Anterior Nucleus of Thalamus Gates Progression of Mesial Temporal Seizures by Modulating Thalamocortical Synchrony

Abstract

The anterior nucleus of the thalamus (ANT) mediates cortical-subcortical interactions between the limbic system and is hypothesized to facilitate the early organization of temporal lobe seizures. We set out to investigate the dynamic changes in synchronization parameters between the seizure onset zone (SOZ) and ANT during seizure stages (pre-onset to post-termination) in seven patients (n=26 seizures) with drug-resistant nonlesional temporal lobe epilepsy. Using local field potentials recorded directly from the limbic system and the ANT during stereoelectroencephalography, we confirm that the onset of mesial temporal lobe seizure is associated with increased thalamocortical network excitability and phase-amplitude coupling. The increase in thalamocortical phase synchronization preceded seizure onset, thereby suggesting that the early organization of temporal lobe seizures involves the integration of the ANT within the epileptic network. Towards seizure termination, there is a significant decrease in thalamic excitability, thalamocortical synchronization, and decoupling, thereby suggesting a breakdown in thalamocortical connectivity. A higher disease burden is significantly correlated with increased synchronization between the ANT and epileptic networks. Collectively, the results elucidate mechanistic insights and provide the temporal architecture of thalamocortical interactions that can be targeted in the rational designing of closed-loop seizure abortive interventions. HighlightsO_LIAnterior nucleus of thalamus is coactivated at the onset of temporal lobe seizures C_LIO_LIIncrease thalamocortical synchronization and excitability is observed at seizure onset C_LIO_LISeizure termination is characterized by a breakdown in thalamocortical connectivity C_LIO_LIIncreased seizure burden affects thalamocortical synchronization C_LI