title: Amplified Striatal Responses to Near-Miss Outcomes in Pathological Gamblers.
abstract: Near-misses in gambling games are losing events that come close to a win. Near-misses were previously shown to recruit reward-related brain regions including the ventral striatum, and to invigorate gambling behavior, supposedly by fostering an illusion of control. Given that pathological gamblers are particularly vulnerable to such cognitive illusions, their persistent gambling behavior might result from an amplified striatal sensitivity to near-misses. In addition, animal studies have shown that behavioral responses to near-miss-like events are sensitive to dopamine, but this dopaminergic influence has not been tested in humans. To investigate these hypotheses, we recruited 22 pathological gamblers and 22 healthy controls who played a slot machine task delivering wins, near-misses and full-misses, inside an fMRI scanner. Each participant played the task twice, once under placebo and once under a dopamine D2 receptor antagonist (sulpiride 400 mg), in a double-blind, counter-balanced design. Participants were asked about their motivation to continue gambling throughout the task. Across all participants, near-misses elicited higher motivation to continue gambling and increased striatal responses compared with full-misses. Crucially, pathological gamblers showed amplified striatal responses to near-misses compared with controls. These group differences were not observed following win outcomes. In contrast to our hypothesis, sulpiride did not induce any reliable modulation of brain responses to near-misses. Together, our results demonstrate that pathological gamblers have amplified brain responses to near-misses, which likely contribute to their persistent gambling behavior. However, there is no evidence that these responses are influenced by dopamine. These results have implications for treatment and gambling regulation.
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.|Department of Psychiatry, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Sescousse
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.|Department of Psychiatry, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Lieneke K
authors.initials: LK
authors.lastname: Janssen
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
authors.forename: Mahur M
authors.initials: MM
authors.lastname: Hashemi
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.|Department of Neurology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Monique H M
authors.initials: MH
authors.lastname: Timmer
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.|Department of Psychiatry, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Dirk E M
authors.initials: DE
authors.lastname: Geurts
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.|Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.
authors.forename: Niels P
authors.initials: NP
authors.lastname: Ter Huurne
authors.affiliation: Department of Psychology, Centre for Gambling Research at UBC, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Luke
authors.initials: L
authors.lastname: Clark
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.|Department of Psychiatry, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Roshan
authors.initials: R
authors.lastname: Cools
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects*; D004311:Double-Blind Method; D005715:Gambling / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000523:psychology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009042:Motivation / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D012201:Reward; D013469:Sulpiride / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D013469:Sulpiride; D010100:Oxygen