Noradrenergic and Cholinergic Modulation of Belief Updating

J Cogn Neurosci. 2018 Dec;30(12):1803-1820. doi: 10.1162/jocn_a_01317. Epub 2018 Jul 31.

Abstract

To make optimal predictions in a dynamic environment, the impact of new observations on existing beliefs-that is, the learning rate-should be guided by ongoing estimates of change and uncertainty. Theoretical work has proposed specific computational roles for various neuromodulatory systems in the control of learning rate, but empirical evidence is still sparse. The aim of the current research was to examine the role of the noradrenergic and cholinergic systems in learning rate regulation. First, we replicated our recent findings that the centroparietal P3 component of the EEG-an index of phasic catecholamine release in the cortex-predicts trial-to-trial variability in learning rate and mediates the effects of surprise and belief uncertainty on learning rate (Study 1, n = 17). Second, we found that pharmacological suppression of either norepinephrine or acetylcholine activity produced baseline-dependent effects on learning rate following nonobvious changes in an outcome-generating process (Study 1). Third, we identified two genes, coding for α2A receptor sensitivity (ADRA2A) and norepinephrine reuptake (NET), as promising targets for future research on the genetic basis of individual differences in learning rate (Study 2, n = 137). Our findings suggest a role for the noradrenergic and cholinergic systems in belief updating and underline the importance of studying interactions between different neuromodulatory systems.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Adolescent
  • Adrenergic alpha-2 Receptor Agonists / pharmacology
  • Adult
  • Anticipation, Psychological / drug effects
  • Anticipation, Psychological / physiology
  • Brain / drug effects
  • Brain / physiology*
  • Cholinergic Antagonists / pharmacology
  • Clonidine / pharmacology
  • Cross-Over Studies
  • Double-Blind Method
  • Electroencephalography
  • Female
  • Genetic Association Studies
  • Humans
  • Learning / drug effects
  • Learning / physiology*
  • Male
  • Norepinephrine / metabolism*
  • Norepinephrine Plasma Membrane Transport Proteins / genetics
  • Receptors, Adrenergic, alpha-2 / genetics
  • Scopolamine / pharmacology
  • Uncertainty
  • Young Adult

Substances

  • ADRA2A protein, human
  • Adrenergic alpha-2 Receptor Agonists
  • Cholinergic Antagonists
  • Norepinephrine Plasma Membrane Transport Proteins
  • Receptors, Adrenergic, alpha-2
  • SLC6A2 protein, human
  • Scopolamine
  • Clonidine
  • Acetylcholine
  • Norepinephrine