Epileptic discharges initiate from brain areas with elevated accumulation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors

Abstract

Presurgical identification of the epileptogenic zone is a critical determinant of seizure control following surgical resection in epilepsy. Excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is a major component of neurotransmission. Although elevated AMPAR levels are observed in surgically resected brain areas of patients with epilepsy, it remains unclear whether increased AMPAR-mediated currents initiate epileptic discharges. We have recently developed the first positron emission tomography (PET) tracer for AMPAR, [11C]K-2, to visualize and quantify the density of AMPARs in living human brains. Here, we detected elevated [11C]K-2 uptake in the epileptogenic temporal lobe of patients with mesial temporal lobe epilepsy. Brain areas with high [11C]K-2 uptake are closely colocalized with the location of equivalent current dipoles estimated by magnetoencephalography or with seizure onset zones detected by intracranial electroencephalogram. These results suggest that epileptic discharges initiate from brain areas with increased AMPARs, providing a biological basis for epileptic discharges and an additional non-invasive option to identify the epileptogenic zone in patients with mesial temporal lobe epilepsy.