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Previous animal work has shown strong inhibition of hippocampal seizures through on-demand optogenetic manipulation of the cerebellum. However, decades of work examining electrical stimulation\u2014a more immediately translatable approach\u2014targeting the cerebellum has produced very mixed results. We were therefore interested in exploring the impact that stimulation parameters may have on seizure outcomes. Using a mouse model of temporal lobe epilepsy, we conducted on-demand electrical stimulation of the cerebellar cortex, and varied stimulation charge, frequency and pulse width, resulting in over 1000 different potential combinations of settings. To explore this parameter space in an efficient, data-driven, manner, we utilized Bayesian optimization with Gaussian process regression, implemented in MATLAB with an Expected Improvement Plus acquisition function. We examined three different fitting conditions and two different electrode orientations. Following the optimization process, we conducted additional on-demand experiments to test the effectiveness of selected settings. Regardless of experimental setup, we found that Bayesian optimization allowed identification of effective intervention settings. Additionally, generally similar optimal settings were identified across animals, suggesting that personalized optimization may not always be necessary. While optimal settings were effective, stimulation with settings predicted from the Gaussian process regression to be ineffective failed to provide seizure control. Taken together, our results provide a blueprint for exploration of a large parameter space for seizure control and illustrate that robust inhibition of seizures can be achieved with electrical stimulation of the cerebellum, but only if the correct stimulation parameters are used.<\/jats:p>","DOI":"10.1093\/brain\/awac051","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T23:33:30Z","timestamp":1644017610000},"page":"91-108","source":"Crossref","is-referenced-by-count":59,"title":["Optimization of closed-loop electrical stimulation enables robust cerebellar-directed seizure control"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8030-6805","authenticated-orcid":false,"given":"Bethany J","family":"Stieve","sequence":"first","affiliation":[{"name":"Graduate Program in Neuroscience, University of Minnesota , Minneapolis 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J","family":"Richner","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Minnesota , Minneapolis 55455 , USA"},{"name":"Department of Neuroscience, University of Minnesota , Minneapolis 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Krook-Magnuson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Minnesota , Minneapolis 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theoden I","family":"Netoff","sequence":"additional","affiliation":[{"name":"Graduate Program in Neuroscience, University of Minnesota , Minneapolis 55455 , USA"},{"name":"Department of Biomedical Engineering, University of Minnesota , Minneapolis 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6119-0165","authenticated-orcid":false,"given":"Esther","family":"Krook-Magnuson","sequence":"additional","affiliation":[{"name":"Graduate Program in Neuroscience, University of Minnesota , Minneapolis 55455 , USA"},{"name":"Department of Neuroscience, University of Minnesota , Minneapolis 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,8]]},"reference":[{"issue":"2","key":"2023052218133749100_awac051-B1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.yebeh.2012.06.016","article-title":"Epilepsy across the spectrum: promoting health and understanding. 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