F05. Neurophysiological effects of chronic subthreshold cortical stimulation for focal epilepsy: Spike and spontaneous ECoG activity

Abstract

Neurostimulation is a treatment option for drug-resistant focal epilepsy. Chronic subthreshold cortical stimulation (CSCS) is a novel, promising technique that directly targets the seizure onset zone (SOZ) with continuous electrical stimulation. Prior retrospective analyses have shown reduced seizure frequencies and improved quality of life. Here, we investigate underlying neurophysiological changes induced by CSCS in order to gain an insight into the mechanism underlying the clinical effect of chronic electrical stimulation in focal epilepsy. We examined intracranial EEG data from seven patients with drug-resistant focal epilepsy and SOZs located in eloquent cortex who underwent continuous stimulation during their hospitalization. Subdural grid electrodes were implanted, and after the SOZ was localized to eloquent cortex, 2 Hz electrical stimulation was applied to contacts targeting the SOZ. Ninety minutes of intracranial EEG from a 4 × 4 electrode grid was analyzed before and during stimulation. Electrophysiological parameters were estimated for both pre-stimulation and stimulation data. Power spectrum and coherence of background activity was analysed together with spiking activity characteristics including spike rate, spike amplitude, and spike duration. Cortical stimulation resulted in a marked reduction of the amplitudes of background activity across all channel types for frequencies 5–40 Hz, particularly over SOZ electrodes. During cortical stimulation there was increased coherence between all electrodes and a decrease in spike rate, greatest over SOZ (p < 0.001). Spike-rate coherence was greatest within and between SOZ for pre-stimulation recordings and showed a significant decrease with cortical stimulation for electrodes near SOZ (p < 0.001). No such effect was seen for the other electrodes. Analysis of spike amplitudes showed that cortical stimulation resulted in a clear reduction of spikes over SOZ electrodes (p < 0.001) and only minor reductions for other electrodes (p < 0.001). Moreover, stimulation onset resulted in minor changes in the distribution of spike durations over all electrodes (p < 0.001). Spike-rate and power of background activity showed a significant correlation (p < 0.01). These results show changes in cortical electrophysiology during CSCS over the SOZ where reduction in interictal spikes is correlated with an attenuation of background activity. This suggests a possible causal relationship between background activity and interictal spikes and with seizure frequency rate. With an improved understanding of chronic electrical stimulation better stimulation paradigms might be developed for improved suppression of seizure frequency.