Mapping electrophysiological connectivity of pulvinar in seizure propagation and neuromodulation

Abstract Objective The pulvinar is increasingly recognized as a promising target for neuromodulation in drug‐resistant epilepsy (DRE). Despite growing interest, empirical evidence substantiating the efficacy and mechanism of its deep brain stimulation (DBS) in patients with epilepsy remains scarce. This study endeavors to address this knowledge gap by investigating the electrophysiological properties of pulvinar. Methods We enrolled 35 patients with DRE who underwent stereoelectroencephalography with electrodes extended to the pulvinar and analyzed the pulvinar's involvement in seizures originating from different brain lobes. Repeated single electrical pulse stimulation (RSEPS) was employed to map the connectivity of the pulvinar. We also evaluated the effect of pulvinar DBS on interictal epileptic discharges within the epileptogenic zone. Results We observed that greater involvement of the pulvinar exists in temporal lobe epilepsy, with the medial pulvinar (PuM) showing stronger engagement. Findings with RSEPS highlighted significant connections from the PuM to parietal, occipital, and temporal regions, as well as robust connections from the mesial temporal lobes to PuM. Lastly, we found high‐frequency stimulation (140–150 Hz) of PuM significantly reduced interictal epileptic discharges. Significance Our study supports emerging evidence for pulvinar involvement in seizure propagation. The data with RSEPS also map PuM causal connectivity in the human brain. Although the clinical utility of pulvinar neuromodulation in patients with DRE remains to be determined by prospective clinical trials, our findings provide a convincing link between PuM neuromodulation and the reduction of epileptic activity.