Sleep homeostasis

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Irene Tobler and Peter Achermann (2007), Scholarpedia, 2(10):2432. doi:10.4249/scholarpedia.2432 revision #89081 [link to/cite this article]
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Curator: Peter Achermann

Sleep homeostasis denotes a basic principle of sleep regulation. A sleep deficit elicits a compensatory increase in the intensity and duration of sleep, while excessive sleep reduces sleep propensity. Slow waves in the electroencephalogram (EEG), a correlate of sleep intensity, serve as an indicator of sleep homeostasis in nonREM sleep, also referred to as slow-wave sleep in animals.



Homeostasis refers to regulatory mechanisms that maintain the constancy of the physiology of organisms.

The term was applied to sleep by AA Borbély: Sleep has a regulatory system enabling organisms to compensate for the loss of sleep (e.g. due to sleep deprivation) or surplus sleep (e.g by prolonging sleep in the morning or by napping).

The daily monophasic or biphasic sleep-wake cycle, typical for humans, and the polyphasic sleep-wake cycles in animals are regulated by

  • a homeostatic mechanism
  • the circadian system
  • and their interaction

The two main regulated variables are

  • sleep intensity and
  • to a lesser extent, sleep duration (or the amount of sleep)

The homeostatic mechanism regulates sleep intensity, while the circadian clock regulates the timing of sleep.

The intensity component of sleep is slow-wave activity (its level correlates positively with the threshold to arouse subjects or animals). Slow-wave activity is defined as spectral power of the electroencephalogram (EEG) in the frequency range of approximately 0.5 – 4.0 or 4.5 Hz.

Brief history of the concept

The general concept of homeostasis dates back to two pioneers:

  • Claude Bernard (1813-1978) a professor of Physiology at the College of France and the Sorbonne in Paris, and
  • Walter Cannon (1871-1945) (Cannon, 1939), Professor at Harvard University.

Both men engaged in physiology, Bernard defining a milieu interieur and Cannon, coining the term homeostasis.

Alexander Borbély, a Swiss pharmacologist and sleep researcher who began his research by studying sleep regulation in laboratory rats under diverse controlled conditions (Borbély & Neuhaus, 1979) applied the concept of homeostasis to sleep regulation.

Sleep homeostasis: regulated balance between sleep and waking. Homeostatic mechanisms counteract deviations from an average reference level of sleep (Borbély, 1980) .

Based on animal studies, Borbély postulated that a sleep-wake dependent and a circadian process underlie sleep regulation (Borbély 1980). This concept was extended to human sleep (Borbély 1982) and further elaborated by Serge Daan, Domien Beersma from the University of Groningen (The Netherlands) and Alexander Borbély, to a quantitative model (Daan et al, 1984). The two-process model of sleep regulation inspired many researches to test its tenets as well as its applicability to human sleep disorders:

A Process S, the homeostatic process, increases as an exponential saturating function during waking and decreases as an exponential function during sleep. Slow-wave activity in nonREM sleep (sleep is subdivided into rapid-eye movement sleep, REM sleep and nonREM sleep) is the marker for the decrease of Process S.

That slow-wave sleep is dependent on the length of time awake and length of time asleep has been reported previously (Webb & Agnew, 1971). The hypothesis that NREM sleep reverses neuronal effects of waking was proposed in 1974 (Feinberg, 1974).

Figure 1: Simulations of the homeostatic Process S increasing in a saturating exponential fashion during waking and declining exponentially during sleep. Blue: baseline with an 8-h sleep episodes; red: sleep deprivation and recovery sleep after 40 hours of wakefulness; pink: 2-h nap at 18:00 h and subsequent nighttime sleep. Bars on top delineate sleep episodes.

Seminal experimental data demonstrating the existence of sleep homeostasis

Early experiments had shown that sleep deprivation has major effects on the homeostatic regulation of sleep, but has only minor effects or no effect on the circadian pacemaker. Sleep deprivation invariably leads to an increase in slow-wave activity during recovery sleep. The potential confound that the sleep deprivation induced activation can be stressful, and therefore unspecific factors not directly related to the loss of sleep could be responsible for the increase of slow-waves during recovery sleep, was excluded in many studies:

For example, early experiments in two different rat strains (Alan Rechtschaffen, Chicago and Alexander Borbély, Zurich in 1979) showed that doubling the rotation rate of a slowly turning cylinder used to sleep deprive the animals had no additional effect on recovery, and that rats which had no circadian organization of their sleep-wake cycle still showed a compensatory increase of slow waves during recovery from the sleep deprivation (Tobler, Gross & Borbély, 1983).

