Amygdala Low-Frequency Stimulation Reduces Pathological Phase-Amplitude Coupling in the Pilocarpine Model of Epilepsy

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.

Thalamic deep brain stimulation modulates cycles of seizure risk in epilepsy

“…The pivotal study for ANT DBS 27 delivered high frequency stimulation on a duty cycle (1 min on, 5 min off) without clear supporting evidence; DBS for movement disorders is typically provided using continuous high frequency stimulation. Less is known about low frequency DBS, however there is empirical evidence to support low frequency cortical and subcortical stimulation for the treatment of epilepsy 31 , 34 , 35 , 58 , 59 , and evidence that noninvasive low frequency stimulation depresses cortical excitability 32 .…”

Paradoxical effects of posterior intralaminar thalamic calretinin neurons on hippocampal seizure via distinct downstream circuits

“…The LA and ZI are regions of the brain are associated in different types of seizures ( Hamani et al., 2002 ; Mihaly et al., 2020 ; Wang et al., 2014 ). Here, we verified that both LA and ZI exhibited dense c-Fos expression, implying they are active during seizure.…”

Thalamic deep brain stimulation modulates circadian and infradian cycles of seizure risk in epilepsy

“…The pivotal study for ANT DBS [27] delivered high frequency stimulation on a duty cycle (1 minute on, 5 minutes off) without clear supporting evidence; DBS for movement disorders is typically provided using continuous high frequency stimulation. Less is known about low frequency DBS, however there is empirical evidence to support low frequency cortical and subcortical stimulation for the treatment of epilepsy [30,33,34,54,55], and evidence that noninvasive low frequency stimulation depresses cortical excitability [31].…”