Mismatch negativity encoding of prediction errors predicts S-ketamine-induced cognitive impairments
Open accessAbstract
Psychotomimetics like the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine and the 5-hydroxytryptamine2A receptor (5-HT(2A)R) agonist psilocybin induce psychotic symptoms in healthy volunteers that resemble those of schizophrenia. Recent theories of psychosis posit that aberrant encoding of prediction errors (PE) may underlie the expression of psychotic symptoms. This study used a roving mismatch negativity (MMN) paradigm to investigate whether the encoding of PE is affected by pharmacological manipulation of NMDAR or 5-HT(2A)R, and whether the encoding of PE under placebo can be used to predict drug-induced symptoms. Using a double-blind within-subject placebo-controlled design, S-ketamine and psilocybin, respectively, were administrated to two groups of healthy subjects. Psychological alterations were assessed using a revised version of the Altered States of Consciousness (ASC-R) questionnaire. As an index of PE, we computed changes in MMN amplitudes as a function of the number of preceding standards (MMN memory trace effect) during a roving paradigm. S-ketamine, but not psilocybin, disrupted PE processing as expressed by a frontally disrupted MMN memory trace effect. Although both drugs produced positive-like symptoms, the extent of PE processing under placebo only correlated significantly with the severity of cognitive impairments induced by S-ketamine. Our results suggest that the NMDAR, but not the 5-HT(2A)R system, is implicated in PE processing during the MMN paradigm, and that aberrant PE signaling may contribute to the formation of cognitive impairments. The assessment of the MMN memory trace in schizophrenia may allow detecting early phases of the illness and might also serve to assess the efficacy of novel pharmacological treatments, in particular of cognitive impairments.
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S-ketamine reduced repetition effects in the usual roving oddball paradigm.
“In the usual roving oddball paradigm, Schmidt and colleagues showed that S-ketamine reduced repetition effects (31).”
From A Predictive Coding Perspective on Mismatch Negativity Impairment in Schizophrenia (2020) · cites this paper as [31]
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- Authors
- Schmidt, A., Bachmann, R., Kometer, M., Csomor, P. A., Stephan, K. E., Seifritz, E., & Vollenweider, F. X.
- Affiliations
- University of Zurich (CH)
- Wellcome Centre for Human Neuroimaging (GB)
- Psychiatrische Universitätsklinik Zürich (CH)
- Corresponding author
- Schmidt, André
- Venue
- Neuropsychopharmacology
- Published
- 2011-10-26
- Volume
- 37
- Issue
- 4
- Pages
- 865-875
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3280661
- OpenAlex
- W1989324273
- Cited by
- 121
- References
- 94
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 14 · 2023: 7 · 2022: 8 · 2021: 6 · 2020: 9 · 2019: 16 · 2018: 6 · 2017: 7 · 2016: 6 · 2015: 14 · 2014: 5 · 2013: 10 · 2012: 4
- FWCI
- 6.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Wellcome Trust (091593)
- SystemsX.ch
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- mismatch negativity, esketamine, psilocybin, NMDA receptor antagonism, 5-HT2A receptor agonism, psychosis, cognitive impairment, schizophrenia
- MeSH terms
- Adult, Cognition Disorders, Double-Blind Method, Electroencephalography, Female, Forecasting, Humans, Ketamine, Male, Placebos, Psychoses, Substance-Induced, Schizophrenia, Receptors, N-Methyl-D-Aspartate, Excitatory Amino Acid Antagonists, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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