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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 (

During spaceflight, astronauts face a unique set of stressors, including microgravity, isolation, and confinement, as well as environmental and operational hazards. These factors can negatively impact sleep, alertness, and neurobehavioral performance, all of which are critical to mission success. In this paper, we predict neurobehavioral performance over the course of a 6-month mission aboard the International Space Station (ISS), using ISS environmental data as well as self-reported and cognitive data collected longitudinally from 24 astronauts. Neurobehavioral performance was repeatedly assessed via a 3-min Psychomotor Vigilance Test (PVT-B) that is highly sensitive to the effects of sleep deprivation. To relate PVT-B performance to time-varying and discordantly-measured environmental, operational, and psychological covariates, we propose an ensemble prediction model comprising of linear mixed effects, random forest, and functional concurrent models. An extensive cross-validation procedure reveals that this ensemble outperforms any one of its components alone. We also identify the most important predictors of PVT-B performance, which include an individual's previous PVT-B performance, reported fatigue and stress, and temperature and radiation dose. This method is broadly applicable to settings where the main goal is accurate, individualized prediction of human behavior involving a mixture of person-level traits and irregularly measured time series.

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.

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.

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.

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.

Vigilance deficits account for a substantial number of accidents and errors. Current techniques to detect vigilance impairment measure only the most severe level evident in eyelid closure and falling asleep, which is often too late to avoid an accident or error. The present study sought to identify ocular biometrics of intermediate impairment of vigilance and develop a new technique that could detect a range of deficits in vigilant attention (VA). Sixteen healthy adults performed well-validated Psychomotor Vigilance Test (PVT) for tracking vigilance attention while undergoing simultaneous recording of eye metrics every 2 hours during 38 hours of continuous wakefulness. A novel marker was found that measured VA when the eyes were open—the prevalence of microsaccades. Notably, the prevalence of microsaccades decreased in response to sleep deprivation and time-on-task. In addition, a novel algorithm for detecting multilevel VA was developed, which estimated performance on the PVT by integrating the novel marker with other eye-related indices. The novel algorithm also tracked changes in intermediate level of VA (specific reaction times in the PVT, i.e. 300–500 ms) during prolonged time-on-task and sleep deprivation, which had not been tracked previously by conventional techniques. The implication of the findings is that this novel algorithm, named “eye-metrical estimation version of the PVT: PVT-E,” can be used to reduce human-error-related accidents caused by vigilance impairment even when its level is intermediate.

STUDY OBJECTIVES Prescription sleep aids are frequently used in the general population and even more frequently in spaceflight. To evaluate the risk to operational safety, a ground-based, double-blind, placebo-controlled study on the emergent awakening effects of zolpidem and zaleplon was conducted. METHODS N = 34 participants (age M = 42.1 ± 9.7; 25 males; 9 Astronauts, 7 Astronaut candidates, and 18 Flight Controllers) were investigated for three nights separated by M = 10 days. They were randomized to ingestion of one of the following at lights out: placebo, 10 mg zaleplon, and either 5 mg (N = 20) or 10 mg (N = 14) zolpidem. They were awakened abruptly by alarm at the expected PK,max (1 hr after lights out for zaleplon; 1.5 hr for placebo/zolpidem). Participants were required to turn off the alarm and perform a cognitive test battery twice, separated by a 20-30 min reading break. They then returned to sleep and were awakened to perform the same cognitive tasks at an average of 6.7 hr after drug ingestion. RESULTS Relative to placebo, the effects of 10 mg zaleplon and 5 mg zolpidem on cognitive performance were minor. In contrast, 10 mg zolpidem adversely affected cognitive throughput (p < 0.001), psychomotor vigilance (p < 0.001), working memory (p < 0.01), delayed word recall (p < 0.05), and subjective sleepiness (p < 0.01) at the first emergent awakening. At terminal awakening, neither cognitive performance nor subjective sleepiness was impaired after ingestion of zaleplon or zolpidem (5 mg and 10 mg) compared with placebo. CONCLUSIONS Presleep ingestion of sleep medications, especially 10 mg zolpidem, poses a risk for performance errors after emergent awakenings near the expected PK,max. REGISTRATION Optimize Astronaut Sleep Medication Efficacy and Individual Effects (clinicaltrials.gov ID NCT03526575).

STUDY OBJECTIVES Little is known about the effect of lead exposure on children's sleep. This study examined the association between blood lead levels (BLL) and sleep problems in a longitudinal study of children. SETTING Four community-based elementary schools in Jintan City, China. PARTICIPANTS 1,419 Chinese children. MEASUREMENT AND RESULTS BLL were measured when children were aged 3-5 y, and sleep was assessed at ages 9-13 y. Sleep was assessed by both parents' report, using the Children's Sleep Habits Questionnaire (CSHQ), and children's report, using an adolescent sleep questionnaire. A total of 665 children with complete data on BLL and sleep at both ages were included in the current study. Mean age of the sample at BLL assessment was 4.74 y (standard deviation [SD] = 0.89) and at sleep assessment was 11.05 y (SD = 0.88). Mean BLL was 6.26 μg/dL (SD = 2.54). There were significant positive correlations between BLL and 3 CSHQ subscales: Sleep onset delay (r = 0.113, P < 0.01), sleep duration (r = 0.139, P < 0.001), and night waking (r = 0.089, P < 0.05). Excessive daytime sleepiness (EDS) (26.1% versus 9.0%, P < 0.001) and use of sleeping pills (6.5% versus 1.8%, P = 0.03) were more prevalent in children BLL ≥ 10.0 μg/dL than in those children BLL < 10.0 μg/dL. After adjusting for demographics, BLL ≥ 10.0 μg/dL was significantly associated with increased risk for insomnia symptoms (odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.03-3.95) and EDS (OR = 2.90, 95% CI = 1.27-6.61). CONCLUSION The findings indicate that elevated blood lead levels in early childhood are associated with increased risk for sleep problems and excessive daytime sleepiness in later childhood.

