Elsevier

Sleep Medicine Reviews

Volume 11, Issue 6, December 2007, Pages 439-451
Sleep Medicine Reviews

Physiological review
The thermophysiological cascade leading to sleep initiation in relation to phase of entrainment

https://doi.org/10.1016/j.smrv.2007.07.001Get rights and content

Summary

This article reviews circadian thermoregulation in relation to sleep induction and phase of entrainment in the light of the comprehensive thermophysiological and chronobiological concepts of Jürgen Aschoff. The idea that temperature and sleep are interrelated is based on evolutionary history. Mammalian sleep developed in association with endothermy, and all species, independent of temporal niche, usually sleep during the circadian trough of their core body temperature (CBT) rhythm. The circadian pattern of CBT results from the balance between heat production and heat loss, the latter being relevant for sleep induction. Sleep under entrained conditions is typically initiated on the declining portion of the CBT curve when its rate of change and body heat loss is maximal. Body heat loss before lights off, via selective vasodilatation of distal skin regions, promotes sleepiness and the rapid onset of sleep. This thermophysiological effect represents the cement between the circadian clock and the sleep–wake cycle, and in turn determines phase of entrainment (Ψ) and sleep onset latency (SOL). These interrelationships have been recently studied in a particular subset of the general population, mainly women, who suffer from cold hands and feet (the so-called vasospastic syndrome, VS). Women with VS exhibit not only a lower capacity to lose heat during the daytime but also a prolonged SOL, a disturbed Ψ of the circadian clock with respect to the sleep–wake cycle and psychologically, a disposition to turn experienced anger inwards. This naturalistic model leads us to a more general conclusion that regulation of distal skin blood flow may have clinical relevance for insomnia, in particular sleep onset insomnia.

Introduction

The notion that thermoregulation and sleep are interrelated is based on the theory of evolution. There was a convergent evolution for REM sleep and endothermy in mammals and birds, indicating that these parallel developments must have occurred prior to separation of the emerging mammalian and avian lines.1, 2, 3, 4 Based on these observations, some researchers have even deduced causal relationships between induction of sleep (and Slow-Wave-Activity, SWA) and the reduction of core body temperature (CBT).5, 6, 7, 8 The reduction of CBT, which results in energy conservation due to reduced body metabolism, should be the reason why we sleep. However, there is no causality, at least not in humans. We could recently demonstrate that non-REM-sleep and SWA do not influence the thermoregulatory system.9, 10, 11 Nevertheless, this does not mean that the sleep regulatory system and the thermoregulatory system are independent. A further, rather simple, but not meaningless relationship exists, in that all species, independent of whether nocturnal or diurnal in habit, usually sleep or rest during the circadian trough of their CBT rhythm. This observation offers another, inverse explanation, namely, that we rest and sleep when CBT is reduced after heat has been redistributed from the core to the outer layer of the body, the shell. Therefore, heat redistribution from the core to the shell could represent a crucial signal for sleep initiation. Because these thermoregulatory processes are well known to be modulated in a circadian manner, they could additionally serve as an entrainment mechanism for the sleep–wake cycle. Recent findings suggest that the CBT rhythm has internal non-photic zeitgeber properties for the entrainment of multiple peripheral pacemakers distributed all over the body.12(p. 404),13 Based on this, one could consider that increased distal skin temperature in the evening, via enforced skin blood flow, provides a synchronising signal for peripheral circadian oscillators in the extremities. Thermoregulatory heat loss mechanisms could therefore be relevant for ensuring an appropriate phase relationship between the circadian system and the sleep–wake cycle. An important underlying assumption is that phase of entrainment largely determines normal, undisturbed sleep with the criteria of consolidation (sleep continuity) and short sleep onset latency (SOL).14, 15, 16 An abnormal phase of entrainment could thus be a cause of sleep disturbances.14, 15, 16

Sleep is not an isolated phenomenon of the brain alone; sleep is also a behaviour involving the entire body.17, 18 A body that is asleep is in the most relaxed state of normal daily life, and this relaxed state in turn influences the thermoregulatory system, i.e., heat is redistributed from the core to the shell and down-regulates CBT to a lower level.10, 19 Usually this occurs in the evening, when we usually go to sleep, leading to a larger difference between the diurnal maximum and nocturnal minimum values of CBT than without sleep.10, 19, 20, 21, 22, 23, 24 From a functional point of view, it is possible that such an increase of the overt daily amplitude could contribute to entrain a circadian oscillator.25, 26, 27

