Confidence and psychosis: a neuro-computational account of contingency learning disruption by NMDA blockade
Year: 2015
Type: article
Abstract: A state of pathological uncertainty about environmental regularities might represent a key step in the pathway to psychotic illness. Early psychosis can be investigated in healthy volunteers under ketamine, an NMDA receptor antagonist. Here, we explored the effects of ketamine on contingency learning using a placebo-controlled, double-blind, crossover design. During functional magnetic resonance imaging, participants performed an instrumental learning task, in which cue-outcome contingencies were probabilistic and reversed between blocks. Bayesian model comparison indicated that in such an unstable environment, reinforcement learning parameters are downregulated depending on confidence level, an adaptive mechanism that was specifically disrupted by ketamine administration. Drug effects were underpinned by altered neural activity in a fronto-parietal network, which reflected the confidence-based shift to exploitation of learned contingencies. Our findings suggest that an early characteristic of psychosis lies in a persistent doubt that undermines the stabilization of behavioral policy resulting in a failure to exploit regularities in the environment.
Source: Molecular Psychiatry
DOI: 10.1038/mp.2015.73
Institutions: Centre National de la Recherche Scientifique, Inserm, Sorbonne Paris Cité, Pitié-Salpêtrière Hospital, Centre Hospitalier Sainte-Anne, Institut du Cerveau, Université Paris Descartes, Université Pierre-et-Marie-Curie, Université Paris Cité, University of Cambridge, Centre for Psychiatry and Neuroscience, École Normale Supérieure - PSL, Laboratoire de Neurosciences Cognitives, University College London, Monash University, Addenbrooke's Hospital, Cambridgeshire and Peterborough NHS Foundation Trust
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,329
Awards: Understanding the role of brain network dysfunction in risk for schizophrenia, G2743209109, Mapping, understanding and manipulating the human brain connectome with MRI, G5766413236, A combined PET-fMRI study of frontostriatal dysfunction in first episode psychosis, Complementary studies of learning and motivation in psychosis and pathological hyperphagia., Behavioural and Clinical Neuroscience Institute (BCNI)
OpenAlex ID: W1593366978