{"doi":"10.1101/2023.09.21.558812","title":"The gene expression signature of electrical stimulation in the human brain","abstract":"Abstract Direct electrical stimulation (eSTIM) is widely used clinically, from neurosurgical mapping to therapeutic interventions for neurological and neuropsychiatric disorders 1–10 . Despite over a century of application, its molecular and cellular underpinnings remain unknown. Here, using state-of-the-art single-nuclei multiomic profiling, we map changes in cell-type-specific gene expression and chromatin accessibility in vivo in the human cortex following eSTIM of neurosurgery patients. eSTIM impacts a network of cells that extends beyond excitatory neurons to include inhibitory neurons, astrocytes, oligodendrocytes and microglia. We observed an upregulation of canonical immediate-early genes (IEGs: FOS , NPAS4 , EGR4 ) in excitatory and inhibitory neurons and induction of cytokine-related genes CCL3 and CCL4 in microglia. The cross-species conservation of this gene signature, together with our examination of a cohort of both epilepsy and cancer patients, underscores the fundamental role of these changes in stimulation-driven plasticity while controlling for disease and environmental confounds. Our study of changes in chromatin accessibility reveals a common code that involves a cell-type specific signature of transcription factor binding motifs for members of the EGR family. By addressing these previously unexplored questions about activity-induced gene expression in vivo in the human brain, our findings challenge the long-standing neuron-centric view of eSTIM, highlighting the broader role of non-neuronal cells, including microglia, in mediating the impact of brain stimulation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":411709,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9204,"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":1192051,"name":"Muhammad Elsadany","orcid":"0000-0002-1019-3905","position":1,"is_corresponding":false},{"id":456115,"name":"Yann Vanrobaeys","orcid":"0000-0002-7522-3191","position":2,"is_corresponding":false},{"id":1192052,"name":"Angela Gleason","orcid":"0000-0002-9074-6935","position":3,"is_corresponding":false},{"id":1192053,"name":"Brian J. Park","orcid":"0000-0002-0439-0451","position":4,"is_corresponding":false},{"id":689116,"name":"Shane A. Heiney","orcid":"0000-0001-9706-2133","position":5,"is_corresponding":false},{"id":336226,"name":"Ariane E. Rhone","orcid":"0000-0002-5699-8733","position":6,"is_corresponding":false},{"id":299543,"name":"Kirill V. Nourski","orcid":"0000-0002-7152-8473","position":7,"is_corresponding":false},{"id":1192054,"name":"Budhaditya Basu","orcid":"0009-0008-6696-567X","position":8,"is_corresponding":false},{"id":1036212,"name":"Utsav Mukherjee","orcid":"0000-0002-4849-9475","position":9,"is_corresponding":false},{"id":1036213,"name":"Lucy Langmack","orcid":"0000-0001-6819-8525","position":10,"is_corresponding":false},{"id":299540,"name":"Christopher K. Kovach","orcid":"0000-0002-0117-151X","position":11,"is_corresponding":false},{"id":551927,"name":"Zsuzsanna Kocsis","orcid":"0000-0003-2203-2786","position":12,"is_corresponding":false},{"id":551928,"name":"Yukiko Kikuchi","orcid":"0000-0002-0365-0397","position":13,"is_corresponding":false},{"id":1192055,"name":"Yaneri A. Ayala","orcid":"0000-0002-7031-6970","position":14,"is_corresponding":false},{"id":465055,"name":"Mark Bowren","orcid":"0000-0003-3304-6921","position":15,"is_corresponding":false},{"id":343798,"name":"Marco M. Hefti","orcid":"0000-0002-3127-4528","position":16,"is_corresponding":false},{"id":243330,"name":"Ethan Bahl","orcid":"0000-0002-2411-8906","position":17,"is_corresponding":false},{"id":88680,"name":"Kailin Yang","orcid":"0000-0001-5968-6738","position":18,"is_corresponding":false},{"id":1192375,"name":"Jeremy D. Greenlee","orcid":null,"position":19,"is_corresponding":false},{"id":299542,"name":"Hiroto Kawasaki","orcid":"0000-0002-7688-9171","position":20,"is_corresponding":false},{"id":477220,"name":"Hiroyuki Oya","orcid":"0000-0002-1733-5478","position":21,"is_corresponding":false},{"id":808811,"name":"Matthew A. Howard","orcid":"0000-0002-9359-3057","position":22,"is_corresponding":false},{"id":266427,"name":"Christopher I. Petkov","orcid":"0000-0002-4932-7907","position":23,"is_corresponding":false},{"id":809120,"name":"Thomas Nickl‐Jockschat","orcid":"0000-0003-2616-6503","position":24,"is_corresponding":false},{"id":281541,"name":"Li‐Chun Lin","orcid":"0000-0001-6715-6374","position":25,"is_corresponding":false},{"id":62186,"name":"Jacob J. Michaelson","orcid":"0000-0001-9713-0992","position":26,"is_corresponding":false},{"id":376729,"name":"Ted Abel","orcid":"0000-0003-2423-4592","position":27,"is_corresponding":false},{"id":456114,"name":"Snehajyoti Chatterjee","orcid":"0000-0002-4873-9416","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T01:21:42.971455Z","pmid":"37790527","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":[]}