Transcranial Focused Ultrasound and Electrocorticography-Based Closed-Loop Epilepsy Control System for an Awake Rat Model

Abstract

Neurostimulation with closed-loop interaction is one of the clinical solutions for patients with drug-resistant epilepsy. However, there are growing demands for an epilepsy control system with minimized invasiveness. Transcranial focused ultrasound (tFUS) is a promising noninvasive neuromodulation technique for controlling epileptic seizures due to its superior spatial specificity and depth penetrability. Here, we demonstrated a tFUS-based closed-loop system in combination with electrocorticography (ECoG), widely used electrodes for epileptic patients, which provides precise monitoring of epileptic discharge. In-house built 16-ch ECoG electrodes were attached to the Sprague-Dawley rat’s dura for detecting seizure spike-wave proceeding high-frequency oscillations (HFO) and monitoring epileptic discharges. After recovery from the surgery, kainic acid (5 mg/kg) was injected to generate a temporal lobe epilepsy rat model. An ultrasonic transducer operating at a fundamental frequency of 300 kHz was attached to the scalp for tFUS stimulation, which was automatically controlled by the system based on the HFO detection algorithm with real-time ECoG monitoring. The closedloop tFUS stimulation on the right hippocampus with 40 Hz pulse-repetition frequency (PRF) and 5 % duty cycle induced the diminution of the duration of seizure spike-wave and the suppression of the power of brain oscillations such as theta, gamma bands from the bilateral hemisphere, compared to sham stimulation. Furthermore, we build a feedback system that modulates the sonication protocol by seizure spike-wave monitoring. With this system, we were able to provide optimized control of tFUS stimulation for seizure suppression. We demonstrated an ultrasound-based closed-loop system inhibiting epileptiform activities by providing tFUS stimulation before the generation of epileptic spike-wave. The proposed system in this study shows the potentiality of developing a system that provides non-invasive seizure control, without additional surgical burden for patients who are wearing medical brain implants such as ECoG or other types of iEEG electrodes.