Organisms are active during the day (diurnal), night (nocturnal) or during twilight (crepuscular). Crepuscular animals, birds and insects can be matinal or vespertine, that is active in the morning or evening, respectively. There are two ways in which this can be manifested. First, by the well-known mechanisms of synchronising the endogenous pacemaker (e.g., light acting on the suprachiasmatic nuclei, SCN), which in turn entrains the rest–activity cycle, and second, by a route that does not directly involve the main pacemaker (so-called masking; e.g., activity, food intake).27, 28 The ‘masking effect’ was first described in experiments with animals.29 Masking complements clock control as a way of helping organisms specialise in a temporal niche.26 Masking in the first place obscures the behaviour of the pacemaker but may eventually influence the phase of the pacemaker via more indirect pathways (feedback mechanisms, e.g., via temperature).13, 27, 28

Section snippets

Regulation of circadian phase and phase of entrainment

The temporal structure of our daily life is under the control of three different clocks: the solar clock, providing light and heat during the day; the social clock, which determines our working and free day schedule16; and the biological (circadian) clock, which is essential for timing of physiological processes across the 24 h, such as activity and sleep, release of hormones and blood constituents, etc.30, 31 The central circadian clock is localised in the SCN of the hypothalamus; recently

Phase of entrainment in relation to sleep disturbances

In the entrained human circadian system under normal daily life situations, CBT exhibits a maximum in the late afternoon, and a minimum towards the end of the sleep episode. This phase relationship between the sleep–wake cycle and the CBT rhythm (phase of entrainment, Ψ) can be changed by means of zeitgebers, e.g., light. In general, Ψ is dependent on how much and in what direction the endogenous τ deviates from the 24-h solar cycle, that is, how much the daily light signal has to advance or

Homeostatic regulation of CBT

In order to understand circadian regulation of the CBT rhythm, it is important to elucidate first how CBT is homeostatically regulated. There is substantial evidence indicating that homeostatic regulation of CBT is controlled by a hierarchically organised set of neuronal mechanisms, with the pre-optic-anterior-hypothalamus (POAH) as the most important control centre.53, 54 In addition to homeostatic regulation, a rostral projection from the circadian pacemaker localised in the SCN to the

Circadian regulation of CBT

All the thermoregulatory mechanisms described above are also involved in the circadian regulation of CBT. The circadian CBT rhythm is a well-described thermophysiological phenomenon in many animals, as well as humans. The first publication of a daily record of CBT in humans already appeared in the middle of the 19th century by Gierse in the form of a thesis.77 He could show that his own oral temperature revealed a maximum temperature in the early evening and a minimum in the early morning hours

Relationship between thermoregulation and sleepiness/sleep regulation

We have shown that SOL is dependent on DPG level ca. 90 min before lights off. We usually choose our sleep times (lights off) when DPG levels are ca. −1 °C or higher (Figure 6). High DPG has been established as a good predictor for short SOL.10, 19, 86

Many appetitive behaviours preceding sleep are known to promote sleep, and they also influence the thermoregulatory system, such as lying down,87, 88, 89 relaxation, searching for a comfortable thermic environment (using bed socks, bedcovers, etc.;

Acknowledgements

I am grateful to Anna Wirz-Justice for her helpful comments to the manuscript and her excellent continuing support. Our work is supported by the Swiss National Science Foundation (#3100A0-102182/1 & #3130-3054991.98/3100-055385.98), the Schwickert-Stiftung, the 6th European Framework Programme EUCLOCK (018741) and the Daimler-Benz-Stiftung project CLOCKWORK.

References (104)

  • J. Aschoff

    Circadian control of body temperature

    J Therm Biol

    (1983)
  • E. Briese

    Normal body temperature of rats: the setpoint controversy

    Neurosci Biobehav Rev

    (1998)
  • D. Ricquier

    Fundamental mechanisms of thermogenesis

    C R Biol

    (2006)
  • J. Aschoff et al.

    Day night variation in heat balance

  • K. Kräuchi et al.

    Circadian clues to sleep onset mechanisms

    Neuropsychopharmacology

    (2001)
  • C. Van den Heuvel et al.

    Melatonin as a hypnotic: Con

    Sleep Med Rev

    (2005)
  • G.C. Grigg et al.