Sleep restriction (SR) reliably increases caloric intake. It remains unknown whether such intake cumulatively increases with repeated SR exposures and is impacted by the number of intervening recovery sleep opportunities. Healthy adults (33.9 &plusmn, 8.9y, 17 women, Body Mass Index: 24.8 &plusmn, 3.6) participated in a laboratory protocol. N = 35 participants experienced two baseline nights (10 h time-in-bed (TIB)/night, 22:00&ndash, 08:00) followed by 10 SR nights (4 h TIB/night, 04:00&ndash, 08:00), which were divided into two exposures of five nights each and separated by one (n = 13), three (n = 12), or five (n = 10) recovery nights (12 h TIB/night, 10:00). Control participants (n = 10) were permitted 10 h TIB (22:00&ndash, 08:00) on all nights. Food and drink consumption were ad libitum and recorded daily. Compared to baseline, sleep-restricted participants increased daily caloric (+527 kcal) and saturated fat (+7 g) intake and decreased protein (&minus, 1.2% kcal) intake during both SR exposures, however, intake did not differ between exposures or recovery conditions. Similarly, although sleep-restricted participants exhibited substantial late-night caloric intake (671 kcal), such intake did not differ between exposures or recovery conditions. By contrast, control participants showed no changes in caloric intake across days. We found consistent caloric and macronutrient intake increases during two SR exposures despite varying intervening recovery nights. Thus, energy intake outcomes do not cumulatively increase with repeated restriction and are unaffected by recovery opportunities.

IntroductionMedical trainees’ duty hours have received attention globally; restrictions in Europe, New Zealand and some Canadian provinces are much lower than the 80 hours per week enforced in USA. In USA, resident duty hours have been implemented without evidence simultaneously reflecting competing concerns about patient safety and physician education. The objective is to prospectively evaluate the implications of alternative resident duty hour rules for patient safety, trainee education and intern sleep and alertness.Methods and analysis63 US internal medicine training programmes were randomly assigned 1:1 to the 2011 Accreditation Council for Graduate Medical Education resident duty hour rules or to rules more flexible in intern shift length and number of hours off between shifts for academic year 2015–2016. The primary outcome is calculated for each programme as the difference in 30-day mortality rate among Medicare beneficiaries with any of several prespecified principal diagnoses in the intervention year minus 30-day mortality in the preintervention year among Medicare beneficiaries with any of several prespecified principal diagnoses. Additional safety outcomes include readmission rates, prolonged length of stay and costs. Measures derived from trainees’ and faculty responses to surveys and from time-motion studies of interns compare the educational experiences of residents. Measures derived from wrist actigraphy, subjective ratings and psychomotor vigilance testing compare the sleep and alertness of interns. Differences between duty hour groups in outcomes will be assessed by intention-to-treat analyses.Ethics and disseminationThe University of Pennsylvania Institutional Review Board (IRB) approved the protocol and served as the IRB of record for 40 programmes that agreed to sign an Institutional Affiliation Agreement. Twenty-three programmes opted for a local review process.Trial registration numberNCT02274818; Pre-results.

INTRODUCTION To date, 559 humans have been flown into space, but long-duration (>300 days) missions are rare (n = 8 total). Long-duration missions that will take humans to Mars and beyond are planned by public and private entities for the 2020s and 2030s; therefore, comprehensive studies are needed now to assess the impact of long-duration spaceflight on the human body, brain, and overall physiology. The space environment is made harsh and challenging by multiple factors, including confinement, isolation, and exposure to environmental stressors such as microgravity, radiation, and noise. The selection of one of a pair of monozygotic (identical) twin astronauts for NASA’s first 1-year mission enabled us to compare the impact of the spaceflight environment on one twin to the simultaneous impact of the Earth environment on a genetically matched subject. RATIONALE The known impacts of the spaceflight environment on human health and performance, physiology, and cellular and molecular processes are numerous and include bone density loss, effects on cognitive performance, microbial shifts, and alterations in gene regulation. However, previous studies collected very limited data, did not integrate simultaneous effects on multiple systems and data types in the same subject, or were restricted to 6-month missions. Measurement of the same variables in an astronaut on a year-long mission and in his Earth-bound twin indicated the biological measures that might be used to determine the effects of spaceflight. Presented here is an integrated longitudinal, multidimensional description of the effects of a 340-day mission onboard the International Space Station. RESULTS Physiological, telomeric, transcriptomic, epigenetic, proteomic, metabolomic, immune, microbiomic, cardiovascular, vision-related, and cognitive data were collected over 25 months. Some biological functions were not significantly affected by spaceflight, including the immune response (T cell receptor repertoire) to the first test of a vaccination in flight. However, significant changes in multiple data types were observed in association with the spaceflight period; the majority of these eventually returned to a preflight state within the time period of the study. These included changes in telomere length, gene regulation measured in both epigenetic and transcriptional data, gut microbiome composition, body weight, carotid artery dimensions, subfoveal choroidal thickness and peripapillary total retinal thickness, and serum metabolites. In addition, some factors were significantly affected by the stress of returning to Earth, including inflammation cytokines and immune response gene networks, as well as cognitive performance. For a few measures, persistent changes were observed even after 6 months on Earth, including some genes’ expression levels, increased DNA damage from chromosomal inversions, increased numbers of short telomeres, and attenuated cognitive function. CONCLUSION Given that the majority of the biological and human health variables remained stable, or returned to baseline, after a 340-day space mission, these data suggest that human health can be mostly sustained over this duration of spaceflight. The persistence of the molecular changes (e.g., gene expression) and the extrapolation of the identified risk factors for longer missions (>1 year) remain estimates and should be demonstrated with these measures in future astronauts. Finally, changes described in this study highlight pathways and mechanisms that may be vulnerable to spaceflight and may require safeguards for longer space missions; thus, they serve as a guide for targeted countermeasures or monitoring during future missions.

