Dopaminergic medication reduces striatal sensitivity to negative outcomes in Parkinson's disease

Bronagh McCcoy*, Sara Jahfari, Gwenda Engels, Tomas Knapen, Jan Theeuwes

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Reduced levels of dopamine in Parkinson's disease contribute to changes in learning, resulting from the loss of midbrain neurons that transmit a dopaminergic teaching signal to the striatum. Dopamine medication used by patients with Parkinson's disease has previously been linked to behavioural changes during learning as well as to adjustments in value-based decision-making after learning. To date, however, little is known about the specific relationship between dopaminergic medication-driven differences during learning and subsequent changes in approach/avoidance tendencies in individual patients. Twenty-four Parkinson's disease patients ON and OFF dopaminergic medication and 24 healthy controls subjects underwent functional MRI while performing a probabilistic reinforcement learning experiment. During learning, dopaminergic medication reduced an overemphasis on negative outcomes. Medication reduced negative (but not positive) outcome learning rates, while concurrent striatal blood oxygen level-dependent responses showed reduced prediction error sensitivity. Medication-induced shifts in negative learning rates were predictive of changes in approach/avoidance choice patterns after learning, and these changes were accompanied by systematic striatal blood oxygen level-dependent response alterations. These findings elucidate the role of dopamine-driven learning differences in Parkinson's disease, and show how these changes during learning impact subsequent value-based decision-making.

Original languageEnglish
Pages (from-to)3605-3620
JournalBrain
Volume142
DOIs
Publication statusPublished - 2019

Keywords

  • Parkinson's disease
  • dopamine
  • reinforcement learning
  • Bayesian hierarchical modelling
  • functional MRI
  • VENTRAL TEGMENTAL AREA
  • BASAL GANGLIA
  • COGNITIVE FUNCTION
  • CAUDATE-NUCLEUS
  • REWARD
  • MODEL
  • MODULATION
  • PREDICTION
  • MEMORY
  • CONNECTIVITY

Cite this

McCcoy, B., Jahfari, S., Engels, G., Knapen, T., & Theeuwes, J. (2019). Dopaminergic medication reduces striatal sensitivity to negative outcomes in Parkinson's disease. Brain, 142, 3605-3620. https://doi.org/10.1093/brain/awz276