Low frequency stimulation decreases seizure activity in a mutation model of epilepsy

Abstract

Purpose: To investigate brain electrical activity in Q54 mice that display spontaneous seizures because of a gain‐of‐function mutation of the Scn2a sodium channel gene, and to evaluate the efficacy of low frequency deep brain stimulation (DBS) for seizure frequency reduction. Methods: Electroencephalography (EEG), electromyography (EMG), and hippocampal deep electrodes were implanted into Q54 mice expressing an epileptic phenotype (n = 6). Chronic six channel recordings (wideband, 0.1–300 Hz) were stored 24 h a day for more than 12 days. Low frequency stimulation (LFS) (3 Hz, square wave, biphasic, 100 μs, 400 μA) was applied to the ventral hippocampal commissure (VHC) in alternating 5 min cycles (on or off) 24 h a day for a period of 4 days. Results: LFS (3 Hz) resulted in a significant reduction in seizure frequency and duration (21% and 35%, p < 0.05), when applied to the VHC of epileptic Q54 mice (n = 6). Seizure frequency was not directly affected by stimulation state (“on” vs. “off”). Conclusion: LFS applied at a frequency of 3 Hz significantly reduced seizure frequency and duration in the Q54 model. Furthermore, the reduction of seizure frequency and duration by LFS was not immediate but had a delayed and lasting effect, supporting complex, indirect mechanisms of action.