University students' diurnal learning-directed behavior is strongly influenced by school start times with implications for grades.

STUDY OBJECTIVES: School start times impose constraints on sleep-wake timing that may influence academic achievement. We used large university archived datasets to test the hypothesis that larger differences in timing of students' diurnal learning behavior on school days relative to non-school days would be associated with lower grades. METHODS: Diurnal learning-directed behavior was examined in 33 645 university students by analyzing their learning management system (LMS) login rhythm. We tested the associations between the phase-difference in students' behavioral rhythm on school days versus non-school days with grade point average, LMS-login phase on non-school days (LMS-login chronotype), and school start time. We also tested the chronotype-dependent effects of school start times on diurnal behavior to determine whether students obtained better course grades when their first class of the day was in synch with their LMS-login chronotype. RESULTS: Students whose LMS-login rhythm was more than 2 hours earlier on school days had significantly lower grades than their peers. The change in LMS-login phase was larger in students with a later LMS-login chronotype and for earlier school start times. Minimal changes in LMS-login phase and higher course grades were observed when students' first class of the day was aligned with their LMS-login chronotype. CONCLUSIONS: Our findings demonstrate that school start times have a profound impact on students' diurnal learning behavior with implications for grades. Universities can potentially improve learning by starting school later to minimize differences in diurnal learning behavior between school days and non-school days.

Early morning university classes are associated with impaired sleep and academic performance.

Attending classes and sleeping well are important for students' academic success. Here, we tested whether early morning classes are associated with lower attendance, shorter sleep and poorer academic achievement by analysing university students' digital traces. Wi-Fi connection logs in 23,391 students revealed that lecture attendance was about ten percentage points lower for classes at 08:00 compared with later start times. Diurnal patterns of Learning Management System logins in 39,458 students and actigraphy data in 181 students demonstrated that nocturnal sleep was an hour shorter for early classes because students woke up earlier than usual. Analyses of grades in 33,818 students showed that the number of days per week they had morning classes was negatively correlated with grade point average. These findings suggest concerning associations between early morning classes and learning outcomes.

A targeted e-learning approach for keeping universities open during the COVID-19 pandemic while reducing student physical interactions.

The COVID-19 pandemic led to widespread closure of universities. Many universities turned to e-learning to provide educational continuity, but they now face the challenge of how to reopen safely and resume in-class learning. This is difficult to achieve without methods for measuring the impact of school policies on student physical interactions. Here, we show that selectively deploying e-learning for larger classes is highly effective at decreasing campus-wide opportunities for student-to-student contact, while allowing most in-class learning to continue uninterrupted. We conducted a natural experiment at a large university that implemented a series of e-learning interventions during the COVID-19 outbreak. The numbers and locations of 24,000 students on campus were measured over a 17-week period by analysing >24 million student connections to the university Wi-Fi network. We show that daily population size can be manipulated by e-learning in a targeted manner according to class size characteristics. Student mixing showed accelerated growth with population size according to a power law distribution. Therefore, a small e-learning dependent decrease in population size resulted in a large reduction in student clustering behaviour. Our results suggest that converting a small number of classes to e-learning can decrease potential for disease transmission while minimising disruption to university operations. Universities should consider targeted e-learning a viable strategy for providing educational continuity during periods of low community disease transmission.

Circadian regulation of breath alcohol concentration.

STUDY OBJECTIVES: The role of the circadian clock in regulating blood/breath alcohol levels after consuming alcohol is uncertain. Our goal was to evaluate the degree to which the circadian system regulates breath alcohol concentration (BrAC) pharmacokinetic parameters. METHODS: Twenty healthy adults aged 21-30 years took part in a 4-day laboratory study. A 40-h constant routine procedure was used to assess circadian rhythms. Every 4 h, participants were given a fixed oral dose of alcohol with breathalyzer measurements taken every 5 min to construct BrAC curves. Sinusoidal models were used to test for circadian variation of the peak BrAC, the time to reach peak BrAC, the absorption rate, the elimination rate, and the time for BrAC to return to zero after alcohol was ingested. RESULTS: A significant circadian rhythm was detected for group-averaged peak BrAC values and the time for BrAC to return to zero, but not other BrAC variables. Peak BrAC values were lowest in the evening near the peak of the core body temperature rhythm and nadir of the salivary cortisol rhythm. Peak BrAC values increased during the night and reached their highest levels in the morning and afternoon. The time needed for BrAC to return to zero was also longest in the late morning and afternoon. CONCLUSION: The circadian system modulates some BrAC pharmacokinetic parameters. In normally entrained individuals, taking the same oral dose of alcohol at different times of day can result in different BrAC responses. These findings have potential implications for alcohol-related accidents and alcohol toxicity.

