{"doi":"10.1016/j.brs.2022.02.017","title":"Local and distant cortical responses to single pulse intracranial stimulation in the human brain are differentially modulated by specific stimulation parameters","abstract":"BACKGROUND: Electrical neuromodulation via direct electrical stimulation (DES) is an increasingly common therapy for a wide variety of neuropsychiatric diseases. Unfortunately, therapeutic efficacy is inconsistent, likely due to our limited understanding of the relationship between the massive stimulation parameter space and brain tissue responses. OBJECTIVE: To better understand how different parameters induce varied neural responses, we systematically examined single pulse-induced cortico-cortico evoked potentials (CCEP) as a function of stimulation amplitude, duration, brain region, and whether grey or white matter was stimulated. METHODS: We measured voltage peak amplitudes and area under the curve (AUC) of intracranially recorded stimulation responses as a function of distance from the stimulation site, pulse width, current injected, location relative to grey and white matter, and brain region stimulated (N = 52, n = 719 stimulation sites). RESULTS: Increasing stimulation pulse width increased responses near the stimulation location. Increasing stimulation amplitude (current) increased both evoked amplitudes and AUC nonlinearly. Locally (<15 mm), stimulation at the boundary between grey and white matter induced larger responses. In contrast, for distant sites (>15 mm), white matter stimulation consistently produced larger responses than stimulation in or near grey matter. The stimulation location-response curves followed different trends for cingulate, lateral frontal, and lateral temporal cortical stimulation. CONCLUSION: These results demonstrate that a stronger local response may require stimulation in the grey-white boundary while stimulation in the white matter could be needed for network activation. Thus, stimulation parameters tailored for a specific anatomical-functional outcome may be key to advancing neuromodulatory therapy.","journal":"Brain stimulation","year":2022,"id":235806,"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":75,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":554700,"name":"Rina Zelmann","orcid":"0000-0002-2142-7324","position":1,"is_corresponding":false},{"id":338077,"name":"Britni Crocker","orcid":null,"position":2,"is_corresponding":false},{"id":274326,"name":"Alik S. Widge","orcid":"0000-0001-8510-341X","position":3,"is_corresponding":false},{"id":336140,"name":"Darin D. Dougherty","orcid":"0000-0003-4691-4353","position":4,"is_corresponding":false},{"id":333806,"name":"Emad N. Eskandar","orcid":"0000-0003-4743-2938","position":5,"is_corresponding":false},{"id":336139,"name":"Daniel S. Weisholtz","orcid":"0000-0001-6277-4894","position":6,"is_corresponding":false},{"id":329101,"name":"R. Mark Richardson","orcid":"0000-0003-2620-7387","position":7,"is_corresponding":false},{"id":87173,"name":"G. Rees Cosgrove","orcid":"0000-0002-6220-5752","position":8,"is_corresponding":false},{"id":123809,"name":"Ziv M. Williams","orcid":null,"position":9,"is_corresponding":false},{"id":227177,"name":"Sydney S. Cash","orcid":"0000-0002-4557-6391","position":10,"is_corresponding":false},{"id":338076,"name":"Angelique C. Paulk","orcid":null,"position":0,"is_corresponding":true}],"reference_count":131,"raw_metadata":null,"created_at":"2026-07-19T00:21:53.333008Z","pmid":"35247646","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":[]}