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Local sleep and wakefulness—the concept and its potential for the understanding and treatment of insomnia disorder

Lokaler Schlaf- und Wachzustand – das Konzept und sein Potenzial für Verständnis und Therapie von Insomnien

Abstract

In ancient mythology, sleep was often regarded as an inactive state, close to death. Research in the past century has, however, demonstrated that the brain is highly active and oscillates through well-defined stages during sleep. Yet it is only over the past decade that accumulating evidence has shown that sleep and wake processes can occur simultaneously, localized in distinct areas of the brain. The aim of this article is to review relevant aspects of the shift from global to local concepts of sleep–wake regulation and to further translate this perspective to the clinical problem of insomnia. Animal and human studies show that local wake-like activations (‘islands of wakefulness’) can occur during both major sleep stages, i.e. non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Preliminary evidence suggests that higher levels of local wake-like activity, not captured in standard polysomnographic recordings, might underlie the perception of disrupted sleep or even wakefulness during polysomnographic epochs of sleep in patients with chronic insomnia. To further decipher the neural mechanisms, advanced techniques of high-density electroencephalography (hdEEG) and non-invasive brain stimulation techniques can be applied. Furthermore translating the concept of local sleep and wakefulness to the prevalent health problem of chronic insomnia might help to reduce the current mismatch between subjective sleep–wake perception and standard recordings, and might inform the development of new treatments.

Zusammenfassung

Im antiken Griechenland und über nachfolgende Jahrhunderte wurde Schlaf oftmals als ein inaktiver Zustand mit einer Nähe zum Tod angesehen. Arbeiten im letzten Jahrhundert zeigen hingegen, dass das Gehirn im Schlaf sehr aktiv ist und durch verschiedene, gut charakterisierte Schlafstadien oszilliert. Erst in den letzten Jahren wird zunehmend deutlich, dass Schlaf- und Wachprozesse zeitgleich nebeneinander in umschriebenen Arealen des Gehirns auftreten können. Das Ziel der vorliegenden Arbeit ist es, relevante Aspekte dieses Wechsels von globalen zu lokalen Konzepten der Schlaf-Wach-Regulation weiter herauszuarbeiten und diese Perspektive weiter für den Bereich der klinisch relevanten Insomnie zu erschließen. Studien an Tieren und Menschen zeigen, dass wachähnliche Aktivierungsmuster („lokale Inseln von Wachheit“) in beiden Hauptschlafstadien auftreten können, dem Non-Rapid-Eye-Movement(NREM)- und dem Rapid-Eye-Movement(REM)-Schlaf. Erste, jedoch nicht ausreichend replizierte Befunde weisen darauf hin, dass höhere Level von lokaler wachähnlicher Aktivität, die in Standardableitungen der Polysomnographie nicht erfasst werden, der oft berichteten Wahrnehmung von gestörtem Schlaf oder sogar dem Erleben von Wachheit während polysomnographischer Schlafphasen bei Patienten mit chronischer Insomnie zugrunde liegen könnten. Um die neuronalen Mechanismen lokaler Schlaf- und Wachaktivität näher zu verstehen, sind neuere Untersuchungsmethoden wie die High-Density-Elektroenzephalographie (hdEEG) oder nichtinvasive Gehirnstimulationsverfahren notwendig. Die weitere Übertragung des Konzepts lokaler Schlaf-Wach-Regulation auf das häufige Gesundheitsproblem Insomnie könnte die aktuell unzureichende Passung zwischen subjektiver Schlaf-Wach-Wahrnehmung und Standarduntersuchungsmethoden verbessern und eventuell zur Entwicklung neuer Therapieverfahren beitragen.

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References

  1. Anch AM, Salamy JG, Mccoy GF et al (1982) Behaviorally signalled awakenings in relationship to duration of alpha activity. Psychophysiology 19:528–530

    CAS  PubMed  Article  Google Scholar 

  2. Andersson JL, Onoe H, Hetta J et al (1998) Brain networks affected by synchronized sleep visualized by positron emission tomography. J Cereb Blood Flow Metab 18:701–715

    CAS  PubMed  Article  Google Scholar 

  3. Aserinsky E, Kleitman N (2003) Regularly occurring periods of eye motility, and concomitant phenomena, during sleep. 1953. J Neuropsychiatry Clin Neurosci 15:454–455

    PubMed  Article  Google Scholar 

  4. Baglioni C, Regen W, Teghen A et al (2014) Sleep changes in the disorder of insomnia: a meta-analysis of polysomnographic studies. Sleep Med Rev 18:195–213

    PubMed  Article  Google Scholar 

  5. Baird B, Castelnovo A, Riedner BA et al (2018) Human rapid eye movement sleep shows local increases in low-frequency oscillations and global decreases in high-frequency oscillations compared to resting wakefulness. eNeuro 5(4):ENEURO.0293-18.2018. https://doi.org/10.1523/ENEURO.0293-18.2018

