Abstracts

Rationale: Temporal lobe epilepsy, the most common of the epilepsies, is characterized in the brain by sclerosis, fiber sprouting, and the eventual emergence seizures. Epileptogenesis is defined as the progressive slow process between when the normal healthy brain transitions into a diseased state over months to years. Ictogenesis describes how the epileptic brain transitions from normal state to seizure on a shorter time scale of seconds to minutes. Previous results show Granger causal interactions from the dentate gyrus (DG) to the CA1 increase during ictogenesis, while the interactions from the CA1 to the DG remain constant. Our hypothesis is that slow changes in the functional connectivity of the temporal lobe occur during epileptogensis are indicative of potential network level reorganization underlying the eventual emergence of seizure behavior. Additionally, previous work using magnetic resonance imaging show specific gradual structural changes in the temporal lobe during epileptogenesis that support this hypothesis. Methods: We use a spontaneously seizing animal model of temporal lobe epilepsy that is continuously monitored electrophysiologicaly using 32 channel microarray electrodes over 6-8 weeks. This model produces electrophysiological data that enables us to study epileptogenic and ictogenic transitions using functional and effective connectivity measures such as correlation and Granger causality. Results: An analysis of functional connectivity using normalized covariance over the longer time scale of epileptogenesis demonstrates the slow degradation of functional connectivity within the hippocampus post stimulation into status epilepticus relative to age matched controls. A circadian like cycle embedded within the cross correlation measure. Qualitative analysis suggest that this pattern is disrupted post status epilepticus, a result consistent with previous studies in our lab using this animal model. Conclusions: The abnormal functional connectivity patterns seen during seizure epochs suggest that specific functional changes have occurred within the hippocampal-entorhinal network . Indeed, long term changes in functional connectivity seen during epileptogenesis support the hypothesis that functional connections within the limbic networks are changing gradually over time rather than large acute changes following status epilepticus.