Circadian Regulation Of Sleep Research Articles

Weekday and weekend sleep times across the human lifespan: a model-based simulation.

The shifts in the opposite directions, toward later and earlier sleep timing, occur during the transition through adolescence and adulthood, respectively. Such a n-shape of age-associated change in sleep timing does not resemble the inverse relationship of sleep duration with ages. Age-associated variation in the parameters of the mechanisms of circadian and homeostatic regulation of sleep would underlie these different shapes of relationship of sleep times with ages. Here, we searched for a parsimonious explanation of these different shapes by simulating sleep times on weekdays and weekends with one of the variants of the two-process model of sleep regulation. Using mean age of a sample with reported sleep times on weekdays and weekends, the whole set of 1404 such samples was subdivided into 15 age subsets. Simulations of sleep times in these subsets were performed with and without the suggestion of age-associated variation in the circadian phase. Simulations showed that the age-associated decay of slow-wave activity can parsimoniously explain not only the parallel decreases in weekend sleep duration and rate of the buildup of sleep pressure during the wake phase of the sleep-wake cycle, but also both the delay and advance of sleep timing during the transition through adolescence and adulthood, respectively. The almost functional relationships were revealed between the age-related changes in sleep duration, rate of the buildup of sleep pressure, and slow-wave activity that is a good electrophysiological marker of cortical metabolic rate and synaptic density, strength and efficacy.

Fundamentals of sleep regulation: Model and benchmark values for fractal and oscillatory neurodynamics

Homeostatic, circadian and ultradian mechanisms play crucial roles in the regulation of sleep. Evidence suggests that ratios of low-to-high frequency power in the electroencephalogram (EEG) spectrum indicate the instantaneous level of sleep pressure, influenced by factors such as individual sleep-wake history, current sleep stage, age-related differences and brain topography characteristics. These effects are well captured and reflected in the spectral exponent, a composite measure of the constant low-to-high frequency ratio in the periodogram, which is scale-free and exhibits lower interindividual variability compared to slow wave activity, potentially serving as a suitable standardization and reference measure. Here we propose an index of sleep homeostasis based on the spectral exponent, reflecting the level of membrane hyperpolarization and/or network bistability in the central nervous system in humans. In addition, we advance the idea that the U-shaped overnight deceleration of oscillatory slow and fast sleep spindle frequencies marks the biological night, providing somnologists with an EEG-index of circadian sleep regulation. Evidence supporting this assertion comes from studies based on sleep replacement, forced desynchrony protocols and high-resolution analyses of sleep spindles. Finally, ultradian sleep regulatory mechanisms are indicated by the recurrent, abrupt shifts in dominant oscillatory frequencies, with spindle ranges signifying non-rapid eye movement and non-spindle oscillations – rapid eye movement phases of the sleep cycles. Reconsidering the indicators of fundamental sleep regulatory processes in the framework of the new Fractal and Oscillatory Adjustment Model (FOAM) offers an appealing opportunity to bridge the gap between the two-process model of sleep regulation and clinical somnology.

Circadian sleep regulation and brain tissue microstructure in cognitively unimpaired older adults

