Interference Effect of 3 Hz Brain Stimulation on Kindling Behavior Induced by 60 Hz Stimulation

Abstract

Experiments were conducted to evaluate the effect of 3 Hz brain stimulation on kindling behavior induced by 60 Hz sine waves stimulation. In Experiment 1, 12 rats were subjected to 40 or 60 convulsion trials with 60 Hz stimulation and then given 36 trials of 3 Hz stimulation. When these rats were stimulated again with 60 Hz sine wave current at the same brain site, none of the rats showed a convulsion in nine test trials. The intensity of stimulation had to be increased on test trial 10 to elicit convulsions for each rat. Of 10 rats in two control groups, only 1 did not convulse during the nine test trials. In Experiment 2 the effective threshold intensity (ETI) to elicit a convulsion was determined on five separate occasions with 10 days of daily trials between determinations. On each day experimental rats were stimulated with 3 Hz current on the first and third trials and with 60 Hz current on the second trial (3-60-3 group). A steady increase in the intensity required to elicit a convulsion with 60 Hz current from ETI1 to ETI5 resulted. Rats stimulated only with 60 Hz sine waves on the second trial each day (X-60-X grou,) maintained relatively stable values from ETI1 to ETI5. In the four, 10-day blocks of trials, convulsions were suppressed in 20% to 80% of the trials over the 10 day period for the 3-60-3 group, with the greatest effect occurring after about 4 days of stimulation. This suppressive effect was prominent both with rats that were at the convulsion stage prior to the first application of 3 Hz stimulation and with rats that were at preconvulsion stages. In Experiment 3 the permanency of the suppressive effect was evaluated. Eight suppressed rats from the experimental group in Experiment 2 and 4 control rats were stimulated for 90 trials over 30 days with 60 Hz current, and ETI values were determined after each set of six trials. Four of the 8 experimental rats were convulsing at ETI1 within 20 days.

Toward rational design of electrical stimulation strategies for epilepsy control

“…It should also be noted that there is a line of in vivo animal studies centered around kindling models investigating low-frequency, typically 3 Hz sinusoids, that originated with Gaito et al139, but was continued by others140,141,142. In the original studies, animals are given high frequency (50–60 Hz) pulse trains through electrode in the amygdala until they have a seizure.…”

Low Frequency Electrical Stimulation Either Prior to Or after Rapid Kindling Stimulation Inhibits the Kindling-Induced Epileptogenesis

“…Administration of LFS is considered to inhibit the seizure activity by inducing long term depression (LTD) and removing kindling-induced synaptic potentiation [26]. The antiepileptogenic role of LFS during the kindling procedure was first introduced by Gaito et al [27, 28]. Following that, several studies revealed that LFS can prevent generalization of seizures and inhibit boosting induction of the kindling phenomenon through alteration of electrophysiological features and inhibition of the synaptic activity [20, 25, 29–32].…”

Interference effects within the kindling paradigm

“…In a series of experiments, 3-Hz stimulation consistently produced an interference effect, that is, suppression of convulsions initiated by 60-Hz stimulation (Gaito, 1979b(Gaito, , 1979cGaito, Nobrega, & Gaito, 1980). Another experiment evaluated the effect of varying durations of I-Hz stimulation, namely, 0, 5, 15, 30, 60, 120, 180, and 600 sec (Gaito, 1980).…”