AUTHOR=Zhang Fang , Yang Yufang , Zheng Yongte , Zhu Junming , Wang Ping , Xu Kedi 

TITLE=Combination of Matching Responsive Stimulations of Hippocampus and Subiculum for Effective Seizure Suppression in Temporal Lobe Epilepsy

JOURNAL=Frontiers in Neurology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.638795

DOI=10.3389/fneur.2021.638795

ISSN=1664-2295

ABSTRACT=Responsive neural stimulations (RNS) is deemed as a promising neural modulation therapy for refractory epilepsy. Combined stimulation on different targets may hold great promise for improving the efficacy of seizure control since neural activity changed dynamically within associated brain targets in the epileptic network. Three major issues need to be further explored to achieve better efficacy of combined stimulation: 1) which nodes within the epileptogenic network should be chosen as stimulation targets? 2) what stimulus frequency should be delivered to different targets? 3) Could the efficacy of RNS for seizure control be optimized by combined different stimulation targets together. In our current study, Granger causality (GC) method was applied to analyze epileptogenic networks for finding key targets of RNS. Single target stimulation (100 µA amplitude, 300 µs pulse width, 5s duration, biphasic, charge-balanced) with high frequency (130Hz, HFS) or low frequency (5 Hz, LFS) was firstly delivered by our lab designed RNS systems to CA3, CA1, subiculum (SUB) of hippocampi and anterior nucleus of thalamus (ANT). The efficacy of combined stimulation with different groups of frequencies was finally assessed to find out better combined key targets with optimal stimulus frequency. Our results showed that stimulation individually delivered to SUB and CA1 could shorten the average duration of seizures. Different stimulation frequency impacted the efficacy of seizure control, as HFS delivered to CA1 and LFS delivered to SUB respectively were more effective for shortening the average duration of afterdischarge in Sprague-Dawley rats (n = 3). Moreover, the synchronous stimulation of HFS in CA1 combined with LFS in SUB reduced the duration of discharge significantly in rats (n = 6). The combination of responsive stimulation at different targets may be an inspiration to optimize stimulation therapy for epilepsy.