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Mechanisms related to reward processing might mediate ghrelin\u2019s broader effects on complex behaviors, as indicated by animal studies and mostly correlative human studies. Here, using a within-subject double-blind placebo-controlled design with intravenous ghrelin infusion in healthy volunteers (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200930), we tested whether ghrelin alters sensitivity to reward and punishment in a reward learning task. Parameters were derived from a computational model of participants\u2019 task behavior. The reversal learning task with monetary rewards was performed during functional brain imaging to investigate ghrelin effects on brain signals related to reward prediction errors. Compared to placebo, ghrelin decreased punishment sensitivity (\n                    <jats:italic>t<\/jats:italic>\n                    \u2009=\u2009\u22122.448,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.021), while reward sensitivity was unaltered (\n                    <jats:italic>t<\/jats:italic>\n                    \u2009=\u20090.8,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.43). We furthermore found increased prediction-error related activity in the dorsal striatum during ghrelin administration (region of interest analysis:\n                    <jats:italic>t-<\/jats:italic>\n                    values\u2009\u2265\u20094.21,\n                    <jats:italic>p<\/jats:italic>\n                    -values\u2009\u2264\u20090.044). Our results support a role for ghrelin in reward processing that extends beyond food-related rewards. Reduced sensitivity to negative outcomes and increased processing of prediction errors may be beneficial for food foraging when hungry but could also relate to increased risk taking and impulsivity in the broader context of addictive behaviors.\n                  <\/jats:p>","DOI":"10.1038\/s41386-024-01821-6","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T14:02:42Z","timestamp":1708956162000},"page":"1042-1049","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Ghrelin decreases sensitivity to negative feedback and increases prediction-error related caudate activity in humans, a randomized controlled trial"],"prefix":"10.1038","volume":"49","author":[{"given":"Michal","family":"Pietrzak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1012-7286","authenticated-orcid":false,"given":"Adam","family":"Yngve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7982-4659","authenticated-orcid":false,"given":"J. Paul","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Asratian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emelie","family":"Gauffin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"L\u00f6fberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Gustavson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2994-0541","authenticated-orcid":false,"given":"Emil","family":"Persson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1758-2206","authenticated-orcid":false,"given":"Andrea J.","family":"Capusan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7284-8754","authenticated-orcid":false,"given":"Lorenzo","family":"Leggio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5972-0913","authenticated-orcid":false,"given":"Irene","family":"Perini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8159-1249","authenticated-orcid":false,"given":"Gustav","family":"Tingh\u00f6g","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Heilig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2803-3069","authenticated-orcid":false,"given":"Rebecca","family":"Boehme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,26]]},"reference":[{"key":"1821_CR1","doi-asserted-by":"crossref","first-page":"E297","DOI":"10.1152\/ajpendo.00582.2003","volume":"287","author":"DE Cummings","year":"2004","unstructured":"Cummings DE, Frayo RS, Marmonier C, Aubert R, Chapelot D. 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