Abstracts

RATIONALE: Interictal epileptiform discharges (IEDs) in the human electroencephalogram (EEG) are an important diagnostic feature of temporal lobe epilepsy, although they have proven to be of little use in short-term seizure prediction. Seizures are preceded by increases in the extracellular potassium concentration, and in vitro studies have confirmed a corresponding pre-ictal depolarization of the neuronal membrane potential. More recently, nonlinear time series analyses of electroencephalographic activity have demonstrated reproducible changes in brainwave activity minutes before a seizure. Together, these observations suggest that the operations of epileptic neural networks undergo predictable alterations for some time prior to a seizure. However, there are no clinically accessible and physiologically interpretable parameters that can be used to address a fundamental question: what changes in the epileptic network lead to seizures?
METHODS: 1mm thick dorsal transverse hippocampal slices were prepared from Wistar rats at postnatal age P10-20, a stage of development at which seizure threshold is decreased in humans and rodents. Simultaneous extracellular field potential recordings were made in the hippocampal slice preparation using arrays of tungsten microelectrodes placed in the granular cell layer of dentate gyrus, pyramidal cell layer of CA3a, b and c, proximal and distal CA1 areas.
RESULTS: The transition to seizures was characterized by: (i) increase in IED afterdischarges; (ii) increase in the velocity of IED propagation; (iii) shift in the IED initiation area from CA3a to CA3c-hilus.
CONCLUSIONS: Here we demonstrate that both the site of initiation and the propagation velocity of IEDs are consistently altered pre-ictally in the hippocampal CA3 network in vitro. These findings elucidate new targets for investigating the proximate causes of seizures, and provide a simple and robust new method for seizure prediction. Pre-ictal alterations in IEDs can be detected with much greater computational efficiency than is currently possible with nonlinear techniques: by measuring the difference in population spike timing in CA3a and CA3c, seizure onset could be predicted up to 1 minute in advance.
[Supported by: NIH]; (Disclosure: Grant - NIH)