1. Premature commitment to uncertain decisions during human NMDA receptor hypofunction
- Author
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Alexandre Salvador, Luc H. Arnal, Fabien Vinckier, Philippe Domenech, Raphaël Gaillard, Valentin Wyart, Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), GHU Paris Psychiatrie et Neurosciences, Laboratoire de Neurosciences Cognitives & Computationnelles (LNC2), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Cité (UPCité), Institut de l'Audition [Paris] (IDA), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Motivation, cerveau et comportement = Motivation, Brain and Behavior [ICM Paris] (MBB), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neurophysiologie des comportements répétitifs [ICM Paris], Pôle de psychiatrie et d'addictologie des Hôpitaux Universitaires Henri-Mondor [Créteil], Centre hospitalier universitaire Henri-Mondor [Créteil], Neuropathologie expérimentale / Experimental neuropathology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), This work was supported by a starting grant from the European Research Council (ERC-StG-759341) awarded to V.W., a junior researcher grant from the French National Research Agency (ANR-14-CE13-0028-01) awarded to V.W., a young investigator award from the Fyssen Foundation to V.W., a donation from the Schizo-oui association to R.G., and a starting grant from the Institut de Psychiatrie et de Neurosciences de Paris awarded to R.G. A.S. was funded by a doctoral fellowship from the Fondation pour la Recherche Médicale., ANR-14-CE13-0028,SUB-DECISION,Sous-optimalité de la prise de décision humaine : redéfinir les modèles du choix en termes en contraintes neurobiologiques(2014), European Project: 759341,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC),ERC-2017-STG,OPTIMIZERR(2018), Gestionnaire, Hal Sorbonne Université, Appel à projets générique - Sous-optimalité de la prise de décision humaine : redéfinir les modèles du choix en termes en contraintes neurobiologiques - - SUB-DECISION2014 - ANR-14-CE13-0028 - Appel à projets générique - VALID, and Errors as cost-optimizing decisions? Redefining the origin and nature of human decision errors in light of associated neural computations - OPTIMIZERR - - H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)2018-05-01 - 2023-04-30 - 759341 - VALID
- Subjects
Adult ,Male ,Time Factors ,Psychometrics ,Science ,Decision Making ,Decision ,General Physics and Astronomy ,Receptors, N-Methyl-D-Aspartate ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,Task Performance and Analysis ,Human behaviour ,Humans ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Uncertainty ,Brain ,Bayes Theorem ,Electroencephalography ,General Chemistry ,Female ,Ketamine ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Cues ,030217 neurology & neurosurgery - Abstract
Making accurate decisions based on unreliable sensory evidence requires cognitive inference. Dysfunction of n-methyl-d-aspartate (NMDA) receptors impairs the integration of noisy input in theoretical models of neural circuits, but whether and how this synaptic alteration impairs human inference and confidence during uncertain decisions remains unknown. Here we use placebo-controlled infusions of ketamine to characterize the causal effect of human NMDA receptor hypofunction on cognitive inference and its neural correlates. At the behavioral level, ketamine triggers inference errors and elevated decision uncertainty. At the neural level, ketamine is associated with imbalanced coding of evidence and premature response preparation in electroencephalographic (EEG) activity. Through computational modeling of inference and confidence, we propose that this specific pattern of behavioral and neural impairments reflects an early commitment to inaccurate decisions, which aims at resolving the abnormal uncertainty generated by NMDA receptor hypofunction., In uncertain conditions, people make accurate decisions by considering multiple pieces of information. Here, the authors show that pharmacological n-methyl-d-aspartate (NMDA) receptor hypofunction is associated with elevated uncertainty and premature decisions based on unreliable evidence.
- Published
- 2022