AbstractBackgroundCircadian dysfunction increases with age, leading to changes in the circadian regulation of physiological and biological rhythms, including sleep. Actigraphy studies demonstrated that altered 24‐h rest‐activity patterns, an estimate of circadian sleep‐wake regulation, is related to cognitive decline and tightly linked to Alzheimer’s disease progression. Here, we assessed whether circadian sleep regulation, measured during a multiple naps protocol, is related to brain microstructural integrity in a group of cognitively unimpaired older adults.MethodEighty‐six retired older individuals (mean age [SD] = 69.9 ± 5.2 y.o., 32 females, Table 1) with no major sleep disorders or medical condition, underwent an in‐lab 40‐h multiple naps protocol and brain structural magnetic resonance imaging. As rapid eye movement (REM) sleep is under strong circadian control, circadian REM sleep amplitude was computed by fitting a Gaussian curve on REM sleep duration (% of total sleep time) measured for each nap opportunity. The multiparametric mapping protocol was used to derive indices of brain tissue microstructure using magnetization transfer saturation (MTsat), R1 and R2* maps (hMRI toolbox v0.2.2). Statistical models were adjusted for age, sex, education, and for additional covariates related to sleep architecture and its circadian modulation, including mean REM% and sleep efficiency (SE), the accumulation of REM sleep and sleep need (slope of a fitted first‐order polynomial curve), and circadian SE amplitude.ResultsWhole‐brain voxel‐based quantification analysis revealed that low circadian REM amplitude was related to low MTsat, R1 and R2* values in several white matter regions mostly located around the lateral ventricles (Figure 1A). In addition, a significant association was observed between low circadian REM amplitude and low R1 values in two grey matter clusters encompassing the hippocampus, entorhinal cortex, thalamus and hypothalamus (Figure 1B).ConclusionOur findings provide first evidence that changes in circadian sleep regulation is associated with microstructural changes in key brain regions sensitive to the aging process and involved in sleep‐wake regulation. These results further emphasize the relevance of monitoring circadian sleep regulation for the early detection of individuals at risk for neurodegeneration and cognitive decline.

Napping and circadian sleep-wake regulation during healthy aging.

Daytime napping is frequently reported among the older population and has attracted increasing attention due to its association with multiple health conditions. Here, we tested whether napping in the aged is associated with altered circadian regulation of sleep, sleepiness, and vigilance performance. Sixty healthy older individuals (mean age: 69 years, 39 women) were recruited with respect to their napping habits (30 nappers, 30 non-nappers). All participants underwent an in-lab 40-hour multiple nap protocol (10 cycles of 80 minutes of sleep opportunity alternating with 160 minutes of wakefulness), preceded and followed by a baseline and recovery sleep period. Saliva samples for melatonin assessment, sleepiness, and vigilance performance were collected during wakefulness and electrophysiological data were recorded to derive sleep parameters during scheduled sleep opportunities. The circadian amplitude of melatonin secretion was reduced in nappers, compared to non-nappers. Furthermore, nappers were characterized by higher sleep efficiencies and REM sleep proportion during day- compared to nighttime naps. The nap group also presented altered modulation in sleepiness and vigilance performance at specific circadian phases. Our data indicate that napping is associated with an altered circadian sleep-wake propensity rhythm. They thereby contribute to the understanding of the biological correlates underlying napping and/or sleep-wake cycle fragmentation during healthy aging. Altered circadian sleep-wake promotion can lead to a less distinct allocation of sleep into nighttime and/or a reduced wakefulness drive during the day, thereby potentially triggering the need to sleep at adverse circadian phase.

Sleep tight, beat right: Does nucleus of the solitary tract circadian rhythmicity influence blood pressure and sleep regulation?

Sleep tight, beat right: Does nucleus of the solitary tract circadian rhythmicity influence blood pressure and sleep regulation?

Sleep disturbance induces a modulation of clock gene expression and alters metabolism regulation in drosophila

Sleep disorders are catching attention worldwide as they can induce dyshomeostasis and health issues in all animals, including humans. Circadian rhythms are biological 24-hour cycles that influence physiology and behavior in all living organisms. Sleep is a crucial resting state for survival and is under the control of circadian rhythms. Studies have shown the influence of sleep on various pathological conditions, including metabolic diseases; however, the biological mechanisms involving the circadian clock, sleep, and metabolism regulation are not well understood. In previous work, we standardized a sleep disturbance protocol and, observed that short-time sleep deprivation and sleep-pattern alteration induce homeostatic sleep regulation, locomotor deficits, and increase oxidative stress. Now, we investigated the relationship between these alterations with the circadian clock and energetic metabolism. In this study, we evaluated the expression of the circadian clock and drosophila insulin-like peptides (DILPs) genes and metabolic markers glucose, triglycerides, and glycogen in fruit flies subjected to short-term sleep disruption protocols. The sleep disturbance altered the expression of clock genes and DILPs genes expression, and modulated glucose, triglycerides, and glycogen levels. Moreover, we demonstrated changes in mTor/dFoxo genes, AKT phosphorylation, and dopamine levels in nocturnal light-exposed flies. Thus, our results suggest a connection between clock genes and metabolism disruption as a consequence of sleep disruption, demonstrating the importance of sleep quality in health maintenance.

