Abstracts

Rationale: Seizures in individuals with epilepsy are often accompanied by disordered sleep: this may present as reduced sleep depth, altered proportions of rapid eye movement (REM) and non-REM (NREM) sleep, brief apnea or transient arousal, and other phenomena. Poor sleep in turn can precipitate seizures, thus sustaining a vicious cycle. While it is easy to believe that seizure control will improve sleep as a byproduct, we hypothesize that active modulation of sleep quality can be used as a strategy for alleviating seizures. It is well known that changes in ambient temperature elicit thermoregulatory responses that also influence the sleep-wake cycle. As a small first step toward the objective of sleep modulation in epilepsy, we characterize the effects of acutely elevated temperature on vigilance states in mice.Methods: Seven adult male C57BL/6J mice, 6-8 weeks old, were instrumented under anesthesia for tethered EEG/EMG recording with IACUC approval. Each mouse was housed independently with free access to food and water and monitored using video and EEG. After allowing the animal to recover completely from EEG implantation, a custom-built thermostatic control system was used to maintain cage temperature at one of four values (24, 27, 30, and 33 Celsius) around the thermoneutral zone on each of four consecutive days from 11 a.m. to 5 p.m. during the light period (day), when mice are most somnolent. Vigilance state was scored manually from the recordings in consecutive 4s epochs as Wake, REM, or NREM. The effect of temperature on conventional sleep metrics was studied.Results: Acute exposure to elevated temperature over a few hours significantly decreased the mean % time spent in Wake, while significantly increasing both the mean % time in REM and NREM sleep. While this effect confirms previous observations in chronic experiments, we also found that mean NREM bout duration increases with temperature (p<0.05) but not the mean number of NREM bouts. This trend suggests that NREM sleep occurs more often and is less likely to be interrupted by brief arousals (less fragmented). The distribution of delta band EEG power (0.5-4 Hz) shifted upward with temperature, which suggests that sleep depth is also increased. At the same time, the mean number of REM bouts increases (though not significantly) but not mean REM bout duration. The implication of these opposing trends for REM and NREM sleep is not yet clear.Conclusions: Vigilance state and changes in sleep quality are both critical in determining seizure likelihood. Manipulation of ambient temperature offers a simple and minimally obtrusive way to titrate sleep quality and study the consequences on seizure burden in epilepsy. We are currently using this technique to study temperature effects on sleep dynamics and seizures in the pilocarpine mouse model of chronic temporal lobe epilepsy with spontaneously recurring seizures. Acknowledgement: Supported in part by NINDS (grant NS083218) and the University of Kentucky Epilepsy Research Center (EpiC). A. Ajwad received scholarship support from the Higher Committee of Education in Iraq.