Experimental Manipulation of Sleep to Combat Epilepsy (RPA Pilot / Seed Project)

Disordered sleep is common in persons with epilepsy (PWE). Seizures disrupt sleep, and disrupted sleep in turn precipitates seizures; and the correlations vary with stage of sleep and type of epilepsy. This sleep-seizure interplay is a vicious cycle that is detrimental to the health and well-being of PWE. Anti-seizure therapies can also disrupt sleep or impair vigilance (e.g., drugs, neurostimulation). Thus, seizure control strategies that conserve or enhance sleep are critically needed. Animal models reproduce key features of epilepsy pathophysiology and allow us to probe mechanisms and interventions in ways that are difficult in humans, but while sleep deprivation has been studied in epilepsy models, the effects of selective sleep loss—and sleep enhancement—remain unclear. Our central hypothesis is that selective manipulation of sleep architecture will help clarify the impact of different kinds of sleep disruption on seizures and pathology, and that active sleep enhancement, particularly in the developmental stages, will improve outcomes for PWE. Our strong preliminary data supports the feasibility of selective sleep restriction and the correlation between sleep enhancement and pathology. Objectives: We seek to investigate the effects of clinically relevant alterations in sleep architecture on epileptogenesis and epilepsy pathology using suitable animal models and proven methods for sleep tracking and modulation developed in our lab through the specific aims below.