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dc.contributor.authorClarke, Hannahen
dc.contributor.authorHorst, Nicoleen
dc.contributor.authorRoberts, Angelaen
dc.date.accessioned2015-05-26T14:53:27Z
dc.date.available2015-05-26T14:53:27Z
dc.date.issued2015-03-16en
dc.identifier.citationClarke HF, Horst NK, Roberts AC, PNAS 2015, 112, 13, 4176-4181, doi:10.1073/pnas.1422440112en
dc.identifier.issn0027-8424
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/247998
dc.description.abstractDysregulation of the orbitofrontal and ventrolateral prefrontal cortices is implicated in anxiety and mood disorders, but the specific contributions of each region are unknown, including how they gate the impact of threat on decision making. To address this, the effects of GABAergic inactivation of these regions were studied in marmoset monkeys performing an instrumental approach–avoidance decision-making task that is sensitive to changes in anxiety. Inactivation of either region induced a negative bias away from punishment that could be ameliorated with anxiolytic treatment. However, whereas the effects of ventrolateral prefrontal cortex inactivation on punishment avoidance were seen immediately, those of orbitofrontal cortex inactivation were delayed and their expression was dependent upon an amygdala–anterior hippocampal circuit. We propose that these negative biases result from deficits in attentional control and punishment prediction, respectively, and that they provide the basis for understanding how distinct regional prefrontal dysregulation contributes to the heterogeneity of anxiety disorders with implications for cognitive-behavioral treatment strategies.
dc.description.sponsorshipAll authors contributed extensively to the work presented in this article, and we thank Rudolf Cardinal for helpful advice and discussion and Mercedes Arroyo for histology. This research was funded by a Medical Research Council Programme Grant (to A.C.R.) and Career Development Award (to H.F.C.). The research was conducted at the Behavioural and Clinical Neuroscience Institute, which is supported by a joint award from the Medical Research Council and Wellcome Trust (G00001354).
dc.languageEnglishen
dc.language.isoenen
dc.publisherNational Academy of Sciences
dc.rightsAttribution-NonCommercial 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/2.0/uk/*
dc.subjectanxietyen
dc.subjectorbitofrontal cortexen
dc.subjectventrolateral prefrontal cortexen
dc.subjectnegative biasen
dc.titleRegional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision makingen
dc.typeArticle
dc.description.versionThis is the accepted manuscript of a paper published in PNAS (Clarke HF, Horst NK, Roberts AC, PNAS 2015, 112, 13, 4176-4181, doi:10.1073/pnas.1422440112). The final version is available at http://dx.doi.org/10.1073/pnas.1422440112en
prism.endingPage4181
prism.number13en
prism.publicationDate2015en
prism.publicationNamePNASen
prism.startingPage4176
prism.volume112en
dc.rioxxterms.funderMRC
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.projectidG00001354
rioxxterms.versionofrecord10.1073/pnas.1422440112en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-03-16en
dc.contributor.orcidClarke, Hannah [0000-0002-1289-8917]
dc.contributor.orcidHorst, Nicole [0000-0002-7145-8911]
dc.contributor.orcidRoberts, Angela [0000-0003-2873-157X]
dc.identifier.eissn1091-6490
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (G1000183)
pubs.funder-project-idMRC (G0901884)
pubs.funder-project-idMEDICAL RESEARCH COUNCIL (G0001354)
pubs.funder-project-idMRC (G1100307)
pubs.funder-project-idMedical Research Council (MR/M023990/1)
pubs.funder-project-idWellcome Trust (093875/Z/10/Z)
rioxxterms.freetoread.startdate2015-09-16


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Attribution-NonCommercial 2.0 UK: England & Wales
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