Closed-Loop Control of Epileptic Seizures by Low-Intensity Focused Ultrasound Brain Stimulation on the Awake Rodent Model

Abstract

A non-invasive closed-loop control of the seizure activity is a goal of minimum-risk treatment for drug-resistant epilepsy patients. This study aims to suppress seizures with low-intensity focused ultrasound during the awake condition. For this purpose, we investigated the effect of sonication parameters on the rodent epilepsy model while monitoring with EEG. For the epilepsy model generation, intraperitoneal injection of pentylenetetrazole (80mg/kg) was performed on a Sprague-Dawley rat. Two EEG electrodes were fixed on the rat skull for brain monitoring. Acoustic stimulation was delivered to the hippocampus by a transducer with the fundamental frequency of 450 kHz. Stimulation parameters with pulse-repetition frequency (PRF) of 100 Hz or 500 Hz and 5% duty cycle were tested for seizure suppression. These stimulation parameters were selected from our preliminary experiments performed on the ketamine-xylazine anesthetized seizure model. Amplitude correlation was used for detecting seizures, which triggered the acoustic stimulation system for seizure suppression. The seizure spike-wave was diminished after the closed-loop ultrasound stimulation of 500 Hz PRF with a 5% duty cycle on an awake animal, while 100 Hz PRF with a 5% duty cycle did not show a suppressive effect compared to sham stimulation. Our results demonstrated that seizures could be controlled by ultrasound stimulation with a closed-loop system on the awake condition. The present study suggests that focused ultrasound brain stimulation may offer a new application of real-time control of epilepsy due to its non-invasiveness and spatial selectivity.