Optimizing stimulation paradigms to improve the suppression effect of ultrasonic brain stimulation on seizures

Ultrasound (US) brain stimulation is a promising treatment for epilepsy. However., the mechanism of how US suppresses seizures is unclear. Most of the preclinical tests were performed on anesthetic animals, which limits the accurate assessment of US suppression. In this study, we applied transcranial US with different stimulation paradigms on awake epileptic mice models induced by pentylenetetrazol (PTZ), and evaluated the suppression effects by analyzing the electroencephalographic (EEG) signals, including firing rate of epileptic spikes and spike-wave discharge (SWD). The mice were recovered for 7 days after surgery and then fixed to a constructed platform to perform ultrasound stimulation with fixed or dynamic pulse repetition frequency (PRF). The results showed that sonication of fixed-PRF US 10 minutes before PTZ administration could significantly reduce the number of SWD, and had a tendency to reduce the spike firing rate. In addition, both fixed and dynamic US sonicated right after PTZ administration for 10 minutes had tendency to reduce the spike firing rate. This study explored the suppressive effect of different ultrasound stimulation paradigms on awake and epileptic mice., which shed light on the optimizing stimulation paradigms used in the future clinical application.