Closed-loop direct control of seizure focus in a rodent model of temporal lobe epilepsy via localized electric fields applied sequentially

Abstract

Direct electrical stimulation of the seizure focus can achieve the early termination of epileptic oscillations. However, direct intervention of the hippocampus, the most prevalent seizure focus in temporal lobe epilepsy is thought to be not practicable due to its large size and elongated shape. Here, in a rat model, we report a sequential narrow-field stimulation method for terminating seizures, while focusing stimulus energy at the spatially extensive hippocampal structure. The effects and regional specificity of this method were demonstrated via electrophysiological and biological responses. Our proposed modality demonstrates spatiotemporal preciseness and selectiveness for modulating the pathological target region which may have potential for further investigation as a therapeutic approach.

Preferential pruning of inhibitory synapses by microglia contributes to alteration of the balance between excitatory and inhibitory synapses in the hippocampus in temporal lobe epilepsy

“…The Racine scores were applied to rate seizure severity: category 1, immobility and facial twitch; category 2, head nodding; category 3, forelimb clonus; category 4, rearing; and category 5, rearing and falling 46 . According to previous studies, the onset of epilepsy was defined when at least two generalized motor seizures (stage 4–5) were observed 48 h post status epilepticus 47,48 . Seizures were terminated by 0.1% diazepam (10 mg/kg) when the rats exhibited status epilepticus, 3 h after the KA induction.…”

“…Among the rats that exhibited stage 4–5 seizures, six rats were randomly drawn for EEG recording to verify that the dose of KA led to stable SRSs. Among the remaining rats, we screened out those exhibiting stage 4–5 seizures 14 days after KA injection for subsequent studies 47,48 …”

Closing the Loop for Precise Seizure Control

“…In this critical proof-of-concept study, Kang et al present a new sequentially organized microstimulation method termed coined as sequential narrow-field (SNF) stimulation, that can reduce hippocampal seizures while limiting the fringing field effects that can evoke adverse responses. 2 Using the systemic kainic acid status epilepticus (KA-SE) model of temporal lobe epilepsy (TLE) in rats, the authors first compared the effects of various stimulation configurations, including open-loop wide-field (WF) stimulation, unilateral and bilateral closed-loop WF stimulation, and the newly orchestrated SNF stimulation. The SNF approach involves spatially restricted stimulus pulses delivered sequentially through the hippocampus.…”

On-demand low-frequency stimulation for seizure control: efficacy and behavioral implications

“…Hence, we initiated LFS during transition phases to stabilize the hippocampal network state at low excitability, thus preventing a focal seizure cluster. In contrast, various studies in other rodent models focused on the identification of seizure onsets with the drawback of delayed action for seizure control [59][60][61][65][66][67][68] .…”

“…Regarding the second requirement, we applied LFS in the sclerotic hippocampus that, despite the extensive neuronal loss, rewiring, and reactive gliosis, proved to be a suitable target for continuous LFS, suppressing epileptiform activity 35,67 . Here, we assessed the efficacy of ondemand LFS in comparison to continuous and regular discontinuous LFS.…”