Microgravity and elevated levels of CO

The high prevalence of chronic insufficient sleep in the population has been a concern due to the associated health and safety risks. We evaluated secular trends in sleep duration over the most recent 14-year period.The American Time Use Survey, representative of US residents ≥15 years, was used to investigate trends in self-reported sleep duration and waking activities for the period 2003-2016 (N = 181335 respondents).Sleep duration increased across survey years both on weekdays (+1.40 min/year) and weekends (+0.83 min/year, both p.0001, adjusted models). This trend was observed in students, employed respondents, and retirees, but not in those unemployed or not in the labor force. On workdays, the prevalence of short (≤7 hr), average (7-9 hr), and long (9 hr) sleep changed by -0.44% per year (p.0001), -0.03% per year (p = .5515), and +0.48% per year (p.0001), respectively. The change in sleep duration was predominantly explained by respondents retiring earlier in the evening. The percentage of respondents who watched TV or read before bed-two prominent waking activities competing with sleep-decreased over the same time period, suggesting that portions of the population are increasingly willing to trade time in leisure activities for more sleep. The results also suggest that increasing online opportunities to work, learn, bank, shop, and perform administrative tasks from home freed up time that likely contributed to increased sleep duration.The findings indicate first successes in the fight against sleep deficiency. Public health consequences of the observed increase in the prevalence of long sleep remain unclear and warrant further investigation.

Accurately collected 24-hour urine collections are presumed to be valid for estimating salt intake in individuals. We performed 2 independent ultralong-term salt balance studies lasting 105 (4 men) and 205 (6 men) days in 10 men simulating a flight to Mars. We controlled dietary intake of all constituents for months at salt intakes of 12, 9, and 6 g/d and collected all urine. The subjects’ daily menus consisted of 27 279 individual servings, of which 83.0% were completely consumed, 16.5% completely rejected, and 0.5% incompletely consumed. Urinary recovery of dietary salt was 92% of recorded intake, indicating long-term steady-state sodium balance in both studies. Even at fixed salt intake, 24-hour urine collection for sodium excretion (UNaV) showed infradian rhythmicity. We defined a ±25 mmol deviation from the average difference between recorded sodium intake and UNaV as the prediction interval to accurately classify a 3-g difference in salt intake. Because of the biological variability in UNaV, only every other daily urine sample correctly classified a 3-g difference in salt intake (49%). By increasing the observations to 3 consecutive 24-hour collections and sodium intakes, classification accuracy improved to 75%. Collecting seven 24-hour urines and sodium intake samples improved classification accuracy to 92%. We conclude that single 24-hour urine collections at intakes ranging from 6 to 12 g salt per day were not suitable to detect a 3-g difference in individual salt intake. Repeated measurements of 24-hour UNaV improve precision. This knowledge could be relevant to patient care and the conduct of intervention trials.

The American Academy of Sleep Medicine and Sleep Research Society recently released a Consensus Statement regarding the recommended amount of sleep to promote optimal health in adults. This paper describes the methodology, background literature, voting process, and voting results for the consensus statement. In addition, we address important assumptions and challenges encountered during the consensus process. Finally, we outline future directions that will advance our understanding of sleep need and place sleep duration in the broader context of sleep health.

Study objectives Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Design Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. Methods The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. Results The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Conclusion Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity.

Study objectives Chronic sleep restriction is prevalent in the U.S. population and associated with increased morbidity and mortality. The primary reasons for reduced sleep are unknown. Using population data on time use, we sought to identify individual characteristics and behaviors associated with short sleep that could be targeted for intervention programs. Design Analysis of the American Time Use Survey (ATUS). Setting Cross-sectional annual survey conducted by the U.S. Bureau of Labor Statistics. Participants Representative cohort (N = 124,517) of Americans 15 years and older surveyed between 2003 and 2011. Interventions None. Measurements and results Telephone survey of activities over 24 hours. Relative to all other waking activities, paid work time was the primary waking activity exchanged for sleep. Time spent traveling, which included commuting to/ from work, and immediate pre- and post-sleep activities (socializing, grooming, watching TV) were also reciprocally related to sleep duration. With every hour that work or educational training started later in the morning, sleep time increased by approximately 20 minutes. Working multiple jobs was associated with the highest odds for sleeping ≤6 hours on weekdays (adjusted OR 1.61, 95% CI 1.44; 1.81). Self-employed respondents were less likely to be short sleepers compared to private sector employees (OR 0.83, 95% CI 0.72; 0.95). Sociodemographic characteristics associated with paid work (age 25-64, male sex, high income, and employment per se) were consistently associated with short sleep. Conclusions U.S. population time use survey findings suggest that interventions to increase sleep time should concentrate on delaying the morning start time of work and educational activities (or making them more flexible), increasing sleep opportunities, and shortening morning and evening commute times. Reducing the need for multiple jobs may increase sleep time, but economic disincentives from working fewer hours will need to be offset. Raising awareness of the importance of sufficient sleep for health and safety may be necessary to positively influence discretionary behaviors that reduce sleep time, including television viewing and morning grooming.

