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000893882 1001_ $$00000-0002-2256-1648$$aHawkins, Peter C. T.$$b0$$eCorresponding author
000893882 245__ $$aThe effect of risperidone on reward‐related brain activity is robust to drug‐induced vascular changes
000893882 260__ $$aNew York, NY$$bWiley-Liss$$c2021
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000893882 520__ $$aDopamine (DA) mediated brain activity is intimately linked to reward-driven cerebralresponses, while aberrant reward processing has been implicated in several psychiatricdisorders. fMRI has been a valuable tool in understanding the mechanism by which DAmodulators alter reward-driven responses and how they may exert their therapeuticeffect. However, the potential effects of a pharmacological compound on aspects ofneurovascular coupling may cloud the interpretability of the BOLD contrast. Here, weassess the effects of risperidone on reward driven BOLD signals produced by rewardanticipation and outcome, while attempting to control for potential drug effects onregional cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). Healthy malevolunteers (n = 21) each received a single oral dose of either 0.5 mg, 2 mg of risperi-done or placebo in a double-blind, placebo-controlled, randomised, three-period cross-over study design. Participants underwent fMRI scanning while performing the widelyused Monetary Incentive Delay (MID) task to assess drug impact on reward function.Measures of CBF (Arterial Spin Labelling) and breath-hold challenge induced BOLD sig-nal changes (as a proxy for CVR) were also acquired and included as covariates. Risperi-done produced divergent, dose-dependent effects on separate phases of rewardprocessing, even after controlling for potential nonneuronal influences on the BOLDsignal. These data suggest the D2 antagonist risperidone has a wide-ranging influenceon DA-mediated reward function independent of nonneuronal factors. We also illus-trate that assessment of potential vascular confounds on the BOLD signal may beadvantageous when investigating CNS drug action and advocate for the inclusion ofthese additional measures into future study designs.
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000893882 7001_ $$0P:(DE-HGF)0$$aZelaya, Fernando O.$$b1
000893882 7001_ $$0P:(DE-HGF)0$$aO'Daly, Owen$$b2
000893882 7001_ $$0P:(DE-HGF)0$$aHoliga, Stefan$$b3
000893882 7001_ $$0P:(DE-Juel1)177727$$aDukart, Jürgen$$b4$$ufzj
000893882 7001_ $$0P:(DE-HGF)0$$aUmbricht, Daniel$$b5
000893882 7001_ $$0P:(DE-HGF)0$$aMehta, Mitul A.$$b6
000893882 773__ $$0PERI:(DE-600)1492703-2$$a10.1002/hbm.25400$$gVol. 42, no. 9, p. 2766 - 2777$$n9$$p2766 - 2777$$tHuman brain mapping$$v42$$x1097-0193$$y2021
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