Abstracts

Rationale: Nearly thirty percent of patients continue to have recurrent spontaneous temporal lobe seizures after pharmacological intervention. Current clinical trials use an open-loop simulation approach. Success of a closed-loop seizure prevention system would require identification of a measurable EEG feature. Spike wave discharges often accompany epilepsy; however, the relationship between interictal spike and seizure onset is largely unknown. Here, we present a method for both sorting interictal spikes and relating their occurrence with seizure onset in a rat model of temporal lobe epilepsy (TLE). Methods: Fifty-six-day-old male Sprague-Dawley rats, weighing between 200-250 g, were implanted with 330 micron, Teflon-coated, stainless steel bilateral bipolar twist electrodes into the hippocampal CA1 region. An additional stimulating bipolar twist electrode was implanted into the ventral hippocampus in order to induce electrical self-sustaining status epilepticus. After 2-6 weeks, spontaneous Racine grade 5 seizures developed in 80% of rats. Rats were monitored with continuous time-locked video/ EEG in order to screen for seizures. A threshold was set five standard deviations above the medium of the absolute value of the recording. Population spikes (PS) which crossed this threshold were extracted from each data set. Extracted PS time series were grouped using a modified version of the well-known clustering algorithm by Fee et. al (J Neurosci Methods 69(2): 175-88.). Results: Two primary categories of PS were detected. When the number of PS occurring per 10 min of recording was binned and plotted, a decrease in PS1 spikes firing rate was observed at seizure onset (figure 1A). PS2 spikes have the greatest correlation between firing rate and seizure onset. PS2 increased from minutes to hours before seizure onset (figure 1B). Conclusions: Our results suggest there is a temporal relationship between CA1 region PS rate and seizure onset in an animal model of TLE. Direct modulation of PS activity will be used to generate a closed-loop seizure prevention system. Funding: National Institutes of Health R01-EB004752-01 and R01 EB002089, and Wilder Center of Excellence for Epilepsy Research.