Dissociating the Cognitive Effects of Levodopa versus Dopamine Agonists in aNeurocomputational Model of Learning in Parkinson's Disease
Date
2012-11-01
Authors
Moustafa, Ahmed A.
Herzallah, Mohammad M.
Gluck, Mark A.
Journal Title
Journal ISSN
Volume Title
Publisher
Karger AG, Basel
Abstract
Background/Aims: Levodopa and dopamine agonists have
different effects on the motor, cognitive, and psychiatric aspects
of Parkinson’s disease (PD). Methods: Using a computational
model of basal ganglia (BG) and prefrontal cortex
(PFC) dopamine, we provide a theoretical synthesis of the
dissociable effects of these dopaminergic medications on
brain and cognition. Our model incorporates the findings
that levodopa is converted by dopamine cells into dopamine,
and thus activates prefrontal and striatal D 1 and D 2 dopamine
receptors, whereas antiparkinsonian dopamine agonists
directly stimulate D 2 receptors in the BG and PFC (although
some have weak affinity to D 1 receptors). Results: In
agreement with prior neuropsychological studies, our model
explains how levodopa enhances, but dopamine agonists
impair or have no effect on, stimulus-response learning and
working memory. Conclusion: Our model explains how levodopa
and dopamine agonists have differential effects on
motor and cognitive processes in PD.
Description
Keywords
Basal ganglia , Dopamine agonists , Levodopa , Parkinson’s disease , Prefrontal cortex , Reinforcement , Stimulus-response learning , Working memory