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However, it is unclear whether drugs that increase catecholamine transmission, such as methylphenidate, optimize this balance in a task-dependent manner or bias the system toward stability at the expense of flexibility (or vice versa). Here we demonstrate, using pharmacological fMRI, that methylphenidate improves the ability to resist distraction (cognitive stability) but impairs the ability to flexibly update items currently held in working memory (cognitive flexibility). These behavioral effects were accompanied by task-general effects in the striatum and opposite and task-specific effects on neural signal in the pFC. This suggests that methylphenidate exerts its cognitive enhancing and impairing effects through acting on the pFC, an effect likely associated with methylphenidate's action on the striatum. These findings highlight that methylphenidate acts as a double-edged sword, improving one cognitive function at the expense of another, while also elucidating the neurocognitive mechanisms underlying these paradoxical effects.<\/jats:p>","DOI":"10.1162\/jocn_a_01065","type":"journal-article","created":{"date-parts":[[2016,10,25]],"date-time":"2016-10-25T18:35:16Z","timestamp":1477420516000},"page":"652-663","update-policy":"https:\/\/doi.org\/10.1162\/mitpressjournals.corrections.policy","source":"Crossref","is-referenced-by-count":56,"title":["The Neurocognitive Cost of Enhancing Cognition with Methylphenidate: Improved Distractor Resistance but Impaired Updating"],"prefix":"10.1162","volume":"29","author":[{"given":"Sean James","family":"Fallon","sequence":"first","affiliation":[{"name":"1Radboud University Donders Institute of Brain, Cognition, and Behavior"},{"name":"3University of Oxford"}]},{"given":"Marieke E.","family":"van der Schaaf","sequence":"additional","affiliation":[{"name":"1Radboud University Donders Institute of Brain, Cognition, and Behavior"},{"name":"2Radboud University Nijmegen Medical Centre"}]},{"given":"Niels","family":"ter Huurne","sequence":"additional","affiliation":[{"name":"2Radboud University Nijmegen Medical Centre"}]},{"given":"Roshan","family":"Cools","sequence":"additional","affiliation":[{"name":"1Radboud University Donders Institute of Brain, Cognition, and Behavior"},{"name":"2Radboud University Nijmegen Medical Centre"}]}],"member":"281","published-online":{"date-parts":[[2017,4,1]]},"reference":[{"key":"2021073021073079200_R1","doi-asserted-by":"crossref","first-page":"e89","DOI":"10.1016\/j.biopsych.2011.01.027","article-title":"Catecholamine influences on dorsolateral prefrontal cortical networks","volume":"69","author":"Arnsten","year":"2011","journal-title":"Biological 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