Purpose: We recorded with intracerebral electrodes the onset of limbic seizures in patients with mesial temporal lobe epilepsy (MTLE) to identify the dynamic interactions between the hippocampus (HIP), amygdala (AMY) and entorhinal cortex (EC).
Methods: Interactions were quantified by analyzing the interdependencies between stereo-electroencephalographic (SEEG) signals using a nonlinear cross-correlation method. Seizures from 12 patients were analyzed by identifying three periods of interest: (i) the rapid discharge that occurs at seizure onset ("during rapid discharge", DRD period); (ii) the time interval that precedes this rapid discharge ("before rapid discharge", BRD period); and the time that follows the rapid discharge ("after rapid discharge", ARD period). The transition from interictal to ictal discharge was classified into: (i) "type 1 transition" in which the emergence of pre-ictal spiking was followed by a rapid discharge; and (ii) "type 2 transition" that was associated with rapid discharge onset without prior spiking.
Results: In both types of transition the BRD period was characterized by significant cross-correlation values indicating strong interactions among mesial temporal structures as compared to those seen during background activity. Interactions between HIP and EC were predominant in 10 of 12 patients (83%). Interactions between EC and AMY were observed in 6 of 12 cases (50%) and between AMY and HIP in 7 of 12 cases (58%). Analysis of coupling directionality indicated that most of the couplings were driven either by HIP (six patients) or by the EC (four patients). The DRD period was characterized by a significant decrease of cross-correlation values. In addition, type 1 transition was characterized by interactions that uniformly involved the three structures, while type 2 transition was associated with interactions between EC and HIP. Finally, analysis of coupling direction demonstrated that the HIP was always the leader in type 1 transition whereas in type 2 the EC was most often the leading structure.
Conclusions: This study demonstrates that pre-ictal synchronization between mesial structures is the initial event for seizures starting in the mesial temporal region.