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Prediction error, ketamine and psychosis: An updated model

Philip R. Corlett, Garry D Honey, P. Fletcher

Journal of Psychopharmacology May 25, 2016 DOI: 10.1177/0269881116650087 (opens in new tab)

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AI-extracted from the abstract
Characteristics Theoretical or philosophical paper Peer reviewed
Topics Esketamine Ketamine
Key points Argues that an expanded predictive-processing model, incorporating the precision of prediction errors and prior expectations, can explain hallucinations as a perturbation of the uncertainty-mediated balance between expectation and prediction error, and negative symptoms as poor reliability of predictions serving action. The authors contend this account may explain the heterogeneity of psychotic illness and why pharmacologically different drugs produce psychotomimetic effects.

Abstract

In 2007, we proposed an explanation of delusion formation as aberrant prediction error-driven associative learning. Further, we argued that the NMDA receptor antagonist ketamine provided a good model for this process. Subsequently, we validated the model in patients with psychosis, relating aberrant prediction error signals to delusion severity. During the ensuing period, we have developed these ideas, drawing on the simple principle that brains build a model of the world and refine it by minimising prediction errors, as well as using it to guide perceptual inferences. While previously we focused on the prediction error signal per se, an updated view takes into account its precision, as well as the precision of prior expectations. With this expanded perspective, we see several possible routes to psychotic symptoms – which may explain the heterogeneity of psychotic illness, as well as the fact that other drugs, with different pharmacological actions, can produce psychotomimetic effects. In this article, we review the basic principles of this model and highlight specific ways in which prediction errors can be perturbed, in particular considering the reliability and uncertainty of predictions. The expanded model explains hallucinations as perturbations of the uncertainty mediated balance between expectation and prediction error. Here, expectations dominate and create perceptions by suppressing or ignoring actual inputs. Negative symptoms may arise due to poor reliability of predictions in service of action. By mapping from biology to belief and perception, the account proffers new explanations of psychosis. However, challenges remain. We attempt to address some of these concerns and suggest future directions, incorporating other symptoms into the model, building towards better understanding of psychosis.

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A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics 2020 Theoretical or philosophical paper
Neuroscience and the Near-Death Experience: Roles for the NMSA-PCP receptor, the sigma receptor and the endopsychosins 1990 Theoretical or philosophical paper
A unified model of ketamine's dissociative and psychedelic properties. 2022 Theoretical or philosophical paper
An Integrative Approach to Ketamine Therapy May Enhance Multiple Dimensions of Efficacy: Improving Therapeutic Outcomes With Treatment Resistant Depression. 2021 Theoretical or philosophical paper

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