Catecholamine Modulation of Evidence Accumulation during Perceptual Decision Formation: A Randomized Trial

J Cogn Neurosci. 2019 Jul;31(7):1044-1053. doi: 10.1162/jocn_a_01393. Epub 2019 Mar 18.


Recent behavioral modeling and pupillometry studies suggest that neuromodulatory arousal systems play a role in regulating decision formation but neurophysiological support for these observations is lacking. We employed a randomized, double-blinded, placebo-controlled, crossover design to probe the impact of pharmacological enhancement of catecholamine levels on perceptual decision-making. Catecholamine levels were manipulated using the clinically relevant drugs methylphenidate and atomoxetine, and their effects were compared with those of citalopram and placebo. Participants performed a classic EEG oddball paradigm that elicits the P3b, a centro-parietal potential that has been shown to trace evidence accumulation, under each of the four drug conditions. We found that methylphenidate and atomoxetine administration shortened RTs to the oddball targets. The neural basis of this behavioral effect was an earlier P3b peak latency, driven specifically by an increase in its buildup rate without any change in its time of onset or peak amplitude. This study provides neurophysiological evidence for the catecholaminergic enhancement of a discrete aspect of human decision-making, that is, evidence accumulation. Our results also support theoretical accounts suggesting that catecholamines may enhance cognition via increases in neural gain.

Publication types

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

MeSH terms

  • Adolescent
  • Adrenergic Uptake Inhibitors / administration & dosage
  • Adult
  • Atomoxetine Hydrochloride / administration & dosage
  • Brain / drug effects
  • Brain / physiology*
  • Catecholamines / physiology*
  • Citalopram / administration & dosage
  • Cross-Over Studies
  • Decision Making / drug effects
  • Decision Making / physiology*
  • Dopamine Uptake Inhibitors / administration & dosage
  • Double-Blind Method
  • Electroencephalography
  • Evoked Potentials, Visual / drug effects
  • Humans
  • Male
  • Methylphenidate / administration & dosage
  • Middle Aged
  • Serotonin Uptake Inhibitors / administration & dosage
  • Visual Perception / drug effects
  • Visual Perception / physiology*
  • Young Adult


  • Adrenergic Uptake Inhibitors
  • Catecholamines
  • Dopamine Uptake Inhibitors
  • Serotonin Uptake Inhibitors
  • Citalopram
  • Methylphenidate
  • Atomoxetine Hydrochloride

Associated data

  • ANZCTR/ACTRN12609000625279