Comparative analysis of seizure control efficacy of 5Hz and 20Hz responsive deep brain stimulation in rodent models of epilepsy

We assess the effects of low-frequency (5Hz) responsive stimulation (LFRS) and high-frequency (20Hz) responsive stimulation (HFRS) of the rat hippocampus on the spontaneous seizure suppression in two rodent models of epilepsy. Acute seizures in 12 rats were induced by intra-hippocampal injection of 4-amynopyridine (4-AP) and chronic seizures in six rats were induced by intraperitoneal injection of kainic acid. Two bipolar electrodes were implanted into the CA1 regions of both hippocampi. The electrodes were connected to a custom-built responsive neurostimulator that detects the intracerebral electroencephalographic (icEEE) seizure onset and triggers a responsive electrical stimulation. The rats were randomly divided into two groups: non-stimulation and stimulation group. The non-stimulation group did not receive stimulation, whereas the stimulation group received LFRS and HFRS. The baseline average seizure rate in the non-stimulation group was ~6.5 seizures per 30-minute in the acute model and ~5 seizures per day in the chronic model. The seizure rate in the stimulation group was reduced by 80.8% during the LFRS, while the HFRS reduced seizure frequency only by 26.9% and in the chronic model, 91.6% during the LFRS, while the HFRS reduced seizure frequency only by 15%. The seizure formation was effectively aborted using the LFRS by means of the neural inhibition mechanism, which is similar to that of anti-epileptic drugs. In this responsive stimulation technique, the inhibition lasted only for several seconds, as needed for the seizure suppression, unlike the continuous inhibition (neural activity suppression) in the case of anti-epileptic drugs.