Polarity-dependent effect of low-frequency stimulation on amygdaloid kindling in rats

Background: Low-frequency stimulation (LFS, <5 Hz) has been proposed as an alternative option for the treatment of epilepsy. The stimulation pole, anode and cathode, may make different contributions to the anti-epileptic effect of LFS. Objective: To determine whether electrode polarity influences the anti-epileptic effect of LFS at the kindling focus in amygdaloid kindling rats. Methods: The effect of bipolar and monopolar (or unipolar) LFS at the amygdala in different polarity directions on amygdaloid kindling acquisition, kindled seizures and electroencephalogram (EEG) were tested. Results: Bipolar LFS in the same direction of polarity as the kindling stimulation but not in the reverse direction retarded kindling acquisition. Anodal rather than cathodal monopolar LFS attenuated kindling acquisition and kindled seizures. Bipolar LFS showed a stronger anti-epileptic effect than monopolar LFS. Furthermore, anodal LFS (both bipolar and monopolar) decreased, while cathodal LFS increased the power of the EEG from the amygdala; the main changes in power were in the delta (0.5-4 Hz) band, which was specifically increased during kindling acquisition. Conclusions: Our results provide the first evidence that the effect of LFS at the kindling focus on amygdaloid kindling in rats is polarity-dependent, and this may be due to the different effects of anodal and cathodal LFS on the activity in the amygdala, especially on the delta band activity. So, It is likely that the electrode polarity, especially that for anodal current, is a key factor affecting the clinical effects of LFS on epilepsy. (C) 2013 Elsevier Inc. All rights reserved.