Efficacy of different strategies of responsive neurostimulation on seizure control and their association with acute neurophysiological effects in rats

Responsive neurostimulation (RNS) has shown promising but limited efficacy in the treatment of drug -resistant epilepsy. The clinical utility of RNS is hindered by the incomplete understanding of the mech-anism behind its therapeutic effects. Thus, assessing the acute effects of responsive stimulation (AERS) based on intracranial EEG recordings in the temporal lobe epilepsy rat model may provide a better under-standing of the potential therapeutic mechanisms underlying the antiepileptic effect of RNS. Furthermore, clarifying the correlation between AERS and seizure severity may help guide the optimiza-tion of RNS parameter settings. In this study, RNS with high (130 Hz) and low frequencies (5 Hz) was applied to the subiculum (SUB) and CA1.To quantify the changes induced by RNS, we calculated the AERS during synchronization by Granger causality and analyzed the band power ratio in the classic power band after different stimulations were delivered in the interictal and seizure onset periods, respectively. This demonstrates that only targets combined with an appropriate stimulation frequency could be efficient for seizure control. High -frequency stimulation of CA1 significantly shortened the ongoing seizure duration, which may be cau-sally related to increased synchronization after stimulation. Both high-frequency stimulation of the CA1 and low-frequency stimulation delivered to the SUB reduced seizure frequency, and the reduced sei-zure risk may correlate with the change in power ratio near the theta band. It indicated that different stimulations may control seizures in diverse manners, perhaps with disparate mechanisms. More focus should be placed on understanding the correlation between seizure severity and synchronization and rhythm around theta bands to simplify the process of parameter optimization.(c) 2023 Elsevier Inc. All rights reserved.

Automated summary

Studying the effects of responsive stimulation in a rat model of epilepsy can provide insights into the therapeutic mechanisms and guide parameter optimization. Understanding the correlation between seizure severity and synchronization can help simplify the evaluation process.