Electrical stimulation of the endopiriform nucleus attenuates epilepsy in rats by network modulation

Donghong Li, Deng Luo, Junling Wang, Wei Wang, Zhangyi Yuan, Yue Xing, Jiaqing Yan, Zhiyi Sha, Horace H. Loh, Milin Zhang, Thomas R. Henry, Xiaofeng Yang

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Neuromodulatory anterior thalamic deep brain stimulation (DBS) is an effective therapy for intractable epilepsy, but few patients achieve complete seizure control with thalamic DBS. Other stimulation sites may be considered for anti-seizure DBS. We investigated bilateral low-frequency stimulation of the endopiriform nuclei (LFS-EPN) to control seizures induced by intracortically implanted cobalt wire in rats. Methods: Chronic epilepsy was induced by cobalt wire implantation in the motor cortex unilaterally. Bipolar-stimulating electrodes were implanted into the EPN bilaterally. Continuous electroencephalography (EEG) was recorded using electrodes placed into bilateral motor cortex and hippocampus CA1 areas. Spontaneous seizures were monitored by long-term video-EEG, and behavioral seizures were classified based on the Racine scale. Continuous 1-Hz LFS-EPN began on the third day after electrode implantation and was controlled by a multi-channel stimulator. Stimulation continued until the rats had no seizures for three consecutive days. Results: Compared with the control and sham stimulation groups, the LFS-EPN group experienced significantly fewer seizures per day and the mean Racine score of seizures was lower due to fewer generalized seizures. Ictal discharges at the epileptogenic site had significantly reduced theta band power in the LFS-EPN group compared to the other groups. Interpretation: Bilateral LFS-EPN attenuates cobalt wire-induced seizures in rats by modulating epileptic networks. Reduced ictal theta power of the EEG broadband spectrum at the lesion site may be associated with the anti-epileptogenic mechanism of LFS-EPN. Bilateral EPN DBS may have therapeutic applications in human partial epilepsies.

Original languageEnglish (US)
Pages (from-to)2356-2369
Number of pages14
JournalAnnals of Clinical and Translational Neurology
Volume7
Issue number12
DOIs
StatePublished - Dec 2020
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the National Natural Science Foundation of China (XFY 81671367, 81971202, 81790653, and 81471391). The authors thank Jianfeng Lei from Core Facilities Center, Capital Medical University for his technical help with MRI signal acquisition.

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