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dc.contributor.authorKanen, Jonathan W
dc.contributor.authorErsche, Karen D
dc.contributor.authorFineberg, Naomi
dc.contributor.authorRobbins, Trevor W
dc.contributor.authorCardinal, Rudolf N
dc.date.accessioned2019-08-14T09:35:57Z
dc.date.available2019-08-14T09:35:57Z
dc.date.issued2019-08-01
dc.identifier.citationKanen , J W , Ersche , K D , Fineberg , N , Robbins , T W & Cardinal , R N 2019 , ' Computational modelling reveals contrasting effects on reinforcement learning and cognitive flexibility in stimulant use disorder and obsessive-compulsive disorder : remediating effects of dopaminergic D2/3 receptor agents ' , Psychopharmacology , vol. 236 , no. 8 , pp. 2337-2358 . https://doi.org/10.1007/s00213-019-05325-w
dc.identifier.issn0033-3158
dc.identifier.otherPURE: 17203322
dc.identifier.otherPURE UUID: 12eb7d8e-d8bc-4915-a05e-74a519f84c44
dc.identifier.otherPubMed: 31324936
dc.identifier.otherScopus: 85068864193
dc.identifier.urihttp://hdl.handle.net/2299/21599
dc.description.abstractRATIONALE: Disorders of compulsivity such as stimulant use disorder (SUD) and obsessive-compulsive disorder (OCD) are characterised by deficits in behavioural flexibility, some of which have been captured using probabilistic reversal learning (PRL) paradigms. OBJECTIVES: This study used computational modelling to characterise the reinforcement learning processes underlying patterns of PRL behaviour observed in SUD and OCD and to show how the dopamine D2/3 receptor agonist pramipexole and the D2/3 antagonist amisulpride affected these responses. METHODS: We applied a hierarchical Bayesian method to PRL data across three groups: individuals with SUD, OCD, and healthy controls. Participants completed three sessions where they received placebo, pramipexole, and amisulpride, in a double-blind placebo-controlled, randomised design. We compared seven models using a bridge sampling estimate of the marginal likelihood. RESULTS: Stimulus-bound perseveration, a measure of the degree to which participants responded to the same stimulus as before irrespective of outcome, was significantly increased in SUD, but decreased in OCD, compared to controls (on placebo). Individuals with SUD also exhibited reduced reward-driven learning, whilst both the SUD and OCD groups showed increased learning from punishment (nonreward). Pramipexole and amisulpride had similar effects on the control and OCD groups; both increased punishment-driven learning. These D2/3-modulating drugs affected the SUD group differently, remediating reward-driven learning and reducing aspects of perseverative behaviour, amongst other effects. CONCLUSIONS: We provide a parsimonious computational account of how perseverative tendencies and reward- and punishment-driven learning differentially contribute to PRL in SUD and OCD. D2/3 agents modulated these processes and remediated deficits in SUD in particular, which may inform therapeutic effects.en
dc.format.extent22
dc.language.isoeng
dc.relation.ispartofPsychopharmacology
dc.rightsOpen
dc.titleComputational modelling reveals contrasting effects on reinforcement learning and cognitive flexibility in stimulant use disorder and obsessive-compulsive disorder : remediating effects of dopaminergic D2/3 receptor agentsen
dc.contributor.institutionCognitive Neuropsychology
dc.contributor.institutionDepartment of Clinical and Pharmaceutical Sciences
dc.contributor.institutionCentre for Health Services and Clinical Research
dc.contributor.institutionSchool of Life and Medical Sciences
dc.description.statusPeer reviewed
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/s00213-019-05325-w
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstypeOpen


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