Ruth J. van Holst

Why gamblers fail to win: A review of cognitive and neuroimaging findings in pathological gambling

The purpose of this review is to gain more insight in the neuropathology of pathological gambling (PG) and problem gambling, and to discuss challenges in this research area. Results from the reviewed PG studies show that PG is more than just an impulse control disorder. PG seems to fit very well with recent theoretical models of addiction, which stress the involvement of the ventral tegmental-orbito frontal cortex. Differentiating types of PG on game preferences (slot machines vs. casino games) seems to be useful because different PG groups show divergent results, suggesting different neurobiological pathways to PG. A framework for future studies is suggested, indicating the need for hypothesis driven pharmacological and functional imaging studies in PG and integration of knowledge from different research areas to further elucidate the neurobiological underpinnings of this disorder.

Distorted Expectancy Coding in Problem Gambling: Is the Addictive in the Anticipation?

BACKGROUND Pathologic gamblers are known to have abnormal neural responses associated with experiencing monetary wins and losses. However, neural responsiveness during reward and loss expectations in pathologic gamblers has not yet been investigated. METHODS We used a functional magnetic resonance imaging paradigm that allowed us to investigate the dissociable reward- and loss-related expectancies with various probabilities of winning or losing different amounts of money in 15 patients with problem gambling (PRGs) and 16 healthy control subjects (HCs). RESULTS Compared with HCs, PRGs showed stronger activation in the bilateral ventral striatum to 5 euro than to 1 euro trials. PRGs also showed more activation of the bilateral ventral striatum and left orbitofrontal cortex associated with gain-related expected value than HCs. In addition, regression analyses indicated a highly significant negative correlation between gambling severity scores and right amygdala activation associated with gain-related expected value coding. There were no group differences in brain activation for loss-related expected value. CONCLUSIONS PRGs show higher activity in the reward system during reward expectation than HCs, whereas we observed no difference between PRGs and HC in the loss value system. Furthermore, the negative relation between gambling severity and amygdala activation in gain expected value coding suggests that more severe PRGs are less likely to be risk aversive during gambling. Our study provides evidence that PRGs are characterized by abnormally increased reward expectancy coding, which may render them overoptimistic with regard to gambling outcomes.

Brain Imaging Studies in Pathological Gambling

This article reviews the neuroimaging research on pathological gambling (PG). Because of the similarities between substance dependence and PG, PG research has used paradigms similar to those used in substance use disorder research, focusing on reward and punishment sensitivity, cue reactivity, impulsivity, and decision making. This review shows that PG is consistently associated with blunted mesolimbic-prefrontal cortex activation to nonspecific rewards, whereas these areas show increased activation when exposed to gambling-related stimuli in cue exposure paradigms. Very little is known, and hence more research is needed regarding the neural underpinnings of impulsivity and decision making in PG. This review concludes with a discussion regarding the challenges and new developments in the field of neurobiological gambling research and comments on their implications for the treatment of PG.

Response Inhibition during Cue Reactivity in Problem Gamblers: An fMRI Study

Disinhibition over drug use, enhanced salience of drug use and decreased salience of natural reinforcers are thought to play an important role substance dependence. Whether this is also true for pathological gambling is unclear. To understand the effects of affective stimuli on response inhibition in problem gamblers (PRGs), we designed an affective Go/Nogo to examine the interaction between response inhibition and salience attribution in 16 PRGs and 15 healthy controls (HCs). Four affective blocks were presented with Go trials containing neutral, gamble, positive or negative affective pictures. The No-Go trials in these blocks contained neutral pictures. Outcomes of interest included percentage of impulsive errors and mean reaction times in the different blocks. Brain activity related to No-Go trials was assessed to measure response inhibition in the various affective conditions and brain activity related to Go trials was assessed to measure salience attribution. PRGs made fewer errors during gamble and positive trials than HCs, but were slower during all trials types. Compared to HCs, PRGs activated the dorsolateral prefrontal cortex, anterior cingulate and ventral striatum to a greater extent while viewing gamble pictures. The dorsal lateral and inferior frontal cortex were more activated in PRGs than in HCs while viewing positive and negative pictures. During neutral inhibition, PRGs were slower but similar in accuracy to HCs, and showed more dorsolateral prefrontal and anterior cingulate cortex activity. In contrast, during gamble and positive pictures PRGs performed better than HCs, and showed lower activation of the dorsolateral and anterior cingulate cortex. This study shows that gambling-related stimuli are more salient for PRGs than for HCs. PRGs seem to rely on compensatory brain activity to achieve similar performance during neutral response inhibition. A gambling-related or positive context appears to facilitate response inhibition as indicated by lower brain activity and fewer behavioural errors in PRGs.

