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Cited by 192Parkinson's Disease Mechanisms and TreatmentsNeural and Behavioral Psychology StudiesNeurotransmitter Receptor Influence on Behavior

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A dopaminergic basis for working memory, learning and attentional shifting in Parkinsonism

Moustafa, Ahmed A., Sherman, Scott J., Frank, Michael J.·2008·Neuropsychologia
DOI 10.1016/j.neuropsychologia.2008.07.011
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Abstract

Parkinson's disease (PD) patients exhibit cognitive deficits, including reinforcement learning, working memory (WM) and set shifting. Computational models of the basal ganglia-frontal system posit similar mechanisms for these deficits in terms of reduced dynamic range of striatal dopamine (DA) signals in both medicated and non-medicated states. Here, we report results from the first study that tests PD patients on and off dopaminergic medications in a modified version of the AX continuous performance (AX-CPT) working memory task, consisting of three performance phases and one phase requiring WM associations to be learned via reinforcement feedback. Patients generally showed impairments relative to controls. Medicated patients showed deficits specifically when having to ignore distracting stimuli during the delay. Our models suggest that this impairment is due to medication causing excessive WM updating by enhancing striatal "Go" signals that facilitate such updating, while concurrently suppressing "NoGo" signals. In contrast, patients off medication showed deficits consistent with an overall reduction in striatal DA and associated Go updating signals. Supporting this dichotomy, patients on and off medication both showed attentional shifting deficits, but for different reasons. Deficits in non-medicated patients were consistent with an inability to update the new attentional set, whereas those in medicated patients were evident when having to ignore distractors that had previo…

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Metadata

Authors
Moustafa, A. A., Sherman, S. J., & Frank, M. J.
Affiliations
University of Arizona (US)
Corresponding author
Moustafa, Ahmed A.
ORCID
Venue
Neuropsychologia
Publisher
Elsevier BV
Published
2008-11
Volume
46
Issue
13
Pages
3144-3156
ISSN
0028-3932 (ISSN-L)
DOI
10.1016/j.neuropsychologia.2008.07.011
OpenAlex
W2120653271
Cited by
192
References
132
Citations by year
2026: 1 · 2025: 6 · 2024: 15 · 2023: 12 · 2022: 7 · 2021: 8 · 2020: 8 · 2019: 5 · 2018: 9 · 2017: 11 · 2016: 10 · 2015: 11 · 2014: 11 · 2013: 21 · 2012: 10
FWCI
9.78
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuropsychologia (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
Parkinson's disease, working memory, attentional shift, set-shifting, reinforcement learning, striatal dopamine, dopaminergic therapy, AX-CPT, distraction, neurocomputational model, cognitive impairment
MeSH terms
Aged, Attention, Dopamine, Feedback, Female, Humans, Learning, Male, Memory, Short-Term, Models, Biological, Neuropsychological Tests, Parkinson Disease, Task Performance and Analysis, Dopamine Agonists

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