An Improved Intermittent Electrical Stimulation Therapy for Penicillin-induced Seizure Suppression

Neuromodulation is a promising treating therapy for drug-resistant epilepsy. Studies have shown that electrical stimulation could induce post-stimulus inhibition of neural activity, making it available for aborting seizure. Considering the long-term safety, intermittent open loop electrical stimulations are commonly employed in both experimental studies and clinical trials. Commonly applied stimulations were alternation sequences between stimulation ONs and OFFs, during which both stimulation pulse trains and interval periods lasted several minutes. The long periods of stimulations may lead to damage to both tissue and electrode itself. To optimize treatment efficacy, in current study, a new stimulation paradigm was designed. To reduce charge accumulation, two pairs of cross-located electrodes were implanted for interleaved stimulation delivering. Besides, brief pulse trains with short intervals were applied instead of relatively long stimulation cycle. Key stimulation parameters were tested for efficacy comparison. And long-term seizure suppression effects were monitored and estimated by LFP signals. The results showed that in acute Penicillin-induced seizure model, the new stimulation therapy could significantly reduce seizure durations by 80.3%. The counts of seizure were also found to be reduced by 80.7%. These results demonstrated that with shortened stimulation sequences, seizures could still be suppressed efficiently, providing a new possible stimulation paradigm for seizure treatment.