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dc.contributor.authorVoon, Valerieen
dc.contributor.authorDroux, Fabienen
dc.contributor.authorMorris, Laurelen
dc.contributor.authorChabardes, Stephanen
dc.contributor.authorBougerol, Thierryen
dc.contributor.authorDavid, Olivieren
dc.contributor.authorKrack, Paulen
dc.contributor.authorPolosan, Mirceaen
dc.date.accessioned2017-01-23T15:55:11Z
dc.date.available2017-01-23T15:55:11Z
dc.date.issued2017-02en
dc.identifier.issn0006-8950
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/261978
dc.description.abstractWhy do we make hasty decisions for short-term gain? Rapid decision-making with limited accumulation of evidence and delay discounting are forms of decisional impulsivity. The subthalamic nucleus is implicated in inhibitory function but its role in decisional impulsivity is less well-understood. Here we assess decisional impulsivity in subjects with obsessive compulsive disorder who have undergone deep brain stimulation of the limbic and associative subthalamic nucleus. We show that stimulation of the subthalamic nucleus is causally implicated in increasing decisional impulsivity with less accumulation of evidence during probabilistic uncertainty and in enhancing delay discounting. Subthalamic stimulation shifts evidence accumulation in subjects with obsessive-compulsive disorder towards a functional less cautious style closer to that of healthy controls emphasizing its adaptive nature. Thus, subjects with obsessive compulsive disorder on subthalamic stimulation may be less likely to check for evidence (e.g. checking that the stove is on) with no difference in subjective confidence (or doubt). In a separate study, we replicate in humans (154 healthy controls) using resting state functional connectivity, tracing studies conducted in non-human primates dissociating limbic, associative and motor frontal hyper-direct connectivity with anterior and posterior subregions of the subthalamic nucleus. We show lateralization of functional connectivity of bilateral ventral striatum to right anterior ventromedial subthalamic nucleus consistent with previous observations of lateralization of emotionally evoked activity to right ventral subthalamic nucleus. We use a multi-echo sequence with independent components analysis, which has been shown to have enhanced signal-to-noise ratio, thus optimizing visualization of small subcortical structures. These findings in healthy controls converge with the effective contacts in obsessive compulsive disorder patients localized within the anterior and ventral subthalamic nucleus. We further show that evidence accumulation is associated with anterior associative-limbic subthalamic nucleus and right dorsolateral prefrontal functional connectivity in healthy controls, a region implicated in decision-making under uncertainty. Together, our findings highlight specificity of the anterior associative-limbic subthalamic nucleus in decisional impulsivity. Given increasing interest in the potential for subthalamic stimulation in psychiatric disorders and the neuropsychiatric symptoms of Parkinson's disease, these findings have clinical implications for behavioural symptoms and cognitive effects as a function of localization of subthalamic stimulation.
dc.description.sponsorshipThis work was supported by Agence Nationale de la Recherche (grant number ANR-14-CE13-0030-01 Physiobs); and University Hospital of Grenoble (Direction de la Recherche Clinique et de l’Innovation). This work was supported by a Wellcome Trust Fellowship grant to V.V. (983705/Z/10/Z).
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.language.isoenen
dc.publisherOxford University Press
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/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.subjectLimbic Systemen
dc.subjectSubthalamic Nucleusen
dc.subjectNeural Pathwaysen
dc.subjectHumansen
dc.subjectImaging, Three-Dimensionalen
dc.subjectMagnetic Resonance Imagingen
dc.subjectDeep Brain Stimulationen
dc.subjectStatistics, Nonparametricen
dc.subjectDouble-Blind Methoden
dc.subjectImpulsive Behavioren
dc.subjectDecision Makingen
dc.subjectPsychomotor Performanceen
dc.subjectObsessive-Compulsive Disorderen
dc.subjectAdulten
dc.subjectMiddle Ageden
dc.subjectFemaleen
dc.subjectMaleen
dc.subjectVisual Analog Scaleen
dc.subjectSurveys and Questionnairesen
dc.titleDecisional impulsivity and the associative-limbic subthalamic nucleus in obsessive-compulsive disorder: stimulation and connectivity.en
dc.typeArticle
prism.endingPage456
prism.publicationDate2017en
prism.publicationNameBrain : a journal of neurologyen
prism.startingPage442
prism.volume140en
dc.identifier.doi10.17863/CAM.7221
dcterms.dateAccepted2016-10-21en
rioxxterms.versionofrecord10.1093/brain/aww309en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2017-02en
dc.identifier.eissn1460-2156
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MR/P008747/1)
cam.orpheus.successThu Jan 30 12:56:53 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