Abstract
A new concept of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep is proposed, that of multi-component integrative states that define stable and unstable sleep, respectively, NREMS, NREMUS REMS, and REMUS. Three complementary data sets are used: obstructive sleep apnea (20), healthy subjects (11), and high loop gain sleep apnea (50). We use polysomnography (PSG) with beat-to-beat blood pressure monitoring, and electrocardiogram (ECG)-derived cardiopulmonary coupling (CPC) analysis to demonstrate a bimodal, rather than graded, characteristic of NREM sleep. Stable NREM (NREMS) is characterized by high probability of occurrence of the <1 Hz slow oscillation, high delta power, stable breathing, blood pressure dipping, strong sinus arrhythmia and vagal dominance, and high frequency CPC. Conversely, unstable NREM (NREMUS) has the opposite features: a fragmented and discontinuous <1 Hz slow oscillation, non-dipping of blood pressure, unstable respiration, cyclic variation in heart rate, and low frequency CPC. The dimension of NREM stability raises the possibility of a comprehensive integrated multicomponent network model of NREM sleep which captures sleep onset (e.g., ventrolateral preoptic area-based sleep switch) processes, synaptic homeostatic delta power kinetics, and the interaction of global and local sleep processes as reflected in the spatiotemporal evolution of cortical “UP” and “DOWN” states, while incorporating the complex dynamics of autonomic-respiratory-hemodynamic systems during sleep. Bimodality of REM sleep is harder to discern in health. However, individuals with combined obstructive and central sleep apnea allows ready recognition of REMS and REMUS (stable and unstable REM sleep, respectively), especially when there is a discordance of respiratory patterns in relation to conventional stage of sleep.
Highlights
Sleep is an integrated brain-body state involving multiple coupled physiological systems, it is still categorized into traditional electroencephalographic (EEG)-based subtypes of rapid eye movement (REM) and non-rapid eye movement (NREM)
Analysis was performed on different data sets for the following reasons: (1) the differentiation of NREMS and NREMUS is very clear in patients with sleep apnea – and provides the best resource to establish slow oscillation (SO) dynamics in relation to electrocardiogram (ECG)spectrogram defined NREM sleep states; (2) The relationship of high frequency cardiopulmonary coupling (HFC) and blood pressure profiles is best demonstrated in healthy subjects, so that confounds from autonomic dysfunction seen commonly in sleep apnea patients are avoided; and (3) A third data set focused exclusively on the transition to REM sleep in patients with sleep apnea
(2) The NREM sleep slow oscillation shows two modes, one mode dominated by nearly continuous slow waves/down states and another with intermittent slow waves/down states (K-complexes by conventional characterization; rarely N3, usually N2). (3) Blood pressure during sleep was lowest during stage N3, slow wave sleep
Summary
Sleep is an integrated brain-body state involving multiple coupled physiological systems, it is still categorized into traditional electroencephalographic (EEG)-based subtypes of rapid eye movement (REM) and non-rapid eye movement (NREM). In humans, the latter state is graded, from stage N1 to N3, based on EEG sleep spindles, K-complexes and delta waves of ≥75 μV in amplitude and 0.5–2.0 Hz in frequency. Attempts have been made to differentiate “deep” from “light” NREM sleep, most typically by combining N1 and N2 into the latter, but uncertainty persists. Other approaches have attempted to parse NREM sleep into finer delineations with 9 or more sub-stages of NREM sleep (Ogilvie, 2001), and a continuous analysis of sleep power bands [Odds Ratio Product] (Younes et al, 2015)
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