title: CAP and arousals are involved in the homeostatic and ultradian sleep processes.
abstract: There is growing evidence that cyclic alternating pattern (CAP) and arousals are woven into the basic mechanisms of sleep regulation. In the present study, the overnight sleep cycles (SC) of 20 normal subjects were analyzed according to their stage composition, CAP rate, phase A subtypes and arousals. Individual SC were then divided into 10 normalized temporal epochs. CAP parameters and arousals were measured in each epoch and averaged in relation to the SC order. Subtypes A2 and A3 of CAP in non-rapid eye movement (NREM) sleep, and arousals, both in REM and NREM sleep when not coincident with a A2 or A3 phases, were lumped together as fast electroencephalographic (EEG) activities (FA). Subtypes A1 of CAP, characterized by slow EEG activities (SA), were analyzed separately. The time distribution of SA and FA was compared to the mathematical model of normal sleep structure including functions representing the homeostatic process S, the circadian process C, the ultradian process generating NREM/REM cycles and the slow wave activity (SWA) resulting from the interaction between homeostatic and ultradian processes. The relationship between SA and FA and the sleep-model components was evaluated by multiple regression analysis in which SA and FA were considered as dependent variables while the covariates were the process S, process C, SWA, REM-on and REM-off activities and their squared values. Regression was highly significant (P < 0.0001) for both SA and FA. SA were prevalent in the first three SC, and exhibited single or multiple peaks immediately before and in the final part of deep sleep (stages 3 + 4). The peaks of FA were delayed and prevailed during the pre-REM periods of light sleep (stages 1 + 2) and during REM sleep. SA showed an exponential decline across the successive SC, according to the homeostatic process. In contrast, the distribution of FA was not influenced by the order of SC, with periodic peaks of FA occurring before the onset of REM sleep, in accordance with the REM-on switch. The dynamics of CAP and arousals during sleep can be viewed as an intermediate level between cellular activities and macroscale EEG phenomena as they reflect the decay of the homeostatic process and the interaction between REM-off and REM-on mechanisms while are slightly influenced by circadian rhythm.
authors.affiliation: Department of Neuroscience, Sleep Disorders Center, University of Parma, Parma, Italy. mterzano@unipr.it
authors.forename: Mario Giovanni
authors.initials: MG
authors.lastname: Terzano
authors.forename: Liborio
authors.initials: L
authors.lastname: Parrino
authors.forename: Arianna
authors.initials: A
authors.lastname: Smerieri
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carli
authors.forename: Lino
authors.initials: L
authors.lastname: Nobili
authors.forename: Stefania
authors.initials: S
authors.lastname: Donadio
authors.forename: Franco
authors.initials: F
authors.lastname: Ferrillo
mesh_terms: D000204:Activity Cycles / Q000502:physiology*; D000328:Adult; D001143:Arousal / Q000502:physiology*; D004569:Electroencephalography; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010507:Periodicity; D017286:Polysomnography; D012894:Sleep Stages / Q000502:physiology