Levodopa medication improves incidental sequence learning in Parkinson's disease.
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.
Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK; Division of Psychology, Department of Life Sciences, Brunel University, Uxbridge UB8 3PH, UK.
M
M
Beigi
Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK; Behavioral Neurology Unit, National Institute for Neurological Disorders and Stroke, 10 Center Drive, Bethesda, MD, United States.
L
L
Wilkinson
Department of Psychological Sciences, University of Liverpool, Liverpool L69 7ZA, UK.
F
F
Gobet
Division of Psychology, Department of Life Sciences, Brunel University, Uxbridge UB8 3PH, UK.
A
A
Parton
Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK. Electronic address: m.jahanshahi@ucl.ac.uk.
M
M
Jahanshahi
D000368:Aged; D000704:Analysis of Variance; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001364:Awareness / Q000187:drug effects; D015259:Dopamine Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009048:Motor Skills / Q000187:drug effects*; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D011337:Probability Learning; D011930:Reaction Time; D021641:Recognition, Psychology / Q000187:drug effects; D012720:Severity of Illness Index
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D018697:Nootropic Agents; D007980:Levodopa
Basal ganglia; Incidental sequence learning; Levodopa medication; Parkinson's disease; Serial reaction time; Striatum
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