A phosphorylation-deficient mutant of Sik3, a homolog of Sleepy, alters circadian sleep regulation by PDF neurons in Drosophila.

Sleep behavior has been observed from non-vertebrates to humans. Sleepy mutation in mice resulted in a notable increase in sleep and was identified as an exon-skipping mutation of the salt-inducible kinase 3 (Sik3) gene, conserved among animals. The skipped exon includes a serine residue that is phosphorylated by protein kinase A. Overexpression of a mutant gene with the conversion of this serine into alanine (Sik3-SA) increased sleep in both mice and the fruit fly Drosophila melanogaster. However, the mechanism by which Sik3-SA increases sleep remains unclear. Here, we found that Sik3-SA overexpression in all neurons increased sleep under both light-dark (LD) conditions and constant dark (DD) conditions in Drosophila. Additionally, overexpression of Sik3-SA only in PDF neurons, which are a cluster of clock neurons regulating the circadian rhythm, increased sleep during subjective daytime while decreasing the amplitude of circadian rhythm. Furthermore, suppressing Sik3-SA overexpression specifically in PDF neurons in flies overexpressing Sik3-SA in all neurons reversed the sleep increase during subjective daytime. These results indicate that Sik3-SA alters the circadian function of PDF neurons and leads to an increase in sleep during subjective daytime under constant dark conditions.

A ketogenic diet containing medium-chain triglycerides reduces REM sleep duration without significant influence on mouse circadian phenotypes

Ketogenic diets (KDs) affect the circadian rhythms of behavior and clock gene expression in experimental animals. However, these diets were designed to simulate a fasting state; thus, whether these effects are caused by diet-induced ketogenesis or persistent starvation is difficult to distinguish. The present study aimed to define the effects of a KD containing medium-chain triglycerides (MCT-KD) that increase blood ketone levels without inducing carbohydrate starvation, on circadian rhythms and sleep regulation. Mice were fed with a normal diet (CTRL) or MCT-KD for 2 weeks. Blood β-hydroxybutyrate levels were significantly increased up to 2 mM by the MCT-KD, whereas body weight gain and blood glucose levels were identical between the groups, suggesting that ketosis accumulated without carbohydrate starvation in the MCT-KD mice. Circadian rhythms of wheel-running activity and core body temperature were almost identical, although wheel-running was slightly reduced in the MCT-KD mice. The circadian expression of the core clock genes, Per1, Per2, Bmal1, and Dbp in the hypothalamus, heart, liver, epididymal adipose tissues, and skeletal muscle were almost identical between the CTRL and MCT-KD mice, whereas the amplitude of hepatic Per2 and adipose Per1 expression was increased in MCT-KD mice. The MCT-KD reduced the duration of rapid-eye-movement (REM) sleep without affecting the duration of non-REM sleep and the duration of wakefulness. These findings suggested that the impact of ketone bodies on circadian systems are limited, although they might reduce locomotor activity and REM sleep duration.

Association between circadian sleep regulation and cortical gyrification in young and older adults.

