Amplified Striatal Responses to Near Miss Outcomes in Pathological Gamblers (2016)

COMMENTS: I find it hard to believe dopamine is not involved, as the authors suggest. First, they used a D2 antagonist. What about D1 activation which is the key to sensitization? Also, we know that sensitization involves PFC and amygdala glutamate inputs acting on the NaC. Is it simply glutamate facilitating D1 receptors?  But here’s the big gap in logic: while near misses are “MORE rewarding” for gambling addicts, near misses aren’t really the reward – winning is. Dopamine drops when expectations are not met. The expectation in this case is winning.

Guillaume Sescousse1,2, Lieneke K Janssen1,2, Mahur M Hashemi1, Monique HM Timmer1,3,4, Dirk EM Geurts1,2, Niels P ter Huurne1,2, Luke Clark3,4 and Roshan Cools1,2

  1. 1Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands
  2. 2Department of Psychiatry
  3. 3Department of Neurology, Radboud University Medical Centre, Nijmegen, the Netherlands
  4. 4Centre for Gambling Research at UBC, Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada

Correspondence: Dr G Sescousse, Donders Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Kappitelweg 29, P.O. Box 9101, Nijmegen 6500 HB, the

Netherlands, Tel: +31 0 24 36 10618, Fax: +31 0 24 36 10989, E-mail: [email protected]


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.