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dc.contributor.authorMurray, Graham
dc.contributor.authorKnolle, Franziska
dc.contributor.authorErsche, Karen D
dc.contributor.authorCraig, Kevin J
dc.contributor.authorAbbott, Sanja
dc.contributor.authorShabbir, Shaila S
dc.contributor.authorFineberg, Naomi
dc.contributor.authorSuckling, John
dc.contributor.authorSahakian, Barbara J.
dc.contributor.authorBullmore, Edward T.
dc.contributor.authorRobbins, Trevor W.
dc.date.accessioned2019-08-07T17:31:32Z
dc.date.available2019-08-07T17:31:32Z
dc.date.issued2019-08-01
dc.identifier.citationMurray , G , Knolle , F , Ersche , K D , Craig , K J , Abbott , S , Shabbir , S S , Fineberg , N , Suckling , J , Sahakian , B J , Bullmore , E T & Robbins , T W 2019 , ' Dopaminergic drug treatment remediates exaggerated cingulate prediction error responses in obsessive-compulsive disorder ' , Psychopharmacology , vol. 236 , no. 8 , pp. 2325-2336 . https://doi.org/10.1007/s00213-019-05292-2
dc.identifier.issn0033-3158
dc.identifier.otherPURE: 16847281
dc.identifier.otherPURE UUID: 87636b09-c0a5-4b3d-8ab5-ddfc15100ed1
dc.identifier.otherScopus: 85067789621
dc.identifier.urihttp://hdl.handle.net/2299/21576
dc.description© The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
dc.description.abstractRationale: Patients with obsessive-compulsive disorder (OCD) have been found to show exaggerated error responses and prediction error learning signals in a variety of EEG and fMRI tasks, with data converging on the anterior cingulate cortex as a key locus of dysfunction. Considerable evidence has linked prediction error processing to dopaminergic function. Objective: In this study, we investigate potential dopaminergic dysfunction during reward processing in the context of OCD. Methods: We studied OCD patients (n = 18) and controls (n = 18) whilst they learned probabilistic associations between abstract stimuli and monetary rewards in the fMRI scanner involving administration (on separate visits) of a dopamine receptor agonist, pramipexole 0.5 mg; a dopamine receptor antagonist, amisulpride 400 mg; and placebo. We fitted a Q-learning computational model to fMRI prediction error responses; group differences were examined in anterior cingulate and nucleus accumbens regions of interest. Results: There were no significant group, drug, or interaction effects in the number of correct choices; computational modeling suggested a marginally significant difference in learning rates between groups (p = 0.089, partial ƞ 2 = 0.1). In the imaging results, there was a significant interaction of group by drug (p = 0.013, partial ƞ 2 = 0.13). OCD patients showed abnormally strong cingulate signaling of prediction errors during omission of an expected reward, with unexpected reduction by both pramipexole and amisulpride (p = 0.014, partial ƞ 2 = 0.26, 1-β error probability = 0.94). Exaggerated cingulate prediction error signaling to omitted reward in placebo was related to trait subjective difficulty in self-regulating behavior in OCD. Conclusions: Our data support cingulate dysfunction during reward processing in OCD, and bidirectional remediation by dopaminergic modulation, suggesting that exaggerated cingulate error signals in OCD may be of dopaminergic origin. The results help to illuminate the mechanisms through which dopamine receptor antagonists achieve therapeutic benefit in OCD. Further research is needed to disentangle the different functions of dopamine receptor agonists and antagonists during bidirectional modulation of cingulate activation.en
dc.format.extent12
dc.language.isoeng
dc.relation.ispartofPsychopharmacology
dc.rightsOpen
dc.subjectAmisulpride
dc.subjectAnterior cingulate
dc.subjectComputational model
dc.subjectNucleus accumbens
dc.subjectObsessive-compulsive disorder
dc.subjectPramipexole
dc.subjectPrediction error
dc.subjectReward learning
dc.subjectPharmacology
dc.titleDopaminergic drug treatment remediates exaggerated cingulate prediction error responses in obsessive-compulsive disorderen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionDepartment of Clinical and Pharmaceutical Sciences
dc.contributor.institutionCentre for Health Services and Clinical Research
dc.description.statusPeer reviewed
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85067789621&partnerID=8YFLogxK
dc.relation.schoolSchool of Life and Medical Sciences
dc.description.versiontypeFinal Published version
dcterms.dateAccepted2019-08-01
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.1007/s00213-019-05292-2
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstypeOpen


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