The magnetoencephalogram (MEG) is a recently developed method of noninvasively localizing and studying the summed intracellular currents of epileptic paroxysms in animal and man by mapping the extranial magnetic fields that they produce. The long-term goal of this project is to use a penicillin model of epilepsy in rat cortex to establish an empirical basis for the neurogenesis of epileptiform magnetic fields in man, and to combine MEG with detailed electrical arecording to obtain information about the intra and extracellular currents produced by excitability changes in the in vivo epileptic neocortex. The present proposal consist of an integrated series of 5 experiments that combine MEG with laminar microelectrod recording of field potentials to study the eletrophysicolgical differences between norman and epileptic cortex in response to direct erlectrical stimulation(direct cortical response or DCR). The first experiment introduces a quantitative computer model to relate the MEG to current source-density. The second experiment is a comprehensive study of the slow wave components of the DCR complex designed to evaluate their possibile thalamocortical basis and their relation to excitability cycles. The third experiment extends the analysis of the DCR to steady electrical and magnetic field shifts produced by extended stimulation bursts. In the forth experiment, these responses in norman cortex are re-analized in the penicillin focus as epileptic excitability is periodically increased and decreased during the """"""""cyclical spike driving"""""""" phenomena. Finally in the fifth experiment, possible steady magnetic field shifts accompanying the slow excitability changes of cyclical spike driving in the pencillin focus are studied to determine if these are associated wiwth organized intracellular currents. The results of this work will not only provide insights into membrane excitability changes that result in epileptic seizures, but will also be directly relevant to the intrpretation of extracranial magnetic fields measured from normal and epiletic human neocortex.
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