Epileptogenic Focus Localization and Closed-loop Control of Brain Dynamics in Epilepsy

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This project deals with the development of multivariable feedback decoupling controllers for the suppression of epileptic seizures by altering the brain dynamics through the use of deep-brain electrical stimulation. The key enabling concepts are a quantifiable relationship between the epileptic state and measures of brain?s spatial synchronization, and the ability to disrupt this synchronization by means of electrical stimulation. Intellectual MeritPrior work with electroencephalographic (EEG) data from epileptic patients and animals has indicated that such measures can be consistent indicators of the epileptic state of the brain and that electrical stimulation has generally beneficial, though not quite consistent effects. The novel idea behind the proposed control strategy is to combine our recent epileptogenic focus localization techniques with real-time delivery of practical stimuli in the form of biphasic, pulse-train-modulated, electrical signals to disentrain the brain. The controller design will rely on control-oriented models, describing the relationships between electrical stimuli and selected measures of spatial brain synchronization. The success of these experiments in rodents with chronic epilepsy, together with the physiological evaluation of the subjects, will provide a quantitative assessment of the effectiveness and possible side effects in the control of seizures, as well as important clues on the validity of the underlying theory about the mechanisms of seizure generation (ictogenesis).Broader Impacts:Expected intellectual benefits range from the solution of nonstandard problems in the regime of control of chaotic systems, to yet untapped engineering applications to biological systems. This research, if successful, will contribute to the new treatment modalities of neuromodulation for epilepsy and form a basis for economic growth and reduction of associated medical costs. It may also provide data for new applications in medicine and neuroscience, such as the treatment of Parkinson?s tremors, migraines, sleep disorders and other brain dynamical disorders.