Study objectives The Psychomotor Vigilance Test (PVT) is reported to be free of practice effects that can otherwise confound the effects of sleep loss and circadian misalignment on performance. This differentiates the PVT from more complex cognitive tests. To the best of our knowledge, no study has systematically investigated practice effects on the PVT across multiple outcome domains, depending on administration interval, and in ecologically more valid settings. Methods We administered a validated 3-minute PVT (PVT-B) 16 times in 45 participants (23 male, mean ± SD age 32.6 ± 7.3 years, range 25-54 years) with administration intervals of ≥10 days, ≤5 days, or 4 times per day. We investigated linear and logarithmic trends across repeated administrations in 10 PVT-B outcome variables. Results The fastest 10% of response times (RT; plin = .0002), minimum RT (plog = .0010), and the slowest 10% of reciprocal RT (plog = .0124) increased while false starts (plog = 0.0050) decreased with repeated administration, collectively decreasing RT variability (plog = .0010) across administrations. However, the observed absolute changes were small (e.g., -0.03 false starts per administration, linear fit) and are probably irrelevant in practice. Test administration interval did not modify the effects of repeated administration on PVT-B performance (all p > .13 for interaction). Importantly, mean and median RT, response speed, and lapses, which are among the most frequently used PVT outcomes, did not change systematically with repeated administration. Conclusions PVT-B showed stable performance across repeated administrations. Combined with its high sensitivity, this corroborates the status of the PVT as the de facto gold standard measure of the neurobehavioral effects of sleep loss and circadian misalignment.

Background Neuropsychological changes that may occur due to the environmental and psychological stressors of prolonged spaceflight motivated the development of the Cognition Test Battery. The battery was designed to assess multiple domains of neurocognitive functions linked to specific brain systems. Tests included in Cognition have been validated, but not in high-performing samples comparable to astronauts, which is an essential step toward ensuring their usefulness in long-duration space missions. Methods We administered Cognition (on laptop and iPad) and the WinSCAT, counterbalanced for order and version, in a sample of 96 subjects (50% women; ages 25-56 yr) with at least a Master's degree in science, technology, engineering, or mathematics (STEM). We assessed the associations of age, sex, and administration device with neurocognitive performance, and compared the scores on the Cognition battery with those of WinSCAT. Confirmatory factor analysis compared the structure of the iPad and laptop administration methods using Wald tests. Results Age was associated with longer response times (mean β = 0.12) and less accurate (mean β = -0.12) performance, women had longer response times on psychomotor (β = 0.62), emotion recognition (β = 0.30), and visuo-spatial (β = 0.48) tasks, men outperformed women on matrix reasoning (β = -0.34), and performance on an iPad was generally faster (mean β = -0.55). The WinSCAT appeared heavily loaded with tasks requiring executive control, whereas Cognition assessed a larger variety of neurocognitive domains. Discussion Overall results supported the interpretation of Cognition scores as measuring their intended constructs in high performing astronaut analog samples.Moore TM, Basner M, Nasrini J, Hermosillo E, Kabadi S, Roalf DR, McGuire S, Ecker AJ, Ruparel K, Port AM, Jackson CT, Dinges DF, Gur RC. Validation of the Cognition Test Battery for spaceflight in a sample of highly educated adults. Aerosp Med Hum Perform. 2017; 88(10):937-946.

Study Objectives Fatigue from sleep loss is a risk to physician and patient safety, but objective data on physician sleep and alertness on different duty hour schedules is scarce. This study objectively quantified differences in sleep duration and alertness between medical interns working extended overnight shifts and residents not or rarely working extended overnight shifts. Methods Sleep-wake activity of 137 interns and 87 PGY-2/3 residents on 2-week Internal Medicine and Oncology rotations was assessed with wrist-actigraphy. Alertness was assessed daily with a brief Psychomotor Vigilance Test (PVT) and the Karolinska Sleepiness Scale. Results Interns averaged 6.93 hours (95% confidence interval [CI] 6.84-7.03 hours) sleep per 24 hours across shifts, significantly less than residents not working overnight shifts (7.18 hours, 95% CI 7.06-7.30 hours, p = .007). Interns obtained on average 2.19 hours (95% CI 2.02-2.36 hours) sleep during on-call nights (17.5% obtained no sleep). Alertness was significantly lower on mornings after on-call nights compared to regular shifts (p < .001). Naps between 9 am and 6 pm on the first day post-call were frequent (90.8%) and averaged 2.84 hours (95% CI 2.69-3.00 hours), but interns still slept 1.66 hours less per 24 hours (95% CI 1.56-1.76 hours) compared to regular shift days (p < .001). Sleep inertia significantly affected alertness in the 60 minutes after waking on-call. Conclusions Extended overnight shifts increase the likelihood of chronic sleep restriction in interns. Reduced levels of alertness after on-call nights need to be mitigated. A systematic comparison of sleep, alertness, and safety outcomes under current and past duty hour rules is encouraged.

