Role of Dopamine D2 Receptors in Human Reinforcement Learning

Eisenegger, Christoph; Naef, Michael; Linssen, A.M.W.; Clark, Luke; Gandamaneni, Praveen K.; Müller, Ulrich; Robbins, Trevor W.

doi:10.1038/npp.2014.84

Cited by 131 publications

(152 citation statements)

References 71 publications

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“…Computational models can guide the investigation of specific mechanisms that might generate individual differences in learning performance in such experiments (e.g., Cavanagh et al, 2010;Eisenegger et al, 2014;Krugel et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms that affect GABA neurotransmission predict processing of aversive prediction errors in humans

et al. 2018

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Learning is one of our most adaptive abilities, allowing us to adjust our expectations about future events. Aberrant learning processes may underlie disorders such as anxiety, motivating the search for the neural mechanisms that underpin learning. Animal studies have shown that the neurotransmitter GABA is required for the computation of prediction errors, the mismatches between anticipated and experienced outcomes, which drive new learning. Given that evidence from human studies is lacking, we sought to determine whether these findings extend to humans. Here, in two samples of Caucasian individuals, we investigated whether genetically determined individual differences in GABA neurotransmission predict the P3 event-related potential, an EEG component known to reflect prediction error processing.Consistent with the results of animal studies, we show that a weighted genetic risk score computed from the number of GABRB2 rs1816072 A alleles (associated with increased expression of the GABAA receptor β2 subunit gene) and the number of ErbB4 rs7598440 T alleles (associated with increased GABA concentration) predicts optimal prediction error processing during aversive classical conditioning with both visual (Experiment 1, N = 90; p = .010) and auditory (Experiment 2; N = 92; p = .031) unconditioned stimuli. Our finding that optimal processing of aversive prediction errors is reduced in individuals genetically predisposed towards decreased GABA neurotransmission suggests a potential mechanism linking GABA and anxiety. Specifically, reduced GABA signalling via GABAA receptors could result in aberrant learning from aversive experiences and vulnerability to anxiety disorders.

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Section: Introductionmentioning

confidence: 99%

Polymorphisms that affect GABA neurotransmission predict processing of aversive prediction errors in humans

et al. 2018

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“…We manipulated dopamine in a placebo-controlled, withinsubjects manner using the selective D2/D3 receptor antagonist sulpiride. Sulpiride has previously been shown to modulate learning (Eisenegger et al, 2014;Mehta et al, 2008;van der Schaaf et al, 2014) as well as brain and behavioral responses to reward and punishment (Becker et al, 2013;Jocham et al, 2014;McCabe et al, 2011). Our primary interest was in the comparison of near-miss and full-miss events.…”

Section: Introductionmentioning

confidence: 99%

Amplified Striatal Responses to Near-Miss Outcomes in Pathological Gamblers

Sescousse

Janssen

Hashemi

et al. 2016

Neuropsychopharmacol

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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...

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“…Dopaminergic medication was either levodopa or dopamine agonists which address different dopaminergic receptors (Brusa et al 2005;Cox et al 2015;Dirnberger and Jahanshahi 2013;Moustafa et al 2013;Vaillancourt et al 2013). For example, Eisenegger et al (2014) reported that administering the dopamine D2/D3 receptor agonist sulpride impairs choice performance but not learning. In contrast, levodopa leads to a non-specific increase in brain dopamine level (Eisenegger et al 2014).…”

Section: Discussionmentioning

confidence: 99%

Toward a computational cognitive neuropsychology of Wisconsin card sorts: a showcase study in Parkinson’s disease

et al. 2018

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The Wisconsin Card Sorting Test (WCST) is an instrument for the clinical assessment of executive functions. Computational modeling of latent cognitive processes offers a route toward improved interpretability of performance on neuropsychological tests. We implemented a computational model by Bishara et al. (Journal of Mathematical Psychology, 54(1), 5-13, 2010) that allows for evaluating the role of feedback-based attentional learning. We investigated if the model differentiates between Parkinson's disease (PD) patients on and off dopaminergic medication. We reanalyzed data from 32 patients with idiopathic PD and 35 matched healthy controls, which completed a computerized version of the WCST. The PD sample was divided into patients tested on (n = 18) and off (n = 14) dopaminergic medication. Model performance was assessed via posterior probabilities and simulations of WCST error scores. Individual model parameters were used for group comparisons. The best performing model configuration showed a single learning rate parameter for positive and negative feedback and recovered the observed WCST perseveration error and set-loss error rates. The occurrence of inference errors could not be accounted for by that model configuration. We did not observe evidence for differences in model parameters between the examined groups of individuals. Our results indicate that assuming distinct, feedback-specific learning processes are not superior to feedback-type unspecific processes in accounting for performance on the computerized WCST. Specifically, the studied model successfully accounted for some, but not all, aspects of test performance. The model parameters did not differentiate between PD patients on and off their dopaminergic medication, a finding that we discuss in the context of study design. (WCST;Berg 1948;Grant and Berg 1948;Heaton et al. 1993; Schretlen 2010) represents a standard tool for the neuropsychological assessment of executive functions (Diamond 2013;Miller and Cohen 2001). Performance on the WCST is sensitive to frontal lobe lesions (e.g., Alvarez and Emory 2006;Barceló and Knight 2002;Demakis 2003;Milner 1963) and to numerous neurological diseases, including Parkinson's disease (PD; e.g., Kudlicka et al. 2011;Dirnberger and Jahanshahi 2013) or amyotrophic lateral sclerosis (e.g., Lange et al. 2016c). However, the complexity of the WCST renders it difficult to infer which cognitive processes generate the observable behavior on the test. In this study, we apply computational modeling as a possible route toward a better interpretability of WCST performance.The WCST is considered as an assessment instrument for individual abilities in cognitive flexibility (Diamond 2013;Miller and Cohen 2001). Participants are instructed to sort a stimulus according to one of four key cards. Card sorts can accord to one of three viable rules that refer to the color, the shape, or the number of displayed objects. In order to figure out the prevailing rule, the participant has to follow the examiners feedback, as shown...

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Role of Dopamine D2 Receptors in Human Reinforcement Learning

Cited by 131 publications

References 71 publications

Polymorphisms that affect GABA neurotransmission predict processing of aversive prediction errors in humans

Polymorphisms that affect GABA neurotransmission predict processing of aversive prediction errors in humans

Amplified Striatal Responses to Near-Miss Outcomes in Pathological Gamblers

Toward a computational cognitive neuropsychology of Wisconsin card sorts: a showcase study in Parkinson’s disease

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