Role Of Vigilance State And Circadian Phase In Seizure-Related Death

Sudden unexpected death in epilepsy (SUDEP) most commonly occurs at night, but why this happens is unknown. We hypothesize that this may be due to sleep state-dependent and/or circadian (time-of-day) variation in the respiratory and cardiac consequences of seizures. We further postulate that impaired functioning of the brain signaling molecule serotonin may be involved. To test this, we will employ a genetic mouse model of serotonin depletion to evaluate the effects of seizures which occur during different sleep-wake states and circadian times on breathing, heart control, and mortality. Understanding factors causing SUDEP to occur at night may lend insights regarding why it occurs at all, and ultimately lead to measures to prevent it.