Epileptic seizures are a common disease that afflicts over 2.5 million Americans. These seizures can sometimes be prevented with pharmaceutical treatment; however, over 25% of epilepsy patients cannot be helped by antiepileptic drugs. For these patients in whom seizures are sufficiently severe, the only remaining option is surgical removal of brain tissue which can sometimes result in severe neurological deficits. The ultimate goal of the research described in this proposal is to develop a less invasive and potentially far less damaging alternative to surgery for drug-refractory epilepsy patients. The overall objective is to engineer a device similar in concept to an implantable cardiac defribrillator in that it would detect the earliest stages of a seizure and prevent or revert it using electrical stimulation. This research requires exploration in diverse but related fields such as nonlinear chaos theory and computer programming as well as expertise in experimental biology. Experiments will be focused on the hippocampus, a region of the brain that is a frequent foci for generation of epileptiform electical activity. Continuing experiments will perform nonlinear mathematical analysis followed by testing of control algorithms on rat hippocampal slices which can be induced to produce spontaneous discharges analogous to epileptic behavior seen in whole animals. Electrical stimulation will be applied via an electrode according to control algorithms to revert the bursting. Because neuronal dynamics in a network can be quite complex, techniques of both control and anti-control will be researched. Recent advances in understanding and controlling chaotic systems have provided an invaluable opportunity to apply these principles toward manipulation of pathological electrical activity in the brain. It would ultimately permit the ability to prevent or revert seizures in the brain which would have enormous benefits to public health as well as overall cost savings to society. ? ?
|Fine, Ananda S; Nicholls, David P; Mogul, David J (2010) Assessing instantaneous synchrony of nonlinear nonstationary oscillators in the brain. J Neurosci Methods 186:42-51|
|Slutzky, Marc W; Jordan, Luke R; Krieg, Todd et al. (2010) Optimal spacing of surface electrode arrays for brain-machine interface applications. J Neural Eng 7:26004|
|Li, Yue; Fleming, Ioana Nicolaescu; Colpan, Mustafa Efkan et al. (2008) Neuronal desynchronization as a trigger for seizure generation. IEEE Trans Neural Syst Rehabil Eng 16:62-73|