Control of sleep and wakefulness in health and disease.

Sleep and wake are actively promoted states of consciousness that are dependent on a network of state-modulating neurons arising from both the brain stem and hypothalamus. This network helps to coordinate the occurrence of a sleep state in billions of cortical neurons. In many neurological diseases, there is a specific disruption to one of the components of this network. Under conditions of such disruptions, we often gain an improved understanding of the underlying function of the specific component under nonpathological conditions. The loss or dysfunction of one of the hypothalamic or brain stem regions that are responsible for promotion of sleep or wake can lead to disruptions in sleep and wake states that are often subtle, but sometime quite pronounced and of significant medical importance. By understanding the neural substrate and its pathophysiology, one can more appropriately target therapies that might help the specific sleep disruption. This chapter reviews what is currently understood about the neurobiological underpinnings of sleep and wake regulation and how various pathologies evoke changes in these regulatory mechanisms.