title: Arousal state feedback as a potential physiological generator of the ultradian REM/NREM sleep cycle.
abstract: Human sleep episodes are characterized by an approximately 90-min ultradian oscillation between rapid eye movement (REM) and non-REM (NREM) sleep stages. The source of this oscillation is not known. Pacemaker mechanisms for this rhythm have been proposed, such as a reciprocal interaction network, but these fail to account for documented homeostatic regulation of both sleep stages. Here, two candidate mechanisms are investigated using a simple model that has stable states corresponding to Wake, REM sleep, and NREM sleep. Unlike other models of the ultradian rhythm, this model of sleep dynamics does not include an ultradian pacemaker, nor does it invoke a hypothetical homeostatic process that exists purely to drive ultradian rhythms. Instead, only two inputs are included: the homeostatic drive for Sleep and the circadian drive for Wake. These two inputs have been the basis for the most influential Sleep/Wake models, but have not previously been identified as possible ultradian rhythm generators. Using the model, realistic ultradian rhythms are generated by arousal state feedback to either the homeostatic or circadian drive. For the proposed 'homeostatic mechanism', homeostatic pressure increases in Wake and REM sleep, and decreases in NREM sleep. For the proposed 'circadian mechanism', the circadian drive is up-regulated in Wake and REM sleep, and is down-regulated in NREM sleep. The two mechanisms are complementary in the features they capture. The homeostatic mechanism reproduces experimentally observed rebounds in NREM sleep duration and intensity following total sleep deprivation, and rebounds in both NREM sleep intensity and REM sleep duration following selective REM sleep deprivation. The circadian mechanism does not reproduce sleep state rebounds, but more accurately reproduces the temporal patterns observed in a normal night of sleep. These findings have important implications in terms of sleep physiology and they provide a parsimonious explanation for the observed ultradian rhythm of REM/NREM sleep.
authors.affiliation: Division of Sleep Medicine, Brigham & Women's Hospital, Harvard Medical School, 221 Longwood Ave., Suite 438, Boston, MA 02115, USA. ajphillips@partners.org
authors.forename: A J K
authors.initials: AJ
authors.lastname: Phillips
authors.forename: P A
authors.initials: PA
authors.lastname: Robinson
authors.forename: E B
authors.initials: EB
authors.lastname: Klerman
mesh_terms: D001683:Biological Clocks / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D012895:Sleep, REM / Q000502:physiology*