Abstracts

Suppression of ictal activity, and ultimately behavioral seizures, with high frequency (HF) stimulation is a goal of recent device-based neurological therapy development. To the best of our knowledge, [italic]in vivo[/italic] stimulation to suppress epileptic activity has not been used in a freely-moving rodent model of spontaneous, recurrent seizures. The present study interrogates candidate target sites seeking optimal stimulation parameters for suppression of interictal events (IIEs) in the epileptic hippocampus.
Bipolar recording [mu]electrodes were implanted bilaterally in the dentate gyrus (DG) of the pilocarpine rat epilepsy model. Bipolar stimulating [mu]electrodes were implanted in the right perforant path (RPP), and bilaterally in both the caudate-putamen (CPU) and ventral anterior thalamus (VAT). During [italic]in vivo[/italic] EEG recording in DG, stimulation trains (1 ms pulse duration, biphasic sine wave) that varied in frequency (50, 100, 130 or 200 Hz), current intensity (200-500 [mu]A) and duration (0.1s [ndash] 1s) were delivered to candidate sites. IIE[rsquo]s were defined as spikes of at least 2 SD above baseline. IIE suppression was quantified: 1) by latency to first IIE after a single stimulus train, and 2) comparison of IIE rate during a 5 m period of repeated stimulus trains compared to equal pre- and post-stimulation time periods. Data was analyzed by ANOVA and t-test.
Initial results demonstrate that, compared to bilateral CPU and VAT, unilateral RPP stimulation more effectively suppressed IIE[rsquo]s as a function of current intensity. Latency to the first hippocampal IIE recorded after a single HF train (100 Hz, 1 s) was significantly longer following stimulation of RPP, compared to bilateral CPU (p [lt] .001) and VAT (p [lt] .001) with equivalent parameters. Repeated HF trains delivered to RPP (100 Hz, 250 ms every 5 s) over a 5 m period significantly suppressed DG IIE rate by 52% (p [lt] .001) and 86% (p [lt] .001) from pre-stimulus baseline with 250 and 300 [mu]A stimulation, respectively. IIE suppression with 300 [mu]A trains was significantly greater than that with 250 [mu]A trains (p [lt] .001).
The greater suppression of DG IIE[rsquo]s with RPP stimulation demonstrates that sites monosynaptically connected to DG are more effective in IIE suppression. Assuming electrical suppression of interictal pathology may be a first step toward suppression of seizures, it would be worthwhile to discern the most effective targets and stimulation parameters. Subsequent studies are aimed at comparing the same sites for efficacy of spontaneous seizure blockade in this animal model.
[Supported by: NSF IGERT Neuroengineering Training Grant DGE-9972802, NIH NS-08208, NS-33310 [amp] NeuroPace, Inc.]