title: Top-down control of arousal and sleep: Fundamentals and clinical implications.
abstract: Mammalian sleep emerges from attenuated activity in the ascending reticular arousal system (ARAS), the main arousal network of the brain. This system originates in the brainstem and activates the thalamus and cortex during wakefulness via a well-characterized 'bottom-up' pathway. Recent studies propose that a less investigated cortico-thalamic 'top-down' pathway also regulates sleep. The present work integrates the current evidence on sleep regulation with a focus on the 'top-down' pathway and explores the potential to translate this information into clinically relevant interventions. Specifically, we elaborate the concept that arousal and sleep continuity in humans can be modulated by non-invasive brain stimulation (NIBS) techniques that increase or decrease cortical excitability. Based on preclinical studies, the modulatory effects of the stimulation are thought to extend to subcortical arousal networks. Further exploration of the 'top-down' regulation of sleep and its modulation through non-invasive brain stimulation techniques may contribute to the development of novel treatments for clinical conditions of disrupted arousal and sleep, which are among the major health problems worldwide.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Freiburg Medical Center, Germany; Department of Clinical Psychology and Psychophysiology/ Sleep Medicine, University of Freiburg Medical Center, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Krone
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Freiburg Medical Center, Germany; Department of Clinical Psychology and Psychophysiology/ Sleep Medicine, University of Freiburg Medical Center, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Frase
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Freiburg Medical Center, Germany; Department of Clinical Psychology and Psychophysiology/ Sleep Medicine, University of Freiburg Medical Center, Germany.
authors.forename: Hannah
authors.initials: H
authors.lastname: Piosczyk
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Freiburg Medical Center, Germany; Department of Clinical Psychology and Psychophysiology/ Sleep Medicine, University of Freiburg Medical Center, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Selhausen
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Freiburg Medical Center, Germany; Department of Clinical Psychology and Psychophysiology/ Sleep Medicine, University of Freiburg Medical Center, Germany.
authors.forename: Sulamith
authors.initials: S
authors.lastname: Zittel
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Freiburg Medical Center, Germany; Department of Clinical Psychology and Psychophysiology/ Sleep Medicine, University of Freiburg Medical Center, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Jahn
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Freiburg Medical Center, Germany; Department of Clinical Psychology and Psychophysiology/ Sleep Medicine, University of Freiburg Medical Center, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Kuhn
authors.affiliation: Department of Clinical Psychology and Psychophysiology/ Sleep Medicine, University of Freiburg Medical Center, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Feige
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Freiburg Medical Center, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Mainberger
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Freiburg Medical Center, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Klöppel
authors.affiliation: Department of Clinical Psychology and Psychophysiology/ Sleep Medicine, University of Freiburg Medical Center, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Riemann
authors.affiliation: Department of Clinical Psychology and Psychophysiology/ Sleep Medicine, University of Freiburg Medical Center, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Spiegelhalder
authors.affiliation: Department of Clinical Psychology and Psychophysiology/ Sleep Medicine, University of Freiburg Medical Center, Germany.
authors.forename: Chiara
authors.initials: C
authors.lastname: Baglioni
authors.affiliation: Department of Psychology, University of Surrey, UK.
authors.forename: Annette
authors.initials: A
authors.lastname: Sterr
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Freiburg Medical Center, Germany; Department of Clinical Psychology and Psychophysiology/ Sleep Medicine, University of Freiburg Medical Center, Germany. Electronic address: christoph.nissen@uniklinik-freiburg.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Nissen
mesh_terms: D000818:Animals; D001143:Arousal / Q000502:physiology*; D001921:Brain; D002540:Cerebral Cortex / Q000502:physiology; D004569:Electroencephalography; D006801:Humans; D012890:Sleep / Q000502:physiology*; D013788:Thalamus / Q000502:physiology; D065908:Transcranial Direct Current Stimulation
keywords: Arousal; Brain stimulation; Cortex; Cortico-thalamic feedback; Sleep; Sleep continuity; Thalamus; Transcranial direct current stimulation