Multisite Thalamic Recordings to Characterize Seizure Propagation in the Human Brain

Neuromodulation of the anterior nuclei of the thalamus (ANT) has shown to be efficacious in patients with refractory focal epilepsy, but it is not uniformly effective. One important uncertainty is to what extent thalamic subregions other than the ANT are recruited earlier and more prominently in the propagation of seizures in patients with presumed temporal lobe epilepsy (TLE). To address this unknown, we studied 11 patients with clinical manifestations of TLE planned to undergo invasive stereo-encephalography (sEEG) monitoring. We extended cortical electrodes to reach thalamic nuclear subdivisions in the anterior (ANT), middle (mediodorsal) and or posterior (pulvinar) sites. This multisite thalamic sampling was without any adverse events. Intracranial EEG (iEEG) recordings confirmed seizure-onset in medial temporal lobe, insula, orbitofrontal and temporal neocortical sites – highlighting the importance of iEEG for more accurate localization of seizure foci. Visual review of EEGs documented early and prominent involvement of specific thalamic sites. Seizures originating from the same brain origin produced a stereotyped thalamic EEG signature. Visual review of EEGs, validated with singlepulse corticothalamic evoked potentials, documented early and prominent involvement of thalamic sites that would have not been predicted given the anatomy of seizure onset zones. Pulvinar was involved earlier and more prominently than other sampled nuclear subgroups in 60% of patients, even though all patients had a presumed diagnosis of TLE prior to invasive monitoring. Our findings document the feasibility and safety of multisite sampling from the human thalamus and suggest that the anatomy of thalamic involvement may not be entirely predictable on the basis of clinical information or lobar localization of seizures. Future clinical trials can establish whether offering more personalized targets for thalamic neuromodulation will lead to greater meaningful improvements in outcome.