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In this single-blind, placebo-controlled, crossover study, 28 healthy participants received 0.5\u2009mg\/kg racemic ketamine or placebo via a 40\u2009min intravenous infusion. Functional magnetic resonance imaging was acquired approximately 5\u2009h post-infusion during the Monetary Incentive Delay (MID) task, targeting the subacute phase after resolution of acute dissociative effects. Plasma concentrations of ketamine and norketamine were obtained for pharmacokinetic modeling and area under the curve estimation. At 5\u2009h post-administration, ketamine did not significantly modulate brain activation during the MID task in either ROI-based or whole-brain analyses, despite measurable subjective drug effects. Pharmacokinetic modeling yielded ketamine and norketamine concentration-time profiles consistent with expected pharmacokinetic patterns, however, neither individual drug exposure nor psychometric measures showed robust associations with MID task-related neural activation. These findings suggest an absence of detectable task-evoked effects under the present methodological conditions. When considered alongside prior work, they are consistent with the possibility that ketamine\u2019s effects on reward circuitry are time-sensitive and may be more prominent during the acute post-administration phase or in clinical populations with pre-existing reward dysfunction.<\/jats:p>","DOI":"10.1038\/s41398-026-04485-6","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:33:51Z","timestamp":1790292831000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Subacute effects of ketamine on neural correlates of reward processing"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4311-4031","authenticated-orcid":false,"given":"Elisa","family":"Briem","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7324-0414","authenticated-orcid":false,"given":"Peter","family":"St\u00f6hrmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"D\u00f6rl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1347-0744","authenticated-orcid":false,"given":"Christian","family":"Milz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Schlosser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Kl\u00f6bl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray","family":"Reed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1054-8374","authenticated-orcid":false,"given":"Matthieu","family":"Atger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3138-6869","authenticated-orcid":false,"given":"Clemens","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Graf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8249-3237","authenticated-orcid":false,"given":"Maximilian","family":"Kathofer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9739-0724","authenticated-orcid":false,"given":"Godber Mathis","family":"Godbersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia Sophia","family":"Crone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4641-9539","authenticated-orcid":false,"given":"Rupert","family":"Lanzenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Spies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"4485_CR1","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/S0006-3223(99)00230-9","volume":"47","author":"RM Berman","year":"2000","unstructured":"Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, et al. 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Lanzenberger received investigator-initiated research funding from Siemens Healthcare regarding clinical research using PET\/MR and travel grants and\/or conference speaker honoraria from Janssen-Cilag Pharma GmbH in 2023, and Bruker BioSpin, Shire, AstraZeneca, Lundbeck A\/S, Dr. Willmar Schwabe GmbH, Orphan Pharmaceuticals AG, Janssen-Cilag Pharma GmbH, Heel and Roche Austria GmbH in the years before 2020. He is a shareholder of the company BM Health GmbH, Austria since 2019. M. Spies has received travel grants from AOP Orphan Pharmaceuticals, Janssen and Austroplant, speaker honoraria from Janssen and Austroplant, and workshop participation from Eli Lilly. C. Schmidt has received a travel grant from Eli Lilly to attend a scientific exchange meeting. All other authors declare no potential conflicts of interest with respect to the research, authorship, and\/or publication of this article.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"This study was approved by the ethics committee of the Medical University of Vienna, Austria (EK 1572\/2021) and performed in accordance with the Declaration of Helsinki.","order":2,"name":"Ethics","label":"Ethics declaration","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"521"}}