Skip to main content
SpringerLink
Log in

Desynchrony and synchronisation underpinning sleep–wake cycles

  • Regular Article
  • Published:
The European Physical Journal Plus Aims and scope Submit manuscript

Abstract

This paper studies mechanisms of synchronisation and loss of synchrony among the three key oscillatory processes controlling sleep–wake cycles in the human brain: the 24-h circadian oscillator, the homeostatic sleep drive, and the environmental light–dark cycle. Synchronisation of these three rhythms promotes sleep and brain clearance and is critical for human health. Their desynchrony, on the other hand, is associated with impaired performance and disease development, including cancer, cardiovascular disease, and mental disorders. A biophysical model of arousal dynamics simulating sleep–wake cycles and circadian rhythms is used as the study system. It is based on established neurobiological mechanisms controlling sleep–wake transitions and incorporates the three oscillatory processes. Nonlinear dynamics methods and synchronisation theory are used to numerically investigate model dynamics under conditions that are not easily achievable in experiments. The role of homeostatic brain clearance rate in synchronisation is investigated, and selective turning on and off of coupling strengths between the oscillators allows us to determine their role in oscillators’ dynamics. We find that, in the absence of coupling between the circadian and homeostatic oscillators, the default state of the model corresponds to the endogenous homeostatic period that is far from \(\sim \)24-h rhythm of the circadian and light–dark cycles. Combined action of light and circadian oscillator on the homeostatic rhythm is required to achieve the typical sleep–wake pattern that is observed in young healthy people. Under 12-/12-h light–dark conditions with light at 80 lux, change of homeostatic clearance rate is found to induce two types of desynchronisation: (i) fast clearance rates \(\tau _H<58.1\) h desynchronise the homeostatic oscillator from the circadian, while the circadian rhythm remains entrained to the light–dark cycle, and (ii) slow clearance rates \(\tau _H>69\) h maintain synchronisation between the homeostatic and circadian oscillators, but the period of both is different from that of the light–dark cycle. Between these regimes, all three rhythms are synchronised under the studied conditions. The model predicts that the system is highly sensitive to external inputs to the neuronal populations of the sleep–wake switch, which affect the endogenous period of the homeostatic oscillator and can lead to complete loss of sleep. Model dynamics show that loss of synchronisation, which is traditionally ascribed solely to impairment of the circadian oscillator, can be caused by changes in the homeostatic clearance rate of the brain or external input to the neuronal populations of the sleep–wake switch. Thus, changes in circadian, homeostatic, and external factors (combined or specific) may be responsible for conditions of desynchronisation. This has significant implications for understanding individual variability in sleep–wake patterns and in mechanisms of sleep and circadian disorders, indicating that both the homeostatic and circadian mechanisms can be responsible for the same clinical or behavioural presentation of a disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. L. Xie, H. Kang, Q. Xu, M.J. Chen, Y. Liao, M. Thiyagarajan, J. O’Donnel, D.J. Christensen, C. Nicholson, J.J. Iliff et al., Sleep drives metabolite clearance from the adult brain. Science 342(6156), 373–377 (2013)

  2. J.J. Iliff, M. Wang, Y. Liao, B.A. Plogg, W. Peng, G.A. Gundersen, H. Benveniste, G.E. Vates, R. Deane, S.A. Goldman, E.A. Nagelhus, M. Nedergaard, A paravascular pathway facilitates csf flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid \(\beta \). Sci. Transl. Med. 4(147) (2012)

  3. N.E. Fultz, G. Bonmassar, K. Setsompop, R.A. Stickgold, B.R. Rosen, J.R. Polimeni, L.D. Lewis, Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep. Science 366(6465), 628–631 (2019)

    Article  ADS  Google Scholar 

  4. Y.-E.S. Ju, S.J. Ooms, C. Sutphen, S.L. Macauley, M.A. Zangrilli, G. Jerome, A.M. Fagan, E. Mignot, J.M. Zempel, J.A.H.R. Claassen, Slow wave sleep disruption increases cerebrospinal fluid amyloid-\(\beta \) levels. Brain 140(8), 2104–2111 (2017)

    Article  Google Scholar 

  5. J.-E. Kang, M.M. Lim, R.J. Bateman, J.J. Lee, L.P. Smyth, J.R. Cirrito, N. Fujiki, S. Nishino, D.M. Holtzman, Amyloid-\(\beta \) dynamics are regulated by orexin and the sleep-wake cycle. Science 326(5955), 1005–1007 (2009)

