Adi Cymerblit-Sabba1, Maya Schiller, Yitzhak Schiller. 1. Department of Physiology, The Rappaport Faculty of Medicine and Research Institute, Technion - Israel Institute of Technology, Haifa, Israel.
Abstract
BACKGROUND: Neurostimulation has been proposed as a potential new treatment modality for pharmacoresistant epilepsy. Yet the effect of the different stimulation parameters on the efficacy of stimulation is not sufficiently known. OBJECTIVE: Investigate the effect of different stimulation parameters on the efficacy of neurostimulation in terminating acute chemoconvulsant-induced hippocampal seizures in-vivo. METHODS: Seizures were induced in rats in-vivo either by systemic or local intra hippocampal application of chemoconvulsants, and bipolar electrical stimulation was applied during seizures by stimulating the perforant pathway of the hippocampus. The stimulus intensity, frequency, and duration were altered. RESULTS: Increasing the stimulus intensity and train duration increased the probability for seizure termination. The efficacy of stimulus intensity peaked at 250-300 μA. Low stimulation frequencies (≤13 Hz) were inefficient in terminating seizures. Increasing the stimulation frequency (up to 250 Hz) enhanced seizure termination, reaching a plateau effect at frequencies of 50-100 Hz. When we simultaneously applied the same stimulation frequency in two adjacent electrodes (synchronous stimulation) the probability for seizure termination did not significantly change. In contrast when the two stimulating electrodes were simultaneously activated with different asynchronous stimulation frequencies (30 and 100 Hz or 60 and 200 Hz, asynchronous stimulation) the probability for terminating seizures more than doubled. Similar results were also observed with local intra hippocampal-induced seizures. CONCLUSIONS: Asynchronous stimulation paradigms enhanced the antiepileptic efficacy of neurostimulation, possibly by desynchronizing and functionally subdividing the network.
BACKGROUND: Neurostimulation has been proposed as a potential new treatment modality for pharmacoresistant epilepsy. Yet the effect of the different stimulation parameters on the efficacy of stimulation is not sufficiently known. OBJECTIVE: Investigate the effect of different stimulation parameters on the efficacy of neurostimulation in terminating acute chemoconvulsant-induced hippocampal seizures in-vivo. METHODS:Seizures were induced in rats in-vivo either by systemic or local intra hippocampal application of chemoconvulsants, and bipolar electrical stimulation was applied during seizures by stimulating the perforant pathway of the hippocampus. The stimulus intensity, frequency, and duration were altered. RESULTS: Increasing the stimulus intensity and train duration increased the probability for seizure termination. The efficacy of stimulus intensity peaked at 250-300 μA. Low stimulation frequencies (≤13 Hz) were inefficient in terminating seizures. Increasing the stimulation frequency (up to 250 Hz) enhanced seizure termination, reaching a plateau effect at frequencies of 50-100 Hz. When we simultaneously applied the same stimulation frequency in two adjacent electrodes (synchronous stimulation) the probability for seizure termination did not significantly change. In contrast when the two stimulating electrodes were simultaneously activated with different asynchronous stimulation frequencies (30 and 100 Hz or 60 and 200 Hz, asynchronous stimulation) the probability for terminating seizures more than doubled. Similar results were also observed with local intra hippocampal-induced seizures. CONCLUSIONS: Asynchronous stimulation paradigms enhanced the antiepileptic efficacy of neurostimulation, possibly by desynchronizing and functionally subdividing the network.