Sleep and circadian rhythms modeling: From hypothalamic regulatory networks to cortical dynamics and behavior.

Abstract

Sleep and circadian rhythms are regulated by dynamic physiologic processes that operate across multiple spatial and temporal scales. These include, but are not limited to, genetic oscillators, clearance of waste products from the brain, dynamic interplay among brain regions, and propagation of local dynamics across the cortex. The combination of these processes, modulated by environmental cues, such as light-dark cycles and work schedules, represents a complex multiscale system that regulates sleep-wake cycles and brain dynamics. Physiology-based mathematical models have successfully explained the mechanisms underpinning dynamics at specific scales and are a useful tool to investigate interactions across multiple scales. They can help answer questions such as how do electroencephalographic (EEG) features relate to subthalamic neuron activity? Or how are local cortical dynamics regulated by the homeostatic and circadian mechanisms? In this chapter, we review two types of models that are well-positioned to consider such interactions. Part I of the chapter focuses on the subthalamic sleep regulatory networks and a model of arousal dynamics capable of predicting sleep, circadian rhythms, and cognitive outputs. Part II presents a model of corticothalamic circuits, capable of predicting spatial and temporal EEG features. We then discuss existing approaches and unsolved challenges in developing unified multiscale models.