    Article  ADS  Google Scholar 

  6. D.A. Golombek, R.E. Rosenstein, Physiology of circadian entrainment. Physiol. Rev. 90(3), 1063–1102 (2010)

    Article  Google Scholar 

  7. D.-J. Dijk, C.A. Czeisler, Contribution of the circadian pacemaker and the sleep homeostat to sleep propensity, sleep structure, electroencephalographic slow waves, and sleep spindle activity in humans. J. Neurosci. 15(5 I), 3526–3538 (1995)

  8. D.-J. Dijk, T.L. Shanahan, J.F. Duffy, J.M. Ronda, C.A. Czeisler, Variation of electroencephalographic activity during non-rapid eye movement and rapid eye movement sleep with phase of circadian melatonin rhythm in humans. J. Physiol. 505(3), 851–858 (1997)

    Article  Google Scholar 

  9. L.M. Hablitz, V. Plá, M. Giannetto, H.S. Vinitsky, F.F. Stæger, T. Metcalfe, R. Nguyen, A. Benrais, Circadian control of brain glymphatic and lymphatic fluid flow. Nat. Commun. 111(1), 1–11 (2020)

    Google Scholar 

  10. F. Ding, J. O’Donnell, Q. Xu, N. Kang, N. Goldman, M. Nedergaard, Changes in the composition of brain interstitial ions control the sleep-wake cycle. Science 352(6285), 550–555 (2016)

    Article  ADS  Google Scholar 

  11. A.M. Ingiosi, C.R. Hayworth, D.O. Harvey, K.G. Singletary, M.J. Rempe, J.P. Wisor, M.G. Frank, A role for astroglial calcium in mammalian sleep and sleep regulation. Curr. Biol. (2020)

  12. A.A. Borbély, A two process model of sleep regulation. Hum. Neurobiol. 1(3), 195–204 (1982)

    Google Scholar 

  13. A.A. Borbély, F. Baumann, D. Brandeis, I. Strauch, D. Lehmann, Sleep deprivation: effect on sleep stages and eeg power density in man. Electroencephalogr. Clin. Neurophysiol. 51(5), 483–493 (1981)

    Article  Google Scholar 

  14. T. Porkka-Heiskanen, R.E. Strecker, R.W. McCarley, Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep: An in vivo microdialysis study. Neuroscience 99(3), 507–517 (2000)

    Article  Google Scholar 

  15. S. Datta, Cellular and chemical neuroscience of mammalian sleep. Sleep Med. 11(5), 431–440 (2010)

    Article  Google Scholar 

  16. R. Allada, C. Cirelli, and A. Sehgal. Molecular mechanisms of sleep homeostasis in flies and mammals. Cold Spring Harb. Perspect. Biol., 9(8), 2017

  17. A. Kalsbeek, S. La Fleur, E. Fliers, Circadian control of glucose metabolism. Molecular Metabolism 3(4), 372–383 (2014)

    Article  Google Scholar 

  18. S.D. Youngstedt, J.A. Elliott, D.F. Kripke, Human circadian phase-response curves for exercise. J. Physiol. 597(8), 2253–2268 (2019)

    Article  Google Scholar 

  19. A.-M. Finger, A. Kramer, Mammalian circadian systems: organization and modern life challenges. Acta Physiol. (2020)

  20. R.A. Wever, The Circadian System of Man, Results of Experiments Under Temporal Isolation (Springer, New York, 1979)

    Book  Google Scholar 

  21. A.J.K. Phillips, C.A. Czeisler, E.B. Klerman, Revisiting spontaneous internal desynchrony using a quantitative model of sleep physiology. J. Biol. Rhythms 26(5), 441–453 (2011)

    Article  Google Scholar 

  22. J. Aschoff, U. Gerecke, R. Wever, Desynchronization of human circadian rhythms. Jpn. J. Physiol. 17(4), 450–457 (1967)

    Article  Google Scholar 

  23. J. Aschoff, M. Fatranská, H. Giedke, P. Doerr, D. Stamm, H. Wisser, Human circadian rhythms in continuous darkness: entrainment by social cues. Science 171(3967), 213–215 (1971)

    Article  ADS  Google Scholar 

  24. R.D. Gleit, C.G. Diniz Behn, V. Booth, Modeling interindividual differences in spontaneous internal desynchrony patterns. J. Biol. Rhythms 28(5), 339–355 (2013)

  25. K.G. Baron, K.J. Reid, Circadian misalignment and health. Int. Rev. Psychiatry 26(2), 139–154 (2014)

    Article  Google Scholar 

  26. J.K. Holth, S.K. Fritschi, C. Wang, N.P. Pedersen, J.R. Cirrito, T.E. Mahan, M.B. Finn, M. Manis, J.C. Geerling, P.M. Fuller, B.P. Lucey, D.M. Holtzman, The sleep-wake cycle regulates brain interstitial fluid tau in mice and csf tau in humans. Science 363(6429), 80–884 (2019)