Associations of time spent on homework or studying with nocturnal sleep behavior and depression symptoms in adolescents from Singapore.

OBJECTIVE: To investigate associations of adolescents' time spent on homework/studying with nocturnal time for sleep and depression symptoms, in a competitive academic environment. DESIGN: Cross-sectional, anonymous survey of sleep habits, school life, and health-related measures. SETTING: Eight schools in Singapore. PARTICIPANTS: Total 1225 adolescents aged 13-19 years. MEASUREMENTS: Self-reported sleep behavior and time use data were collected separately for school days and weekends. Multiple regression models were used to test covariation of time spent on homework/studying with other activities, and associations of homework/studying duration with depression symptoms. RESULTS: Time in bed for sleep and media use were inversely related with homework/studying duration on both school days and weekends, adjusting for time spent on other activities and demographic variables. Face-to-face family time and hanging out with friends were also reciprocally related with homework/studying duration on weekends. Depression scores were higher in adolescents who spent long hours on homework/studying. On school days, this was mediated by reduced time in bed for sleep. On weekends, homework/studying duration associated with depression symptoms, adjusting for time in bed and other covariates. Adolescents who spent ≥5 hours on homework/studying per day on weekends had greater symptoms of anhedonia and anxiety. CONCLUSIONS: In a competitive academic setting, adolescents who spent more time on homework/studying spent less time on sleep, media use, and social activities. Independent of effects on sleep, long hours on homework/studying on weekends may be a risk factor for depression. Reducing adolescents' workload outside of class may benefit their sleep, schoolwork-life balance, and mental well-being.

Associations of sleep duration on school nights with self-rated health, overweight, and depression symptoms in adolescents: problems and possible solutions.

OBJECTIVE: To investigate associations between sleep duration and health-related measures, and factors associated with short sleep, in adolescents in an East Asian society with strong emphasis on academic achievement. METHODS: Adolescents aged 13-19 years (n = 2346) from eight schools in Singapore (five local, three international) took part in a cross-sectional survey of sleep habits, school life, and health. Self-rated health, overweight (International Obesity Task Force Criteria), and depression symptoms were compared in adolescents with short (<7 h), moderately short (7 to <8 h), or an appropriate amount of sleep (8-10 h) on school nights. RESULTS: Short sleep on school nights was associated with poorer self-rated health, increased odds of being overweight (adjusted odds ratio [ORadj] = 2.56, 95% confidence interval = 1.39-4.70), and increased odds of feeling depression symptoms (sadness, irritability, worthlessness, low motivation, difficulty concentrating, anhedonia, anxiety, and thoughts of self-harm/suicide) compared with an appropriate sleep duration (ORadj = 2.10-4.33, p < 0.05 for each symptom). Barriers to healthy sleep included later preferred sleep timing (a relative indicator of later chronotype), lower parental supervision of bedtime, longer study time, early school start time, and longer travel time. Students at local schools were less likely to have a parent-set bedtime, and spent more time on homework/studying. Later bedtime in local schools attenuated the benefit of later school start time on nocturnal sleep duration. CONCLUSIONS: Short sleep may contribute to poorer adolescent health and well-being. Strategies for improving sleep in hard-driving East Asian societies should take into account sociocultural factors that may impede removal of barriers to healthy sleep.

Sleep Restriction Impairs Vocabulary Learning when Adolescents Cram for Exams: The Need for Sleep Study.

