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dc.contributor.authorBorchert, Robin Jen
dc.contributor.authorRittman, Timothyen
dc.contributor.authorPassamonti, Lucaen
dc.contributor.authorYe, Zhengen
dc.contributor.authorSami, Saberen
dc.contributor.authorJones, Simonen
dc.contributor.authorNombela, Cristinaen
dc.contributor.authorRodríguez, Patricia Vázquezen
dc.contributor.authorVatansever, Denizen
dc.contributor.authorRae, Charlotte Len
dc.contributor.authorHughes, Lauraen
dc.contributor.authorRobbins, Trevoren
dc.contributor.authorRowe, Jamesen
dc.date.accessioned2016-02-09T15:06:54Z
dc.date.available2016-02-09T15:06:54Z
dc.date.issued2016-02-03en
dc.identifier.issn0893-133X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/253680
dc.description.abstractCognitive impairment is common in Parkinson’s disease (PD), but often not improved by dopaminergic treatment. New treatment strategies targeting other neurotransmitter deficits are therefore of growing interest. Imaging the brain at rest (‘task-free’) provides the opportunity to examine the impact of a candidate drug on many of the brain networks that underpin cognition, while minimizing task-related performance confounds. We test this approach using atomoxetine, a selective noradrenaline reuptake inhibitor that modulates the prefrontal cortical activity and can facilitate some executive functions and response inhibition. Thirty-three patients with idiopathic PD underwent task-free fMRI. Patients were scanned twice in a double-blind, placebo-controlled crossover design, following either placebo or 40-mg oral atomoxetine. Seventy-six controls were scanned once without medication to provide normative data. Seed-based correlation analyses were used to measure changes in functional connectivity, with the right inferior frontal gyrus (IFG) a critical region for executive function. Patients on placebo had reduced connectivity relative to controls from right IFG to dorsal anterior cingulate cortex and to left IFG and dorsolateral prefrontal cortex. Atomoxetine increased connectivity from the right IFG to the dorsal anterior cingulate. In addition, the atomoxetine-induced change in connectivity from right IFG to dorsolateral prefrontal cortex was proportional to the change in verbal fluency, a simple index of executive function. The results support the hypothesis that atomoxetine may restore prefrontal networks related to executive functions. We suggest that task-free imaging can support translational pharmacological studies of new drug therapies and provide evidence for engagement of the relevant neurocognitive systems.
dc.description.sponsorshipThis work was funded by the Wellcome trust (103838), Parkinson’s UK, National Institute for Health Research’s Cambridge Biomedical Research Centre and the Medical Research Council (MC_US_A060_0016 and RG62761) and the James F McDonnell Foundation (21st century science initiative on Understanding Human Cognition). The BCNI is supported by a joint award from the Wellcome Trust and Medical Research Council.
dc.languageEnglishen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleAtomoxetine Enhances Connectivity of Prefrontal Networks in Parkinson’s Diseaseen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/npp.2016.18en
prism.endingPage2177
prism.publicationDate2016en
prism.publicationNameNeuropsychopharmacologyen
prism.startingPage2171
prism.volume41en
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.funderMRC
dc.rioxxterms.funderNIHR
dc.rioxxterms.projectid103838
dc.rioxxterms.projectidMC_US_A060_0016 and RG62761
dcterms.dateAccepted2016-01-26en
rioxxterms.versionofrecord10.1038/npp.2016.18en
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2016-02-03en
dc.contributor.orcidRittman, Timothy [0000-0003-1063-6937]
dc.contributor.orcidPassamonti, Luca [0000-0002-7937-0615]
dc.contributor.orcidJones, Simon [0000-0001-9695-0702]
dc.contributor.orcidVatansever, Deniz [0000-0002-2494-9945]
dc.contributor.orcidHughes, Laura [0000-0002-1065-7175]
dc.contributor.orcidRobbins, Trevor [0000-0003-0642-5977]
dc.contributor.orcidRowe, James [0000-0001-7216-8679]
dc.identifier.eissn1740-634X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMEDICAL RESEARCH COUNCIL (G0001354)
pubs.funder-project-idMRC (G1000183)
pubs.funder-project-idParkinson's UK (K-1702)
pubs.funder-project-idJames S McDonnell Foundation (220020289)
pubs.funder-project-idWELLCOME TRUST (103838/Z/14/Z)
pubs.funder-project-idMedical Research Council (MC_U105597119)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
pubs.funder-project-idMedical Research Council (G1100464)
pubs.funder-project-idMEDICAL RESEARCH COUNCIL (MR/M009041/1)
pubs.funder-project-idWellcome Trust (093875/Z/10/Z)
pubs.funder-project-idMEDICAL RESEARCH COUNCIL (MR/M024873/1)
cam.orpheus.successThu Jan 30 12:55:21 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International