{"doi":"10.1093/brain/awad343","title":"Closed-loop stimulation in periods with less epileptiform activity drives improved epilepsy outcomes","abstract":"In patients with drug-resistant epilepsy, electrical stimulation of the brain in response to epileptiform activity can make seizures less frequent and debilitating. This therapy, known as closed-loop responsive neurostimulation (RNS), aims to directly halt seizure activity via targeted stimulation of a burgeoning seizure. Rather than immediately stopping seizures as they start, many RNS implants produce slower, long-lasting changes in brain dynamics that better predict clinical outcomes. Here we hypothesize that stimulation during brain states with less epileptiform activity drives long-term changes that restore healthy brain networks. To test this, we quantified stimulation episodes during low- and high-risk brain states-that is, stimulation during periods with a lower or higher risk of generating epileptiform activity-in a cohort of 40 patients treated with RNS. More frequent stimulation in tonic low-risk states and out of rhythmic high-risk states predicted seizure reduction. Additionally, stimulation events were more likely to be phase-locked to prolonged episodes of abnormal activity for intermediate and poor responders when compared to super-responders, consistent with the hypothesis that improved outcomes are driven by stimulation during low-risk states. These results support the hypothesis that stimulation during low-risk periods might underlie the mechanisms of RNS, suggesting a relationship between temporal patterns of neuromodulation and plasticity that facilitates long-term seizure reduction.","journal":"Brain","year":2023,"id":317774,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":73,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9493,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":483454,"name":"Chantel M. Charlebois","orcid":"0000-0002-4139-3539","position":1,"is_corresponding":false},{"id":240428,"name":"Elliot H. Smith","orcid":"0000-0003-4323-4643","position":2,"is_corresponding":false},{"id":314117,"name":"Tyler S. Davis","orcid":"0000-0001-8823-6189","position":3,"is_corresponding":false},{"id":314120,"name":"Angela Peters","orcid":"0000-0001-5140-0619","position":4,"is_corresponding":false},{"id":315909,"name":"Blake Newman","orcid":null,"position":5,"is_corresponding":false},{"id":314119,"name":"Amir Arain","orcid":"0000-0003-0572-0552","position":6,"is_corresponding":false},{"id":454963,"name":"Karen S. Wilcox","orcid":"0000-0003-2660-8826","position":7,"is_corresponding":false},{"id":298969,"name":"Christopher R. Butson","orcid":"0000-0002-2319-1263","position":8,"is_corresponding":false},{"id":286734,"name":"John D. Rolston","orcid":"0000-0002-8843-5468","position":9,"is_corresponding":false},{"id":298961,"name":"Daria Nesterovich Anderson","orcid":"0000-0002-9093-7504","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T01:06:55.884740Z","pmid":"37796038","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}