Abstract

Temporal-lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy and warrants the development of new therapies, such as deep-brain stimulation (DBS). DBS was applied to different brain regions for patients with epilepsy; however, the mechanisms of action are not fully understood. Therefore, we tried to characterize the effect of amygdala DBS on hippocampal electrical activity in the lithium-pilocarpine model in male Wistar rats. After status epilepticus (SE) induction, seizure patterns were determined based on continuous video recordings. Recording electrodes were inserted in the left and right hippocampus and a stimulating electrode in the left basolateral amygdala of both Pilo and age-matched control rats 10 weeks after SE. Daily stimulation protocol consisted of 4 × 50 s stimulation trains (4-Hz, regular interpulse interval) for 10 days. The hippocampal electroencephalogram was analyzed offline: interictal epileptiform discharge (IED) frequency, spectral analysis, and phase-amplitude coupling (PAC) between delta band and higher frequencies were measured. We found that the seizure rate and duration decreased (by 23% and 26.5%) and the decrease in seizure rate correlated negatively with the IED frequency. PAC was elevated in epileptic animals and DBS reduced the pathologically increased PAC and increased the average theta power (25.9% ± 1.1 vs. 30.3% ± 1.1; p < 0.01). Increasing theta power and reducing the PAC could be two possible mechanisms by which DBS may exhibit its antiepileptic effect in TLE; moreover, they could be used to monitor effectiveness of stimulation.

Highlights

  • Temporal lobe epilepsy (TLE) is one of the most common chronic neurological disorder and it severely affects the person’s quality of life [1]

  • The amygdala plays an important role in temporal lobe epilepsy [17,18], and its electrical stimulation with low frequency (LFS, e.g., with 1-4 Hz) can decrease the epileptiform electrical activity if at least four packages with at least 200 pulses are administered with 5 min pauses between the stimuli [19,20]

  • Racine 3–6 stage seizures were identified based on video recordings

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Summary

Introduction

Temporal lobe epilepsy (TLE) is one of the most common chronic neurological disorder and it severely affects the person’s quality of life [1]. The amygdala plays an important role in temporal lobe epilepsy [17,18], and its electrical stimulation with low frequency (LFS, e.g., with 1-4 Hz) can decrease the epileptiform electrical activity if at least four packages with at least 200 pulses are administered with 5 min pauses between the stimuli [19,20]. High frequency stimulation (HFS) was demonstrated to be more effective in reducing seizures and is often used in DBS therapies [21,22], but LFS showed antiepileptic effect in a couple of human trials [23,24] and in several animal models of epilepsy [25,26,27,28]

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