Fronto-striatal dysregulation in drug addiction and pathological gambling: Consistent inconsistencies?

Alterations in appetitive processing are central to the major psychological theories of addiction, with differential predictions made by the reward deficiency, incentive salience, and impulsivity hypotheses. Functional MRI has become the chief means of testing these predictions, with experiments reliably highlighting disturbances at the level of the striatum, medial prefrontal cortex, and affiliated regions. However, demonstrations of hypo-reactivity and hyper-reactivity of this circuitry in drug addicted groups are reported in approximately equal measure. Similar findings are echoed in the emergent neuroimaging literature on pathological gambling, which has recently witnessed a coming of age. The first aim of this article is to consider some of the methodological aspects of these experiments that could influence the observed direction of group-level effects, including the baseline condition, trial structure and timing, and the nature of the appetitive cues (drug-related, monetary, or primary rewards). The second aim is to highlight the conceptual traction that is offered by pathological gambling, as a model of a ‘toxicity free’ addiction and an illness where tasks of monetary reinforcement afford a more direct mapping to the abused commodity. Our conclusion is that relatively subtle decisions in task design appear capable of driving group differences in fronto-striatal circuitry in entirely opposing directions, even with tasks and task variants that look ostensibly similar. Differentiation between the psychological theories of addiction will require a greater breadth of experimental designs, with more research needed on processing of primary appetitive cues, aversive processing, and in vulnerable/at-risk groups.

A voxel-based morphometry study comparing problem gamblers, alcohol abusers, and healthy controls

BACKGROUND Alcohol use disorders (AUDs) are associated with smaller grey matter volumes in cortical and subcortical brain regions which are related to cognitive impairments often found in these disorders. Similar cognitive impairments have been found in patients suffering from problem gambling behaviour. However, in contrast to AUDs, gambling behaviour does not entail brain exposure to toxic agents. Although there are many clinical, neuropsychological, and neurobiological similarities between PG and substance use disorders it has not yet been established whether pathological gambling, similar to alcohol use disorders, is associated with abnormal regional grey matter volumes. METHODS With whole-brain voxel-based morphometry we compared a group of 40 treatment seeking problem gamblers, 36 subjects with an alcohol use disorder, and 54 healthy controls to evaluate potential group differences in regional grey matter volumes, corrected for age, IQ, smoking status, and total intracranial volume (TIV). RESULTS Significantly smaller grey matter volumes in left superior frontal cortex, left precentral cortex, right insula, right putamen, left thalamus, bilateral superior parietal cortex and right supramarginal cortex were present in subjects with an alcohol use disorder compared to healthy controls and problem gamblers. No significant grey matter volume differences were present between problem gamblers and healthy controls. CONCLUSION In conclusion, we replicated previous findings of smaller grey matter volumes in subjects with an alcohol use disorder and found no significant morphological brain abnormalities in problem gamblers.

Getting a grip on problem gambling: what can neuroscience tell us?

In problem gamblers, diminished cognitive control and increased impulsivity is present compared to healthy controls. Moreover, impulsivity has been found to be a vulnerability marker for the development of pathological gambling (PG) and problem gambling (PrG) and to be a predictor of relapse. In this review, the most recent findings on functioning of the brain circuitry relating to impulsivity and cognitive control in PG and PrG are discussed. Diminished functioning of several prefrontal areas and of the anterior cingulate cortex (ACC) indicate that cognitive-control related brain circuitry functions are diminished in PG and PrG compared to healthy controls. From the available cue reactivity studies on PG and PrG, increased responsiveness towards gambling stimuli in fronto-striatal reward circuitry and brain areas related to attentional processing is present compared to healthy controls. At this point it is unresolved whether PG is associated with hyper- or hypo-activity in the reward circuitry in response to monetary cues. More research is needed to elucidate the complex interactions for reward responsivity in different stages of gambling and across different types of reward. Conflicting findings from basic neuroscience studies are integrated in the context of recent neurobiological addiction models. Neuroscience studies on the interface between cognitive control and motivational processing are discussed in light of current addiction theories. Clinical implications: We suggest that innovation in PG therapy should focus on improvement of dysfunctional cognitive control and/or motivational functions. The implementation of novel treatment methods like neuromodulation, cognitive training and pharmacological interventions as add-on therapies to standard treatment in PG and PrG, in combination with the study of their effects on brain-behavior mechanisms could prove an important clinical step forward towards personalizing and improving treatment results in PG.

