Focused ultrasound suppresses pentylenetetrazol-induced epileptiform activity in rats and alters connectivity measured by functional MRI

Focused ultrasound (FUS) has emerged as a promising neuromodulation technique for reducing regional brain excitability, offering a potential therapeutic approach for drug-resistant epilepsy (DRE). However, its underlying mechanisms remain unclear, particularly regarding functional connectivity alterations in seizure-related brain networks. This study investigates the relationship between FUS-induced seizure suppression and brain functional connectivity using EEG and resting-state fMRI (rs-fMRI). Using a pentylenetetrazol (PTZ)-induced epilepsy rat model (n = 28), we applied burst-mode FUS with 0.25 MI, I_SPTA = 0.3 W/cm² with low (30s-on-90s-off)/high (90s-on-30s-off) doses with 10-minute sonication durations to the anterior nucleus of the thalamus (ANT), resulting in approximately 36% reduction in hippocampal spike activity. Rs-fMRI analysis (36 × 36 connectivity matrix) revealed that the PTZ-induced seizure reduction strongly correlates with significant whole-brain connectivity changes, including a 45.1% decrease in connectivity between the anterior thalamic and hippocampal networks. Histological analysis confirmed that FUS preferentially modulates key brain regions involved in epileptic circuits, particularly the thalamus and hippocampus. These findings provide compelling evidence that FUS selectively alters seizure-related functional networks, highlighting its potential as a noninvasive therapeutic approach for epilepsy.