Thalamocortical hodology to personalize electrical stimulation for focal epilepsy

Thalamic electrical stimulation offers a therapeutic approach for refractory epilepsy patients ineligibles for resective surgery. Yet, there is currently no consensus on the optimal stimulation site. We hypothesized that targeting thalamic nuclei with precise anatomical and functional connections (hodological matching) to cortical seizure onset zones (SOZs) could enhance neuromodulatory effects. Thus, we examined three subnuclei (pulvinar, anterior, and ventral intermediate/oral posterior, VIM/VOP) in 41 focal epilepsy patients. Combining neuroimaging and electrophysiology, we identified hodologically-matched targets: pulvinar for posterior-quadrant and temporal SOZs, anterior for frontotemporal, and VIM/VOP for rolandic. Analysis of 274 seizures revealed the critical role of matched nuclei in seizure termination. Stimulation of hodologically-matched (but not unmatched) nuclei immediately suppressed interictal epileptiform discharges. Finally, in 10 chronically implanted patients, matched stimulation substantially reduced seizure frequency (87.5%), compared to unmatched targets (8.3%) over time. Our results underscore the potential of hodological thalamic targeting to modulate epileptiform activity in focal epilepsy.