Is there such a thing as online video game addiction? A cross-disciplinary review

Drawing on explanatory pluralism this cross-disciplinary theoretical study asks whether excessive compulsive online gaming can be called an addiction on the basis of what is known about the disorder. This article discusses the concept of addiction; the social seating of the problems and it reviews, recent scientific literature on criteria used for diagnosing addictions. In addition, contributions by brain science are discussed. The study unfolds different dimensions of the problem and concludes by stating that research indicate that there indeed seems to be a type of problematic online gaming behavior, which bears similarities to such an extent with the essence of the concept and the phenomenon of addiction that it can beneficially lend itself and be compared to it. The authors suggest that this behavioral addiction may differ from drug addictions in magnitude, but not in kind. In addition, the authors find a possible solution for conceptualizing behavioral addictions by a general de-medicalization of the concept of addiction.

Contingency Learning in Alcohol Dependence and Pathological Gambling: Learning and Unlearning Reward Contingencies

Background Patients with alcohol dependence (AD) and pathological gambling (PG) are characterized by dysfunctional reward processing and their ability to adapt to alterations of reward contingencies is impaired. However, most neurocognitive tasks investigating reward processing involve a complex mix of elements, such as working memory, immediate and delayed rewards, and risk-taking. As a consequence, it is not clear whether contingency learning is altered in AD or PG. Therefore, the current study aimed to examine performance in a deterministic contingency learning task, investigating discrimination, reversal, and extinction learning. Methods Thirty-three alcohol-dependent patients (ADs), 28 pathological gamblers (PGs), and 18 healthy controls (HCs) performed a contingency learning task in which they learned stimulus–reward associations that were first reversed and later extinguished while receiving deterministic feedback throughout. Accumulated points, number of perseverative errors and trials required to reach a criterion in each learning phase were compared between groups using nonparametric Kruskal–Wallis rank-sum tests. Regression analyses were performed to compare learning curves. Results PGs and ADs did not differ from HCs in discrimination learning, reversal learning, or extinction learning, on the nonparametric tests. Regression analyses, however, showed differences in the initial speed of learning: PGs were significantly faster in discrimination learning compared to ADs, and both PGs and ADs learned slower than HCs in the reversal learning and extinction phases of the task. Conclusions Learning rates for reversal and extinction were slower for the alcohol-dependent group and PG group compared to HCs, suggesting that reversing and extinguishing learned contingencies require more effort in ADs and PGs. This implicates a diminished flexibility to overcome previously learned contingencies.

Striatal connectivity changes following gambling wins and near-misses: Associations with gambling severity

Frontostriatal circuitry is implicated in the cognitive distortions associated with gambling behaviour. ‘Near-miss’ events, where unsuccessful outcomes are proximal to a jackpot win, recruit overlapping neural circuitry with actual monetary wins. Personal control over a gamble (e.g., via choice) is also known to increase confidence in ones chances of winning (the ‘illusion of control’). Using psychophysiological interaction (PPI) analyses, we examined changes in functional connectivity as regular gamblers and non-gambling participants played a slot-machine game that delivered wins, near-misses and full-misses, and manipulated personal control. We focussed on connectivity with striatal seed regions, and associations with gambling severity, using voxel-wise regression. For the interaction term of near-misses (versus full-misses) by personal choice (participant-chosen versus computer-chosen), ventral striatal connectivity with the insula, bilaterally, was positively correlated with gambling severity. In addition, some effects for the contrast of wins compared to all non-wins were observed at an uncorrected (p < .001) threshold: there was an overall increase in connectivity between the striatal seeds and left orbitofrontal cortex and posterior insula, and a negative correlation for gambling severity with the connectivity between the right ventral striatal seed and left anterior cingulate cortex. These findings corroborate the ‘non-categorical’ nature of reward processing in gambling: near-misses and full-misses are objectively identical outcomes that are processed differentially. Ventral striatal connectivity with the insula correlated positively with gambling severity in the illusion of control contrast, which could be a risk factor for the cognitive distortions and loss-chasing that are characteristic of problem gambling.