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

Ahmed A. Moustafa, Scott J Sherman, Michael J. Frank

Research output: Contribution to journalArticle

113 Citations (Scopus)

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 previously been task relevant. Finally, in the feedback-based WM phase, medicated patients were better than unmedicated patients, suggesting a key role of striatal DA in using feedback to update information into WM. These results lend further insight into the role of basal ganglia dopamine in WM and broadly support predictions from neurocomputational models.

Original languageEnglish (US)
Pages (from-to)3144-3156
Number of pages13
JournalNeuropsychologia
Volume46
Issue number13
DOIs
StatePublished - Nov 2008

Fingerprint

Parkinsonian Disorders
Short-Term Memory
Learning
Corpus Striatum
Dopamine
Basal Ganglia
Parkinson Disease

Keywords

  • Dopamine
  • Neurocomputational models
  • Parkinson's disease
  • Reward
  • Working memory

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Neuropsychology and Physiological Psychology

Cite this

A dopaminergic basis for working memory, learning and attentional shifting in Parkinsonism. / Moustafa, Ahmed A.; Sherman, Scott J; Frank, Michael J.

In: Neuropsychologia, Vol. 46, No. 13, 11.2008, p. 3144-3156.

Research output: Contribution to journalArticle

Moustafa, Ahmed A. ; Sherman, Scott J ; Frank, Michael J. / A dopaminergic basis for working memory, learning and attentional shifting in Parkinsonism. In: Neuropsychologia. 2008 ; Vol. 46, No. 13. pp. 3144-3156.
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