Modeling ketamine effects on synaptic plasticity during the mismatch negativity
Open accessAbstract
This paper presents a model-based investigation of mechanisms underlying the reduction of mismatch negativity (MMN) amplitudes under the NMDA-receptor antagonist ketamine. We applied dynamic causal modeling and Bayesian model selection to data from a recent ketamine study of the roving MMN paradigm, using a cross-over, double-blind, placebo-controlled design. Our modeling was guided by a predictive coding framework that unifies contemporary "adaptation" and "model adjustment" MMN theories. Comparing a series of dynamic causal models that allowed for different expressions of neuronal adaptation and synaptic plasticity, we obtained 3 major results: 1) We replicated previous results that both adaptation and short-term plasticity are necessary to explain MMN generation per se; 2) we found significant ketamine effects on synaptic plasticity, but not adaptation, and a selective ketamine effect on the forward connection from left primary auditory cortex to superior temporal gyrus; 3) this model-based estimate of ketamine effects on synaptic plasticity correlated significantly with ratings of ketamine-induced impairments in cognition and control. Our modeling approach thus suggests a concrete mechanism for ketamine effects on MMN that correlates with drug-induced psychopathology. More generally, this demonstrates the potential of modeling for inferring on synaptic physiology, and its pharmacological modulation, from electroencephalography data.
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Prediction error signaling in cortex likely rests on fast glutamatergic transmission, probably involving fast AMPA receptors under regulation by slower NMDA receptors.
“For example, prediction error signaling in cortex likely rests on fast glutamatergic transmission, probably involving fast AMPA receptors under regulation by slower NMDA receptors (91, 108);”
From Can Bayesian Theories of Autism Spectrum Disorder Help Improve Clinical Practice? (2016) · cites this paper as [108]
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Ketamine improves short-term plasticity in depression by enhancing sensitivity to prediction errors
Sumner, R. L., McMillan, R., Spriggs, M. J., Campbell, D., Malpas, G., Maxwell, E., Deng, C., Hay, J., Ponton, R., Sundram, F., et al. (2020) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2020.07.009 · Cited by 32 · see citing works
Model-based prediction of muscarinic receptor function from auditory mismatch negativity responses
Schöbi, D., Homberg, F., Frässle, S., Endepols, H., Moran, R. J., Friston, K. J., Tittgemeyer, M., Heinzle, J., & Stephan, K. E. (2021) · NeuroImage · doi:10.1016/j.neuroimage.2021.118096 · Cited by 25 · see citing works
Self-citationThalamocortical inhibitory dynamics support conscious perception
Min, B.-K., Kim, H. S., Pinotsis, D. A., & Pantazis, D. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.117066 · Cited by 14 · see citing works
Suicide prevention and ketamine: insights from computational modeling
Charlton, C. E., Karvelis, P., McIntyre, R. S., & Diaconescu, A. O. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1214018 · Cited by 7 · see citing works
Self-citationEvidence and implications of abnormal predictive coding in dementia
Kocagoncu, E., Klimovich-Gray, A., Hughes, L. E., & Rowe, J. B. (2021) · Brain · doi:10.1093/brain/awab254 · Cited by 3 · see citing works
- Authors
- Schmidt, A., Diaconescu, A. O., Kometer, M., Friston, K. J., Stephan, K. E., & Vollenweider, F. X.
- Affiliations
- University of Zurich (CH)
- Wellcome Centre for Human Neuroimaging (GB)
- Corresponding author
- Schmidt, A.
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-08-08
- Volume
- 23
- Issue
- 10
- Pages
- 2394-2406
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- PMC
- PMC3767962
- OpenAlex
- W2122940730
- Cited by
- 109
- References
- 84
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 3 · 2023: 7 · 2022: 3 · 2021: 7 · 2020: 14 · 2019: 3 · 2018: 13 · 2017: 10 · 2016: 11 · 2015: 13 · 2014: 6 · 2013: 8 · 2012: 2
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cerebral Cortex (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- reroDoc Digital Library (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- ETH Zürich Research Collection
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Wellcome Trust (091593, 088130)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neuroscience and Music Perception
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- ketamine, mismatch negativity, synaptic plasticity, NMDA receptor antagonism, dynamic causal modeling, predictive coding, neural adaptation, short-term plasticity, primary auditory cortex, superior temporal gyrus, cognitive impairment
- MeSH terms
- Adult, Evoked Potentials, Female, Humans, Ketamine, Male, Models, Neurological, Neuronal Plasticity, Receptors, N-Methyl-D-Aspartate, Excitatory Amino Acid Antagonists
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