Abstracts

Epilepsy is characterized as a chronic brain state with a very low seizure threshold. In people that develop epilepsy, there must be changes in brain functioning that results in a lowered seizure threshold prior to the appearance of the first seizure. Currently there is no animal model of induced epilepsy that allows for the exploration of the neural basis of a low seizure threshold without the elicitation of seizures. For instance stimulation that results in kindling both lowers thresholds and elicits seizures. Likewise the models that develop spontaneous seizures result from a treatment that elicits seizures. In this study we employed repeated application of subthreshold electrical stimulation in an attempt to lower seizure thresholds without eliciting seizures., Expt 1: Rats were implanted with bipolar stimulating and recording electrodes in the corpus callosum and sensorimotor cortex respectively. Once daily stimulation consisted of biphasic rectangular waves (1 ms, 60 Hz, for 1 sec). A range of stimulation intensities (20, 30, 40, 50, and 500 uA) was used. Prior to, and following 20 stimulation sessions at a single intensity, the afterdischarge (seizure) threshold was determined.
Expt 2: The goal of this experiment was to reduce seizure thresholds in the absence of ANY seizures. Because the measurement of afterdischarge threshold (ADT) necessitates one AD, the initial ADT measurement was excluded for Expt 2. The intensity groups chosen for Expt 2 were 20, 50, and 500 uA as well as two additional groups (150, 250 uA)., Repeated stimulation at 50 uA was most effective at reducing the ADT in sensorimotor neocortex. However, even at this intensity, it was difficult to achieve a complete absence of seizure activity. Unexpectedly the highest intensity stimulation groups (250, [amp] 500 uA) showed repeated seizure activity but did not show a reduction of ADT., Low intensity electrical stimulation allowed for the reduction of seizure thresholds with few seizures, while high intensity electrical stimulation reliably elicits seizures without lowering seizure thresholds. These two stimulation protocols can be used to dissociate the neural basis of a low seizure threshold from the reorganizing effect of repeated seizures., (Supported by NSERC.)