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We have previously demonstrated that increased E-field strength improves ECT\u2019s antidepressant effect but worsens cognitive outcomes. Amplitude-determined seizure titration may reduce the E-field variability relative to fixed amplitude ECT. In this investigation, we assessed the relationships among amplitude-determined seizure-threshold (ST<jats:sub>a<\/jats:sub>), E-field magnitude, and clinical outcomes in older adults (age range 50 to 80 years) with depression. Subjects received brain imaging, depression assessment, and neuropsychological assessment pre-, mid-, and post-ECT. ST<jats:sub>a<\/jats:sub> was determined during the first treatment with a Soterix Medical 4\u00d71 High Definition ECT Multi-channel Stimulation Interface (Investigation Device Exemption: G200123). Subsequent treatments were completed with right unilateral electrode placement (RUL) and 800\u2009mA. We calculated <jats:italic>E<\/jats:italic><jats:sub>brain<\/jats:sub> defined as the 90th percentile of E-field magnitude in the whole brain for RUL electrode placement. Twenty-nine subjects were included in the final analyses. <jats:italic>E<\/jats:italic><jats:sub>brain<\/jats:sub> per unit electrode current, <jats:italic>E<\/jats:italic><jats:sub>brain<\/jats:sub>\/<jats:italic>I<\/jats:italic>, was associated with ST<jats:sub>a<\/jats:sub>. ST<jats:sub>a<\/jats:sub> was associated with antidepressant outcomes at the mid-ECT assessment and bitemporal electrode placement switch. <jats:italic>E<\/jats:italic><jats:sub>brain<\/jats:sub>\/<jats:italic>I<\/jats:italic> was associated with changes in category fluency with a large effect size. The relationship between ST<jats:sub>a<\/jats:sub> and <jats:italic>E<\/jats:italic><jats:sub>brain<\/jats:sub>\/<jats:italic>I<\/jats:italic> extends work from preclinical models and provides a validation step for ECT E-field modeling. ECT with individualized amplitude based on E-field modeling or ST<jats:sub>a<\/jats:sub> has the potential to enhance neuroscience-based ECT parameter selection and improve clinical outcomes.<\/jats:p>","DOI":"10.1038\/s41386-023-01780-4","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T17:02:22Z","timestamp":1704992542000},"page":"640-648","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Amplitude-determined seizure-threshold, electric field modeling, and electroconvulsive therapy antidepressant and cognitive outcomes"],"prefix":"10.1038","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6884-2464","authenticated-orcid":false,"given":"Christopher C.","family":"Abbott","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Farrar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miklos","family":"Argyelan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Lloyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Squillaci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Kimbrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sephira","family":"Ryman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Upston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davin K.","family":"Quinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4385-065X","authenticated-orcid":false,"given":"Angel V.","family":"Peterchev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Erhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Datta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn M.","family":"McClintock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8925-0871","authenticated-orcid":false,"given":"Zhi-De","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,11]]},"reference":[{"key":"1780_CR1","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/S0140-6736(03)12705-5","volume":"361","author":"UK ECT Review Group.","year":"2003","unstructured":"UK ECT Review Group. 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