Abstract
Empirical evidence suggests that levodopa medication used to treat the motor symptoms of Parkinson's disease (PD) may either improve, impair or not affect specific cognitive processes. This evidence led to the ‘dopamine overdose’ hypothesis that levodopa medication impairs performance on cognitive tasks if they recruit fronto-striatal circuits which are not yet dopamine-depleted in early PD and as a result the medication leads to an excess of dopamine. This hypothesis has been supported for various learning tasks including conditional associative learning, reversal learning, classification learning and intentional deterministic sequence learning, on all of which PD patients demonstrated significantly worse performance when tested on relative to off dopamine medication. Incidental sequence learning is impaired in PD, but how such learning is affected by dopaminergic therapy remains undetermined. The aim of the current study was to investigate the effect of dopaminergic medication on incidental sequence learning in PD. We used a probabilistic serial reaction time task (SRTT), a sequence learning paradigm considered to make the sequence less apparent and more likely to be learned incidentally rather than intentionally. We compared learning by the same group of PD patients (n=15) on two separate occasions following oral administration of levodopa medication (on state) and after overnight withdrawal of medication (off state). Our results demonstrate for the first time that levodopa medication enhances incidental learning of a probabilistic sequence on the serial reaction time task in PD. However, neither group significantly differed from performance of a control group without a neurological disease, which indicates the importance of within group comparisons for identifying deficits. Levodopa medication enhanced incidental learning by patients with PD on a probabilistic sequence learning paradigm even though the patients were not aware of the existence of the sequence or their acquired knowledge. The results suggest a role in acquiring incidental motor sequence learning for dorsal striatal areas strongly affected by dopamine depletion in early PD.
Highlights
Levodopa medication has been described as the most significant advance in the treatment of Parkinson's disease (PD) (Olanow et al, 2004; Poewe, et al, 2010; Stocchi, 2005)
Patients with Parkinson's disease showed significantly greater incidental sequence learning on an incidental probabilistic serial reaction time task (SRTT) while tested on dopaminergic medication than when assessed off medication
There was no evidence for any significant overall difference in reaction times (RTs) between the medication conditions, which makes it unlikely that differences in learning on and off medication can be explained by greater motor difficulties when off medication
Summary
Levodopa medication has been described as the most significant advance in the treatment of Parkinson's disease (PD) (Olanow et al, 2004; Poewe, et al, 2010; Stocchi, 2005). The consequent widespread increase in dopamine levels can impair functions in brain networks that are relatively spared in the early stages of the disease, such as the limbic and orbitofrontal striatal circuits This ‘dopamine overdose’ can result in cognitive deficits that have a negative impact on the quality of life of patients with the disease (Schrag et al, 2000). Fundamental processes such as learning and memory have been linked to dopamine release, especially within the pre-frontal cortex and striatum (see for example Gabrieli, 1998; Packard and Knowlton, 2002; Shohamy et al, 2008; Williams and Goldman-Rakic, 1995). Studying such effects has potentially important implications for the management of PD as well as increasing our theoretical understanding of the role of dopamine in modulating neural pathways instantiating cognition and learning
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