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dc.contributor.authorMandali, Alekhya
dc.contributor.authorSethi, Arjun
dc.contributor.authorCercignani, Mara
dc.contributor.authorHarrison, Neil A.
dc.contributor.authorVoon, Valerie
dc.date.accessioned2021-01-08T17:21:57Z
dc.date.available2021-01-08T17:21:57Z
dc.date.issued2021-01-06
dc.date.submitted2020-01-22
dc.identifier.others41398-020-01118-4
dc.identifier.other1118
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/315926
dc.description.abstractAbstract: Risk evaluation is a critical component of decision making. Risk tolerance is relevant in both daily decisions and pathological disorders such as attention-deficit hyperactivity disorder (ADHD), where impulsivity is a cardinal symptom. Methylphenidate, a commonly prescribed drug in ADHD, improves attention but has mixed reports on risk-based decision making. Using a double-blinded placebo protocol, we studied the risk attitudes of ADHD patients and age-matched healthy volunteers while performing the 2-step sequential learning task and examined the effect of methylphenidate on their choices. We then applied a novel computational analysis using the hierarchical drift–diffusion model to extract parameters such as threshold (‘a’—amount of evidence accumulated before making a decision), drift rate (‘v’—information processing speed) and response bias (‘z’ apriori bias towards a specific choice) focusing specifically on risky choice preference. Critically, we show that ADHD patients on placebo have an apriori bias towards risky choices compared to controls. Furthermore, methylphenidate enhanced preference towards risky choices (higher apriori bias) in both groups but had a significantly greater effect in the patient population independent of clinical scores. Thus, methylphenidate appears to shift tolerance towards risky uncertain choices possibly mediated by prefrontal dopaminergic and noradrenergic modulation. We emphasise the utility of computational models in detecting underlying processes. Our findings have implications for subtle yet differential effects of methylphenidate on ADHD compared to healthy population.
dc.languageen
dc.publisherNature Publishing Group UK
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectArticle
dc.subject/692/53/2423
dc.subject/631/477/2811
dc.subject/692/699/476/1311
dc.subjectarticle
dc.titleShifting uncertainty intolerance: methylphenidate and attention-deficit hyperactivity disorder
dc.typeArticle
dc.date.updated2021-01-08T17:21:57Z
prism.issueIdentifier1
prism.publicationNameTranslational Psychiatry
prism.volume11
dc.identifier.doi10.17863/CAM.63037
dcterms.dateAccepted2020-11-16
rioxxterms.versionofrecord10.1038/s41398-020-01118-4
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidCercignani, Mara [0000-0002-4550-2456]
dc.contributor.orcidHarrison, Neil A. [0000-0002-9584-3769]
dc.contributor.orcidVoon, Valerie [0000-0001-6790-1776]
dc.identifier.eissn2158-3188
pubs.funder-project-idRCUK | Medical Research Council (MRC) (MR/P008747/1)


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