Functional MRI of Rat and Monkey Models of Absence Epilepsy: A Dissertation

A seizure is defined as an abnormal electrical discharge from the brain that results in the affected area losing its normal function and reacting uncontrollably. A particular subset of seizures , known as absence seizures , are characterized by brief, paroxysmal losses of consciousness that are associated with bilaterally synchronous 3 Hz spike and wave discharges (SWDs) on electroencephalography (EEG). The optimal way to understand any disease state is to study it within the human. Unfortunately, well controlled experiments in humans are difficult due to small patient populations , treatment medications which alter the seizure , and the ethical problems associated with invasive experimental procedures. Animal models of absence seizures provide a means of avoiding the above difficulties but the model should mimic, as closely as possible , the human condition. The goal of this thesis was to develop an animal model of absence epilepsy that could be used to explore, non-invasively, the underlying mechanisms of absence seizures. Functional magnetic resonance imaging (fMRI) was used to noninvasively monitor brain activity during absence seizures in various animal models. In this dissertation I report the development of a pharmacological rat model of absence seizures for use in fMRI investigations. Imaging was performed after absence seizure induction using y-butyrolactone (GBL) and it was found that the cortico-thalamic circuitry, critical for the formation of SWDs