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Jumping the Gun: Mapping Neural Correlates of Waiting Impulsivity and Relevance Across Alcohol Misuse.

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Morris, Laurel S 
Kundu, Prantik 
Baek, Kwangyeol 
Irvine, Michael A 
Mechelmans, Daisy J 


BACKGROUND: 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 dissociated it from stopping, both fundamental mechanisms of behavioral 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 magnetic resonance imaging 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 hyperdirect connections of the pre-supplementary area and subthalamic nucleus. We further showed that binge drinkers, like those with alcohol use disorders, had elevated premature responding and emphasized the relevance of this subthalamic network across alcohol misuse. Using machine learning techniques we showed 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 hyperdirect connections with the subthalamic nucleus in modulating waiting and stopping and their importance across dimensions of alcohol misuse.



Addiction, Binge drinking, Connectivity, Impulsivity, Machine learning, Subthalamic nucleus, Adult, Behavior, Addictive, Binge Drinking, Brain Mapping, Corpus Striatum, Female, Healthy Volunteers, Humans, Impulsive Behavior, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Reaction Time, Subthalamic Nucleus, Young Adult

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Biol Psychiatry

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Elsevier BV
Medical Research Council (G1000183)
Medical Research Council (G0001354)
Wellcome Trust (093705/Z/10/Z)
Wellcome Trust (095844/Z/11/Z)
Wellcome Trust (093875/Z/10/Z)
The 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.