Dataset Information

Premature commitment to uncertain decisions during human NMDA receptor hypofunction.

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.

SUBMITTER: Salvador A

PROVIDER: S-EPMC8763907 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Premature commitment to uncertain decisions during human NMDA receptor hypofunction.

Salvador Alexandre A Arnal Luc H LH Vinckier Fabien F Domenech Philippe P Gaillard Raphaël R Wyart Valentin V

Nature communications 20220117 1

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 ...[more]

PMID: 35039498

Similar Datasets

Project description:Hallucinations, a hallmark of psychosis, can be induced by the psychotomimetic N-methyl-D-aspartic acid (NMDA) receptor antagonists, ketamine and phencyclidine (PCP), and are associated with hypersynchronization in the ?-frequency band, but it is unknown how reduced interneuron activation associated with NMDA receptor hypofunction can cause hypersynchronization or distorted perception. Low-frequency ?-oscillations (LF?) and high-frequency ?-oscillations (HF?) serve different aspects of perception. In this study, we test whether ketamine and PCP affect the interactions between HF? and LF? in the rat visual cortex in vitro. In slices of the rat visual cortex, kainate and carbachol induced LF? (? 34 Hz at 32°C) in layer V and HF? (? 54 Hz) in layer III of the same cortical column. In controls, HF? and LF? were independent, and pyramidal neurons recorded in layer III were entrained by HF?, but not by LF?. Sub-anesthetic concentrations of ketamine selectively decelerated HF? by 22 Hz (EC(50)=2.7 ?M), to match the frequency of LF? in layer V. This caused phase coupling of the two ?-oscillations, increased spatial coherence in layer III, and entrained the firing of layer III pyramidal neurons by LF? in layer V. PCP similarly decelerated HF? by 22 Hz (EC(50)=0.16 ?M), causing cross-layer phase coupling of ?-oscillations. Selective NMDA receptor antagonism, selective NR2B subunit-containing receptor antagonism, and reduced D-serine levels caused a similar selective deceleration of HF?, whereas increasing NMDA receptor activation through exogenous NMDA, D-serine, or mGluR group 1 agonism selectively accelerated HF?. The NMDA receptor hypofunction-induced phase coupling of the normally independent ?-generating networks is likely to cause abnormal cross-layer interactions, which may distort perceptions due to aberrant matching of top-down information with bottom-up information. If decelerated HF? and subsequent cross-layer synchronization also underlie pathological psychosis, acceleration of HF? could be the target for improved antipsychotic therapy.

Dataset Information

Premature commitment to uncertain decisions during human NMDA receptor hypofunction.

Publications

Premature commitment to uncertain decisions during human NMDA receptor hypofunction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets