Fractionating the Neurocognitive Mechanisms Underlying Working Memory: Independent Effects of Dopamine and Parkinson's Disease

Cereb Cortex. 2017 Dec 1;27(12):5727-5738. doi: 10.1093/cercor/bhx242.

Abstract

Deficits in working memory (WM) in Parkinson's disease (PD) are often considered to be secondary to dopaminergic depletion. However, the neurocognitive mechanisms by which dopamine causes these deficits remain highly contested, and PD is now also known to be associated with nondopaminergic pathology. Here, we examined how PD and dopaminergic medication modulate three components of WM: maintenance over time, updating contents with new information and making memories distracter-resistant. Compared with controls, patients were disproportionately impaired when retaining information for longer durations. By applying a probabilistic model, we were able to reveal that the source of this error was selectively due to precision of memory representations degrading over time. By contrast, replenishing dopamine levels in PD improved executive control over both the ability to ignore and update, but did not affect maintenance of information across time. This was due to a decrease in guess responses, consistent with the view that dopamine serves to prevent WM representations being corrupted by irrelevant information, but has no impact on information decay. Cumulatively, these results reveal a dissociation in the neural mechanisms underlying poor WM: whereas dopamine reduces interference, nondopaminergic systems in PD appear to modulate processes that prevent information decaying more quickly over time.

Keywords: Cognitive control; Parkinson’s disease; dopamine; working memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antiparkinson Agents / therapeutic use
  • Attention / drug effects
  • Attention / physiology
  • Dopamine / metabolism*
  • Dopamine Agents / therapeutic use
  • Executive Function / drug effects
  • Executive Function / physiology
  • Female
  • Humans
  • Male
  • Memory Disorders* / etiology
  • Memory Disorders* / metabolism
  • Memory, Short-Term / drug effects
  • Memory, Short-Term / physiology*
  • Mental Recall / drug effects
  • Mental Recall / physiology
  • Models, Neurological
  • Models, Statistical
  • Neuropsychological Tests
  • Parkinson Disease / complications
  • Parkinson Disease / drug therapy
  • Parkinson Disease / metabolism*
  • Parkinson Disease / psychology*
  • Probability
  • Time Factors

Substances

  • Antiparkinson Agents
  • Dopamine Agents
  • Dopamine