title: Neural substrates of cue reactivity and craving in gambling disorder.
abstract: Cue reactivity is an established procedure in addictions research for examining the subjective experience and neural basis of craving. This experiment sought to quantify cue-related brain responses in gambling disorder using personally tailored cues in conjunction with subjective craving, as well as a comparison with appetitive non-gambling stimuli. Participants with gambling disorder (n=19) attending treatment and 19 controls viewed personally tailored blocks of gambling-related cues, as well as neutral cues and highly appetitive (food) images during a functional magnetic resonance imaging (fMRI) scan performed ~2-3 h after a usual meal. fMRI analysis examined cue-related brain activity, cue-related changes in connectivity and associations with block-by-block craving ratings. Craving ratings in the participants with gambling disorder increased following gambling cues compared with non-gambling cues. fMRI analysis revealed group differences in left insula and anterior cingulate cortex, with the gambling disorder group showing greater reactivity to the gambling cues, but no differences to the food cues. In participants with gambling disorder, craving to gamble correlated positively with gambling cue-related activity in the bilateral insula and ventral striatum, and negatively with functional connectivity between the ventral striatum and the medial prefrontal cortex. Gambling cues, but not food cues, elicit increased brain responses in reward-related circuitry in individuals with gambling disorder (compared with controls), providing support for the incentive sensitization theory of addiction. Activity in the insula co-varied with craving intensity, and may be a target for interventions.
authors.affiliation: Centre for Gambling Research at UBC, Department of Psychology, University of British Columbia, Vancouver, BC, Canada.|Department of Psychology, University of Cambridge, Cambridge, UK.
authors.forename: E H
authors.initials: EH
authors.lastname: Limbrick-Oldfield
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Mick
authors.affiliation: Department of Psychology, University of Cambridge, Cambridge, UK.|Centre for Neuropsychopharmacology, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors.forename: R E
authors.initials: RE
authors.lastname: Cocks
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: McGonigle
authors.affiliation: Department of Psychology, University of Cambridge, Cambridge, UK.|School of Psychology, College of Social Science, University of Lincoln, Lincoln, UK.
authors.forename: S P
authors.initials: SP
authors.lastname: Sharman
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.|Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences, Imperial College London, London, UK.
authors.forename: A P
authors.initials: AP
authors.lastname: Goldstone
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.|Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, Centre for Affective Disorders, King's College London, London, UK.
authors.forename: P R A
authors.initials: PR
authors.lastname: Stokes
authors.affiliation: Division of Experimental Medicine, Department of Imaging, Imperial College London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Waldman
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Erritzoe
authors.affiliation: National Problem Gambling Clinic, CNWL NHS Foundation Trust, Imperial College London, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Bowden-Jones
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors.forename: D
authors.identifier: 0000-0002-1286-1401
authors.initials: D
authors.lastname: Nutt
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.|Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences, Imperial College London, London, UK.|National Problem Gambling Clinic, CNWL NHS Foundation Trust, Imperial College London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Lingford-Hughes
authors.affiliation: Centre for Gambling Research at UBC, Department of Psychology, University of British Columbia, Vancouver, BC, Canada.|Department of Psychology, University of Cambridge, Cambridge, UK.
authors.forename: L
authors.initials: L
authors.lastname: Clark
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology; D066249:Craving; D003463:Cues; D059907:Functional Neuroimaging; D005715:Gambling / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009042:Motivation; D009434:Neural Pathways / Q000000981:diagnostic imaging; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology; D012201:Reward; D066328:Ventral Striatum / Q000000981:diagnostic imaging / Q000503:physiopathology