Cerebellum-targeted Transcranial Focused Ultrasound Stimulation Inhibits Hippocampal Neural Activity and Suppresses Epileptiform Activity.

Epilepsy affects millions worldwide, necessitating novel therapeutic approaches. Transcranial focused ultrasound (tFUS), as a non-invasive neuromodulation technique, shows therapeutic potential. We hypothesize that cerebellum-targeted tFUS can modulate brain-wide neural activity in vivo to achieve effective seizure control. We evaluated two different pulse repetition frequencies (PRF) of tFUS at 1kHz and 10kHz. We found that the tFUS at PRF of 10kHz could more effectively inhibit brain-wide neural activity recorded with multichannel ECoG, particularly around hippocampus. Reduced glutaminase (GLS) expression was also demonstrated in the hippocampus after tFUS. We also showed that the tFUS could significantly suppress hippocampal neural activities in an acute epileptic rat model. Our results show that cerebellum is a promising target for tFUS neuromodulation and by carefully selecting the stimulus parameters, such as PRF, we can achieve effective therapeutic application.