Multisite thalamic recordings to characterize seizure propagation in the human brain

Abstract

Neuromodulation of the anterior nuclei of the thalamus (ANT) has shown to be efficacious in a subset of patients with refractory focal epilepsy. One important uncertainty is to what extent thalamic subregions other than the ANT could be recruited more prominently in the propagation of focal onset seizures. We designed the current study to simultaneously monitor the engagement of the ANT, mediodorsal (MD) and pulvinar (PUL) nuclei during seizures in patients who could be candidates for thalamic neuromodulation. We studied 11 patients with clinical manifestations of presumed temporal lobe epilepsy (TLE) undergoing invasive stereo-encephalography (sEEG) monitoring to confirm the source of their seizures. We extended cortical electrodes to reach the ANT, MD and PUL nuclei of the thalamus. More than one thalamic subdivision was simultaneously interrogated in nine patients. We recorded seizures with implanted electrodes across various regions of the brain and documented seizure onset zones (SOZ) in each recorded seizure. We visually identified the first thalamic subregion to be involved in seizure propagation. Additionally, in eight patients, we applied repeated single pulse electrical stimulation in each SOZ and recorded the time and prominence of evoked responses across the implanted thalamic regions. Our approach for multisite thalamic sampling was safe and caused no adverse events. Intracranial EEG recordings confirmed SOZ in medial temporal lobe, insula, orbitofrontal and temporal neocortical sites, highlighting the importance of invasive monitoring for accurate localization of SOZs. In all patients, seizures with the same propagation network and originating from the same SOZ involved the same thalamic subregion, with a stereotyped thalamic EEG signature. Qualitative visual reviews of ictal EEGs were largely consistent with the quantitative analysis of the corticothalamic evoked potentials, and both documented that thalamic nuclei other than ANT could have the earliest participation in seizure propagation. Specifically, pulvinar nuclei were involved earlier and more prominently than ANT in more than half of the patients. However, which specific thalamic subregion first demonstrated ictal activity could not be reliably predicted based on clinical semiology or lobar localization of SOZs. Our findings document the feasibility and safety of bilateral multisite sampling from the human thalamus. This may allow more personalized thalamic targets to be identified for neuromodulation. Future studies are needed to determine if a personalized thalamic neuromodulation leads to greater improvements in clinical outcome.

Keywords: corticothalamic interaction; epilepsy; evoked potentials; multisite thalamic recordings; neuromodulation; stereo-encephalography.

Figure 1

Thalamic electrode parcellation across subjects. The trajectories pass through opercular and insular structures which were desired by the clinical sampling strategy (boxed area on the right) and are simply extended into the thalamus. Right: Coronal and axial views of an MNI space representation of all thalamic electrode trajectories are shown across 10 subjects. Each line is one electrode shaft with dots denoting the individual recording contacts. The location and relative size of ANT, MD and PUL nuclei can be appreciated in the anterior to posterior order within the boundaries of the thalamus (outer shape model). Images were reconstructed using the THOMAS atlas.

Figure 2

Electrode coverage. Electrodes in the thalamus and SOZs for all recorded seizures are shown on the right hemisphere. See Table 2 for additional details about SOZs. Each patient was implanted with many more electrodes throughout the brain, not shown here. Also, note that the electrodes are projected to the surface for 3D visualization.

Figure 3

Electrophysiological thalamic ictal signature. Left: The location of electrodes in three subregions of the thalamus bilaterally (ANT, MD and PUL) in a single subject (Patient 9). Note the single electrode targeting the MD traverses across the massa intermedia. Right: A selection of EEG tracings from two SOZs and the thalamic subregions in the left (L) and right (R) hemispheres during interictal (top) and two types of seizures (middle and bottom). In this patient, we found two types of seizures with two different SOZs. The left SOZ was located in the neocortical inferior temporal region and the right SOZ was in the hippocampus. Note the relationship between the hippocampus (R-SOZ) and the ANT during inter-ictal and ictal conditions, and the relationship between the left inferior temporal cortex (R-SOZ) and the ipsilateral PUL.