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Differential influence of levodopa on reward-based learning in Parkinson's disease.

Graef S, Biele G, Krugel LK, Marzinzik F, Wahl M, Wotka J, Klostermann F, Heekeren HR - Front Hum Neurosci (2010)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute for Human Development Berlin, Germany.

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.

No MeSH data available.


Related in: MedlinePlus

Performance of ON-beginner (“ON first”) and OFF-beginner subgroups (“OFF first”) across sessions on the instrumental learning task. Covariate-corrected estimated means of percentage of correct choices are shown in boxes.
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Figure 3: Performance of ON-beginner (“ON first”) and OFF-beginner subgroups (“OFF first”) across sessions on the instrumental learning task. Covariate-corrected estimated means of percentage of correct choices are shown in boxes.

Mentions: For the instrumental learning task with constant reward contingencies, we expected that the “ON first” subgroup would perform better on their first session (i.e., while the patients were on medication) than on the second session (while they were off medication). The opposite was expected for the “OFF first” subgroup, with a poorer performance expected on the first assessment (off medication) and better performance on the second assessment (on medication). As in the analysis of the reversal learning task, this effect should result in a significant group × session interaction in the ANCOVA. Again, the results confirmed our hypotheses (see Figure 3).


Differential influence of levodopa on reward-based learning in Parkinson's disease.

Graef S, Biele G, Krugel LK, Marzinzik F, Wahl M, Wotka J, Klostermann F, Heekeren HR - Front Hum Neurosci (2010)

Performance of ON-beginner (“ON first”) and OFF-beginner subgroups (“OFF first”) across sessions on the instrumental learning task. Covariate-corrected estimated means of percentage of correct choices are shown in boxes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2967381&req=5

Figure 3: Performance of ON-beginner (“ON first”) and OFF-beginner subgroups (“OFF first”) across sessions on the instrumental learning task. Covariate-corrected estimated means of percentage of correct choices are shown in boxes.
Mentions: For the instrumental learning task with constant reward contingencies, we expected that the “ON first” subgroup would perform better on their first session (i.e., while the patients were on medication) than on the second session (while they were off medication). The opposite was expected for the “OFF first” subgroup, with a poorer performance expected on the first assessment (off medication) and better performance on the second assessment (on medication). As in the analysis of the reversal learning task, this effect should result in a significant group × session interaction in the ANCOVA. Again, the results confirmed our hypotheses (see Figure 3).

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute for Human Development Berlin, Germany.

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.

No MeSH data available.


Related in: MedlinePlus