Transcranial Focused Ultrasound Stimulation Targeting White Matter Inhibits Seizures in a Rat Model of Epilepsy

Transcranial Focused Ultrasound Stimulation (tFUS) is a promising non-invasive technique capable of modulating brain activity with high spatial precision. However, its efficacy for seizure suppression requires further exploration. This study aims to address whether tFUS of white matter can suppress seizures non-invasively. Repeated injections of a 4-Aminopyridine (4-AP) cocktail into the right somatosensory cortex (S1) induced cortical seizures in male rats under anesthesia with recording of both EEG and intracranial signals. Approximately one hour of tFUS was applied to the corpus callosum (CC) using a 128-element random-array transducer with 20 ms pulse duration, 1 Hz pulse repetition frequency, 2% duty cycle, and ~127 kPa pressure. Another 2-3 hours were used to assess post-stimulation effects. Seizure duration, seizure count, percent time in seizure, and inter-seizure interval were compared to a sham control for quantifying efficacy. The absolute frequency power, asymmetry index (AI), and phase lag index (PLI) were calculated to analyze brain activity changes induced by tFUS. CC tFUS can significantly reduce percent time in seizure, seizure duration, and seizure count, as well as increase inter-seizure interval. These effects extended up to 2 hours post-stimulation. We also observed a decrease in absolute power of the beta band and changes in the brain network, as evidenced by a decrease in synchronization and an improvement in interhemispheric balance. Our study is the first to show that white matter tFUS can significantly suppress seizures with a lasting post stimulation effect, potentially providing a safer alternative for drug-resistant epilepsy patients.