Circadian and Homeostatic Regulation of Human Sleep and Cognitive Performance and Its Modulation by PERIOD3

Sleep physiology and waking performance are regulated through the interaction of an endogenous circadian process and a sleep-wake-dependent homeostatic process. The two processes are not independent: the observed circadian amplitude of waking performance depends on homeostatic sleep pressure, so that the negative effects of sleep loss are most pronounced in the early morning if homeostatic sleep pressure is high. These findings underscore the close interrelations between sleep, circadian rhythmicity, and waking performance and suggest that some circadian phenotypes are related to changes in sleep-regulatory processes. Understanding the effects of these alterations in clock genes, such as PER3, at the cellular and biochemical level may provide insights into the nature of the sleep homeostat and its interaction with circadian rhythmicity in the regulation of waking performance.