To investigate effects of microburst vagus nerve stimulation (μVNS) on resting-state functional connectivity (rsFC) in treatment resistant epilepsy (TRE).
μVNS can reduce seizure frequency in TRE via targeted thalamic plasticity as potential mechanism of action. Relationships between thalamus rsFC and μVNS have not been explored. We hypothesized that thalamus rsFC would be associated with seizure frequency changes from μVNS.
18 focal (FocTRE) and 10 generalized (GenTRE) TRE patients with VNS underwent 3T resting-state fMRI at 2 weeks post-implantation (baseline) and after 6 months of μVNS (6moμVNS). Resting-state fMRI preprocessing and analyses were performed using in-house Matlab scripts. Nonparametric permutation tests assessed baseline group differences in region-of-interest rsFC between automated anatomical atlas (AAL) brain regions and baseline-to-6moμVNS rsFC changes (significant at pcorrected<0.05). Significant baseline differences prompted separate group longitudinal analyses. Z-scores were extracted for significant thalamus rsFC changes. Spearman correlations were performed between thalamus rsFC and percent change in seizures after 6 (PCHG-6) and 12 months (PCHG-12) of μVNS (significant at p<0.05).
At baseline, GenTRE had higher correlation between AAL regions compared to FocTRE. Baseline-to-6moμVNS rsFC changes were few for GenTRE and numerous for FocTRE. GenTRE showed baseline-to-6moμVNS connectivity decrease between left thalamus and left superior parietal lobule. FocTRE showed baseline-to-6moμVNS connectivity increases between left thalamus and right middle cingulum (Lthal-Rmidcing), right and left angular gyrus (Lthal-Rangular; Lthal-Langular), and left precuneus (Lthal-Lprecuneus); right thalamus showed connectivity increases with left angular gyrus (Rthal-Langular). PCHG-6 and PCHG-12 were not significantly correlated with thalamus rsFC changes. FocTRE showed significant negative correlations between PCHG-12 and baseline rsFC for Lthal-Rmidcing (rho=-0.613; p=0.0069), Lthal-Rangular (rho=-0.506; p=0.0323) and Rthal-Langular (rho=-0.516; p=0.0283).
Baseline-to-6moμVNS rsFC changes differed between focal and generalized TRE. Baseline thalamus rsFC is associated with long-term seizure frequency reduction with μVNS in TRE. Larger samples are necessary to further assess these relationships.