Impulsive choice and response in dopamine agonist-related impulse control behaviors

Abstract

Rationale Dopaminergic medication-related Impulse Control Disorders (ICDs) such as pathological gambling and compulsive shopping have been reported in Parkinson disease (PD). Hypothesis We hypothesized that dopamine agonists (DAs) would be associated with greater impulsive choice, or greater discounting of delayed rewards, in PD patients with ICDs (PDI). Methods Fourteen PDI patients, 14 PD controls without ICDs and 16 medication-free matched normal controls were tested on (i) the Experiential Discounting Task (EDT), a feedback-based intertemporal choice task, (ii) spatial working memory and (iii) attentional set shifting. The EDT was used to assess impulsivity choice (hyperbolic K-value), reaction time (RT) and decision conflict RT (the RT difference between high conflict and low conflict choices). PDI patients and PD controls were tested on and off DA. Results On the EDT, there was a group by medication interaction effect [F(1,26)=5.62; p=0.03] with pairwise analyses demonstrating that DA status was associated with increased impulsive choice in PDI patients (p=0.02) but not in PD controls (p=0.37). PDI patients also had faster RT compared to PD controls F(1,26)=7.51 p=0.01]. DA status was associated with shorter RT [F(3,24)=8.39, p=0.001] and decision conflict RT [F(1,26)=6.16, p=0.02] in PDI patients but not in PD controls. There were no correlations between different measures of impulsivity. PDI patients on DA had greater spatial working memory impairments compared to PD controls on DA (t=2.13, df=26, p=0.04). Conclusion Greater impulsive choice, faster RT, faster decision conflict RT and executive dysfunction may contribute to ICDs in PD.

Cognitive and neuroanatomical correlates of neuropsychiatric symptoms in Parkinson's disease: A systematic review

“…This cognitive impairment specifically was found in general frontal lobe function (detected by the TMT part B) and in shifting abilities as measured by the TMT part B minus part A score [85]. Furthermore, other studies have reported memory impairment in PD patients with ICDs, particularly, in spatial working memory tasks assessed by the Cambridge Automated Neuropsychological Test Battery [89] (In this study the average age at PD onset was 53.49 and patients were treated with Levodopa and a dopamine agonist), short-term memory and working memory as measured by digit span forward and backward [86].…”

“…The cognitive domain that appears to be mostly impaired in PD patients with ICDs is executive functioning [85][86][87][88][89] (See table 3). Biundo and others [85] reported executive dysfunction in PD patients with ICDs (Average disease duration was 8.81 years, age at onset was 53.18 and all patients treated with dopamine agonist).…”

Computational models of reinforcement learning: the role of dopamine as a reward signal

“…The algorithms above, in particular Q learning, have been applied to understand reinforcement-based decision making in humans (e.g., O'Doherty et al 2004;Frank et al 2007;Voon et al 2010). In two recent studies, human subjects learned to select among symbols presented on a computer screen, where the selection of some symbols were associated with a greater probability of reward (points or financial gains), and others were associated with a greater probability of negative outcome (losses) (Frank et al 2007;Voon et al 2010). A modified Q-learning algorithm was used to model the probability that an individual would select a particular symbol in a given trial as a function of reinforcement history.…”

“…The authors found that the bestfitting learning rate parameters which provided the best objective fit to each participant's choices (using maximum likelihood), were predicted by variations in genetic factors affecting striatal D1 and D2 receptor mechanisms (Frank et al 2007). Others have used a similar approach to show that these learning rate parameters are differentially modulated by dopaminergic medications administered to patients with Parkinson's (Voon et al 2010). Finally, another recent study replicated the striatal D1/D2 genetic variation effects on positive and negative learning rates in the context of a task that required participants to adjust response times to maximize rewards, which had also been shown to be sensitive to dopaminergic manipulation (Moustafa et al 2008;Frank et al 2009).…”

“…Dopamine has been shown to play a role in motivation (Fibiger and Phillips 1986;Robbins and Everitt 1996;Wise and Hoffman 1992;Wise 2004Wise , 2005, in the acquisition of appetitive conditioning tasks (Berridge and Robinson 1998;Everitt et al 1999;Ikemoto and Panksepp 1999), in many aspects of drug addiction (Berke and Hyman 2000;Di Chiara 2002;Everitt and Robbins 2005;Kelley and Berridge 2002;Koob 1992;Robinson and Berridge 2008;Wise 1996a, b) and is involved in disorders such as Parkinson disease (Canavan et al 1989;Voon et al 2010;Frank 2005;Knowlton et al 1996;Moustafa et al 2008).…”