The circadian system orchestrates sleep timing and structure and is altered with increasing age. Sleep propensity, and particularly REM sleep is under strong circadian control and has been suggested to play an important role in brain plasticity. In this exploratory study, we assessed whether surface-based brain morphometry indices are associated with circadian sleep regulation and whether this link changes with age. Twenty-nine healthy older (55-82 years; 16 men) and 28 young participants (20-32 years; 13 men) underwent both structural magnetic resonance imaging and a 40-h multiple nap protocol to extract sleep parameters over day and night time. Cortical thickness and gyrification indices were estimated from T1-weighted images acquired during a classical waking day. We observed that REM sleep was significantly modulated over the 24-h cycle in both age groups, with older adults exhibiting an overall reduction in REM sleep modulation compared to young individuals. Interestingly, when taking into account the observed overall age-related reduction in REM sleep throughout the circadian cycle, higher day-night differences in REM sleep were associated with increased cortical gyrification in the right inferior frontal and paracentral regions in older adults. Our results suggest that a more distinctive allocation of REM sleep over the 24-h cycle is associated with regional cortical gyrification in aging, and thereby point towards a protective role of circadian REM sleep regulation for age-related changes in brain organization.

The duration of caffeine treatment plays an essential role in its effect on sleep and circadian rhythm.

Sleep is regulated by the homeostatic system and the circadian clock. Caffeine intake promotes wakefulness in Drosophila. In humans, caffeine is consumed on a daily basis and hence it is important to understand the effect of prolonged caffeine intake on both circadian and homeostatic regulation of sleep. Furthermore, sleep changes with age and the impact of caffeine on age-dependent sleep fragmentation are yet to be understood. Hence in the present study, we examined the effect of short exposure to caffeine on homeostatic sleep and age-dependent sleep fragmentation in Drosophila. We further assessed the effect of prolonged exposure to caffeine on homeostatic sleep and circadian clock. The results of our study showed that short exposure to caffeine reduces sleep and food intake in mature flies. It also enhances sleep fragmentation with increasing age. However, we have not assessed the effect of caffeine on food intake in older flies. On the other hand, prolonged caffeine exposure did not exert any significant effect on the duration of sleep and food intake in mature flies. Nevertheless, prolonged caffeine ingestion decreased the morning and evening anticipatory activity in these flies indicating that it affects the circadian rhythm. These flies also exhibited phase delay in the clock gene timeless transcript oscillation and exhibited either behavioral arrhythmicity or a longer free-running period under constant darkness. In summary, the results of our studies showed that short exposure to caffeine increases the sleep fragmentation with age whereas prolonged caffeine exposure disrupts the circadian clock.

Hyperammonaemia disrupts daily rhythms reversibly by elevating glutamate in the central circadian pacemaker.

Patients with cirrhosis exhibit features of circadian disruption. Hyperammonaemia has been suggested to impair both homeostatic and circadian sleep regulation. Here, we tested if hyperammonaemia directly disrupts circadian rhythm generation in the central pacemaker, the suprachiasmatic nuclei (SCN) of the hypothalamus. Wheel-running activity was recorded from mice fed with a hyperammonaemic or normal diet for ~35 days in a 12:12 light-dark (LD) cycle followed by ~15 days in constant darkness (DD). The expression of the clock protein PERIOD2 (PER2) was recorded from SCN explants before, during and after ammonia exposure, ±glutamate receptor antagonists. In LD, hyperammonaemic mice advanced their daily activity onset time by ~1h (16.8 ± 0.3 vs. 18.1 ± 0.04 h, p=.009) and decreased their total activity, concentrating it during the first half of the night. In DD, hyperammonaemia reduced the amplitude of daily activity (551.5 ± 27.7 vs. 724.9 ± 59 counts, p=.007), with no changes in circadian period. Ammonia (≥0.01 mM) rapidly and significantly reduced PER2 amplitude, and slightly increased circadian period. The decrease in PER2 amplitude correlated with decreased synchrony among circadian cells in the SCN and increased extracellular glutamate, which was rescued by AMPA glutamate receptor antagonists. These data suggest that hyperammonaemia affects circadian regulation of rest-activity behaviour by increasing extracellular glutamate in the SCN.

