title: Catecholamine-Mediated Increases in Gain Enhance the Precision of Cortical Representations.
abstract: Neurophysiological evidence suggests that neuromodulators, such as norepinephrine and dopamine, increase neural gain in target brain areas. Computational models and prominent theoretical frameworks indicate that this should enhance the precision of neural representations, but direct empirical evidence for this hypothesis is lacking. In two functional MRI studies, we examine the effect of baseline catecholamine levels (as indexed by pupil diameter and manipulated pharmacologically) on the precision of object representations in the human ventral temporal cortex using angular dispersion, a powerful, multivariate metric of representational similarity (precision). We first report the results of computational model simulations indicating that increasing catecholaminergic gain should reduce the angular dispersion, and thus increase the precision, of object representations from the same category, as well as reduce the angular dispersion of object representations from distinct categories when distinct-category representations overlap. In Study 1 (N = 24), we show that angular dispersion covaries with pupil diameter, an index of baseline catecholamine levels. In Study 2 (N = 24), we manipulate catecholamine levels and neural gain using the norepinephrine transporter blocker atomoxetine and demonstrate consistent, causal effects on angular dispersion and brain-wide functional connectivity. Despite the use of very different methods of examining the effect of baseline catecholamine levels, our results show a striking convergence and demonstrate that catecholamines increase the precision of neural representations.
  
  
  
  Norepinephrine and dopamine are among the most widely distributed and ubiquitous neuromodulators in the mammalian brain and have a profound and pervasive impact on cognition. Baseline catecholamine levels tend to increase with increasing task engagement in tasks involving perceptual decisions, yet there is currently no direct evidence of the specific impact of these increases in catecholamine levels on perceptual encoding. Our results fill this void by showing that catecholamines enhance the precision of encoding cortical object representations, and by suggesting that this effect is mediated by increases in neural gain, thus offering a mechanistic account of our key finding.
authors.affiliation: Department of Psychology, Leiden University, 2333 AK Leiden, The Netherlands, Leiden Institute for Brain and Cognition, Leiden University, Leiden, 2300 RC Leiden, The Netherlands, c.m.warren@fsw.leidenuniv.nl.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Warren
authors.affiliation: Welcome Trust Centre for Neuroimaging, University College London, London WC1N 3BG, United Kingdom.
authors.forename: Eran
authors.initials: E
authors.lastname: Eldar
authors.affiliation: Department of Psychology, Leiden University, 2333 AK Leiden, The Netherlands, Leiden Institute for Brain and Cognition, Leiden University, Leiden, 2300 RC Leiden, The Netherlands.
authors.forename: Ruud L
authors.initials: RL
authors.lastname: van den Brink
authors.affiliation: Department of Psychology, Leiden University, 2333 AK Leiden, The Netherlands, Leiden Institute for Brain and Cognition, Leiden University, Leiden, 2300 RC Leiden, The Netherlands.
authors.forename: Klodianna-Daphne
authors.initials: KD
authors.lastname: Tona
authors.affiliation: Leiden Institute for Brain and Cognition, Leiden University, Leiden, 2300 RC Leiden, The Netherlands, Department of Psychiatry, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors.forename: Nic J
authors.initials: NJ
authors.lastname: van der Wee
authors.affiliation: Department of Psychiatry, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors.forename: Eric J
authors.identifier: 0000-0001-8874-2292
authors.initials: EJ
authors.lastname: Giltay
authors.affiliation: Department of Psychiatry, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors.forename: Martijn S
authors.initials: MS
authors.lastname: van Noorden
authors.affiliation: Department of Clinical Psychology, University of Amsterdam, 1018 XA Amsterdam, The Netherlands, Mannheim Institute of Public Health, Heidelberg University, 68167 Mannheim, Germany.
authors.forename: Jos A
authors.initials: JA
authors.lastname: Bosch
authors.affiliation: Department of Psychology, University of Arizona, Tucson, Arizona 85721, and.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Wilson
authors.affiliation: Department of Psychology, Leiden University, 2333 AK Leiden, The Netherlands, Leiden Institute for Brain and Cognition, Leiden University, Leiden, 2300 RC Leiden, The Netherlands.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Cohen
authors.affiliation: Department of Psychology and Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08540.
authors.forename: Sander
authors.initials: S
authors.lastname: Nieuwenhuis
mesh_terms: D000328:Adult; D001931:Brain Mapping; D002395:Catecholamines / Q000378:metabolism*; D003198:Computer Simulation; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology; D010364:Pattern Recognition, Visual / Q000502:physiology*; D021641:Recognition, Psychology / Q000502:physiology*; D013647:Task Performance and Analysis; D013702:Temporal Lobe / Q000502:physiology*; D014793:Visual Cortex / Q000502:physiology*; D055815:Young Adult
chemical_list: D002395:Catecholamines; D018377:Neurotransmitter Agents
keywords: catecholamine; dopamine; fMRI; norepinephrine; perception; psychopharmacology