Resting-state functional connectivity changes with microburst vagus nerve stimulation therapy.

Objective: 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.

Methods: 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).

Results: 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).

Significance: 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.

Plain language summary: 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.