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dc.contributor.authorMorris, Laurelen
dc.contributor.authorKundu, Prantiken
dc.contributor.authorBaek, Kwangyeolen
dc.contributor.authorIrvine, Michael Aen
dc.contributor.authorMechelmans, Daisy Jen
dc.contributor.authorWood, Jonathanen
dc.contributor.authorHarrison, Neil Aen
dc.contributor.authorRobbins, Trevoren
dc.contributor.authorBullmore, Edwarden
dc.contributor.authorVoon, Valerieen
dc.identifier.citationMorris et al. Biological Psychiatry (2015) Vol. 79, Issue 6, pp. 499–507. doi:10.1016/j.biopsych.2015.06.009en
dc.description.abstractBackground: Why do we ‘jump the gun’ or speak out of turn? Waiting impulsivity has a preclinical basis as a predictor for the development of addiction. Here we mapped the intrinsic neural correlates of waiting and dissociate it from stopping, both fundamental mechanisms of behavioural control. Methods: We used a recently developed translational task to assess premature responding and assess response inhibition using the stop signal task. We mapped the neural correlates in 55 healthy volunteers using a novel multi-echo resting-state functional MRI sequence and analysis, which robustly boosts signal-to-noise ratio. We further assessed 32 young binge drinkers and 36 abstinent subjects with alcohol use disorders. Results: Connectivity of limbic and motor cortical and striatal nodes mapped onto a mesial-lateral axis of the subthalamic nucleus. Waiting impulsivity was associated with lower connectivity of the subthalamic nucleus with ventral striatum and subgenual cingulate, regions similarly implicated in rodent lesion studies. This network was dissociable from fast reactive stopping involving hyper-direct connections of the pre-supplementary area and subthalamic nucleus. We further show that binge drinkers, like those with alcohol use disorders, had elevated premature responding and emphasize the relevance of this subthalamic network across alcohol misuse. Using machine learning techniques we show that subthalamic connectivity differentiates binge drinkers and individuals with alcohol use disorders from healthy volunteers. Conclusions: We highlight the translational and clinical relevance of dissociable functional systems of cortical, striatal and hyper-direct connections with the subthalamic nucleus in modulating waiting and stopping and their importance across dimensions of alcohol misuse.
dc.description.sponsorshipThe study was funded by the Wellcome Trust Fellowship grant for VV (093705/Z/10/Z) and Cambridge NIHR Biomedical Research Centre. VV and NAH are Wellcome Trust (WT) intermediate Clinical Fellows. The BCNI is supported by a WT and MRC grant. ETB is employed part-time by the University of Cambridge and part-time by GSK PLC and is a shareholder of GSK. TWR is a consultant for Cambridge Cognition, Eli Lilly, GSK, Merck, Sharpe and Dohme, Lundbeck, Teva and Shire Pharmaceuticals. He is or has been in receipt of research grants from Lundbeck, Eli Lilly and GSK and is an editor for Springer-Verlag (Psychopharmacology). The remaining authors declare no competing financial interests.
dc.rightsAttribution 2.0 UK: England & Wales*
dc.subjectsubthalamic nucleusen
dc.subjectbinge drinkingen
dc.subjectmachine learningen
dc.titleJumping the Gun: Mapping Neural Correlates of Waiting Impulsivity and Relevanceen
dc.description.versionThis is the final version of the article. It first appeared from Elsevier via
prism.publicationNameBiological Psychiatryen
dc.rioxxterms.funderWellcome Trust
dc.contributor.orcidRobbins, Trevor [0000-0003-0642-5977]
dc.contributor.orcidBullmore, Edward [0000-0002-8955-8283]
dc.contributor.orcidVoon, Valerie [0000-0001-6790-1776]
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (G1000183)
pubs.funder-project-idMEDICAL RESEARCH COUNCIL (G0001354)
pubs.funder-project-idWellcome Trust (093705/Z/10/Z)
pubs.funder-project-idWellcome Trust (095844/Z/11/Z)
pubs.funder-project-idWellcome Trust (093875/Z/10/Z)

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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales