both rat and human studies of sleep restriction. We used DNA from hypervariable regions (V1-V2) of 16S bacteria rRNA to define operational taxonomic units (OTUs) of the microbiome. Although the OTU richness of the microbiome is decreased by sleep restriction in rats, major microbial populations are not altered. Only a single OTU, TM7-3a, was found to increase with sleep restriction of rats. In the human microbiome, we find no overt changes in the richness or composition induced by sleep restriction. Together, these results suggest that the microbiome is largely resistant to changes during sleep restriction.

Introduction Sleep restriction disturbs mood, impairs neurocognitive performance, and elevates proinflammatory cytokine levels. However, whether basal inflammation influences mood and neurocognitive performance across sleep restriction is unknown. This study examines whether baseline IL-6, cortisol, and TNF-α levels predict the deterioration of mood and working memory performance across sleep restriction. Methods N=124 healthy participants (52% female; n=64), 22–45 years of age, had valid protein, mood, and working memory data. The study included two baseline nights (8h time in bed [TIB]) followed by five nights of 4h TIB. Venous blood was collected on the second baseline day and IL-6, cortisol, and TNF-α levels were measured via commercially available ELISA assays. The profile of mood states (POMS) and the digit span test (DST) were completed every 2h during wakefulness and daily averages were computed. Mixed-effects multi-level models, adjusted for baseline, evaluated the main effect of IL-6, cortisol, and TNF-α levels on the POMS and DST independently and examined the trajectory of POMS and DST by the interaction of protein levels and day of sleep restriction. Results At baseline, IL-6, cortisol, and TNF-α levels were not associated with POMS or DST. There was a main effect of IL-6, but not cortisol or TNF-α, levels on mood disturbance (β=3.811; P=0.015); IL-6 levels did not predict the trajectory of mood across sleep restriction (β=0.187; P=0.57). Higher baseline cortisol levels predicted increasing mood disturbance across days (β=-1.329; P Conclusion The study findings suggest that basal inflammatory cytokine and cortisol levels are implicated in the individual risk of mood disturbance and working memory deficits resulting from chronic sleep restriction and highlight the need to consider biological processes and phenotypes together. Support This work was supported by National Institute of Health NIH R01NR004281 and National Space and Biomedical Research Institute NSRBI NCC 5–98.

Introduction Chronic restriction of nighttime sleep to less than ~8h/day leads to build-up of neurobehavioral impairment across days. Although it is known that sleep loss effects depend on the circadian timing of sleep, it is not known how the timing of restricted sleep influences the accumulation of neurobehavioral impairment over days. Here we studied the accumulation of impairment across days of restricted sleep placed in the morning or afternoon. Methods N=71 healthy young adults (39% female; ages 21-45y, mean±SD: 27.9±6.6y) completed a 14-day laboratory study. After two baseline days with nighttime sleep (8h TIB: 23:30-07:30), subjects were randomized to 10 consecutive days of A) morning sleep at 4h, 6h, or 8h TIB ending at 11:30 each day (n=18, 8, 8, respectively), or B) afternoon sleep at 4h, 6h, or 8h TIB ending at 19:30 each day (n=13, 17, 7, respectively). Subjects were tested on the 10min psychomotor vigilance test (PVT) every ~2 hours during scheduled wakefulness. Daily averages for PVT lapses (RTs>500ms) observed between 2h and 14h after awakening were analyzed with non-linear mixed-effects regression to investigate differences in the neurobehavioral impairment build-up rate between sleep restriction conditions. Results Afternoon sleep conditions showed a significant sleep dose-response effect (p Conclusion In this sample of young adults, sleep dosages ending in the morning (at 11:30) appear to provide considerable protection against cumulative performance deficits from sleep restricted to 4h-6h/day over 10 days, suggesting that the afternoon circadian promotion of wakefulness can sustain behavioral alertness even over multiple days of repeated sleep restriction. Support NIH grants R01-NR04281 and M01-RR00040

