Cognitive brain responses during circadian wake-promotion: evidence for sleep-pressure-dependent hypothalamic activations

The two-process model of sleep-wake regulation posits that sleep-wake-dependent homeostatic processes interact with the circadian timing system to affect human behavior. The circadian timing system is fundamental to maintaining stable cognitive performance, as it counteracts growing homeostatic sleep pressure during daytime. Using magnetic resonance imaging, we explored brain responses underlying working memory performance during the time of maximal circadian wake-promotion under varying sleep pressure conditions. Circadian wake-promoting strength was derived from the ability to sleep during an evening nap. Hypothalamic BOLD activity was positively linked to circadian wake-promoting strength under normal, but not under disproportionally high or low sleep pressure levels. Furthermore, higher hypothalamic activity under normal sleep pressure levels predicted better performance under sleep loss. Our results reappraise the two-process model by revealing a homeostatic-dose-dependent association between circadian wake-promotion and cognition-related hypothalamic activity.