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Cited by 229Schizophrenia research and treatmentPsychedelics and Drug StudiesNeurotransmitter Receptor Influence on Behavior

Glutamatergic model psychoses: prediction error, learning, and inference

Open access
Corlett, Philip R, Honey, Garry D, Krystal, John H, Fletcher, Paul C·2011·Neuropsychopharmacology
DOI 10.1038/npp.2010.163PMC PMC3055519
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Abstract

Modulating glutamatergic neurotransmission induces alterations in conscious experience that mimic the symptoms of early psychotic illness. We review studies that use intravenous administration of ketamine, focusing on interindividual variability in the profundity of the ketamine experience. We will consider this individual variability within a hypothetical model of brain and cognitive function centered upon learning and inference. Within this model, the brains, neural systems, and even single neurons specify expectations about their inputs and responding to violations of those expectations with new learning that renders future inputs more predictable. We argue that ketamine temporarily deranges this ability by perturbing both the ways in which prior expectations are specified and the ways in which expectancy violations are signaled. We suggest that the former effect is predominantly mediated by NMDA blockade and the latter by augmented and inappropriate feedforward glutamatergic signaling. We suggest that the observed interindividual variability emerges from individual differences in neural circuits that normally underpin the learning and inference processes described. The exact source for that variability is uncertain, although it is likely to arise not only from genetic variation but also from subjects' previous experiences and prior learning. Furthermore, we argue that chronic, unlike acute, NMDA blockade alters the specification of expectancies more profoundly and permanently. Scrutinizing individual differences in the effects of acute and chronic ketamine administration in the context of the Bayesian brain model may generate new insights about the symptoms of psychosis; their underlying cognitive processes and neurocircuitry.

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Crossref · 10.1038/npp.2010.163

Cites

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  • The main problem in schizophrenia lies not with the prediction of sensory input per se, but in the delicate balance of precision ascribed to prior beliefs and sensory evidence.

    “the main problem in schizophrenia lies not with the prediction of sensory input per se, but in the delicate balance of precision ascribed to prior beliefs and sensory evidence (Friston, 2005; Corlett et al., 2011).”

    From The Computational Anatomy of Psychosis (2013) · cites this paper as Corlett et al., 2011

    The ‘Slower Neuromodulators—Precision, Uncertainty, and Learning’ section distinguishes prediction errors from their precision, and ‘Prediction Error and Psychosis’ describes aberrant prediction errors and excessively strong predictions in psychotic symptoms (page numbers unavailable). These passages support a role for precision and prior expectations, but do not establish that the main problem in schizophrenia is the balance of precision assigned to priors versus sensory evidence, rather than sensory prediction itself. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Ketamine induces a delusional mood.

    “induction of a delusional mood (Corlett et al., 2011)”

    From The Computational Anatomy of Psychosis (2013) · cites this paper as Corlett et al., 2011

    The Delusions section (page not supplied) says ketamine may be a good model for the delusional mood of early psychosis and describes similarities between patients’ and ketamine recipients’ experiences. That supports the association, but the source hedges it as a model rather than stating definitively that ketamine induces a delusional mood. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Aberrant encoding of precision could lead to an abnormally strong weighting of prediction error, which in turn leads to aberrant learning and the formation of delusional beliefs.

    “The resulting aberrant encoding of precision could lead to an abnormally strong weighting of PE, which in turn leads to aberrant learning and the formation of delusional beliefs (53, 58, 59, 64).”

    From The Predictive Coding Account of Psychosis (2018) · cites this paper as [64]

    The ‘Slower Neuromodulators—Precision, Uncertainty, and Learning’ section (page unavailable) says neuromodulators encode or modulate the precision of prediction errors. ‘Prediction Error and Psychosis’ (page unavailable) links aberrant prediction errors to delusions. The copy does not establish the specific intervening step that aberrant precision encoding gives prediction errors abnormally strong weight and thereby causes aberrant learning. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Neurodevelopmental disorders such as autism spectrum disorder and schizophrenia have been linked to an atypical integration of prior and incoming information.

    “neurodevelopmental disorders such as autism spectrum disorder [132,133] and schizophrenia [134,135] have been linked to an atypical integration of prior and incoming information”

    From How Do Expectations Shape Perception? (2018) · cites this paper as [135]

  • Similar Bayesian theories have previously been stated in the context of schizophrenia.

    “It is of interest to note that similar Bayesian theories have previously been stated in the context of schizophrenia (63, 68, 89–92).”

    From Can Bayesian Theories of Autism Spectrum Disorder Help Improve Clinical Practice? (2016) · cites this paper as [91]

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Cites

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4 of the 300 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. [185]185. Matussek P (1952). Studies in delusional perception. In: J Cutting, M Shepherd (eds). The clinical roots of the schizophrenia concept. Transaltions of seminal European contributions on schizophrenia ; pp 89-103, Cambridge University Press: Cambridge.
  2. [195]195. Moreau JJ (1845/1973). Du Haschisch et l'alienation mentale. Raven Press: New York.
  3. [248]248. Schneider C (1930). Die Psychologie der Schizophrenen. Germany Thieme: Leipzig.

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Authors
Corlett, P. R., Honey, G. D., Krystal, J. H., & Fletcher, P. C.
Affiliations
  • Yale University (US)
  • Pfizer (United States) (US)
  • University of Cambridge (GB)
Corresponding author
Corlett, Philip R
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2010-09-22
Volume
36
Issue
1
Pages
294-315
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/npp.2010.163
PMC
PMC3055519
OpenAlex
W2094348922
Cited by
229
References
300
Citations by year
2026: 3 · 2025: 7 · 2024: 14 · 2023: 10 · 2022: 9 · 2021: 19 · 2020: 13 · 2019: 9 · 2018: 12 · 2017: 21 · 2016: 20 · 2015: 29 · 2014: 19 · 2013: 18 · 2012: 17
FWCI
1.97
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Neuropsychopharmacology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Wellcome Trust (064351)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
ketamine, psychosis, glutamatergic neurotransmission, NMDA receptor blockade, prediction error, interindividual variability, subjective experience, expectancy violation, individual differences
MeSH terms
Animals, Bayes Theorem, Cognition, Humans, Learning, Models, Neurological, Psychoses, Substance-Induced, Psychotic Disorders, Receptors, Glutamate, Excitatory Amino Acid Antagonists, Glutamic Acid

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