    Article  Google Scholar 

  27. from the clinic to society and disease, J.H. Abel, K. Lecamwasam, M.A. St Hilaire, and E.B. Klerman. Recent advances in modeling sleep. Curr. Opin. Physiol. 15, 37–46 (2020)

  28. S. Postnova, Sleep modelling across physiological levels. Clocks & Sleep 1, 166–184 (2019)

    Article  Google Scholar 

  29. S. Postnova, S.W. Lockley, P.A. Robinson, Sleep propensity under forced desynchrony in a model of arousal state dynamics. J. Biol. Rhythms 31(5), 498–508 (2016)

    Article  Google Scholar 

  30. R.G Abeysuriya, S.W Lockley, P. A Robinson, S. Postnova. A unified model of melatonin, 6-sulfatoxymelatonin, and sleep dynamics. J. Pineal Research, 64(4):e12474, 5 2018

  31. T. Tekieh, S.W. Lockley, P.A. Robinson, S. McCloskey, M.S. Zobaer, S. Postnova, Modeling melanopsin-mediated effects of light on circadian phase, melatonin suppression, and subjective sleepiness. J. Pineal Res.69(3) (2020)

  32. C.J. Gordon, M. Comas, S. Postnova, C.B. Miller, D. Roy, D.J. Bartlett, R.R. Grunstein, The effect of consecutive transmeridian flights on alertness, sleep-wake cycles and sleepiness: A case study. Chronobiol. Int. 35(11), 1471–1480 (2018)

    Article  Google Scholar 

  33. A. Pikovsky, J. Kurths, M. Rosenblum, J. Kurths, Synchronization: A Universal Concept in Nonlinear Sciences, vol. 12 (Cambridge University Press, Cambridge, 2003)

    MATH  Google Scholar 

  34. A. Balanov, N. Janson, D. Postnov, O. Sosnovtseva, Synchronization: From Simple to Complex (Springer Science & Business Media, Berlin, 2008)

    MATH  Google Scholar 

  35. S. Postnova, S. Lockley, P.A. Robinson, Prediction of cognitive performance and subjective sleepiness using a model of arousal dynamics. J. Biol. Rhythms 33(2), 203–218 (2018)

    Article  Google Scholar 

  36. R. FitzHugh, Impulses and physiological states in theoretical models of nerve membrane. Biophys. J. 1(6), 445 (1961)

    Article  ADS  Google Scholar 

  37. A.J.K. Phillips, P.A. Robinson, A quantitative model of sleep-wake dynamics based on the physiology of the brainstem ascending arousal system. J. Biol. Rhythms 22(2), 167–179 (2007)

    Article  Google Scholar 

  38. M.A. St Hilaire, E.B. Klerman, S.B.S. Khalsa, K.P. Wright, C.A. Czeisler, R.E. Kronauer, Addition of a non-photic component to a light-based mathematical model of the human circadian pacemaker. J. Theor. Biol. 247(2), 583–599 (2007)

  39. R.E. Kronauer, G. Gunzelmann, H.P.A. Van Dongen, F.J. Doyle, E.B. Klerman, Uncovering physiologic mechanisms of circadian rhythms and sleep/wake regulation through mathematical modeling. J. Biol. Rhythms 22(3), 233–45 (2007)

    Article  Google Scholar 

  40. C. B. Saper, P. M. Fuller, N. P. Pedersen, J.Lu, T. E., Sleep state switching. Neuron 68(6), 1023–1042 (2010)

  41. E.M. Izhikevich, Dynamical Systems in Neuroscience (MIT Press, Cambridge, 2007)

    Google Scholar 

  42. M. Krupa, P. Szmolyan, Relaxation oscillation and canard explosion. J. Differ. Equ. 174(2), 312–368 (2001)

    Article  ADS  MathSciNet  MATH  Google Scholar 

  43. Balth Van der Pol, Lxxxviii. on “relaxation-oscillatiors”. The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science 2(11), 978–992 (1926)

  44. T. Kanamaru, Van der pol oscillator. Scholarpedia 2(1), 2202 (2007)

    Article  ADS  Google Scholar 

  45. D. Ruelle, F. Takens. On the nature of turbulence. Les rencontres physiciens-mathématiciens de Strasbourg-RCP25, 12:1–44, 1971

  46. M. Yoshimoto, K. Yoshikawa, Y. Mori, Coupling among three chemical oscillators: synchronization, phase death, and frustration. Phys. Rev. E 47(2), 864 (1993)

    Article  ADS  Google Scholar 

  47. V Anishchenko, S Nikolaev, and J Kurths. Bifurcational mechanisms of synchronization of a resonant limit cycle on a two-dimensional torus. Chaos: An Interdisciplinary Journal of Nonlinear Science, 18(3):037123, 2008

