Commentary: models of sleep regulation: successes and continuing challenges.

Quantitative models have been developed to describe salient aspects of human sleep regulation. The two-process model of sleep regulation and the thermoregulatory model of sleep control highlight the interaction between sleep homeostasis and circadian rhythmicity and the association between sleep and temperature regulation, respectively. These models have been successful and inspiring, but continuing progress remains dependent on rigorous testing of some of their basic assumptions. Whereas it has been established that EEG slow-wave activity is a marker of sleep homeostasis, its causal role in regulating the timing of sleep and wakefulness remains to be demonstrated conclusively. Likewise, the causal role of the temperature regulatory system in sleep timing requires further investigation. In both models, many parameters have yet to be associated with specific physiologic processes. This makes it challenging, at least within the framework of these models, to account for interindividual differences or age-related changes in such features as sleep duration and sleep timing, as well as changes in the phase angle between the sleep-wake cycle and accepted markers of the circadian pacemaker, such as the body temperature or melatonin rhythm. Although the models may describe adequately global sleep patterns and their circadian modulation, detailed modeling of the frequent short awakenings from, and the subsequent transitions back to, sleep, as well as the variation of the propensity to awaken across the ultradian non-REM-REM cycle, is not addressed. Incoporation of these aspects of sleep in mathematical models of sleep regulation may further our understanding of a key aspect of sleep regulation, that is, its timing.