Circadian Rhythm Sleep-Wake Disorders in Older Adults.

The timing, duration, and consolidation of sleep result from the interaction of the circadian timing system with a sleep-wake homeostatic process. When aligned and functioning optimally, this allows for wakefulness throughout the day and a long consolidated sleep episode at night. Changes to either the sleep regulatory process or how they interact can result in an inability to fall asleep at the desired time, difficulty remaining asleep, waking too early, and/or difficulty remaining awake throughout the day. This mismatch between the desired timing of sleep and the ability to fall asleep and remain asleep is a hallmark of a class of sleep disorders called the circadian rhythm sleep-wake disorders. In this updated article, we discuss typical changes in the circadian regulation of sleep with aging; how age influences the prevalence, diagnosis, and treatment of circadian rhythm sleep disorders; and how neurologic diseases in older patient impact circadian rhythms and sleep.

Extracting Circadian and Sleep Parameters from Longitudinal Data in Schizophrenia for the Design of Pragmatic Light Interventions.

Sleep and circadian rhythm dysfunction is prevalent in schizophrenia, is associated with distress and poorer clinical status, yet remains an under-recognized therapeutic target. The development of new therapies requires the identification of the primary drivers of these abnormalities. Understanding of the regulation of sleep–wake timing is now sufficiently advanced for mathematical model-based analyses to identify the relative contribution of endogenous circadian processes, behavioral or environmental influences on sleep-wake disturbance and guide the development of personalized treatments. Here, we have elucidated factors underlying disturbed sleep-wake timing by applying a predictive mathematical model for the interaction of light and the circadian and homeostatic regulation of sleep to actigraphy, light, and melatonin profiles from 20 schizophrenia patients and 21 age-matched healthy unemployed controls, and designed interventions which restored sleep-circadian function. Compared to controls, those with schizophrenia slept longer, had more variable sleep timing, and received significantly fewer hours of bright light (light > 500 lux), which was associated with greater variance in sleep timing. Combining the model with the objective data revealed that non 24-h sleep could be best explained by reduced light exposure rather than differences in intrinsic circadian period. Modeling implied that late sleep offset and non 24-h sleep timing in schizophrenia can be normalized by changes in environmental light–dark profiles, without imposing major lifestyle changes. Aberrant timing and intensity of light exposure patterns are likely causal factors in sleep timing disturbances in schizophrenia. Implementing our new model-data framework in clinical practice could deliver personalized and acceptable light–dark interventions that normalize sleep-wake timing.

The neural architecture of sleep regulation – insights from Drosophila

Abstract The neural mechanisms that balance waking and sleep to ensure adequate sleep quality in mammals are highly complex, often eluding functional insight. In the last two decades, researchers made impressive progress in studying the less complex brain of the invertebrate model organism Drosophila melanogaster, which has led to a deeper understanding of the neural principles of sleep regulation. Here, we will review these findings to illustrate that neural networks require sleep to undergo synaptic reorganization that allows for the incorporation of experiences made during the waking hours. Sleep need, therefore, can arise as a consequence of sensory processing, often signalized by neural networks as they synchronize their electrical patterns to generate slow-wave activity. The slow-wave activity provides the neurophysiological basis to establish a sensory gate that suppresses sensory processing to provide a resting phase which promotes synaptic rescaling and clearance of metabolites from the brain. Moreover, we demonstrate how neural networks for homeostatic and circadian sleep regulation interact to consolidate sleep into a specific daily period. We particularly highlight that the basic functions and physiological principles of sleep are highly conserved throughout the phylogenetic spectrum, allowing us to identify the functional components and neural interactions that construct the neural architecture of sleep regulation.

Behaviorally and environmentally induced non-24-hour sleep-wake rhythm disorder in sighted patients.

