Chu Po-Chun, Ruan Wei-Hong, Huang Chen-Syuan, Juan Yi-Jing, Chen Jyh-Horng, Yu Hsiang-Yu, Fisher Robert S, Liu Hao-Li
Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan, ROC.
Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan, ROC.
Sci Rep. 2025 Aug 12;15(1):29551. doi: 10.1038/s41598-025-15305-0.
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 = 0.3 W/cm 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.
聚焦超声（FUS）已成为一种有前景的神经调节技术，可降低局部脑兴奋性，为耐药性癫痫（DRE）提供了一种潜在的治疗方法。然而，其潜在机制仍不清楚，特别是在癫痫相关脑网络中的功能连接改变方面。本研究使用脑电图（EEG）和静息态功能磁共振成像（rs-fMRI）研究FUS诱导的癫痫抑制与脑功能连接之间的关系。使用戊四氮（PTZ）诱导的癫痫大鼠模型（n = 28），我们以0.25的机械指数（MI）、0.3W/cm²的强度，低剂量（开30秒-关90秒）/高剂量（开90秒-关30秒），超声处理10分钟，作用于丘脑前核（ANT），导致海马棘波活动降低约36%。Rs-fMRI分析（36×36连接矩阵）显示，PTZ诱导的癫痫发作减少与全脑连接的显著变化密切相关，包括丘脑前核与海马网络之间的连接减少45.1%。组织学分析证实，FUS优先调节癫痫环路中涉及的关键脑区，特别是丘脑和海马。这些发现提供了令人信服的证据，表明FUS选择性地改变癫痫相关功能网络，突出了其作为癫痫非侵入性治疗方法的潜力。
