Prefrontal Markers and Cognitive Performance Are Dissociated during Progressive Dopamine Lesion

PLoS Biol. 2016 Nov 8;14(11):e1002576. doi: 10.1371/journal.pbio.1002576. eCollection 2016 Nov.


Dopamine is thought to directly influence the neurophysiological mechanisms of both performance monitoring and cognitive control-two processes that are critically linked in the production of adapted behaviour. Changing dopamine levels are also thought to induce cognitive changes in several neurological and psychiatric conditions. But the working model of this system as a whole remains untested. Specifically, although many researchers assume that changing dopamine levels modify neurophysiological mechanisms and their markers in frontal cortex, and that this in turn leads to cognitive changes, this causal chain needs to be verified. Using longitudinal recordings of frontal neurophysiological markers over many months during progressive dopaminergic lesion in non-human primates, we provide data that fail to support a simple interaction between dopamine, frontal function, and cognition. Feedback potentials, which are performance-monitoring signals sometimes thought to drive successful control, ceased to differentiate feedback valence at the end of the lesion, just before clinical motor threshold. In contrast, cognitive control performance and beta oscillatory markers of cognitive control were unimpaired by the lesion. The differing dynamics of these measures throughout a dopamine lesion suggests they are not all driven by dopamine in the same way. These dynamics also demonstrate that a complex non-linear set of mechanisms is engaged in the brain in response to a progressive dopamine lesion. These results question the direct causal chain from dopamine to frontal physiology and on to cognition. They imply that biomarkers of cognitive functions are not directly predictive of dopamine loss.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Biomarkers
  • Cognition*
  • Dopamine / physiology*
  • Electroencephalography
  • Evoked Potentials
  • Female
  • Macaca mulatta
  • Male
  • Motivation
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiopathology*
  • Task Performance and Analysis


  • Biomarkers
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Dopamine

Grant support

This work was supported by Agence National de la Recherche, Fondation Neurodis, the LabEx CORTEX ANR-11-LABX-0042, Fondation de France, an ECOS-CONICYT Franco-Chilean cooperation project #C12S02, Fondation pour la Recherche Médicale (JV, FMS, MCMF), and Fondation Caisse d’Epargne Rhône Alpes Lyon (JV). CREW was funded by a Marie Curie Intra-European Fellowship (PIEF-GA-2010-273790) and a Postdoctoral Fellowship from Fondation Neurodis. MCMF is funded by Ministère de l'enseignement et de la recherche. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.