To determine whether there was evidence of circadian or sleep-regulatory dysfunction in sighted individuals with non-24-hour sleep-wake rhythm disorder. Three sighted individuals with signs and/or symptoms of non-24-hour sleep-wake rhythm disorder were studied. Thirty-five- to 332-day laboratory and home-based assessments of sleep-wake and circadian timing, endogenous circadian period, photic input to the circadian pacemaker, and/or circadian and sleep-wake-dependent regulation of sleep were conducted. No evidence of circadian dysfunction was found in these individuals. Instead, sleep-wake timing appeared to dissociate from the circadian timing system, and/or self-selected sleep-wake and associated light/dark timing shifted the circadian pacemaker later, rather than the circadian pacemaker determining sleep-wake timing. These findings suggest that the etiology of this disorder may be light- and/or behaviorally induced in some sighted people, which has implications for the successful treatment of this disorder. Emens JS, St Hilaire MA, Klerman EB, etal. Behaviorally and environmentally induced non-24-hour sleep-wake rhythm disorder in sighted patients. J Clin Sleep Med. 2022;18(2):453-459.

Melanopsin Signaling Pathway in HEK293 Cell Line with Stable Expression of Human Melanopsin: Possible Participation of Phospholipase C beta 4 and Diacylglycerol.

Melanopsin, a member of the G protein-coupled receptors family, is involved in non-image-forming functions including circadian rhythm, sleep regulation and pupil response. In spite of significant research efforts, the signaling cascade involving melanopsin photoactivation remains poorly characterized. Here, we analyzed the effects of photoactivation of melanopsin on phospholipase C (PLC) and diacylglycerol. As an invitro model, HEK293 cells with stable expression of human melanopsin were used. Although both the PLCβ1 and PLCβ4 subtypes were activated by the cell exposure to blue light, only PLCβ4 appeared to play a significant role in the studied melanopsin signaling pathway. We have demonstrated, for the first time, that cells expressing human melanopsin and enriched with 11-cis-retinal exhibited significantly increased diacylglycerol level. To determine the role of phospholipase C and involvement of diacylglycerols, two approaches were employed: inhibition of the G protein and phospholipase C (using the BIM-46187 and U73122 inhibitors, respectively), and gene silencing using siRNA of PLCβ1 and PLCβ4 . While silencing the PLCβ4 gene and using U73122 inhibited the diacylglycerol and calcium ion responses, the FOS gene expression level was only partially reduced. These results may facilitate a better understanding of the role of phospholipase C and diacylglycerols in the melanopsin signaling pathway.

Retraction Statement: Morphological and functional diversity of intrinsically photosensitive retinal ganglion cells.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are a special type of ganglion cell that express the photopigment melanopsin and autonomously respond to light in the mammalian retina. Nearly two decades since their discovery, ipRGCs have been broadly investigated for their basic morphologic features, cell classification, physiologic properties, and functional significance. It is well established that ipRGCs are predominantly responsible for non-image-forming vision, such as circadian rhythm entrainment, pupillary contraction, mood, and sleep regulation. However, there are mounting morphological, physiological, and behavioral pieces of evidence supporting the idea that ipRGCs may contribute to image-forming vision such as color, contrast, and perception. These new compelling pieces of evidence extend our previous thought and provide extensive and profound insights into the melanopsin-mediated light response affecting visual functions. This article summarizes what we currently know about ipRGCs' subtypes, signal transduction, axonal projections, synaptic inputs, and functions with the emphasis on non-image-forming vision and image-forming vision.

Circadian Chimeric Mice Reveal an Interplay Between the Suprachiasmatic Nucleus and Local Brain Clocks in the Control of Sleep and Memory.

