Allendorfer Jane B, Nenert Rodolphe, Shamshiri Elhum, Ranuzzi Giovanni, Begnaud Jason, Verner Ryan, Szaflarski Jerzy P
Department of Neurology and the UAB Epilepsy Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
LivaNova Inc., Houston, Texas, USA.
Epilepsia Open. 2025 Aug;10(4):1054-1064. doi: 10.1002/epi4.70059. Epub 2025 May 27.
Microburst vagus nerve stimulation (μVNS) may reduce seizure frequency in drug-resistant epilepsy (DRE) via targeted thalamic plasticity. We prospectively investigated the role of thalamic resting-state functional connectivity (rsFC) in μVNS effects and hypothesized a relationship between thalamic rsFC and long-term seizure frequency changes.
Eighteen patients with focal (Foc) and 10 with generalized (Gen) DRE underwent 3T resting-state fMRI at 2 weeks post-implantation and before starting (baseline) and after 6 months of μVNS. Resting-state fMRI analyses were performed using in-house Matlab scripts. Nonparametric permutation tests assessed baseline group differences in rsFC between automated anatomical atlas (AAL) brain regions and longitudinal rsFC changes. Spearman correlations were performed between baseline thalamus rsFC and percent change in seizures after 12 months of μVNS (PCHG-12).
Gen had stronger baseline rsFC between AAL regions compared with Foc. Gen showed significant baseline-to-6-month rsFC changes, including a decrease between the left thalamus and left superior parietal lobule. Foc showed significant rsFC changes, including increases between the left thalamus and four regions: right middle cingulum (Lthal-Rmidcing), right angular gyrus (Lthal-Rangular), left angular gyrus (Lthal-Langular), and left precuneus (Lthal-Lprecuneus), and increases between the right thalamus and left angular gyrus (Rthal-Langular). Foc showed negative correlations between PCHG-12 and baseline rsFC for Lthal-Rmidcing (ρ = -0.61; p = 0.007), Lthal-Rangular (ρ = -0.51; p = 0.032), and Rthal-Langular (ρ = -0.52; p = 0.028).
Baseline thalamic rsFC is correlated with long-term seizure frequency reduction with μVNS in focal DRE. RsFC may be a potential biomarker for μVNS response in focal-onset seizure patients; this relationship may be different in DRE with generalized seizures.
We investigated how stimulating the vagus nerve in a specific manner may reduce seizure frequency in people with drug-resistant epilepsy through its actions on how a part of the brain called the thalamus is functionally connected to other brain regions. People with focal seizures showed a different pattern of changes in thalamus functional connectivity than those with generalized seizures after 6 months of stimulation. People with focal seizures also showed that stronger functional connectivity between the thalamus and other brain regions at baseline was related to a greater decrease in seizure frequency after 12 months of stimulation.
微爆发性迷走神经刺激（μVNS）可能通过靶向丘脑可塑性降低药物难治性癫痫（DRE）的发作频率。我们前瞻性地研究了丘脑静息态功能连接（rsFC）在μVNS效应中的作用，并假设丘脑rsFC与长期发作频率变化之间存在关联。
18例局灶性（Foc）和10例全身性（Gen）DRE患者在植入后2周、开始μVNS前（基线）以及μVNS治疗6个月后接受3T静息态功能磁共振成像（fMRI）检查。使用内部Matlab脚本进行静息态fMRI分析。非参数置换检验评估自动解剖图谱（AAL）脑区之间rsFC的基线组差异以及rsFC的纵向变化。对基线丘脑rsFC与μVNS治疗12个月后发作次数的百分比变化（PCHG - 12）进行Spearman相关性分析。
与Foc相比，Gen在AAL区域之间具有更强的基线rsFC。Gen显示出从基线到6个月时rsFC有显著变化，包括左侧丘脑与左侧顶上小叶之间的连接减少。Foc显示出显著的rsFC变化，包括左侧丘脑与四个区域之间的连接增加：右侧中央扣带（Lthal - Rmidcing）、右侧角回（Lthal - Rangular）、左侧角回（Lthal - Langular）和左侧楔前叶（Lthal - Lprecuneus），以及右侧丘脑与左侧角回（Rthal - Langular）之间的连接增加。Foc显示PCHG - 12与Lthal - Rmidcing（ρ = - 0.61；p = 0.007）、Lthal - Rangular（ρ = - 0.51；p = 0.032）和Rthal - Langular（ρ = - 0.52；p = 0.028）的基线rsFC之间呈负相关。
在局灶性DRE中，基线丘脑rsFC与μVNS导致的长期发作频率降低相关。RsFC可能是局灶性发作患者对μVNS反应的潜在生物标志物；在全身性发作的DRE中这种关系可能不同。
我们研究了以特定方式刺激迷走神经如何通过其对大脑中称为丘脑的一部分与其他脑区功能连接方式的作用来降低药物难治性癫痫患者的发作频率。刺激6个月后，局灶性发作患者与全身性发作患者的丘脑功能连接变化模式不同。局灶性发作患者还显示，基线时丘脑与其他脑区之间更强的功能连接与刺激12个月后发作频率的更大降低相关。
