Spatiotemporal neuronal correlates of seizure generation in focal epilepsy
Purpose-Focal seizures are thought to reflect simultaneous activation of a large population of neurons within a discrete region of pathological brain. Resective surgery targeting this focus is an effective treatment in carefully selected patients, but not all. While in vivo recordings of singleneuron (i.e., "unit") activity in patients with epilepsy have a long history, no studies have examined long-term firing rates leading into seizures and the spatial relationship of unit activity with
... t to the seizure onset zone. Methods-Microelectrode arrays recorded action potentials from neurons in mesial temporal structures (often including contralateral mesial temporal structures) in seven patients with mesial temporal lobe epilepsy. Key Findings-Only 7.6% of microelectrode recordings showed increased firing rates prior to seizure onset and only 32.4% of microelectrodes showed any seizure-related activity changes. Surprisingly, firing rates on the majority of microelectrodes (67.6%) did not change throughout the seizure, including some microelectrodes located within the seizure onset zone. Furthermore, changes in firing rate prior to and at seizure onset were observed on microelectrodes located outside the seizure onset zone and even in contralateral mesial temporal lobe. These early changes varied from seizure to seizure, demonstrating the heterogeneity of ensemble activity underlying the generation of focal seizures. Increased neuronal synchrony was primarily observed only following seizure onset. Significance-These results suggest that cellular correlates of seizure initiation and sustained ictal discharge in mesial temporal lobe epilepsy involve a small subset of the neurons within and outside the seizure onset zone. These results further suggest that the "epileptic ensemble or network" responsible for seizure generation are more complex and heterogeneous than previously thought and that future studies may find mechanistic insights and therapeutic treatments outside the clinical seizure onset zone.