Effects of high-frequency stimulation on epileptiform activity in vitro: ON/OFF control paradigm.
OBJECTIVE
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.
Su
Yuzhuo
Y
Department of Biomedical Engineering, The City College of New York, City University of New York, New York, New York 10031, USA.
Radman
Thomas
T
Vaynshteyn
Jake
J
Parra
Lucas C
LC
Bikson
Marom
M
D000818:Animals; D004558:Electric Stimulation / Q000295:instrumentation / Q000379:methods*; D004827:Epilepsy / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D006624:Hippocampus / Q000503:physiopathology; D066298:In Vitro Techniques; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index