The evolutionary advantage of developing an intensity dimension of sleep, provided sleep with a relative independence from the circadian system allowing organisms a more flexible adaptation to changes in sleep, than the strictly controlled timing of sleep within the time constraints set by the circadian pacemaker.

Elegant experiments in human subjects

1. Healthy young men slept at different times of day while their sleep was being recorded. A higher level of EEG slow-waves occurred the later in the day they took their nap or in other words, the longer they had been awake since ending last night’s sleep (Dijk, Beersma, Daan, 1987).

2. Similarly, persons taking a 2-h nap in the evening, simulating what often occurs during a normal day when people fall asleep when relaxing after coming home from work, had a lower level of slow-waves during the subsequent night's sleep (Werth et al, 1996). This finding is in accordance with an earlier report (Feinberg et al. 1985).

These studies demonstrated a predictable increase of sleep pressure as a function of the duration of the previous waking interval. In the two process model the increase occurs according to a saturating exponential function. Campbell et al. (2006) reported a linear increase.

The polyphasic sleep-wake cycle of animals is an ideal feature of animal sleep to examine whether keeping animals awake, in this case many different mouse strains, hamsters, rats, squirrels and even cats, for a varying amount of hours, leads to a predictable change in sleep intensity (reviewed in Tobler, 2005). It did, and the results obtained in the different species were consistent: Slow-wave activity increases as a function of the duration of prior wakefulness. Moreover, the same relationship between the increase in slow-wave activity in nonREM sleep was observed in several species after spontaneous bouts of wakefulness, rather than after experimental intervention.

Later studies extended the variables reflecting sleep homeostasis

  • Very short awakenings from sleep (brief awakenings), typical for most animals, decrease when sleep intensity is high (Franken et al, 1991).
  • Sleep fragmentation decreases in humans as sleep intensity increases.

Elaboration and applications of the two-process model

The original model was able to account for such diverse phenomena as:

  • recovery from sleep deprivation
  • circadian phase dependence of sleep duration
  • sleep during shift work
  • sleep fragmentation during continuous bed rest, and
  • internal desynchronization in the absence of time cues.

The two-process model triggered numerous experimental studies to test its predictions and was used to predict the response of habitual short and long sleepers to sleep deprivation.

Elaborated model

In a later version of the model it is the change of Process S, and not its level, which is proportional to the momentary amount of SWA. The elaborated model addressed not only the global changes of SWA as represented by Process S, but also the changes within nonREM sleep episodes (Achermann et al., 1993).

Figure 2: Time course of simulated slow-wave activity (SWA) and Process S based on the elaborated model. The black horizontal bars and the interrupted vertical lines delineate the REM sleep episodes. Note, that the decline of Process S is no longer exponential.

This elaborated model successfully predicted the magnitude of the intra-night rebound after selective SWS deprivation (nonREM sleep stages 3 and 4 in humans) in the first 3 h of sleep. Also the occurrence of late SWA peaks during extended sleep could be simulated. The simulations demonstrated that the elaborated model accounts in quantitative terms for empirical data and predicts the changes induced by the prolongation of waking or sleep.

This model was also used to simulate the dynamics of SWA in an experimental protocol with an

  • early evening nap and
  • the effect of changes in REM sleep latency on the time course of slow-wave activity.

Finally, not only the timing of sleep but also the changes in daytime vigilance are governed by the interaction of Process S and C. The rising homeostatic sleep pressure during waking seems to be compensated by the declining circadian sleep propensity. Conversely, during sleep the rising circadian sleep propensity may serve to counteract the declining homeostatic sleep pressure, thereby ensuring the maintenance of sleep.


Sleep in depressed patients shows frequently the following changes: prolonged sleep latency, a shallow fragmented sleep process and precocious awakening in the morning. Slow wave sleep is typically reduced (Steiger & Kimura 2010; Germain & Kupfer 2008). Sleep deprivation for one night exerts an immediate antidepressant effect that is short lived. It was hypothesized that sleep regulation (Process S) is deficient in depression (Borbély & Wirz-Justice, 1982). The antidepressant effect of sleep deprivation was attributed to the increased level of Process S attained by prolonging wakefulness.