    Article  PubMed  PubMed Central  Google Scholar 

  6. Bernardi G, Betta M, Ricciardi E et al (2019) Regional delta waves in human rapid eye movement sleep. J Neurosci 39:2686–2697

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. Braun AR, Balkin TJ, Wesenten NJ et al (1997) Regional cerebral blood flow throughout the sleep-wake cycle. An H2(15)O PET study. Brain 120(7):1173–1197

    PubMed  Article  Google Scholar 

  8. Campbell SS, Webb WB (1981) The perception of wakefulness within sleep. Sleep 4:177–183

    CAS  PubMed  Article  Google Scholar 

  9. Czisch M, Wehrle R, Kaufmann C et al (2004) Functional MRI during sleep: BOLD signal decreases and their electrophysiological correlates. Eur J Neurosci 20:566–574

    PubMed  Article  Google Scholar 

  10. D’Ambrosio S, Castelnovo A, Guglielmi O et al (2019) Sleepiness as a local phenomenon. Front Neurosci 13:1086

    PubMed  PubMed Central  Article  Google Scholar 

  11. De Carli F, Proserpio P, Morrone E et al (2016) Activation of the motor cortex during phasic rapid eye movement sleep. Ann Neurol 79:326–330

    PubMed  PubMed Central  Article  Google Scholar 

  12. Dement W, Wolpert EA (1958) The relation of eye movements, body motility, and external stimuli to dream content. J Exp Psychol 55:543–553

    CAS  PubMed  Article  Google Scholar 

  13. Duyn J (2011) Spontaneous fMRI activity during resting wakefulness and sleep. Prog Brain Res 193:295–305

    PubMed  PubMed Central  Article  Google Scholar 

  14. Feige B, Al-Shajlawi A, Nissen C et al (2008) Does REM sleep contribute to subjective wake time in primary insomnia? A comparison of polysomnographic and subjective sleep in 100 patients. J Sleep Res 17:180–190

    PubMed  Article  Google Scholar 

  15. Feige B, Baglioni C, Spiegelhalder K et al (2013) The microstructure of sleep in primary insomnia: an overview and extension. Int J Psychophysiol 89:171–180

    PubMed  Article  Google Scholar 

  16. Feige B, Nanovska S, Baglioni C et al (2018) Insomnia-perchance a dream? Results from a NREM/REM sleep awakening study in good sleepers and patients with insomnia. Sleep. https://doi.org/10.1093/sleep/zsy032

    Article  PubMed  Google Scholar 

  17. Frase L, Piosczyk H, Zittel S et al (2016) Modulation of total sleep time by transcranial direct current stimulation (tDCS). Neuropsychopharmacology 41:2577–2586

    PubMed  PubMed Central  Article  Google Scholar 

  18. Frase L, Selhausen P, Krone L et al (2019) Differential effects of bifrontal tDCS on arousal and sleep duration in insomnia patients and healthy controls. Brain Stimul 12:674–683

    PubMed  Article  Google Scholar 

  19. Funk CM, Honjoh S, Rodriguez AV et al (2016) Local slow waves in superficial layers of primary cortical areas during REM sleep. Curr Biol 26:396–403

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. Kajimura N, Uchiyama M, Takayama Y et al (1999) Activity of midbrain reticular formation and neocortex during the progression of human non-rapid eye movement sleep. J Neurosci 19:10065–10073

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  21. Kaufmann C, Wehrle R, Wetter TC et al (2006) Brain activation and hypothalamic functional connectivity during human non-rapid eye movement sleep: an EEG/fMRI study. Brain 129:655–667

    CAS  PubMed  Article  Google Scholar 

  22. Kay DB, Karim HT, Soehner AM et al (2017) Subjective-objective sleep discrepancy is associated with alterations in regional glucose metabolism in patients with insomnia and good sleeper controls. Sleep. https://doi.org/10.1093/sleep/zsx155

    Article  PubMed  PubMed Central  Google Scholar 

  23. Krueger JM, Nguyen JT, Dykstra-Aiello CJ et al (2019) Local sleep. Sleep Med Rev 43:14–21

    PubMed  Article  Google Scholar 

  24. Langford GW, Meddis R, Pearson AJ (1974) Awakening latency from sleep for meaningful and non-meaningful stimuli. Psychophysiology 11:1–5

    CAS  PubMed  Article  Google Scholar 

  25. Maquet P (2000) Functional neuroimaging of normal human sleep by positron emission tomography. J Sleep Res 9:207–231

    CAS  PubMed  Article  Google Scholar 

  26. Maquet P, Degueldre C, Delfiore G et al (1997) Functional neuroanatomy of human slow wave sleep. J Neurosci 17:2807–2812

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. Maquet P, Dive D, Salmon E et al (1990) Cerebral glucose utilization during sleep-wake cycle in man determined by positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose method. Brain Res 513:136–143

    CAS  PubMed  Article  Google Scholar 

  28. Maquet P, Peters J, Aerts J et al (1996) Functional neuroanatomy of human rapid-eye-movement sleep and dreaming. Nature 383:163–166

