Human Mediodorsal Thalamus in Seizure Propagation

How different thalamic sites are recruited during seizure propagation remains poorly understood. Simultaneous recordings from multiple thalamic sites in patients with focal seizures provide a rare opportunity to investigate the spatiotemporal pattern of thalamic involvement during human epilepsy.

To characterize the recruitment patterns of mediodorsal (MD) thalamic subregion during seizures and their generalization to the contralateral hemisphere.

We analyzed 119 seizures from 23 patients (12 male, age range: 20-57y) undergoing multisite thalamic recordings. In accordance with current clinical standards, we determined the spatial and temporal features of thalamic seizure activity by visually reviewing intracranial EEG recordings from different seizure types in each individual patient.

The procedure of multisite thalamic recordings had no complications. In total, we captured seizures originating from temporal lobes (63%), orbitofrontal (11%), frontotemporal (8%), occipital (8%), lateral frontal (4%), parietal (3%), and cingulate (2%) regions. Seizures were focal (76% in 21 patients), focal-to-bilateral tonic-clonic (FBTC, 9% in nine patients), or only electrographic (15% in six patients). Thalamic engagement was seen in 100% of patients occurring typically early during seizure evolution (83% within 15 seconds of seizure onset). Majority of FBTC seizures (73%) had faster thalamic recruitment, often within the first 5 seconds. The pulvinar (PLV) subregion was the most common first-activated thalamic site, particularly in temporal lobe seizures. Although the MD was involved in most seizures (88.2%), it was rarely the initial or sole thalamic structure engaged and more often followed anterior (ANT) and/or PLV sites. Contralateral propagation occurred in 66% of seizures and was strongly linked to MD involvement: the ipsilateral and contralateral MDs were engaged in about 95% of these cases. When ipsilateral MD engagement was absent, contralateral spread of seizures was uncommon. In majority of seizures (60%) that generalized to the contralateral hemisphere, the ipsilateral MD was involved before or simultaneously with the contralateral cortical sites. Importantly, seizures that first activated the MD originated mainly from the medial temporal lobes, whereas those spreading primarily to the contralateral cortex were mostly neocortical in onset.

The thalamic MD subregion was often involved after the other thalamic sites, but the MD sites, along with the massa intermedia connecting the two thalami, were significantly involved when seizures spread to contralateral hemisphere. Our findings suggest that a single thalamic lead capturing both MD subregions may yield important clinical information about laterality, origin, and generalization of seizures.