OBJECTIVES: To inform the debate over whether human sleep can be chronically reduced without consequences, we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiological functions were monitored and compared to those for total sleep deprivation. DESIGN: The chronic sleep restriction experiment involved randomization to one of three sleep doses (4 h, 6 h, or 8 h time in bed per night), which were maintained for 14 consecutive days. The total sleep deprivation experiment involved 3 nights without sleep (0 h time in bed). Each study also involved 3 baseline (pre-deprivation) days and 3 recovery days. SETTING: Both experiments were conducted under standardized laboratory conditions with continuous behavioral, physiological and medical monitoring. PARTICIPANTS: A total of n = 48 healthy adults (ages 21-38) participated in the experiments. INTERVENTIONS: Noctumal sleep periods were restricted to 8 h, 6 h or 4 h per day for 14 days, or to 0 h for 3 days. All other sleep was prohibited. RESULTS: Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days resulted in significant cumulative, dose-dependent deficits in cognitive performance on all tasks. Subjective sleepiness ratings showed an acute response to sleep restriction but only small further increases on subsequent days, and did not significantly differentiate the 6 h and 4 h conditions. Polysomnographic variables and delta power in the non-REM sleep EEG-a putative marker of sleep homeostasis--displayed an acute response to sleep restriction with negligible further changes across the 14 restricted nights. Comparison of chronic sleep restriction to total sleep deprivation showed that the latter resulted in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost. A statistical model revealed that, regardless of the mode of sleep deprivation, lapses in behavioral alertness were near-linearly related to the cumulative duration of wakefulness in excess of 15.84 h (s.e. 0.73 h). CONCLUSIONS: Since chronic restriction of sleep to 6 h or less per night produced cognitive performance deficits equivalent to up to 2 nights of total sleep deprivation, it appears that even relatively moderate sleep restriction can seriously impair waking neurobehavioral functions in healthy adults. Sleepiness ratings suggest that subjects were largely unaware of these increasing cognitive deficits, which may explain why the impact of chronic sleep restriction on waking cognitive functions is often assumed to be benign. Physiological sleep responses to chronic restriction did not mirror waking neurobehavioral responses, but cumulative wakefulness in excess of a 15.84 h predicted performance lapses across all four experimental conditions. This suggests that sleep debt is perhaps best understood as resulting in additional wakefulness that has a neurobiological "cost" which accumulates over time.

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The Cumulative Cost of Additional Wakefulness: Dose-Response Effects on Neurobehavioral Functions and Sleep Physiology From Chronic Sleep Restriction and Total Sleep Deprivation

To determine whether a cumulative sleep debt (in a range commonly experienced) would result in cumulative changes in measures of waking neurobehavioral alertness, 16 healthy young adults had their sleep restricted 33% below habitual sleep duration, to an average 4.98 hours per night [standard deviation (SD) = 0.57] for seven consecutive nights. Subjects slept in the laboratory, and sleep and waking were monitored by staff and actigraphy. Three times each day (1000, 1600, and 2200 hours) subjects were assessed for subjective sleepiness (SSS) and mood (POMS) and were evaluated on a brief performance battery that included psychomotor vigilance (PVT), probed memory (PRM), and serial-addition testing, Once each day they completed a series of visual analog scales (VAS) and reported sleepiness and somatic and cognitive/emotional problems. Sleep restriction resulted in statistically robust cumulative effects on waking functions. SSS ratings, subscale scores for fatigue, confusion, tension, and total mood disturbance from the POMS and VAS ratings of mental exhaustion and stress were evaluated across days of restricted sleep (p = 0.009 to p = 0.0001). PVT performance parameters, including the frequency and duration of lapses, were also significantly increased by restriction (p = 0.018 to p = 0.0001). Significant time-of-day effects were evident in SSS and PVT data, but time-of-day did not interact with the effects of sleep restriction across days. The temporal profiles of cumulative changes in neurobehavioral measures of alertness as a function of sleep restriction were generally consistent. Subjective changes tended to precede performance changes by 1 day, but overall changes in both classes of measure were greatest during the first 2 days (P1, P2) and last 2 days (P6, P7) of sleep restriction. Data from subsets of subjects also showed: 1) that significant decreases in the MSLT occurred during sleep restriction, 2) that the elevated sleepiness and performance deficits continued beyond day 7 of restriction, and 3) that recovery from these deficits appeared to require two full nights of sleep. The cumulative increase in performance lapses across days of sleep restriction correlated closely with MSLT results (r = -0.95) from an earlier comparable experiment by Carskadon and Dement (1). These findings suggest that cumulative nocturnal sleep debt had a dynamic and escalating analog in cumulative daytime sleepiness and that asymptotic or steady-state sleepiness was not achieved in response to sleep restriction.

