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Closed-loop stimulation at low frequencies for seizure prevention

Closed-loop stimulation for the supression of epileptiform activity (Paschen et al., Brain, 2023). Click on figure for the publication.

Funded by the German Research Foundation (HA 1443/11-1 and HA 1443/12-1) and the “BrainLinks-BrainTools” Center Freiburg

Funding to Prof. Dr. Carola Haas

Project Description

Mesial temporal lobe epilepsy (MTLE) is the most common form of focal, pharmacoresistant epilepsy in adults and is often associated with hippocampal sclerosis. For MTLE patients, one alternative to surgical resection of the epileptic focus is electrical deep brain stimulation in the hippocampus. Due to the low duty cycle, low-frequency stimulation (LFS) may have favorable clinical implementation over high-frequency stimulation, as it requires less electric current injection, thus allowing for longer battery life. In an in vivo mouse model of MTLE, we showed previously that optogenetic LFS (0.5 and 1 Hz) in the hippocampus interferes with the generation of spontaneous epileptiform activity (Paschen et al., eLife, 2020). Whereas stimulation at higher frequencies (5–20 Hz) often results in the induction of behavioral seizures. In this project, we aim for successful closed-loop seizure control by the application of electrical LFS (eLFS) in chronically epileptic mice. We inject kainate (KA) unilaterally into the hippocampus of C57BL/6 mice to induce a status epilepticus. Two weeks later, these mice develop unilateral hippocampal sclerosis and spontaneous recurrent seizures. We implant them with one electrode for local field potential recordings in each hippocampus and a stimulation electrode in the sclerotic hippocampus. This way we can apply unilateral 1 Hz pulses daily over several weeks and assess the effects of closed-loop eLFS on epileptiform activity. In addition, KA- and control mice are subjected to behavioral tests to infer potential impacts of eLFS on cognitive performance following 1 Hz stimulations. With this project, we want to demonstrate that closed-loop eLFS in the sclerotic hippocampus reliably suppresses the generation of spontaneous epileptiform activity without losing its effectiveness over prolonged treatment while preserving hippocampus-related cognitive functions. Thus, eLFS at 1 Hz may constitute a promising approach for future seizure control in MTLE.

This study was published in Brain (Paschen et al., Brain, 2023).