STUDY OBJECTIVES: The ability to recall facts is improved when learning takes place at spaced intervals, or when sleep follows shortly after learning. However, many students cram for exams and trade sleep for other activities. The aim of this study was to examine the interaction of study spacing and time in bed (TIB) for sleep on vocabulary learning in adolescents. METHODS: In the Need for Sleep Study, which used a parallel-group design, 56 adolescents aged 15-19 years were randomly assigned to a week of either 5 h or 9 h of TIB for sleep each night as part of a 14-day protocol conducted at a boarding school. During the sleep manipulation period, participants studied 40 Graduate Record Examination (GRE)-type English words using digital flashcards. Word pairs were presented over 4 consecutive days (spaced items), or all at once during single study sessions (massed items), with total study time kept constant across conditions. Recall performance was examined 0 h, 24 h, and 120 h after all items were studied. RESULTS: For all retention intervals examined, recall of massed items was impaired by a greater amount in adolescents exposed to sleep restriction. In contrast, cued recall performance on spaced items was similar between sleep groups. CONCLUSIONS: Spaced learning conferred strong protection against the effects of sleep restriction on recall performance, whereas students who had insufficient sleep were more likely to forget items studied over short time intervals. These findings in adolescents demonstrate the importance of combining good study habits and good sleep habits to optimize learning outcomes.

Individual differences in physiologic measures are stable across repeated exposures to total sleep deprivation.

Some individuals show severe cognitive impairment when sleep deprived, whereas others are able to maintain a high level of performance. Such differences are stable and trait-like, but it is not clear whether these findings generalize to physiologic responses to sleep loss. Here, we analyzed individual differences in behavioral and physiologic measures in healthy ethnic-Chinese male volunteers (n = 12; aged 22-30 years) who were kept awake for at least 26 h in a controlled laboratory environment on two separate occasions. Every 2 h, sustained attention performance was assessed using a 10-min psychomotor vigilance task (PVT), and sleepiness was estimated objectively by determining percentage eyelid closure over the pupil over time (PERCLOS) and blink rate. Between-subject differences in heart rate and its variability, and electroencephalogram (EEG) spectral power were also analyzed during each PVT. To assess stability of individual differences, intraclass correlation coefficients (ICC) were determined using variance components analysis. Consistent with previous work, individual differences in PVT performance were reproducible across study visits, as were baseline sleep measures prior to sleep deprivation. In addition, stable individual differences were observed during sleep deprivation for PERCLOS, blink rate, heart rate and its variability, and EEG spectral power in the alpha frequency band, even after adjusting for baseline differences in these measures (range, ICC = 0.67-0.91). These findings establish that changes in ocular, ECG, and EEG signals are highly reproducible across a night of sleep deprivation, hence raising the possibility that, similar to behavioral measures, physiologic responses to sleep loss are trait-like.

Effects of exposure to intermittent versus continuous red light on human circadian rhythms, melatonin suppression, and pupillary constriction.

Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21-28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm(-2) s(-1)), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n = 8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light.

Sustained attention performance during sleep deprivation associates with instability in behavior and physiologic measures at baseline.

STUDY OBJECTIVES: To identify baseline behavioral and physiologic markers that associate with individual differences in sustained attention during sleep deprivation. DESIGN: In a retrospective study, ocular, electrocardiogram, and electroencephalogram (EEG) measures were compared in subjects who were characterized as resilient (n = 15) or vulnerable (n = 15) to the effects of total sleep deprivation on sustained attention. SETTING: Chronobiology and Sleep Laboratory, Duke-NUS Graduate Medical School Singapore. PARTICIPANTS: Healthy volunteers aged 22-32 years from the general population. INTERVENTIONS: Subjects were kept awake for at least 26 hours under constant environmental conditions. Every 2 hours, sustained attention was assessed using a 10-minute psychomotor vigilance task (PVT). MEASUREMENTS AND RESULTS: During baseline sleep and recovery sleep, EEG slow wave activity was similar in resilient versus vulnerable subjects, suggesting that individual differences in vulnerability to sleep loss were not related to differences in homeostatic sleep regulation. Rather, irrespective of time elapsed since wake, subjects who were vulnerable to sleep deprivation exhibited slower and more variable PVT response times, lower and more variable heart rate, and higher and more variable EEG spectral power in the theta frequency band (6.0-7.5 Hz). CONCLUSIONS: Performance decrements in sustained attention during sleep deprivation associate with instability in behavioral and physiologic measures at baseline. Small individual differences in sustained attention that are present at baseline are amplified during prolonged wakefulness, thus contributing to large between-subjects differences in performance and sleepiness.

Extensive diversity in circadian regulation of plasma lipids and evidence for different circadian metabolic phenotypes in humans.