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Cumulative sleepiness, mood disturbance, and psychomotor vigilance performance decrements during a week of sleep restricted to 4-5 hours per night

According to the two-process model of sleep regulation, the timing and structure of sleep are determined by the interaction of a homeostatic and a circadian process. The original qualitative model was elaborated to quantitative versions that included the ultradian dynamics of sleep in relation to the non-REM-REM sleep cycle. The time course of EEG slow-wave activity, the major marker of non-REM sleep homeostasis, as well as daytime alertness were simulated successfully for a considerable number of experimental protocols. They include sleep after partial sleep deprivation and daytime napping, sleep in habitual short and long sleepers, and alertness in a forced desynchrony protocol or during an extended photoperiod. Simulations revealed that internal desynchronization can be obtained for different shapes of the thresholds. New developments include the analysis of the waking EEG to delineate homeostatic and circadian processes, studies of REM sleep homeostasis, and recent evidence for local, use-dependent sleep processes. Moreover, nonlinear interactions between homeostatic and circadian processes were identified. In the past two decades, models have contributed considerably to conceptualizing and analyzing the major processes underlying sleep regulation, and they are likely to play an important role in future advances in the field.

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Sleep homeostasis and models of sleep regulation

A model for the timing of human sleep is presented. It is based on a sleep-regulating variable (S)--possibly, but not necessarily, associated with a neurochemical substance--which increases during wakefulness and decreases during sleep. Sleep onset is triggered when S approaches an upper threshold (H); awakening occurs when S reaches a lower threshold (L). The thresholds show a circadian rhythm controlled by a single circadian pacemaker. Time constants of the S process were derived from rates of change of electroencephalographic (EEG) power density during regular sleep and during recovery from sleep deprivation. The waveform of the circadian threshold fluctuations was derived from spontaneous wake-up times after partial sleep deprivation. The model allows computer simulations of the main phenomena of human sleep timing, such as 1) internal desynchronization in the absence of time cues, 2) sleep fragmentation during continuous bed rest, and 3) circadian phase dependence of sleep duration during isolation from time cues, recovery from sleep deprivation, and shift work. The model shows that the experimental data are consistent with the concept of a single circadian pacemaker in humans. It has implications for the understanding of sleep as a restorative process and its timing with respect to day and night.

Timing of human sleep: recovery process gated by a circadian pacemaker

The role of the endogenous circadian pacemaker in the timing of the sleep-wake cycle and the regulation of the internal structure of sleep, including REM sleep, EEG slow-wave (0.75-4.5 Hz) and sleep spindle activity (12.75-15.0 Hz) was investigated. Eight men lived in an environment free of time cues for 33-36 d and were scheduled to a 28 hr rest-activity cycle so that sleep episodes (9.33 hr each) occurred at all phases of the endogenous circadian cycle and variations in wakefulness preceding sleep were minimized. The crest of the robust circadian rhythm of REM sleep, which was observed throughout the sleep episode, was positioned shortly after the minimum of the core body temperature rhythm. Furthermore, a sleep-dependent increase of REM sleep was present, which, interacting with the circadian modulation, resulted in highest values of REM sleep when the end of scheduled sleep episodes coincided with habitual wake-time. Slow-wave activity decreased and sleep spindle activity increased in the course of all sleep episodes. Slow-wave activity in non-REM sleep exhibited a low amplitude circadian modulation which did not parallel the circadian rhythm of sleep propensity. Sleep spindle activity showed a marked endogenous circadian rhythm; its crest coincident with the beginning of the habitual sleep episode. Analyses of the (nonadditive) interaction of the circadian and sleep-dependent components of sleep propensity and sleep structure revealed that the phase relation between the sleep-wake cycle and the circadian pacemaker during entrainment promotes the consolidation of sleep and wakefulness and facilitates the transitions between these vigilance states.

https://www.jneurosci.org/content/jneuro/15/5/3526.full.pdf

Contribution of the circadian pacemaker and the sleep homeostat to sleep propensity, sleep structure, electroencephalographic slow waves, and sleep spindle activity in humans