    The evolution of endothermy and its diversity in mammals and birds

    Physiol Biochem Zool

    (2004)
  • H. Zepelin

    Mammalian sleep

  • D.E. Sewitch

    Slow wave sleep deficiancy insomnia: a problem in thermo-downregulation at sleep onset

    Psychophysiology

    (1987)
  • K. Kräuchi et al.

    Thermoregulatory changes begin after lights off and not after onset of sleep stage 2

    Sleep

    (2001)
  • K. Kräuchi et al.

    Functional link between distal vasodilation and sleep-onset latency?

    Am J Physiol

    (2000)
  • K. Kräuchi et al.

    Challenging the sleep homeostat does not influence the thermoregulatory system in men: evidence from a nap vs. sleep-deprivation study

    Am J Physiol

    (2006)
  • R. Refinetti

    Circadian physiology

    (2006)
  • E.B. Klerman

    Clinical aspects of human circadian rhythms

    J Biol Rhythms

    (2005)
  • T. Roenneberg et al.

    The art of entrainment

    J Biol Rhythms

    (2003)
  • T. Roenneberg et al.

    Life between clocks: daily temporal patterns of human chronotypes

    J Biol Rhythms

    (2003)
  • E.J.W. Van Someren

    More than a marker: interaction between circadian regulation of temperature and sleep, age-related changes, and treatment possibilities

    Chronobiol Int

    (2000)
  • K. Kräuchi et al.

    Warm feet promote the rapid onset of sleep

    Nature

    (1999)
  • C.C. Brown

    Toe temperature change: a measure of sleep onset?

    Wak Sleep

    (1979)
  • S.S. Campbell et al.

    Rapid decline in body temperature before sleep: fluffing the physiological pillow?

    Chronobiol Int

    (1994)
  • P.J. Murphy et al.

    Nighttime drop in body temperature: a physiological trigger for sleep onset?

    Sleep

    (1997)
  • J. Barrett et al.

    The sleep-evoked decrease of body temperature

    Sleep

    (1993)
  • C. van den Heuvel et al.

    Attenuated thermoregulatory response to mild thermal challenge in subjects with sleep-onset insomnia

    Sleep

    (2006)
  • J. Aschoff

    Circadian rhythms: influence with and dependence on work–rest schedules

  • J. Aschoff

    Freerunning and entrained circadian rhythms

  • J. Aschoff

    Masking of circadian rhythms by zeitgebers as opposed to entrainment

  • N. Mrosovsky

    Masking: history, definitions, and measurement

    Chronobiol Int

    (1999)
  • J. Aschoff

    Exogenous and endogenous components in circadian rhythms

    Cold Spring Harb Symp Quant Biol

    (1960)
  • M.H. Hastings et al.

    A clockwork web: circadian timing in brain and periphery, in health and disease

    Nat Rev Neurosci

    (2003)
  • T. Hirota et al.

    Resetting mechanism of central and peripheral circadian clocks in mammals

    Zoolog Sci

    (2004)
  • C.A. Czeisler et al.

    Bright light resets the human circadian pacemaker independent of the timing of the sleep–wake cycle

    Science

    (1986)
  • R.A. Wever

    The circadian system of man: results of experiments under temporal isolation

    (1979)
  • R.A. Wever

    Basic principles of human circadian rhythms

  • C.A. Czeisler et al.

    Bright light induction of strong (type 0) resetting of the human circadian pacemaker

    Science

    (1989)
  • J.F. Duffy et al.

    Entrainment of the human circadian system by light

    J Biol Rhythms

    (2005)
  • J. Aschoff

    Circadian rhythm of activity and of body temperature

  • J. Zulley et al.

    Interaction between the sleep–wake cycle and the rhythm of rectal temperature

  • D.J. Dijk et al.

    Integration of human sleep–wake regulation and circadian rhythmicity

    J Appl Physiol

    (2002)
  • J. Zulley

    Distribution of REM sleep in entrained 24 hour and free-running sleep–wake cycles

    Sleep

    (1980)
  • J. Zulley et al.

    The dependence of onset and duration of sleep on the circadian rhythm of rectal temperature

    Pflugers Arch

    (1981)
  • Cited by (0)

    Dedicated to Anna Wirz-Justice in recognition of her contributions to the field made during her career at the Psychiatric University Clinics Basel.

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    The most important references are denoted by an asterisk.

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