Neural Synchronization in Seizures

Johnson, Sarah, Chemical Engineering - School of Engineering and Applied Science, University of Virginia
Hudson, John, Department of Chemical Engineering, University of Virginia

Persons with epilepsy suffer from recurring seizures thought to be the result of abnormal, hypersynchronous neural activity. Understanding the role that synchronization of neural activity plays in the development and propagation of seizures can lead to improvements of current treatments and aid in designing future treatments. This dissertation looks at the role of synchronization in the whole brain during seizures, between neurons with feedback and in pairs of synaptically connected neurons in an in vitro epilepsy model.

The synchronization index (SI), which combines phase synchronization between two electrodes with the synchronization of neurons at an electrode, was calculated for seizures of four patients with medically intractable mesial temporal lobe epilepsy. After recording multiple seizures per patient, patients underwent surgical resection to remove the part of the temporal lobe visually determined to be the focus of their seizures. SI values calculated from the recorded EEGs were mapped onto a diagram of the EEG electrodes. Examination of seizures across all the patients showed the presence of five distinct stages. However, average values of the synchronization measure were higher for patients whose seizures were not completely cured after surgical resection. SI may provide a metric to predict surgical outcome prior to surgery.

Phase-based models were experimentally constructed from a single synaptically isolated cultured hippocampal neuron. These models were used to determine the stimulation parameters necessary to produce the desired synchronization behavior in the action potentials of a pair of neurons coupled through a global time-delayed interaction. Measurements made using a dynamic clamp system confirm the generation of the synchronized states predicted by the experimentally constructed phase model. This model was then utilized to extrapolate the feedback stimulation parameters necessary to disrupt the action potential synchronization of a large population of globally interacting neurons. These feedback parameters can be used as a starting point for studies using an animal model.

The event synchronization was calculated for pairs of neurons exposed to decreased extracellular Mg2+. As the concentration of Mg2+ was decreased, the synaptic strength between the cells and within the network was increased as demonstrated by two methods of quantal analysis. However, the level of synchronization had a possible dose response relationship as Mg2+ was decreased. This suggests that increased synaptic strength, while initially increasing the synchronization between pairs of neurons, can only increase synchronization to a point. To further examine the effect of synaptic strength on synchronization three common antiepileptic drugs (AEDs) were added to the epileptic solution. Of the three AEDs, two have mechanisms that alter the synaptic strength. None of the AEDs altered the synchronization significantly.

PHD (Doctor of Philosophy)
synchronization, dynamic patch clamp, seizures, epilepsy
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