The circadian system regulates daily rhythms in lipid metabolism and adipose tissue function. Although disruption of circadian clock function is associated with negative cardiometabolic end points, very little is known about interindividual variation in circadian-regulated metabolic pathways. Here, we used targeted lipidomics-based approaches to profile the time course of 263 lipids in blood plasma in 20 healthy individuals. Over a span of 28 h, blood was collected every 4 h and plasma lipids were analyzed by HPLC/MS. Across subjects, about 13% of lipid metabolites showed circadian variation. Rhythmicity spanned all metabolite classes examined, suggesting widespread circadian control of lipid-mediated energy storage, transport, and signaling. Intersubject agreement for lipids identified as rhythmic was only about 20%, however, and the timing of lipid rhythms ranged up to 12 h apart between individuals. Healthy subjects therefore showed substantial variation in the timing and strength of rhythms across different lipid species. Strong interindividual differences were also observed for rhythms of blood glucose and insulin, but not cortisol. Using consensus clustering with iterative feature selection, subjects clustered into different groups based on strength of rhythmicity for a subset of triglycerides and phosphatidylcholines, suggesting that there are different circadian metabolic phenotypes in the general population. These results have potential implications for lipid metabolism disorders linked to circadian clock disruption.

Melanopsin and rod-cone photoreceptors play different roles in mediating pupillary light responses during exposure to continuous light in humans.

In mammals, the pupillary light reflex is mediated by intrinsically photosensitive melanopsin-containing retinal ganglion cells that also receive input from rod-cone photoreceptors. To assess the relative contribution of melanopsin and rod-cone photoreceptors to the pupillary light reflex in humans, we compared pupillary light responses in normally sighted individuals (n = 24) with a blind individual lacking rod-cone function. Here, we show that visual photoreceptors are required for normal pupillary responses to continuous light exposure at low irradiance levels, and for sustained pupillary constriction during exposure to light in the long-wavelength portion of the visual spectrum. In the absence of rod-cone function, pupillomotor responses are slow and sustained, and cannot track intermittent light stimuli, suggesting that rods/cones are required for encoding fast modulations in light intensity. In sighted individuals, pupillary constriction decreased monotonically for at least 30 min during exposure to continuous low-irradiance light, indicating that steady-state pupillary responses are an order of magnitude slower than previously reported. Exposure to low-irradiance intermittent green light (543 nm; 0.1-4 Hz) for 30 min, which was given to activate cone photoreceptors repeatedly, elicited sustained pupillary constriction responses that were more than twice as great compared with exposure to continuous green light. Our findings demonstrate nonredundant roles for rod-cone photoreceptors and melanopsin in mediating pupillary responses to continuous light. Moreover, our results suggest that it might be possible to enhance nonvisual light responses to low-irradiance exposures by using intermittent light to activate cone photoreceptors repeatedly in humans.

Heart rate variability can be used to estimate sleepiness-related decrements in psychomotor vigilance during total sleep deprivation.

STUDY OBJECTIVES: To assess whether changes in psychomotor vigilance during sleep deprivation can be estimated using heart rate variability (HRV). DESIGN: HRV, ocular, and electroencephalogram (EEG) measures were compared for their ability to predict lapses on the Psychomotor Vigilance Task (PVT). SETTING: Chronobiology and Sleep Laboratory, Duke-NUS Graduate Medical School Singapore. PARTICIPANTS: Twenty-four healthy Chinese men (mean age ± SD = 25.9 ± 2.8 years). INTERVENTIONS: Subjects were kept awake continuously for 40 hours under constant environmental conditions. Every 2 hours, subjects completed a 10-minute PVT to assess their ability to sustain visual attention. MEASUREMENTS AND RESULTS: During each PVT, we examined the electrocardiogram (ECG), EEG, and percentage of time that the eyes were closed (PERCLOS). Similar to EEG power density and PERCLOS measures, the time course of ECG RR-interval power density in the 0.02-0.08-Hz range correlated with the 40-hour profile of PVT lapses. Based on receiver operating characteristic curves, RR-interval power density performed as well as EEG power density at identifying a sleepiness-related increase in PVT lapses above threshold. RR-interval power density (0.02-0.08 Hz) also classified subject performance with sensitivity and specificity similar to that of PERCLOS. CONCLUSIONS: The ECG carries information about a person's vigilance state. Hence, HRV measures could potentially be used to predict when an individual is at increased risk of attentional failure. Our results suggest that HRV monitoring, either alone or in combination with other physiologic measures, could be incorporated into safety devices to warn drowsy operators when their performance is impaired.