Dopamine and Gambling Disorder: Prospects for Personalized Treatment

Kayser, Andrew S.

doi:10.1007/s40429-019-00240-8

Cited by 8 publications

(12 citation statements)

References 97 publications

(78 reference statements)

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“…fects. An exploratory analysis of subcortical exploration-related group differences revealed reduced activity in the SN/VTA in gamblers, complementing accumulating evidence for dopaminergic dysfunction associated with this disorder (Boileau et al, 2014;van Holst et al, 2017;van Timmeren et al, 2018;Clark et al, 2019;Kayser, 2019). Taken together, our findings highlight computational mechanisms underlying reinforcement learning in volatile environments in gambling disorder.…”

Section: Discussionsupporting

confidence: 73%

“…Coupling parameters from a dynamic causal model of an exploration-related network contained information predictive of clinical status, raising the possibility that such network interactions might be more diagnostic of this disorder compared to univariate effects. An exploratory analysis of subcortical exploration-related group differences revealed reduced activity in the SN/VTA in gamblers, complementing accumulating evidence for dopaminergic dysfunction associated with this disorder (Boileau et al, 2014; van Holst et al, 2017; van Timmeren et al, 2018; Clark et al, 2019; Kayser, 2019). Taken together, our findings highlight computational mechanisms underlying reinforcement learning in volatile environments in gambling disorder.…”

Section: Discussionmentioning

confidence: 56%

“…There is substantial evidence implicating the neurotransmitter dopamine (DA) in the pathophysiology of gambling disorder (Kayser, 2019). Likewise, a contribution of DA to the regulation of the exploration-exploitation trade-off is suggested both by theory (Beeler, 2012) and empirical data (Frank et al, 2009; Kayser et al, 2014; Gershman and Tzovaras, 2018; Cinotti et al, 2019; Chakroun et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Attenuated directed exploration during reinforcement learning in gambling disorder

Wiehler

Chakroun

Peters

2019

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Gambling disorder is a behavioral addiction associated with impairments in decision-making and reduced behavioral flexibility. Decision-making in volatile environments requires a flexible trade-off between exploitation of options with high expected values and exploration of novel options to adapt to changing reward contingencies. This classical problem is known as the exploration-exploitation dilemma. We hypothesized gambling disorder to be associated with a specific reduction in directed (uncertainty-based) exploration compared to healthy controls, accompanied by changes in brain activity in a fronto-parietal explorationrelated network.Twenty-three frequent gamblers and nineteen matched controls performed a classical four-armed bandit task during functional magnetic resonance imaging. Computational modeling revealed that choice behavior in both groups contained signatures of directed exploration, random exploration and perseveration. Gamblers showed a specific reduction in directed exploration, while random exploration and perseveration were similar between groups.Neuroimaging revealed no evidence for group differences in neural representations of expected value and reward prediction errors. Likewise, our hypothesis of attenuated fronto-parietal exploration effects in gambling disorder was not supported. However, during directed exploration, gamblers showed reduced parietal and substantia nigra / ventral tegmental area activity. Cross-validated classification analyses revealed that connectivity in an exploration-related network was predictive of clinical status, suggesting alterations in network dynamics in gambling disorder.In sum, we show that reduced flexibility during reinforcement learning in volatile environments in gamblers is attributable to a reduction in directed exploration rather than an increase in perseveration. Neuroimaging findings suggest that patterns of network connectivity might be more diagnostic of gambling disorder than univariate value and prediction error effects. We provide a computational account of flexibility impairments in gamblers during reinforcement learning that might arise as a consequence of dopaminergic dysregulation in this disorder.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

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Attenuated directed exploration during reinforcement learning in gambling disorder

Wiehler

Chakroun

Peters

2019

Preprint

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“…Finally, dopamine has different functions in different prefrontal cortex subregions (Robbins and Arnsten, 2009), such that different dopamine-dependent cognitive functions might exhibit different dose-response functions (Floresco, 2013) and thus be differentially modulated by tolcapone. A thorough assessment of these complexities, including process-dependent baseline effects and potential subregionspecific effects of tolcapone will need to be more fully addressed in future studies (Kayser, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Because dysregulation in the dopamine system is implicated in substance use disorders (Robinson and Berridge, 1993;Volkow et al, 2017), similar dysregulation might exist in gambling disorder. Past studies have indeed identified changes in the dopamine system (Clark et al, 2012;Joutsa et al, 2012;Boileau et al, 2013Boileau et al, , 2014van Holst et al, 2018), but there is considerable heterogeneity in the direction of these group differences (Kayser, 2019), and the robustness of some of the reported effects has recently been questioned (Potenza, 2018).…”

Section: Introductionmentioning

confidence: 99%

Dopamine and Risky Decision-Making in Gambling Disorder

Peters

Vega

Weinstein³

et al. 2020

eNeuro

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Gambling disorder is a behavioral addiction associated with impairments in value-based decision-making and cognitive control. These functions are thought to be regulated by dopamine within fronto-striatal circuits, but the role of altered dopamine neurotransmission in the etiology of gambling disorder remains controversial. Preliminary evidence suggests that increasing frontal dopamine tone might improve cognitive functioning in gambling disorder. We therefore examined whether increasing frontal dopamine tone via a single dose of the catechol-O-methyltransferase (COMT) inhibitor tolcapone would reduce risky choice in human gamblers (n = 14) in a randomized double-blind placebo-controlled crossover study. Data were analyzed using hierarchical Bayesian parameter estimation and a combined risky choice drift diffusion model (DDM). Model comparison revealed a nonlinear mapping from value differences to trial-wise drift rates, confirming recent findings. An increase in risk-taking under tolcapone versus placebo was about five times more likely, given the data, than a decrease [Bayes factor (BF) = 0.2]. Examination of drug effects on diffusion model parameters revealed that an increase in the value dependency of the drift rate under tolcapone was about thirteen times more likely than a decrease (BF = 0.073). In contrast, a reduction in the maximum drift rate under tolcapone was about seven times more likely than an increase (BF = 7.51). Results add to previous work on COMT inhibitors in behavioral addictions and to mounting evidence for the applicability of diffusion models in value-based decision-making. Future work should focus on individual genetic, clinical and cognitive factors that might account for heterogeneity in the effects of COMT inhibition.

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