Transcranial focused ultrasound and electrocorticography-based closed-loop epilepsy control system for an awake rat model

Abstract

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 minimal invasiveness. Transcranial focused ultrasound (tFUS) is a promising non-invasive 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), which provides precise monitoring of epileptic discharge for epileptic patients. 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 closed-loop 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, the developed system is able to adjust the sonication protocol by monitoring seizure spike-wave. We therefore could provide optimized control of tFUS stimulation for seizure suppression. We demonstrated an ultrasound-based closed-loop system inhibiting epileptiform activity by providing tFUS stimulation before the generation of an epileptic spike-wave. The proposed system in this study shows the potential for 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 intracranial EEG electrodes. Research Category and Technology and Methods Basic Research: 6. Pulsed Ultrasound (pUS) Keywords: transcranial focused ultrasound, closed-loop control, epilepsy, ECoG