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Testing the noradrenergic framework of learning in the context of human diseases offers a test bed for current normative neuroscience theories and may also indicate therapeutic potential. Parkinson\u2019s disease is often considered as a model of dopamine deficits, including dopamine\u2019s role in reinforcement learning. However, noradrenergic function is also severely impaired by Parkinson\u2019s disease, contributing to cognitive deficits. Using a single dose of the noradrenaline reuptake inhibitor atomoxetine in people with Parkinson\u2019s disease (in a randomised double-blind placebo-controlled crossover design), we show improvements in learning compared to placebo. Computational cognitive modelling confirmed a substantial shift in the decision noise parameter, indicative of more exploitative choices. This response pattern closely resembled that of age-matched controls and simulations of optimal response strategies. Pupillometry revealed increased baseline pupil diameter under atomoxetine, which correlated with behavioural improvements, and a heightened phasic pupillary response to feedback. Our findings confirm the noradrenergic contribution to reinforcement learning, and in doing so they challenge the simple interpretation of tonic-phasic locus coeruleus firing patterns based on pupillometry. Noradrenergic modulation is a potential treatment strategy for cognitive symptoms in Parkinson\u2019s disease and related disorders.<\/jats:p>","DOI":"10.1038\/s42003-025-08627-2","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T14:57:49Z","timestamp":1755183469000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pharmacological and pupillary evidence for the noradrenergic contribution to reinforcement learning in Parkinson\u2019s disease"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5698-6364","authenticated-orcid":false,"given":"Claire","family":"O\u2019Callaghan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0092-3289","authenticated-orcid":false,"given":"Frank H.","family":"Hezemans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naresh","family":"Subramaniam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2529-7755","authenticated-orcid":false,"given":"Rong","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3178-6363","authenticated-orcid":false,"given":"Kamen A.","family":"Tsvetanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0813-0670","authenticated-orcid":false,"given":"Alexander G.","family":"Murley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Negin","family":"Holland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4515-3479","authenticated-orcid":false,"given":"Isabella F.","family":"Orlando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7292-1859","authenticated-orcid":false,"given":"Ralf","family":"Regenthal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8843-7730","authenticated-orcid":false,"given":"Roger A.","family":"Barker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2648-9743","authenticated-orcid":false,"given":"Caroline H.","family":"Williams-Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Passamonti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0642-5977","authenticated-orcid":false,"given":"Trevor W.","family":"Robbins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7216-8679","authenticated-orcid":false,"given":"James B.","family":"Rowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"8627_CR1","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1146\/annurev.neuro.051508.135535","volume":"32","author":"TW Robbins","year":"2009","unstructured":"Robbins, T. 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