Assessing an fMRI-guided titration paradigm for microburst VNS therapy

RATIONALE: VNS is an efficacious therapy for people with epilepsy (PwE), but personalized implementation of VNS dosing and titration could be improved by measuring therapeutic engagement of cortical and subcortical physiology. METHODS: People with Drug-Resistant Epilepsy (DRE) were enrolled into a feasibility study using investigational microburst VNS (NCT03446664). An investigational VNS system with conditional approval for stimulation in the magnetic environment was titrated using an fMRI-guided titration approach to determine VNS therapy settings for each individual participant over 6 months. Stimulation parameter combinations that evoked the highest thalamic BOLD response were chosen in an individual participant as the preferred VNS therapy setting. RESULTS: Thirty-two participants were implanted and 31 participants attended the 6-month study visit and at least one prior fMRI study visit. In all participants, significant VNS-evoked thalamic BOLD responses were found. Participants who experienced significant thalamic BOLD signal among multiple stimulation parameter combinations over multiple visits were most likely to respond to µVNS. Participants responded to µVNS with a median reduction in seizure frequency of 42.6 % at 6 months. There were no MRI-related safety issues associated with active VNS during scanning. CONCLUSION: Titration of VNS using an fMRI-guided approach is feasible and safe in PwE (when using appropriate investigational devices), but our specific biomarker, used in this specific study design, was ultimately too variable to be used for patient-specific titration. An increase in thalamic BOLD signal that occurred across multiple stimulation parameter combinations and multiple visits with microburst settings was associated with seizure response that could be visualized early in the titration process.