STUDY OBJECTIVES: Determine the effects of high versus moderate workload on sleep physiology and neurobehavioral measures, during sleep restriction (SR) and no sleep restriction (NSR) conditions. DESIGN: Ten-night experiment involving cognitive workload and SR manipulations. SETTING: Controlled laboratory environment. PARTICIPANTS: Sixty-three healthy adults (mean ± standard deviation: 33.2 ± 8.7 y; 29 females), age 22-50 y. INTERVENTIONS: Following three baseline 8 h time in bed (TIB) nights, subjects were randomized to one of four conditions: high cognitive workload (HW) + SR; moderate cognitive workload (MW) + SR; HW + NSR; or MW + NSR. SR entailed 5 consecutive nights at 4 h TIB; NSR entailed 5 consecutive nights at 8 h TIB. Subjects received three workload test sessions/day consisting of 15-min preworkload assessments, followed by a 60-min (MW) or 120-min (HW) workload manipulation comprised of visually based cognitive tasks, and concluding with 15-min of postworkload assessments. Experimental nights were followed by two 8-h TIB recovery sleep nights. Polysomnography was collected on baseline night 3, experimental nights 1, 4, and 5, and recovery night 1 using three channels (central, frontal, occipital [C3, Fz, O2]). MEASUREMENTS AND RESULTS: High workload, regardless of sleep duration, increased subjective fatigue and sleepiness (all P CONCLUSIONS: High cognitive workload delayed sleep onset, but it also promoted sleep homeostatic responses by increasing subjective fatigue and sleepiness, and producing a global sleep homeostatic response by reducing wake after sleep onset. When combined with sleep restriction, high workload increased local (occipital) sleep homeostasis, suggesting a use-dependent sleep response to visual work. We conclude that sleep restriction and cognitive workload interact to influence sleep homeostasis. CITATION: Goel N, Abe T, Braun ME, Dinges DF. Cognitive workload and sleep restriction interact to influence sleep homeostatic responses. SLEEP 2014;37(11):1745-1756. Language: en

The success of interplanetary human spaceflight will depend on many factors, including the behavioral activity levels, sleep, and circadian timing of crews exposed to prolonged microgravity and confinement. To address the effects of the latter, we used a high-fidelity ground simulation of a Mars mission to objectively track sleep–wake dynamics in a multinational crew of six during 520 d of confined isolation. Measurements included continuous recordings of wrist actigraphy and light exposure (4.396 million min) and weekly computer-based neurobehavioral assessments ( n = 888) to identify changes in the crew's activity levels, sleep quantity and quality, sleep–wake periodicity, vigilance performance, and workload throughout the record-long 17 mo of mission confinement. Actigraphy revealed that crew sedentariness increased across the mission as evident in decreased waking movement (i.e., hypokinesis) and increased sleep and rest times. Light exposure decreased during the mission. The majority of crewmembers also experienced one or more disturbances of sleep quality, vigilance deficits, or altered sleep–wake periodicity and timing, suggesting inadequate circadian entrainment. The results point to the need to identify markers of differential vulnerability to hypokinesis and sleep–wake changes during the prolonged isolation of exploration spaceflight and the need to ensure maintenance of circadian entrainment, sleep quantity and quality, and optimal activity levels during exploration missions. Therefore, successful adaptation to such missions will require crew to transit in spacecraft and live in surface habitats that instantiate aspects of Earth's geophysical signals (appropriately timed light exposure, food intake, exercise) required for temporal organization and maintenance of human behavior.

Apnea-hypopnea index (AHI) is the primary measure used to confirm a diagnosis of obstructive sleep apnea (OSA). However, there may be significant night-to-night variability (NNV) in AHI, limiting the value of AHI in clinical decision-making related to OSA management. We examined short-term NNV in AHI and its predictors during home portable monitoring (PM).Single center prospective observational study of patients (n = 84) with newly diagnosed OSA by polysomnography (PSG) AHI ≥ 5/h. All participants underwent 2 to 8 consecutive nights of PM.Participants (n = 84) were middle-aged (47 ± 8.3 y, mean ± standard deviation; SD), including 28 women, with mean AHI on baseline PSG (AHIPSG) of 30.1 ± 31.8. Mean AHI on PM (AHIPM) was 27.4 ± 23.7. Intraclass correlation coefficient (ICC) for AHIPM in the entire sample was 0.73 (95% CI 0.66-0.8), indicating that 27% of the variability in AHIPM was due to intra-individual factors. Mild severity of OSA, defined by AHIPSG 5-15/h, was associated with higher NNV (likelihood ratio, -0.4 ± 0.14; p = 0.006) and absence of comorbidity showed a trend towards higher NNV (-0.54 ± 0.27, p = 0.05) on AHIPM.The intraindividual short-term NNV in AHIPM is higher in mild versus moderately severe OSA, even in the home setting, where first-night effect is not expected. Larger studies of NNV focused on patients with mild OSA are needed to identify characteristics that predict need and timing for repeated diagnostic testing and treatment.A commentary on this article appears in this issue on page 787.

