title: Catecholaminergic Regulation of Learning Rate in a Dynamic Environment.
abstract: Adaptive behavior in a changing world requires flexibly adapting one's rate of learning to the rate of environmental change. Recent studies have examined the computational mechanisms by which various environmental factors determine the impact of new outcomes on existing beliefs (i.e., the 'learning rate'). However, the brain mechanisms, and in particular the neuromodulators, involved in this process are still largely unknown. The brain-wide neurophysiological effects of the catecholamines norepinephrine and dopamine on stimulus-evoked cortical responses suggest that the catecholamine systems are well positioned to regulate learning about environmental change, but more direct evidence for a role of this system is scant. Here, we report evidence from a study employing pharmacology, scalp electrophysiology and computational modeling (N = 32) that suggests an important role for catecholamines in learning rate regulation. We found that the P3 component of the EEG-an electrophysiological index of outcome-evoked phasic catecholamine release in the cortex-predicted learning rate, and formally mediated the effect of prediction-error magnitude on learning rate. P3 amplitude also mediated the effects of two computational variables-capturing the unexpectedness of an outcome and the uncertainty of a preexisting belief-on learning rate. Furthermore, a pharmacological manipulation of catecholamine activity affected learning rate following unanticipated task changes, in a way that depended on participants' baseline learning rate. Our findings provide converging evidence for a causal role of the human catecholamine systems in learning-rate regulation as a function of environmental change.
authors: Cognitive Psychology Unit, Institute of Psychology, Leiden University; and Leiden Institute for Brain and Cognition, Leiden University, Leiden, the Netherlands.
authors: Marieke
authors: M
authors: Jepma
authors: Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Peter R
authors: http://orcid.org/0000-0003-1963-185X
authors: PR
authors: Murphy
authors: Department of Cognitive, Linguistic & Psychological Sciences, Brown University, Providence, RI, United States of America.
authors: Matthew R
authors: MR
authors: Nassar
authors: Department of Psychology, University of California, Berkeley, United States of America.
authors: Mauricio
authors: M
authors: Rangel-Gomez
authors: Department of Education Sciences, Vrije Universiteit Amsterdam, The Netherlands.
authors: Martijn
authors: M
authors: Meeter
authors: Cognitive Psychology Unit, Institute of Psychology, Leiden University; and Leiden Institute for Brain and Cognition, Leiden University, Leiden, the Netherlands.
authors: Sander
authors: S
authors: Nieuwenhuis
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000293:Adolescent; D000328:Adult; D001931:Brain Mapping / Q000379:methods; D002395:Catecholamines / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004311:Double-Blind Method; D017753:Ecosystem; D005260:Female; D006801:Humans; D007858:Learning / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010296:Parietal Lobe / Q000502:physiology*; D055815:Young Adult
chemical_list: D002395:Catecholamines; D018377:Neurotransmitter Agents; D004298:Dopamine; D009638:Norepinephrine