Differential Influence of Levodopa on Reward-Based Learning in Parkinson's Disease

Abstract

The mesocorticolimbic dopamine (DA) system linking the dopaminergic midbrain to the prefrontal cortex and subcortical striatum has been shown to be sensitive to reinforcement in animals and humans. Within this system, coexistent segregated striato-frontal circuits have been linked to different functions. In the present study, we tested patients with Parkinson's disease (PD), a neurodegenerative disorder characterized by dopaminergic cell loss, on two reward-based learning tasks assumed to differentially involve dorsal and ventral striato-frontal circuits. 15 non-depressed and non-demented PD patients on levodopa monotherapy were tested both on and off medication. Levodopa had beneficial effects on the performance on an instrumental learning task with constant stimulus-reward associations, hypothesized to rely on dorsal striato-frontal circuits. In contrast, performance on a reversal learning task with changing reward contingencies, relying on ventral striato-frontal structures, was better in the unmedicated state. These results are in line with the “overdose hypothesis” which assumes detrimental effects of dopaminergic medication on functions relying upon less affected regions in PD. This study demonstrates, in a within-subject design, a double dissociation of dopaminergic medication and performance on two reward-based learning tasks differing in regard to whether reward contingencies are constant or dynamic. There was no evidence for a dose effect of levodopa on reward-based behavior with the patients’ actual levodopa dose being uncorrelated to their performance on the reward-based learning tasks.

Genetic Variation in the Human Brain Dopamine System Influences Motor Learning and Its Modulation by L-Dopa

“…This model builds on observations in the experimental literature, where dopamine levels have been found to be related to motor learning and plasticity in a dose-dependent manner, with increased dopamine promoting motor learning and motor cortex plasticity [51], [105], and decreased dopamine impairing motor learning [106] and motor cortex plasticity [105]. Significant evidence exists that enhancements associated with increased dopamine occur in an inverted U-shaped manner [7], [107], [108], [109]. That is, an excess of dopamine can be deleterious, resulting in dyskinesia [110], [111], impaired working memory [7], impulsive-antisocial traits [112], and impulse control disorders such as pathological gambling [113], [114].…”

The Effect of Dopamine Agonists on Adaptive and Aberrant Salience in Parkinson's Disease

“…Therefore, therapies that restore dopamine level in the dorsal striatum result in dopamine 'overdose' in the ventral striatum, which may lead to impaired performance on some cognitive tasks (Gotham et al, 1988;Cools et al, 2001Cools et al, , 2003Shohamy et al, 2006;Jahanshahi et al, 2010;MacDonald et al, 2011) and in some cases psychotic symptoms, including hallucinations and delusions (McGowan et al, 2004;Mehler-Wex et al, 2006;Maia and Frank, 2011). At the same time, there is evidence that dopaminergic therapy enhances learning from reward signals and decreases learning from punishment signals in PD (Frank et al, 2004(Frank et al, , 2007Cools et al, 2006;Bódi et al, 2009;Graef et al, 2010;Kobayakawa et al, 2010), and the ventral striatum has a crucial role in reinforcement learning (Yin and Knowlton, 2006).…”

Transformative Autonomous Entrainment of Gait in Neurological Patients

“…Prior reward learning, possibly facilitated by earlier normal preconditioning or medication, provides response incentive without actual dopamine signaling [33]. In other words, learning to select responses that lead to reward results in reward seeking behavior [34,35]. As novelty and vigilance have been widely recognized as key proponents of dopamine reward, the level of dopamine reward or reward seeking should correspond to the levels of novelty and vigilance.…”