Sleep is regulated by circadian and homeostatic processes. Whereas the suprachiasmatic nucleus (SCN) is viewed as the principal mediator of circadian control, the contributions of sub-ordinate local circadian clocks distributed across the brain are unknown. To test whether the SCN and local brain clocks interact to regulate sleep, we used intersectional genetics to create temporally chimeric CK1ε Tau mice, in which dopamine 1a receptor (Drd1a)-expressing cells, a powerful pacemaking sub-population of the SCN, had a cell-autonomous circadian period of 24 h whereas the rest of the SCN and the brain had intrinsic periods of 20 h. We compared these mice with non-chimeric 24 h wild-types (WT) and 20 h CK1ε Tau mutants. The periods of the SCN ex vivo and the in vivo circadian behavior of chimeric mice were 24 h, as with WT, whereas other tissues in the chimeras had ex vivo periods of 20 h, as did all tissues from Tau mice. Nevertheless, the chimeric SCN imposed its 24 h period on the circadian patterning of sleep. When compared to 24 h WT and 20 h Tau mice, however, the sleep/wake cycle of chimeric mice under free-running conditions was disrupted, with more fragmented sleep and an increased number of short NREMS and REMS episodes. Even though the chimeras could entrain to 20 h light:dark cycles, the onset of activity and wakefulness was delayed, suggesting that SCN Drd1a-Cre cells regulate the sleep/wake transition. Chimeric mice also displayed a blunted homeostatic response to 6 h sleep deprivation (SD) with an impaired ability to recover lost sleep. Furthermore, sleep-dependent memory was compromised in chimeras, which performed significantly worse than 24 h WT and 20 h Tau mice. These results demonstrate a central role for the circadian clocks of SCN Drd1a cells in circadian sleep regulation, but they also indicate a role for extra-SCN clocks. In circumstances where the SCN and sub-ordinate local clocks are temporally mis-aligned, the SCN can maintain overall circadian control, but sleep consolidation and recovery from SD are compromised. The importance of temporal alignment between SCN and extra-SCN clocks for maintaining vigilance state, restorative sleep and memory may have relevance to circadian misalignment in humans, with environmental (e.g., shift work) causes.

Corrigendum to: Circadian regulation of sleep in a pre-clinical model of Dravet syndrome: dynamics of sleep stage and siesta re-entrainment.

Corrigendum to: Circadian regulation of sleep in a pre-clinical model of Dravet syndrome: dynamics of sleep stage and siesta re-entrainment.

The Association Between School Start Time and Sleep Duration, Sustained Attention, and Academic Performance.

PurposeIn adolescence, physiological (circadian and homeostatic regulation of sleep) and social habits contribute to delayed sleep onset, while social obligations impose early sleep offset. The effects of delayed school start time on the subjective/objective measures of sleep–wake patterns and academic achievement have not been established.MethodsThis pre-, post-, and longitudinal non-randomized study included an early (8:00 am; ESC=30 students) and the late (9:00 am; LSC=21 students) start class. Multiple sleep data included a weekly sleep diary, Karolinska Sleepiness Scale, Pittsburgh Sleep Quality Index, and Epworth Sleepiness Scale. Sustained attention was measured using the Psychomotor Vigilance Task. Academic performance was evaluated by two different mathematical and scientific standard tests (entrance and final) and by school attendance indicators. Data were collected at monthly intervals from October 2018 to May 2019 and the beginning and end of the academic year (pre/post).ResultsAll students turned their lights off at similar times (LSC=11:21pm, ESC=11:11pm), but LSC students woke up later (7:23am) than ESC students (6:55am; F1,48=11.81, p=0.001) on school days. The groups did not differ in total sleep duration on non-school days. Longitudinal measures revealed a significant increase (8.9%, 34 min) in total sleep duration of LSC students across the academic year. ESC students maintained approximately the same sleep duration. Furthermore, changes in sleep duration had parallelled significant differences in sustained attention, with LSC students outperforming ESC students. Longitudinal changes of sleep and sustained attention were associated with a coherent pattern of changes in academic performance.ConclusionFindings indicate that a one-hour delay in school start time is associated with longer sleep, better diurnal sustained attention, attendance, and improved academic performance. Notably, sleep changes were limited to school days. A delay in school start time should be seriously considered to improve sleep and academic achievements of students.