Suicide is a major public health problem and the 10th leading cause of death in the United States. The identification of modifiable risk factors is essential for reducing the prevalence of suicide. Recently, it has been shown that insomnia and nightmares significantly increase the risk for suicidal ideation, attempted suicide, and death by suicide. While both forms of sleep disturbance may independently confer risk, and potentially be modifiable risk factors, it is also possible that simply being awake at night represents a specific vulnerability for suicide. The present analysis evaluates the frequency of completed suicide per hour while taking into account the percentage of individuals awake at each hour.Archival analyses were conducted estimating the time of fatal injury using the National Violent Death Reporting System for 2003-2010 and the proportion of the American population awake per hour across the 24-hour day using the American Time Use Survey.The mean ± SD incident rate from 06:00-23:59 was 2.2% ± 0.7%, while the mean ± SD incident rate from 00:00-05:59 was 10.3% ± 4.9%. The maximum incident rate was from 02:00-02:59 (16.3%). Hour-by-hour observed values differed from those that would be expected by chance (P.001), and when 6-hour blocks were examined, the observed frequency at night was 3.6 times higher than would be expected by chance (P.001).Being awake at night confers greater risk for suicide than being awake at other times of the day, suggesting that disturbances of sleep or circadian neurobiology may potentiate suicide risk.

Study Objectives: The primary objective of this study was to describe characteristics of sleep across the three domains of sleep quality, daytime sleepiness, and behavioral alertness in community-dwelling adults with heart failure. The secondary objective was to identify modifiable factors associated with behavioral alertness. Methods: A sample of 280 adults with chronic heart failure was enrolled. Widely used, validated, and sensitive measures of sleep quality ( Pittsburgh Sleep Quality Index ), daytime sleepiness ( Epworth Sleepiness Scale, Stanford Sleepiness Scale ), and behavioral alertness ( Psychomotor Vigilance Test [PVT] ) were collected at baseline, 3 and 6 months. Sociodemographic and clinical characteristics, including exercise, were measured at baseline. Results: Participants were primarily male and functionally compromised with a mean left ventricular ejection fraction of 35 percent. The majority of the sample ( 73% ) reported poor sleep quality. The mean ( ± SD ) Epworth Sleepiness Scale score was low ( 7.0 ± 4.6 ), indicating they did not perceive daytime sleepiness. In contrast, behavioral alertness was relatively poor as evidenced by a slow PVT mean response time ( 3.09 ± 0.76 ). Participants who reported exercising at least one hour in the past week were more alert and had faster response times than those reporting no exercise. Conclusions: Although sleep quality was poor and behavioral alertness was compromised, these heart failure patients did not feel sleepy. Exercise may help to promote behavioral alertness and reduce daytime sleepiness in adults with heart failure.

Individual differences in vulnerability to neurobehavioral performance impairment during sleep deprivation are considerable and represent a neurobiological trait. Genetic polymorphisms reported to be predictors have suggested the involvement of the homeostatic and circadian processes of sleep regulation in determining this trait. We applied mathematical and statistical modeling of these two processes to psychomotor vigilance performance and sleep physiological data from a laboratory study of repeated exposure to 36 h of total sleep deprivation in 9 healthy young adults. This served to quantify the respective contributions of individual differences in the two processes to the magnitudes of participants’ individual vulnerabilities to sleep deprivation. For the homeostatic process, the standard deviation for individual differences was found to be about 60% as expressed relative to its group-average contribution to neurobehavioral performance impairment. The same was found for the circadian process. Across the span of the total sleep deprivation period, the group-average effect of the homeostatic process was twice as big as that of the circadian process. In absolute terms, therefore, the impact of the individual differences in the homeostatic process was twice as large as the impact of the individual differences in the circadian process in this study. These modeling results indicated that individualized applications of mathematical models predicting performance on the basis of a homeostatic and a circadian process should account for individual differences in both processes.

Study Objectives: The Psychomotor Vigilance Test (PVT) is a widely used assay of behavioral alertness sensitive to the effects of sleep loss and circadian misalignment. The standard 10-minute duration of the PVT is often considered impractical for operational or clinical environments. Therefore, we developed and validated an adaptive-duration version of the PVT (PVT-A) that stops sampling once it has gathered enough information to correctly classify PVT performance. Design: Repeated-measures experiments involving 10-minute PVT assessments every 2 hours across both acute total sleep deprivation (TSD) and 5 days of chronic partial sleep deprivation (PSD). Setting: Controlled laboratory environment. Participants: Seventy-four healthy subjects (34 women), aged 22 to 45 years. Interventions: A TSD experiment involving 33 hours awake (n = 31 subjects), and a PSD experiment involving 5 nights of 4 hours time in bed (n = 43 subjects). Measurements and Results: The PVT-A algorithm was trained with 527 TSD test bouts and validated with 880 PSD test bouts. Based on our primary outcome measure “number of lapses (response times ≥ 500 ms) plus false starts (premature responses or response times 5 and ≤ 16 lapses and false starts), or low (> 16 lapses and false starts). The decision threshold for PVT-A termination was set so that at least 95% of training data-set tests were classified correctly and no test was classified incorrectly across 2 performance categories (i.e., high as low or low as high), resulting in an average test duration of 6.0 minutes (SD 2.4 min). In the validation data set, 95.7% of test bouts were correctly classified, and there were no incorrect classifications across 2 categories. Agreement corrected for chance was excellent (κ = 0.92). Across the 3 performance categories, sensitivity averaged 93.7% (range 87.2%-100%), and specificity averaged 96.8% (range 91.6%-99.9%). Test duration averaged 6.4 minutes (SD 1.7 min), with a minimum of 27 seconds. Conclusions: We developed and validated a highly accurate, sensitive, and specific adaptive-duration version of the 10-minute PVT. Test duration of the adaptive PVT averaged less than 6.5 minutes, with 60 tests (4.3%) terminating after less than 2 minutes, increasing the practicability of the test in operational and clinical settings. The adaptive-duration strategy may be superior to a simple reduction of PVT duration in which the fixed test duration may be too short to identify subjects with moderate impairment (showing deficits only later during the test) but unnecessarily long for those who are either fully alert or severely impaired.

