{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:50:55Z","timestamp":1787010655735,"version":"build-2736575974"},"posted":{"date-parts":[[2023,9,22]]},"group-title":"Neuroscience","reference-count":81,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:00:00Z","timestamp":1695340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 DC004290"],"award-info":[{"award-number":["R01 DC004290"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 MH 087463"],"award-info":[{"award-number":["R01 MH 087463"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Direct electrical stimulation (eSTIM) is widely used clinically, from neurosurgical mapping to therapeutic interventions for neurological and neuropsychiatric disorders\n                  <jats:sup>1\u201310<\/jats:sup>\n                  . 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\n                  <jats:italic>in vivo<\/jats:italic>\n                  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:\n                  <jats:italic>FOS<\/jats:italic>\n                  ,\n                  <jats:italic>NPAS4<\/jats:italic>\n                  ,\n                  <jats:italic>EGR4<\/jats:italic>\n                  ) in excitatory and inhibitory neurons and induction of cytokine-related genes\n                  <jats:italic>CCL3 and CCL4<\/jats:italic>\n                  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\n                  <jats:italic>in vivo<\/jats:italic>\n                  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.\n                <\/jats:p>","DOI":"10.1101\/2023.09.21.558812","type":"posted-content","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T04:50:24Z","timestamp":1695358224000},"source":"Crossref","is-referenced-by-count":1,"title":["The gene expression signature of electrical stimulation in the human brain"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4873-9416","authenticated-orcid":false,"given":"Snehajyoti","family":"Chatterjee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1019-3905","authenticated-orcid":false,"given":"Muhammad","family":"Elsadany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7522-3191","authenticated-orcid":false,"given":"Yann","family":"Vanrobaeys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9074-6935","authenticated-orcid":false,"given":"Annie I","family":"Gleason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian 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