Introduction Over 75% of U.S. high school students obtain insufficient amounts of sleep. Identification of modifiable environmental determinants of adolescent sleep is needed to inform interventions and public health strategies, yet little is known about the influence of the built environment on adolescent sleep. We examined associations of the built environment with objectively-measured adolescent sleep outcomes. Methods In this longitudinal, prospective study, we used actigraphy to assess sleep outcomes for 14 days each in 8th grade and 9th grade: duration (hours/night), onset (hours from 00:00), offset (hours from 00:00), and sleeping >8 hours. Home addresses were linked to built environment exposures based on half-mile Euclidian buffers (overall/human-made sound levels, percent tree canopy cover, street density, intersection density) and census block group (population density, housing density). Mixed-effects linear (sleep duration, onset, offset) and logistic (>8 hours) regression estimated associations of each built environment measure with sleep outcomes, adjusting for sex, race, parent education, household income, grade and weeknight status (school or non-school night). Results Among 108 adolescents - 53% female and 25% Black - providing 2,388 nights of sleep data across 8th and 9th grades, a 1-standard deviation increase in neighborhood sound (overall and human-made) associated with 11 minutes later sleep onset (β=0.19; 95% CI: 0.01, 0.38) and 20% lower odds of sleeping for >8 hours (OR=0.80, 95% CI: 0.62, 1.02). A 1-standard deviation increase in neighborhood tree canopy cover associated with 11 minutes earlier sleep onset (β= -0.19, 95% CI: -0.35, -0.03) and 7 minutes earlier sleep offset (β= -0.12, 95% CI: -0.23, -0.02). No associations were observed for “density based” exposures. Conclusion Higher tree canopy cover associated with more favorable sleep timing while higher neighborhood sound level associated with later timing of sleep onset. These modifiable neighborhood built environment factors should be considered when intervening to support healthier sleep among adolescents. Support NIH/NHLBI K01HL123612 (JM) and Sleep Research Society Foundation and K23HD094905 (AAW)

Introduction Negativity bias in depression has been repeatedly demonstrated in the judgment and decision-making literature. Research investigating the impact of sleep deprivation on self-evaluation of performance in healthy or depressed populations is limited. We examined 1) whether individuals with Major Depressive Disorder (MDD) exhibit a negativity bias in subjective ratings of performance on the Psychomotor Vigilance Task (PVT) as compared with healthy adults, and 2) the impact of total sleep deprivation (TSD) on these ratings. Methods N=33 individuals with MDD and n=9 healthy adults completed a 5-day study protocol including two baseline nights (B1-B2, 9h TIB), 36 hours of TSD, and one night of recovery sleep opportunity (Rec). The PVT was administered every 2-4 hours. A brief questionnaire was administered immediately prior to (PRE) and following (POST) the PVT, asking participants to estimate their average reaction time (RT) using a 9-point Likert-type scale. Mixed-effects models examined the impact of group (MDD, Control), protocol day (B1, B2, SD, Rec), and their interaction on objective PVT performance (mean RT) and subjective performance estimates (PRE and POST ratings). Results Mean RT was significantly slower during TSD (p Conclusion This project is the first to investigate subjective estimates of PVT performance in healthy and depressed individuals. Individuals with MDD subjectively reported slower response times as compared with control participants, despite similar objective performance. Depressive symptoms may be a potential confounder of subjective, but not objective, PVT performance. Support 5R01MH107571

Introduction Duty hour regulations affect resident sleep, education, and patient care in complex ways. We performed a national cluster-randomized trial (iCOMPARE) in 63 internal medicine residency programs comparing the effects of the 2011 duty-hour standards to a more flexible set of duty hour rules characterized by maintaining an 80-hour workweek but without limits on shift length or mandatory time off between shifts, relative to patient mortality, intern educational outcomes, and intern sleep and alertness. Methods In the sleep and alertness sub-study, sleep duration and morning sleepiness and alertness were assessed with actigraphy, the Karolinska Sleepiness Scale, and a 3-minute Psychomotor Vigilance Test (PVT-B) for 14 days in 193 interns from 6 standard programs and 205 interns from 6 flexible programs. Results During the 14-day study periods, interns in standard and flexible programs averaged 7.03h sleep/24h (95% confidence interval [CI] 6.78h, 7.27h) and 6.85h sleep/24h (95% CI 6.61h, 7.10h), respectively. Sleep duration (difference between arms of -0.17h/24h; 1-sided lower 95% confidence limit -0.45h; NIM -0.5h; P=0.02 for noninferiority) and KSS sleepiness (difference 0.12 points; 1-sided upper 95% confidence limit 0.31 points; NIM 1 point; P Conclusion There were no signs of relevant chronic sleep loss across shifts in interns in flexible programs relative to their standard program counterparts. Interns were able to compensate for the sleep lost during extended overnight shifts by increasing sleep duration on nights prior to day shifts, night shifts, and days off. Increased sleepiness and reduced alertness of interns following extended overnight shifts need to be mitigated and suggest a role for fatigue-risk management programs. Support Supported by NHLBI grants U01HL125388 and U01HL126088 and grants from the ACGME.