There are a number of different strategies to mitigate the effects of fatigue in transportation and other occupational settings. Many are centered on regulatory or organizational approaches, such as work scheduling restriction and employer screening practices. While these generally benefit safety and productivity, there are clearly limitations to these approaches. Technologies that objectively detect or predict operator fatigue may be used to effectively complement or even supplant organizational or regulatory approaches. Over the past decade and a half, there have been considerable advances in relevant technologies, including onboard devices that monitor drivers' state or level of performance as well as devices that predict fatigue in advance of a work cycle or trip. In this paper, we discuss the challenges and opportunities for technological approaches to fatigue management, beginning with a discussion of the "ideal" system, followed by some of the general issues and limitations of current technologies. We also discuss some of the critical and outstanding issues related to the human interaction with these systems, including user acceptance and compliance. Finally, we discuss future directions in next generation technology for fatigue management.

Introduction: Chronic nocturnal sleep restriction results in accumulation of neurobehavioral impairment across days. The purpose of this study was to determine whether time of day modulates the effects of sleep restriction on objective daytime performance deficits and subjective sleepiness across days of chronic sleep restriction. Methods: There were N = 90 healthy adults (21 – 49 yr; 38 women) who participated in a 14-d laboratory protocol involving randomization to 1 of 18 schedules of restricted nocturnal sleep with and without a diurnal nap for 10 consecutive days. The total time available for daily sleep ranged from 4.2 h to 8.2 h across conditions. Performance lapses on the psychomotor vigilance test (PVT) and subjective sleepiness were measured each day every 2 h during scheduled wakefulness. Nonlinear mixed-effects regression was used to test the hypothesis that there would be an interaction between time of day and the accumulation (slope across days) of neurobehavioral sleepiness. Results: In agreement with earlier studies, less sleep time resulted in faster accumulation of deficits across days.Time of day significantly affected this relationship for both PVT lapses and subjective sleepiness. The build-up rate of cumulative neurobehavioral deficits across days was largest at 0800 and became progressively smaller across the hours of the day, especially between 1600 and 2000.Following 8 d of sleep restricted to 4 h/d, subjects averaged 8.3 more PVT performance lapses at 0800 than at 1800. Discussion: This study provides evidence that the circadian system has a substantial modulatory effect on cumulative impairment from chronic sleep restriction and that it facilitates a period of relatively protected alertness in the late afternoon/early evening hours when nocturnal sleep is chronically restricted. Refereed/Peer-reviewed

This article examines a 3-decades-old unsolved homicide, where the victim's 4-year-and-9-month-old daughter was deemed the only eyewitness ( State of Nebraska v. Donald J. Sykora, 2008). The authors critique the investigative methods employed over 33 years, with particular emphasis on the final “extreme” cognitive interview of the daughter, which persisted for days and incorporated various imaginative techniques. Adverse circumstances pervade the case: (a) the young age of the presumed witness when the murder occurred; (b) the vulnerability of memory to suggestion and revision over time; (c) the possible earlier use of hypnosis to refresh recall; and (d) implementing a poorly documented, 31-hour cognitive interview that encouraged repetition and fantasy. In this case, the prolonged cognitive interview is perilously hypnotic-like, yielding evidence that must be regarded as a product of imagination inflation—defective for sustaining veridical testimony.

A substantial amount of research has been conducted in an effort to understand the impact of short-term (

During sustained periods of a taxing cognitive workload, humans typically display time-on-task (TOT) effects, in which performance gets steadily worse over the period of task engagement. Arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) was used in this study to investigate the neural correlates of TOT effects in a group of 15 subjects as they performed a 20-minute continuous psychomotor vigilance test (PVT). Subjects displayed significant TOT effects, as seen in progressively slower reaction times and significantly increased mental fatigue ratings after the task. Perfusion data showed that the PVT activates a right lateralized fronto-parietal attentional network in addition to the basal ganglia and sensorimotor cortices. The fronto-parietal network was less active during post-task rest compared to pre-task rest, and regional CBF decrease in this network correlated with performance decline. These results demonstrate the persistent effects of cognitive fatigue in the fronto-parietal network after a period of heavy mental work and indicate the critical role of this attentional network in mediating TOT effects. Furthermore, resting regional CBF in the thalamus and right middle frontal gyrus prior to task onset was predictive of subjects' subsequent performance decline, suggesting that resting CBF quantified by ASL perfusion fMRI may be a useful indicator of performance potential and a marker of the level of fatigue in the neural attentional system.

