Related Experiment Video
Updated: May 19, 2026
Pentylenetetrazole-Induced Kindling Mouse Model
Published on: June 12, 2018
Modeling ketamine effects on synaptic plasticity during the mismatch negativity
André Schmidt1, Andreea O Diaconescu, Michael Kometer
1University Hospital of Psychiatry, Neuropsychopharmacology and Brain Imaging.
Abstract:
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.
Insights
Ketamine reduces mismatch negativity (MMN) by altering synaptic plasticity, not neuronal adaptation. This finding, derived from advanced modeling, links neurophysiological changes to ketamine
Area of Science:
- Neuroscience
- Psychopharmacology
- Computational Psychiatry
Background:
- Mismatch negativity (MMN) is an electrophysiological response sensitive to auditory changes.
- Ketamine, an NMDA-receptor antagonist, is known to affect MMN amplitudes.
- Existing MMN theories involve neuronal adaptation and predictive coding mechanisms.
Purpose of the Study:
- To investigate the specific mechanisms by which ketamine reduces MMN amplitudes.
- To differentiate the roles of neuronal adaptation and synaptic plasticity in ketamine's effects on MMN.
- To link model-based estimates of ketamine's neurophysiological effects to cognitive outcomes.
Main Methods:
- Applied dynamic causal modeling (DCM) and Bayesian model selection to EEG data.
- Utilized data from a cross-over, double-blind, placebo-controlled ketamine study.
- Employed a predictive coding framework to unify MMN theories.
Main Results:
- Replicated findings that both adaptation and short-term plasticity are essential for MMN generation.
- Identified significant ketamine effects on synaptic plasticity, but not adaptation.
- Observed a selective ketamine effect on the forward connection from the left auditory cortex to the superior temporal gyrus.
- Found that model-based estimates of ketamine's effects on synaptic plasticity correlated with cognitive and control impairments.
Conclusions:
- Ketamine's reduction of MMN is primarily mediated by effects on synaptic plasticity, not adaptation.
- The study proposes a specific neurophysiological mechanism for ketamine's impact on MMN.
- This modeling approach demonstrates the potential for inferring synaptic function and drug modulation from EEG data.