Sleep homeostasis in narcoleptic patients is functional. However, the decline of Process S appears to be steeper in patients recorded under baseline conditions (Khatami et al., 2007). This may be related to the increased number and longer duration of short wake episodes in the second and third sleep cycle. Thus, the decline of S is not exponential and may be better approximated by the elaborated model. However, during recovery from sleep deprivation, the decline of S no longer differs between the patients and healthy control subjects (Khatami et al., 2008). Slow-wave activity does not reflect the level of process S during baseline conditions, but only does so under the enhanced sleep pressure.


The increase of homeostatic sleep pressure during wakefulness is faster in prepubertal or early pubertal children compared with mature adolescents, while the decrease of Process S is similar in both developmental groups (Jenni et al., 2005). These age-related differences indicate that the brain reaches its capacity to generate slow waves with less time awake in the young than in the mature brain.

Species similarities/differences

Animals ranging from mammals to birds and even to invertebrates show compensatory mechanisms after sleep loss (Tobler, 2005). The first such demonstration was in cockroaches and later in scorpions (Campbell and Tobler, 1984; Tobler, 2005). However, the strict relationship between the amount of sleep lost and the degree of compensation has been demonstrated for a few mammals, such as rats, mice, hamsters, squirrels and humans and the fruit fly.

Especially the discovery that also insects do compensate for the loss of sleep, inspired research on sleep regulation in thousands of mutants of the fruit fly Drosophila, where the genetic mechanisms of the compensatory process can be investigated (cross reference).

Neuronal mechanisms underlying sleep homeostasis

Sleep deprivation causes behavioral, physiological and molecular changes. Despite considerable knowledge about the neuronal mechanisms enabling the transition from wakefulness to sleep (cross reference), and the synchronization of EEG waves in the cortex, the mechanisms leading to the intensity increase are still not fully understood.

A common belief is the existence of a sleep factor (or perhaps several sleep factors) accumulating during waking and dissipating during sleep. Many neurotransmitters and neuropeptides must be involved in sleep regulation, but one such substance, adenosine, a neurotransmitter, is more and more at the center of attention. Manipulating the adenosine system leads to changes in sleep (reviewed in Basheer et al, 2004). Especially an adenosine antagonist, caffeine, is the world-wide most popular wakefulness inducing and maintaining substance. Caffeine reduces slow-wave activity in the subsequent sleep episode and caffeine consumption during prolonged wakefulness counteracts the typical effects of sleep deprivation on the waking and sleep EEG (Landolt et al, 2004).

Open questions and perspectives

It is still unresolved whether REM sleep has a homeostatic regulatory component of its own. REM sleep loss does lead to an increase in the tendency to enter REM sleep, and its loss is compensated up to a certain extent only, with some species differences. However, in contrast to nonREM sleep which has an intensity dimension,

there is no evidence for an intensity dimension of REM sleep.

Recent experiments used exquisite, selective manipulations activating specific brain regions during sleep. In rats and mice, cutting whiskers on one side of the snout and encouraging spontaneous stimulation of the remaining whiskers by placing the animals in an enriched environment, led to a selective increase of slow waves over the stimulated brain region during sleep (Vyazovskiy et al, 2004). Similarly, rats which preferentially use the right or left paw for grabbing food in a food retrieval task, showed a larger increase of slow waves during sleep in the EEG contralateral to the paw preference, supporting the use-dependent notion of slow-wave activity changes (Vyazovskiy et al, 2008).

An early study in humans showed a similar selective increase in slow-waves over the “stimulated hemisphere” during sleep, after one hand had been vibrated previously for several hours (Kattler et al, 1994).

Recordings making use of EEG topography, placing 256 electrodes on the heads of subjects and subjecting them to a motor learning task before sleep, led to a selective increase of slow-waves over the particular brain region where neurons had been stimulated during the learning task (Huber et al., 2004). Furthermore, immobilization of the arm led to a decrease of slow-wave activity in the corresponding motor areas (Huber et al., 2006). The studies in the rat were developed further, showing a causal role for the brain derived nerve growth factor (BDNF) in the homeostatic regulation of sleep (Fargauna et al., 2008).

These studies pursue the hypothesis that sleep may be rescaling neuronal connections and synapses according to their previous use (Tononi and Cirelli, 2006).


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Internal references

See Also

Narcolepsy, REM Sleep, Sleep, Sleep Deprivation

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