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However, the potential effects of a pharmacological compound on aspects of neurovascular coupling may cloud the interpretability of the BOLD contrast. Here, we assess the effects of risperidone on reward driven BOLD signals produced by reward anticipation and outcome, while attempting to control for potential drug effects on regional cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). Healthy male volunteers (<jats:italic>n<\/jats:italic> = 21) each received a single oral dose of either 0.5 mg, 2 mg of risperidone or placebo in a double\u2010blind, placebo\u2010controlled, randomised, three\u2010period cross\u2010over study design. Participants underwent fMRI scanning while performing the widely used Monetary Incentive Delay (MID) task to assess drug impact on reward function. Measures of CBF (Arterial Spin Labelling) and breath\u2010hold challenge induced BOLD signal changes (as a proxy for CVR) were also acquired and included as covariates. Risperidone produced divergent, dose\u2010dependent effects on separate phases of reward processing, even after controlling for potential nonneuronal influences on the BOLD signal. These data suggest the D2 antagonist risperidone has a wide\u2010ranging influence on DA\u2010mediated reward function independent of nonneuronal factors. We also illustrate that assessment of potential vascular confounds on the BOLD signal may be advantageous when investigating CNS drug action and advocate for the inclusion of these additional measures into future study designs.<\/jats:p>","DOI":"10.1002\/hbm.25400","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T10:52:58Z","timestamp":1614941578000},"page":"2766-2777","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The effect of risperidone on reward\u2010related brain activity is robust to drug\u2010induced vascular changes"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2256-1648","authenticated-orcid":false,"given":"Peter C. T.","family":"Hawkins","sequence":"first","affiliation":[{"name":"Department of Neuroimaging Institute of Psychiatry, Psychology and Neuroscience, King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando O.","family":"Zelaya","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging Institute of Psychiatry, Psychology and Neuroscience, King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen","family":"O'Daly","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging Institute of Psychiatry, Psychology and Neuroscience, King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Holiga","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development Roche Innovation Centre Basel, F. Hoffmann\u2010La Roche Ltd.  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Dukart","sequence":"additional","affiliation":[{"name":"Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Umbricht","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development Roche Innovation Centre Basel, F. Hoffmann\u2010La Roche Ltd.  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitul A.","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging Institute of Psychiatry, Psychology and Neuroscience, King's College London  London 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