    CAS  PubMed  Article  Google Scholar 

  29. Maquet P, Ruby P, Maudoux A et al (2005) Human cognition during REM sleep and the activity profile within frontal and parietal cortices: a reappraisal of functional neuroimaging data. Prog Brain Res 150:219–227

    PubMed  Article  Google Scholar 

  30. Marzano C, Ferrara M, Sforza E et al (2008) Quantitative electroencephalogram (EEG) in insomnia: a new window on pathophysiological mechanisms. Curr Pharm Des 14:3446–3455

    CAS  PubMed  Article  Google Scholar 

  31. Marzano C, Moroni F, Gorgoni M et al (2013) How we fall asleep: regional and temporal differences in electroencephalographic synchronization at sleep onset. Sleep Med 14:1112–1122

    PubMed  Article  Google Scholar 

  32. Ngo HV, Martinetz T, Born J et al (2013) Auditory closed-loop stimulation of the sleep slow oscillation enhances memory. Neuron 78:545–553

    CAS  PubMed  Article  Google Scholar 

  33. Nitsche MA, Paulus W (2000) Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol 527(3):633–639

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. Nobili L, Ferrara M, Moroni F et al (2011) Dissociated wake-like and sleep-like electro-cortical activity during sleep. Neuroimage 58:612–619

    PubMed  Article  Google Scholar 

  35. Nofzinger EA (2005) Neuroimaging and sleep medicine. Sleep Med Rev 9:157–172

    PubMed  Article  Google Scholar 

  36. Nofzinger EA, Buysse DJ, Germain A et al (2004) Functional neuroimaging evidence for hyperarousal in insomnia. Am J Psychiatry 161:2126–2128

    PubMed  Article  Google Scholar 

  37. Nofzinger EA, Buysse DJ, Miewald JM et al (2002) Human regional cerebral glucose metabolism during non-rapid eye movement sleep in relation to waking. Brain 125:1105–1115

    PubMed  Article  Google Scholar 

  38. Nofzinger EA, Mintun MA, Wiseman M et al (1997) Forebrain activation in REM sleep: an FDG PET study. Brain Res 770:192–201

    CAS  PubMed  Article  Google Scholar 

  39. Oleksenko AI, Mukhametov LM, Polyakova IG et al (1992) Unihemispheric sleep deprivation in bottlenose dolphins. J Sleep Res 1:40–44

    CAS  PubMed  Article  Google Scholar 

  40. Rattenborg NC, van der Meij J, Beckers GJL et al (2019) Local aspects of avian non-REM and REM sleep. Front Neurosci 13:567

    PubMed  PubMed Central  Article  Google Scholar 

  41. Riedner BA, Goldstein MR, Plante DT et al (2016) Regional patterns of elevated alpha and high-frequency electroencephalographic activity during nonrapid eye movement sleep in chronic insomnia: a pilot study. Sleep 39:801–812

    PubMed  PubMed Central  Article  Google Scholar 

  42. Riemann D, Spiegelhalder K, Feige B et al (2010) The hyperarousal model of insomnia: a review of the concept and its evidence. Sleep Med Rev 14:19–31

    PubMed  Article  Google Scholar 

  43. Sekiguchi Y, Arai K, Kohshima S (2006) Sleep behaviour: sleep in continuously active dolphins. Nature 441:E9–10 (discussion E11)

    CAS  PubMed  Article  Google Scholar 

  44. Siclari F, Tononi G (2017) Local aspects of sleep and wakefulness. Curr Opin Neurobiol 44:222–227

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. Vyazovskiy VV, Olcese U, Hanlon EC et al (2011) Local sleep in awake rats. Nature 472:443–447

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. Wehrle R, Kaufmann C, Wetter TC et al (2007) Functional microstates within human REM sleep: first evidence from fMRI of a thalamocortical network specific for phasic REM periods. Eur J Neurosci 25:863–871

    PubMed  Article  Google Scholar 

  47. World Health Organization (1992) The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. World Health Organization, Geneva

    Google Scholar 

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Correspondence to Christoph Nissen.

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Conflict of interest

L. Stålesen Ramfjord, E. Hertenstein, K. Fehér, C. Mikutta, C. Schneider, C. Nissen and J.G. Maier declare that they have no competing interests.

For this article no studies with human participants or animals were performed by any of the authors. All studies performed were in accordance with the ethical standards indicated in each case.

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Stålesen Ramfjord, L., Hertenstein, E., Fehér, K. et al. Local sleep and wakefulness—the concept and its potential for the understanding and treatment of insomnia disorder. Somnologie 24, 116–120 (2020). https://doi.org/10.1007/s11818-020-00245-w

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  • DOI: https://doi.org/10.1007/s11818-020-00245-w

Keywords

  • Local sleep
  • High-density electroencephalography
  • Non-invasive brain stimulation
  • Insomnia disorder

Schlüsselwörter

  • Lokaler Schlaf
  • High-Density-Elektroenzephalographie
  • Nichtinvasive Gehirnstimulation
  • Insomnie