Effects of high-frequency stimulation on epileptiform activity in vitro: ON/OFF control paradigm

Epilepsia. 2008 Sep;49(9):1586-93. doi: 10.1111/j.1528-1167.2008.01592.x. Epub 2008 Apr 3.

Abstract

Purpose: To determine the effects of high-frequency electrical stimulation on electrographic seizure activity during and after stimulation (ON-effect and OFF-effect).

Methods: The modulation and suppression of epileptiform activity during (ON-effect) and after (OFF-effect) high-frequency electrical stimulation was investigated using the high-K(+) and picrotoxin 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 were monitored during and after stimulation.

Results: The ON-effects of high-frequency stimulation were highly variable across individual slices and models; ON-effects included modulation of activity, pacing, partial suppression, or activity resembling spreading-depression. On average, epileptic activity, measured as power in the extracellular fields, increased significantly during stimulation. Following the termination of electrical stimulation, a robust poststimulation suppression period was observed. This OFF suppression was observed even at relatively moderate stimulation intensities. The duration of OFF suppression increased with stimulation intensity, independent of ON-effects. Antagonism of GABA(A)function did not directly effect OFF suppression duration.

Conclusions: The present results suggest that "rational" seizure control protocols using intermittent high-frequency electrical stimulation should control for both ON and OFF effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Electric Stimulation / instrumentation
  • Electric Stimulation / methods*
  • Epilepsy / diagnosis
  • Epilepsy / physiopathology
  • Epilepsy / therapy*
  • Hippocampus / physiopathology
  • In Vitro Techniques
  • Pyramidal Cells / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Severity of Illness Index