UC San Diego

Epilepsy is a common neurological disorder that is characterized by bouts of synchronized hyperactivation of neuronal networks. The development of new treatment modalities is highly desirable but unfortunately hindered by our limited understanding of the pathophysiology of epileptic seizures. The complexity of neuronal dynamics make computational models an important tool in the research aimed at unraveling the mechanisms underlying epileptogenesis and epileptic seizures. In this dissertation, computational network models were used to study the dynamics of (1) pathological cortical network reorganization and (2) cortical seizures. We found that changes in synaptic properties by homeostatic plasticity after partial deafferentation can explain clinical electroencephalographic observations associated with diffuse and focal central nervous system pathologies. We then show that initiation, maintenance, and termination of cortical seizures can be explained by the dynamic interaction between neural activity and extracellular potassium concentration. Together, this dissertation provides a comprehensive set of specific hypotheses that can now be tested in experiments to further our understanding of neural pathophysiology