{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T23:03:57Z","timestamp":1773961437463,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1010079","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000}}],"reference-count":134,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019544","name":"Cambridge Centre for Parkinson-Plus","doi-asserted-by":"publisher","award":["RG95450"],"award-info":[{"award-number":["RG95450"]}],"id":[{"id":"10.13039\/501100019544","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Parkinson's UK research grant","award":["K-1702"],"award-info":[{"award-number":["K-1702"]}]},{"name":"James S. 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Despite its prevalence and prognostic importance, the mechanisms underlying apathy remain controversial. Degeneration of the locus coeruleus-noradrenaline system is known to contribute to motivational deficits, including apathy. In healthy people, noradrenaline has been implicated in signalling the uncertainty of expectations about the environment. We proposed that noradrenergic deficits contribute to apathy by modulating the relative weighting of prior beliefs about action outcomes. We tested this hypothesis in the clinical context of Parkinson\u2019s disease, given its associations with apathy and noradrenergic dysfunction. Participants with mild-to-moderate Parkinson\u2019s disease (\n                    <jats:italic>N<\/jats:italic>\n                    = 17) completed a randomised double-blind, placebo-controlled, crossover study with 40 mg of the noradrenaline reuptake inhibitor atomoxetine. Prior weighting was inferred from psychophysical analysis of performance in an effort-based visuomotor task, and was confirmed as negatively correlated with apathy. Locus coeruleus integrity was assessed\n                    <jats:italic>in vivo<\/jats:italic>\n                    using magnetisation transfer imaging at ultra-high field 7T. The effect of atomoxetine depended on locus coeruleus integrity: participants with a more degenerate locus coeruleus showed a greater increase in prior weighting on atomoxetine\n                    <jats:italic>versus<\/jats:italic>\n                    placebo. The results indicate a contribution of the noradrenergic system to apathy and potential benefit from noradrenergic treatment of people with Parkinson\u2019s disease, subject to stratification according to locus coeruleus integrity. More broadly, these results reconcile emerging predictive processing accounts of the role of noradrenaline in goal-directed behaviour with the clinical symptom of apathy and its potential pharmacological treatment.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1010079","type":"journal-article","created":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T13:46:11Z","timestamp":1652103971000},"page":"e1010079","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":47,"title":["Noradrenergic deficits contribute to apathy in Parkinson\u2019s disease through the precision of expected outcomes"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0092-3289","authenticated-orcid":true,"given":"Frank H.","family":"Hezemans","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4652-7727","authenticated-orcid":true,"given":"Noham","family":"Wolpe","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5698-6364","authenticated-orcid":true,"given":"Claire","family":"O\u2019Callaghan","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2529-7755","authenticated-orcid":true,"given":"Rong","family":"Ye","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0404-4399","authenticated-orcid":true,"given":"Catarina","family":"Rua","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9695-0702","authenticated-orcid":true,"given":"P. Simon","family":"Jones","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0813-0670","authenticated-orcid":true,"given":"Alexander G.","family":"Murley","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3813-0882","authenticated-orcid":true,"given":"Negin","family":"Holland","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7292-1859","authenticated-orcid":true,"given":"Ralf","family":"Regenthal","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3178-6363","authenticated-orcid":true,"given":"Kamen A.","family":"Tsvetanov","sequence":"additional","affiliation":[]},{"given":"Roger A.","family":"Barker","sequence":"additional","affiliation":[]},{"given":"Caroline H.","family":"Williams-Gray","sequence":"additional","affiliation":[]},{"given":"Trevor 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