Eight subjects were kept awake and active overnight in a sleep lab isolated from environmental time cues. Ambulatory EEG and EOG were continuously recorded and sleepiness ratings carried out every two hours as was a short EEG test session with eyes open for 5 min and closed for 2 min. The EEG was subjected to spectral analysis and the EOG was visually scored for slow rolling eye movements (SEM). Intrusions of SEM and of alpha and theta power density during waking, open-eyed activity strongly differentiated between high and low subjective sleepiness (the differentiation was poorer for closed eyes) and the mean intraindividual correlations between subjective and objective sleepiness were very high. Still, the covariation was curvilinear; physiological indices of sleepiness did not occur reliably until subjective perceptions fell between "sleepy" and "extremely sleepy-fighting sleep"; i.e. physiological changes due to sleepiness are not likely to occur until extreme sleepiness is encountered. The results support the notion that ambulatory EEG/EOG changes may be used to quantify sleepiness.

Subjective and Objective Sleepiness in the Active Individual

The present study validated the nine-point Karolinska Sleepiness Scale (KSS) and the new Accumulated Time with Sleepiness (ATS) scale against performance of laboratory tasks. The ATS scale was designed as a method for integrating subjective sleepiness over longer time periods. The subjects were asked if certain symptoms of sleepiness had occurred and, if so, for how long. Six subjects participated twice. Each time they were kept awake during the night (except for a short nap occurring during one of the nights in a counterbalanced order) and were tested at 2200, 0200, 0400 and 0600 hours. The tests included a 10-minute rest period, a 28-minute visual vigilance task and an 11-minute single reaction time task. KSS and visual analogue scale (VAS) ratings were given before each test, and ATS ratings were given after. Performance deteriorated clearly, and all three rating scales reflected increased sleepiness with time of night. Scores on the KSS and VAS showed high correlations with performance tasks (mean intraindividual correlations were between 0.49 and 0.71). Performance correlated even higher with the ATS ratings (r = 0.73-0.79). Intercorrelations between rating scales were also high (r = 0.65-0.86). It was concluded that there were strong relations between ratings of sleepiness and performance, that the ATS rating scale was at least as good as the other scales and that the ratings were affected by type of task.

Relations between performance and subjective ratings of sleepiness during a night awake

Work load and work hours in relation to disturbed sleep and fatigue in a large representative sample.

Very little is known about the association between sleep and (fatal) occupational accidents. This study investigated this relationship using register data of self-rated sleep difficulties, together with occupational and demographic characteristics. The variables were related to subsequent occupational fatal accidents. A national sample of 47 860 individuals was selected at regular intervals over a period of 20 years, and interviewed over the phone on issues related to work and health. The responses were linked to the cause of death register (suicides excluded) and the data set was subjected to a (multivariate) Cox regression survival analysis. One hundred and sixty six fatal occupational accidents occurred, and the significant predictors were: male vs. female: relative risk (RR)=2.30 with a 95% confidence interval (CI) of 1.56–3.38; difficulties in sleeping (past 2 weeks): RR=1.89 with CI=1.22–2.94; and non-day work: RR=1.63 with CI=1.09–2.45. No significant effect was seen for age, socio-economic group, hectic work, overtime (>50 h per week), or physically strenuous work. It was concluded that self-reported disturbed sleep is a predictor of accidental death at work, in addition to non-day work and male gender.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2869.2002.00287.x

A prospective study of fatal occupational accidents -- relationship to sleeping difficulties and occupational factors.

In a group of 6 male subjects sleep was displaced to seven different times of day (one displacement condition per week). The subjects were isolated from external time cues (daylight, clocks, noise) and sleep was allowed to terminate spontaneously. The results showed a pronounced time-of-day variation of total sleep time, stage 2, and rapid eye movement (REM) sleep. Maxima occurred after bedtimes at 1900 hr and 2300 hr, while the minima occurred after bedtimes at 0700 hr and 1100 hr. The latter also was the time of maximum propensity to wake up. Slow wave sleep showed a rapid decrease from high initial levels, irrespective of time of day. Ratings of sleepiness showed a highly significant circadian variation peaking between 0500 hr and 0700 hr. The lowest level of sleepiness coincided with the maximum tendency to wake up, and it was suggested that sleep termination may be closely related to the sleepiness/alertness rhythm.

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Mats Gillberg

Papers

Subjective and Objective Sleepiness in the Active Individual

Relations between performance and subjective ratings of sleepiness during a night awake

Work load and work hours in relation to disturbed sleep and fatigue in a large representative sample.

A prospective study of fatal occupational accidents -- relationship to sleeping difficulties and occupational factors.

The circadian variation of experimentally displaced sleep.