Modeling Interindividual Differences in Spontaneous Internal Desynchrony Patterns

Abstract

A physiologically based mathematical model of a putative sleep-wake regulatory network is used to investigate the transition from typical human sleep patterns to spontaneous internal desynchrony behavior observed under temporal isolation conditions. The model sleep-wake regulatory network describes the neurotransmitter-mediated interactions among brainstem and hypothalamic neuronal populations that participate in the transitions between wake, rapid eye movement (REM) sleep, and non-REM (NREM) sleep. Physiologically based interactions among these sleep-wake centers and the suprachiasmatic nucleus (SCN), whose activity is driven by an established circadian oscillator model, mediate circadian modulation of sleep-wake behavior. When the sleep-wake and circadian rhythms are synchronized, the model simulates stereotypically normal human sleep-wake behavior within the limits of individual variation, including typical NREM-REM cycling across the night. When effects of temporal isolation are simulated by increasing the period of the sleep-wake cycle, the model replicates spontaneous internal desynchrony with the appropriate dependence of multiple features of REM sleep on circadian phase. In temporal isolation experiments, subjects have exhibited different desynchronized sleep-wake behaviors. Our model can generate similar ranges of desynchronized behaviors by variations in the period of the sleep-wake cycle and the strength of interactions between the SCN and the sleep-wake centers. Analysis of the model suggests that similar mechanisms underlie several different desynchronized behaviors and that the phenomenon of phase trapping may be dependent on SCN modulation of REM sleep-promoting centers. These results provide predictions for physiologically plausible mechanisms underlying interindividual variations in sleep-wake behavior observed during temporal isolation experiments.