Abstracts

Rationale: Investigations in animals and humans have shown that electric cortical stimulation (ECS) has an inhibitory effect on epileptic focus. ECS, such as responsive neurostimulation, has already been applied as one of the effective treatments for epilepsy. However, its inhibitory mechanism has not been well elucidated. Interictal epileptiform discharges (IEDs) usually consist of spike and post-spike slow (PSS), reflecting excitation and inhibition, respectively. Similarly, interictal high frequency oscillations or activities (HFOs/HFAs), especially above 80 Hz, have been reported to reflect the epileptogenicity. In this study, by using IEDs and spike-related HFAs as dynamic measures of cortical excitability, we aimed to clarify the inhibitory mechanism of ECS in human epileptic focus. Methods: We recruited 7 patients with intractable partial epilepsy who underwent invasive presurgical evaluation with subdural electrodes (IRB C580). 50-Hz stimulation (bipolar, alternating square pulse of 0.3 ms duration, 1-15 mA, 1-5 sec) was applied on the seizure onset zone (SOZ) and non-SOZ as a part of functional cortical mapping. For each 5-min period before (5 min) and after ECS (20 min consisting of 4 periods: 0-5, 5-10, 10-15, and 15-20 min), we first semiautomatically detected IEDs at the SOZ and then confirmed the true IEDs with visual inspection. We measured the amplitude of spikes and PSS, and evaluated the power of spike-related HFAs for fast ripple (FR: 200-300 Hz), ripple (R: 80-150 Hz), low gamma (30-50 Hz) and beta (15-30 Hz) bands by Hilbert transform. Taking account of the effects of the stimulation on background activity as reported elsewhere (Kinoshita et al., 2004), we also calculated the power of background activity for each band after excluding the 1000 ms epochs associated with spike (-300 to 700 ms after the spike). Results: In the group analysis, stimulation of the SOZ (a total of 0.3~23.0 mC per patient) significantly decreased the number of IEDs and the amplitude of spikes (repeated one-way ANOVA, p < 0.05). Post-hoc analysis showed significant difference in both number and amplitude between pre-stimulation and post-stimulation (0-5 min). In the individual analysis, the power of spike-related HFAs in FR and R bands significantly decreased in 4 out of 6 patients (Dunn test). Effect of ECS on the power decrement was substantially greater in spike-related HFAs than the background activity. None of these factors changed after stimulating the non-SOZ. Among 3 patients with discrete PSS, ECS significantly increased the amplitude ratio of PSS/spike in 2 patients (Dunn test). Conclusions: Repeated, 50-Hz ECS on SOZ transiently decreased the number of IEDs, the amplitude of spikes, and the power of spike-related HFAs, while it increased the amplitude ratio of PSS/spike in a few patients. These results suggest that ECS potentially modulates cortical excitability toward less excitation and more inhibition. Funding: This work was partly supported by KAKENHI 26293209, 15H05874, 15K10361.