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We hypothesize that non-rapid-eye-movement sleep (NREM) is controlled by thermoregulatory mechanisms of the preoptic/anterior hypothalamus. Circadian and homeostatic thermoregulatory processes may be integrated in this brain area. To investigate this hypothesis, we have developed a mathematical model of qualitative features of human sleep-waking behavior based on a thermoregulatory feedback control mechanism, with modulation by two circadian oscillators, one a temperature rhythm, the other modulating sleepiness. Homeostatic features of the sleep rhythm are generated by integration of a heat load associated with waking. Simulations under entrained conditions show that the model closely mimics typical features of human sleep rhythms, including a biphasic daily pattern of sleepiness and sleep-onsets and awakenings fixed in a descending phase and an ascending phase of the temperature rhythm, respectively. Sleep duration is strongly controlled by the phase difference between the two oscillators with the same period; these could represent two phase-differentiated expressions of a single oscillator. In addition, the simulation of sleep deprivation provides a natural interpretation of the experimentally observed phenomena, which shows that the homeostatic and the oscillatory aspects of the human circadian system is successfully integrated in our model. The promising results obtained suggest that the control of sleep-wake rhythm could be understood within the framework of the thermoregulation.
Nakao et al. (Sun,) studied this question.