  48. D.M. Edgar, W.C. Dement, C.A. Fuller, Effect of scn lesions on sleep in squirrel monkeys: Evidence for opponent processes in sleep-wake regulation. J. Neurosci. 13(3), 1065–1079 (1993)

    Article  Google Scholar 

  49. R. Wever, The circadian multi oscillator system of man. Int. J. Chronobiol. 3(1), 19–55 (1975)

    Google Scholar 

  50. C.A. Czeisler, J.F. Duffy, T.L. Shanahan, E.N. Brown, J.F. Mitchell, D.W. Rimmer, J.M. Ronda, E.J. Silva, J.S. Allan, J.S. Emens, D.-J. Dijk, R.E. Kronauer, Stability, precision, and near-24-hour period of the human circadian pacemaker. Science 284(5423), 2177–2181 (1999)

    Article  Google Scholar 

  51. T.L. Sletten, S. Vincenzi, J.R. Redman, S.W. Lockley, S.W.M. Rajaratnam, Timing of sleep and its relationship with the endogenous melatonin rhythm. Front. Neurol. 1(5423), 137 (2010)

    Google Scholar 

  52. R.L. Sack, D. Auckley, R.R. Auger, M.A. Carskadon, K.P. Wright Jr., M.V. Vitiello, I.V. Zhdanova, Circadian rhythm sleep disorders: Part ii, advanced sleep phase disorder, delayed sleep phase disorder, free-running disorder, and irregular sleep-wake rhythm: An american academy of sleep medicine review. Sleep 30(11), 1484–1501 (2007)

    Article  Google Scholar 

  53. S.M.W. Rajaratnam, L. Licamele, G. Birznieks, Delayed sleep phase disorder risk is associated with absenteeism and impaired functioning. Sleep Health 1(2), 121–127 (2015)

    Article  Google Scholar 

  54. L.G. Goldfarb, R.B. Petersen, M. Tabaton, P. Brown, A.C. LeBlanc, P. Montagna, P. Cortelli, J. Julien, C. Vital, W.W. Pendelbury, M. Haltia, P.R. Wills, J.J. Hauw, P.E. McKeever, L. Monari, B. Schrank, G.D. Swergold, L. Autilio-Gambetti, D.C. Gajdusek, E. Lugaresi, P. Gambetti, Fatal familial insomnia and familial creutzfeldt-jakob disease: Disease phenotype determined by a dna polymorphism. Science 258(5083), 806–808 (1992)

    Article  ADS  Google Scholar 

  55. K. Takahashi, Y. Kayama, J.S. Lin, K. Sakai, Locus coeruleus neuronal activity during the sleep-waking cycle in mice. Neuroscience 169(3), 1115–1126 (2010)

    Article  Google Scholar 

  56. R.W. Logan, C.A. McClung, Rhythms of life: circadian disruption and brain disorders across the lifespan. Nat. Rev. Neurosci. 20(1), 49–65 (2019)

    Article  Google Scholar 

  57. J. O’Donnell, F. Ding, M. Nedergaard, Distinct functional states of astrocytes during sleep and wakefulness: Is norepinephrine the master regulator? Current sleep medicine reports 1(1), 1–8 (2015)

    Article  Google Scholar 

Download references

Acknowledgements

This research was supported by the RF Government grant, project #075-15-2019-1885

Author information

Authors and Affiliations

  1. Saratov State University, 83 Astrakhanskaya Street, Saratov, Russia, 410012

    Dmitry E. Postnov & Ksenia O. Merkulova

  2. School of Physics, University of Sydney, Camperdown, NSW, 2006, Australia

    Svetlana Postnova

  3. The University of Sydney Nano Institute (Sydney Nano), The University of Sydney, Camperdown, NSW, 2006, Australia

    Svetlana Postnova

  4. Charles Perkins Centre, The University of Sydney, Camperdown, NSW, 2006, Australia

    Svetlana Postnova

Authors
  1. Dmitry E. Postnov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ksenia O. Merkulova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Svetlana Postnova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dmitry E. Postnov.

Ethics declarations

Conflict of interest

DEP, KOM, and SP have no conflicting interests to declare. In interest of full disclosure: SP served as a Theme Leader and previously as a Project Leader in the CRC for Alertness, Safety and Productivity which funded development of the model of arousal dynamics. She reports research grants from Qantas Airways Ltd and Alertness CRC, which are not related to this paper.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Postnov, D.E., Merkulova, K.O. & Postnova, S. Desynchrony and synchronisation underpinning sleep–wake cycles. Eur. Phys. J. Plus 136, 488 (2021). https://doi.org/10.1140/epjp/s13360-021-01491-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1140/epjp/s13360-021-01491-z

Search

Navigation