Impaired Learning From Negative Feedback in Stimulant Use Disorder: Dopaminergic Modulation

Abstract

Background Drug-induced alterations to the dopamine system in stimulant use disorder (SUD) are hypothesised to impair reinforcement learning. Computational modelling enables the investigation of the latent processes of reinforcement learning in SUD patients, which could elucidate the nature of their impairments. Methods We investigated reinforcement learning in 44 SUD patients and 41 healthy control participants using a probabilistic reinforcement learning task that assesses learning from reward and punishment separately. In an independent sample, we determined the modulatory role of dopamine in reinforcement learning following a single dose of the dopamine D2/3 receptor antagonist amisulpride (400 mg) and the agonist pramipexole (0.5 mg) in a randomised, double-blind, placebo-controlled, crossover design. We analysed task performance using computational modelling and hypothesised that reinforcement learning impairments in SUD patients would be differentially modulated by a dopamine D2/3 receptor antagonist and agonist. Results Computational analyses in both samples revealed significantly reduced learning rates from punishment in SUD patients compared with healthy controls, whilst their reward learning rates were not measurably impaired. In addition, the dopaminergic receptor agents modulated reinforcement learning parameters differentially in both groups. Both amisulpride and pramipexole impaired reinforcement learning parameters in healthy participants, but ameliorated learning from punishment in SUD patients. Conclusion Our findings suggest that reinforcement learning impairments seen in SUD patients are associated with altered dopamine function.

Neuromolecular Underpinnings of Negative Cognitive Bias in Depression

“…However, other studies in humans [75,76] and in animals [77][78][79][80] pointed to the specific role of dopamine D 2 receptors in avoiding negative outcomes [73,81]. A recent study by Lim and collaborators [82] confirmed the blunting effects of dopamine D 2 receptor agonism on learning from negative feedback in healthy participants and reported similar effects on learning from punishment, following the administration of the dopamine D 2/3 receptor antagonist amisulpride. Such a nonselective effect of dopamine D 2/3 receptor antagonism has already been previously reported [83,84], suggesting that these receptors are generally involved in feedback-based learning.…”

Dysfunctional feedback processing in methamphetamine abuser; evidence from neurophysiological and computational analysis

“…Substance use disorders (SUDs) are associated with loss of control over drug-taking behavior regardless of its negative consequences (R. Smith et al, 2020). Methamphetamine is considered as one of the most widely prevalent illegal narcotics in the world and chronic use of it can alter the feedback processing system of the brain (Lim et al, 2021;R. Smith et al, 2020;Wei et al, 2021;.…”

“…Smith et al, 2020). Methamphetamine is considered as one of the most widely prevalent illegal narcotics in the world and chronic use of it can alter the feedback processing system of the brain (Lim et al, 2021; R. Smith et al, 2020; N.…”

“…D. Volkow, Chang, Wang, Fowler, Ding, et al, 2001; Wei et al, 2021; Zhong et al, 2020). Hence, methamphetamine abuse can induce deficits including insensitivity to the negative consequences of its consumption (Lim et al, 2021; N. D. Volkow, Chang, Wang, Fowler, Franceschi, et al, 2001).…”

“…It’s suggested that the abovementioned impairment in methamphetamine use dependent (MUD) individuals in the laboratory setting, failure in learning from negative feedback, is due to improper negative feedback (reinforce) processing (Wei et al, 2018; Zhong et al, 2020; see Kamarajan et al, 2014 for other group of addicts). To strengthen this vision behavioral, mathematical modeling, and neuroimaging studies have been investigated separately but not in the form of an integrated study (Lim et al, 2021; Wei et al, 2018; Zhong et al, 2020).…”