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 doubleblind, 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.
INTRODUCTIONPathological gambling is a behavioral addiction with dramatic consequences including bankruptcy, unemployment, and relationship problems. The prevalence among college students has risen sharply in the past 10 years (Nowak and Aloe, 2014), while the rate of attempted suicide, approaching 20%, is higher than for any other addictive disorder (Bischof et al, 2015). Central to pathological gambling is the loss of control over gambling behavior and the inability to stop playing. This compulsive behavior is postulated to be fueled by cognitive distortions regarding the game structure. One example is the misappraisal of nearmiss events-losing outcomes that come close to a winwhich invigorate ongoing gambling behavior, conceivably by fostering an illusion of control (Clark, 2010). Although the behavioral vulnerability of pathological gamblers to such cognitive distortions is well established (Michalczuk et al, 2011), the underlying neural and neurochemical mechanisms remain elusive. We aimed to address this question using a combination of fMRI and pharmacological manipulation.Near-miss events are a hallmark of many gambling games and are particularly frequent in slot machines, which are recogniz...