The impact of confinement and sleep deprivation on risk-taking propensity is a key issue in crew management. We investigated both confinement and gender effects on risk propensity and performance during up to 36 h of extended wakefulness.We studied 4 groups of 3 men and 3 women [N = 24, mean age (+/- SD) = 32.9 +/- 5.8 yr] for 10 consecutive days: a 7-d confined period (CONF) or a 7-d baseline (BASE) condition preceding one control night of normal sleep, one night of sleep deprivation, and one recovery night in the laboratory. Risk propensity (EVAR scale) and simple reaction time task (SRTT) performances were monitored every 2.25 h (0930-1945) during CONF and every 2.11 h (0930-0745) during the sleep deprivation condition.Overall risk propensity during extended wakefulness showed a variation in both conditions with two diurnal peaks separated by a nocturnal minima. After the confinement period, no second peak was found. Number of lapses (reaction time500 ms) on the SRTT varied daily in both conditions. In the normal sleep schedule, subjects increased their level of impulsiveness between the first day and the end of confinement (P0.05).During the night of sleep deprivation, risk-taking propensity decreases and remains stable the following day in the confinement condition while it increases after the baseline period. In a confined environment under a normal sleep-wake schedule, impulsiveness increases in men and women.

Night eating syndrome (NES) is characterized by evening hyperphagia and frequent awakenings accompanied by food intake. Patients with NES display a delayed circadian pattern of food intake but retain a normal sleep-wake cycle. These characteristics initiated the current study, in which the phase and amplitude of behavioral and neuroendocrine circadian rhythms in patients with NES were evaluated. Fifteen women with NES (mean age ± SD, 40.8 ± 8.7 y) and 14 control subjects (38.6 ± 9.5 y) were studied in the laboratory for 3 nights, with food intake measured daily. Blood also was collected for 25 h (every 2 h from 0800 to 2000 h, and then hourly from 2100 to 0900 h) and assayed for glucose and 7 hormones (insulin, ghrelin, leptin, melatonin, cortisol, thyroid-stimulating hormone [TSH] and prolactin). Statistical analyses utilized linear mixed-effects cosinor analysis. Control subjects displayed normal phases and amplitudes for all circadian rhythms. In contrast, patients with NES showed a phase delay in the timing of meals, and delayed circadian rhythms for total caloric, fat, and carbohydrate intake. In addition, phase delays of 1.0 to 2.8 h were found in 2 food-regulatory rhythms—leptin and insulin—and in the circadian melatonin rhythm (with a trend for a delay in the circadian cortisol rhythm). In contrast, circulating levels of ghrelin, the primary hormone that stimulates food intake, were phase advanced by 5.2 h. The glucose rhythm showed an inverted circadian pattern. Patients with NES also showed reduced amplitudes in the circadian rhythms of food intake, cortisol, ghrelin, and insulin, but increased TSH amplitude. Thus, patients with NES demonstrated significant changes in the timing and amplitude of various behavioral and physiological circadian markers involved in appetite and neuroendocrine regulation. As such, NES may result from dissociations between central (suprachiasmatic nucleus) timing mechanisms and putative oscillators elsewhere in the central nervous system or periphery, such as the stomach or liver. Considering these results, chronobiologic treatments for NES such as bright light therapy may be useful. Indeed, bright light therapy has shown efficacy in reducing night eating in case studies and should be evaluated in controlled clinical trials.

Among adults in the United States, sleep durations appear to have decreased in recent years. Inadequate sleep and sleep deprivation cause numerous neurobehavioral and physiological changes. A number of recent studies have reported associations between disrupted sleep/sleep deprivation and inflammatory responses, although the physiological mechanisms underlying these relationships remain unclear. Alterations in sleep due to lifestyle factors, the aging process, and disease states have all been associated with increases in a range of inflammatory markers. Several of these inflammatory processes have been associated with reduced health status (e.g., C-reactive protein and cardiovascular disease). Thus, maintaining adequate sleep duration and quality through good sleep habits and treatment of sleep disorders may reduce inflammatory processes associated with aging and increase the wellness phenotype.

Lapses of attention manifest as delayed behavioral responses to salient stimuli. Although they can occur even after a normal night's sleep, they are longer in duration and more frequent after sleep deprivation (SD). To identify changes in task-associated brain activation associated with lapses during SD, we performed functional magnetic resonance imaging during a visual, selective attention task and analyzed the correct responses in a trial-by-trial manner modeling the effects of response time. Separately, we compared the fastest 10% and slowest 10% of correct responses in each state. Both analyses concurred in finding that SD-related lapses differ from lapses of equivalent duration after a normal night's sleep by (1) reduced ability of frontal and parietal control regions to raise activation in response to lapses, (2) dramatically reduced visual sensory cortex activation, and (3) reduced thalamic activation during lapses that contrasted with elevated thalamic activation during nonlapse periods. Despite these differences, the fastest responses after normal sleep and after SD elicited comparable frontoparietal activation, suggesting that performing a task while sleep deprived involves periods of apparently normal neural activation interleaved with periods of depressed cognitive control, visual perceptual functions, and arousal. These findings reveal for the first time some of the neural consequences of the interaction between efforts to maintain wakefulness and processes that initiate involuntary sleep in sleep-deprived persons.