Closed-loop seizure control with transcranial focused ultrasound and electrocortocography-based system on the rat model

Abstract

Purpose 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 with electrocorticography (ECoG) monitoring, which modulates stimulation protocol for precise seizure control on a rodent epilepsy model.

Materials & Methods 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. An ultrasonic transducer operating at a fundamental frequency of 300 kHz was attached to the scalp for tFUS stimulation. A feedback system controlled tFUS stimulation which automatically modulates the sonication protocol by seizure spike-wave monitoring, to suppress kainic acid (5 mg/kg) induced seizure on an awake freely-moving rat model.

Results The tFUS stimulation on the right hippocampus with 40 Hz pulse-repetition frequency 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, our closed-loop feedback system induced seizure suppression by modulating parameters of tFUS stimulation for each animal. With this system, we were able to provide optimized control of tFUS stimulation.

Conclusion 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 electrodes for brain monitoring.