Three different models were developed to investigate the effect of high frequency stimulation on epileptiform activity in vitro. The three models are high–potassium model, picrotoxin model and the high–potassium model plus picrotoxin model. The modulation and suppression of epileptiform activity during (ON-effect) and after (OFF-effect) high-frequency electrical stimulation was investigated using all hippocampal slice epilepsy models. Uniform sinusoidal fields (50 Hz) were applied with various intensity levels for 1 min across brain slices, extracellular and intracellular activity was monitored during and after stimulation.
The results showed that the ON-effects of high-frequency stimulation, including modulation of activity, pacing, partial suppression, or activity resembling spreading-depression, were highly variable across individual slices and models. On average, epileptic activity measured as power in the extracellular fields increased significantly during stimulation. Following the termination of electrical stimulation, a robust post-stimulation suppression period, i.e. OFF-effect, was observed. This OFF-effect was observed even at relatively moderate stimulation intensities. The duration of OFF-effect increased with stimulation intensity, independent of ON-effects. Antagonism of GABAa function did not directly affect OFF suppression duration.
The present results suggest that “rational” seizure control protocols using intermittent high-frequency electrical stimulation should control for both ON and OFF effects.
- Su Y, Radman T, Vaynshteyn J, Parra LC, Bikson M. Effects of High-Frequency Stimulation on Epileptiform Activity In Vitro: ON/OFF Control Paradigm. Epilepsia, 2008, 49 (9): 1586-1593. PDF
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