Robert E. Gross, M.D. Ph.D. (Georgia Institute of Technology/Emory University)
Babak Mahmoudi, Ph.D. (Georgia Institute of Technology/Emory University)
Christopher J. Rozell, Ph.D. (Georgia Institute of Technology)
John T. Gale, Ph.D. (Emory University)
Joseph R. Manns, Ph.D. (Emory University)
Data driven optimization of septo-hippocampal optogenetic stimulation for the treatment of epilepsy
Over 50 million people worldwide suffer from epilepsy, and a large proportion of patients do not achieve seizure freedom with pharmacological therapy. Electrical deep brain stimulation has been shown to reduce seizure frequency, but only a small proportion of patients become seizure free. Therefore, there is a need for a novel target and stimulation techniques, the former of which will require a greater understanding of brain networks, and the latter of which demands the optimization of stimulation parameters and policy. The projections from the medial septum (MS) and its regulatory role on the hippocampus make it an attractive neuromodulation target, and optogenetics will provide a cell type specific excitation or inhibition within MS. The goal of this proposal is to improve the efficacy of MS optogenetic stimulation to modulate hippocampal activity by applying machine learning techniques and to ultimately find the treatment which effectively prevents seizures. First, we will characterize the hippocampal biomarker activity in normal and epileptic rats. Biomarkers of which activity is pronounced during the pre-ictal period will be identified, and the effect of MS optogenetic stimulation on hippocampal local field potentials will be characterized. Second, we will develop a closed-loop optimization platform to effectively modulate the hippocampal biomarkers. The optimization platform is expected to provide a faster and more efficient method compared to the exhaustive parameter search method, which requires a tremendous amount of time and resource along with an increased chance of inducing a side effect. Lastly, we will identify the effect of stimulation which modulates seizure-related biomarkers on seizure properties (e.g. frequency, duration, and severity). Various stimulation strategies will be applied and compared to find the optimal seizure treatment method.