title: Jumping the Gun: Mapping Neural Correlates of Waiting Impulsivity and Relevance Across Alcohol Misuse.
abstract: 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.
authors.affiliation: Department of Psychology, University of Cambridge; Behavioural and Clinical Neuroscience Institute, University of Cambridge.
authors.forename: Laurel S
authors.initials: LS
authors.lastname: Morris
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge; Section on Advanced Functional Neuroimaging, Translational and Molecular Imaging Institution, Icahn School of Medicine at Mt. Sinai, New York, New York.
authors.forename: Prantik
authors.initials: P
authors.lastname: Kundu
authors.affiliation: Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Kwangyeol
authors.initials: K
authors.lastname: Baek
authors.affiliation: Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Irvine
authors.affiliation: Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Daisy J
authors.initials: DJ
authors.lastname: Mechelmans
authors.affiliation: Cambridgeshire and Peterborough National Health Service Foundation Trust, Cambridge.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wood
authors.affiliation: Department of Psychiatry, Brighton and Sussex Medical School, Brighton.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Harrison
authors.affiliation: Department of Psychology, University of Cambridge; Behavioural and Clinical Neuroscience Institute, University of Cambridge.
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge; Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Cambridgeshire and Peterborough National Health Service Foundation Trust, Cambridge; National Institute for Health Research Biomedical Research Council, University of Cambridge, United Kingdom.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Bullmore
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge; Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Cambridgeshire and Peterborough National Health Service Foundation Trust, Cambridge; National Institute for Health Research Biomedical Research Council, University of Cambridge, United Kingdom. Electronic address: voonval@gmail.com.
authors.forename: Valerie
authors.initials: V
authors.lastname: Voon
mesh_terms: D000328:Adult; D016739:Behavior, Addictive / Q000503:physiopathology*; D063425:Binge Drinking / Q000523:psychology*; D001931:Brain Mapping; D003342:Corpus Striatum / Q000473:pathology*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007175:Impulsive Behavior; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011930:Reaction Time; D020531:Subthalamic Nucleus / Q000473:pathology*; D055815:Young Adult
keywords: Addiction; Binge drinking; Connectivity; Impulsivity; Machine learning; Subthalamic nucleus