Modeling Ketamine Effects on Synaptic Plasticity During the Mismatch Negativity
André Schmidt, Andreea O. Diaconescu, Michael Kometer, Karl Friston, Klaas Ε. Stephan, Franz X. Vollenweider
Cerebral Cortex August 8, 2012 DOI: 10.1093/cercor/bhs238 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Cross-over, double-blind, placebo-controlled design Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Ketamine Neuroplasticity Esketamine |
| Keywords | Mismatch negativity Nmda receptor Electroencephalography |
| Citations | 110 |
| Key points | Ketamine reduces MMN amplitudes by affecting synaptic plasticity, not adaptation, and this effect correlates with drug-induced cognitive impairments. |
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.
Comparable studies
Other randomized controlled trials on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Increased global integration in the brain after psilocybin therapy for depression. Patients with treatment-resistant depression and patients with major depressive disorder | 2022 | Open-label trial and double-blind phase II randomized controlled trial | |
| Cognitive-Affective Neural Plasticity following Active-Controlled Mindfulness Intervention Healthy human subjects | 2012 | Randomized controlled trial | |
| LSD-induced entropic brain activity predicts subsequent personality change. Healthy adults | 2016 | Balanced-order, placebo-controlled study | n = 19 |
| Effective connectivity changes in LSD-induced altered states of consciousness in humans. Healthy participants | 2019 | Double-blind, randomized, placebo-controlled, cross-over study | n = 25 |
| Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin. | 2019 | Observational study with placebo session |
Citations in the library
Cited by 16
- Peak experiences and the afterglow phenomenon: When and how do therapeutic effects of hallucinogens depend on psychedelic experiences? Journal of Psychopharmacology February 9, 2015
- LSD modulates effective connectivity and neural adaptation mechanisms in an auditory oddball paradigm. Neuropharmacology November 20, 2017
- Ketamine Affects Prediction Errors about Statistical Regularities: A Computational Single-Trial Analysis of the Mismatch Negativity Journal of Neuroscience June 19, 2020
- Glutamatergic Deficits in Schizophrenia – Biomarkers and Pharmacological Interventions within the Ketamine Model Current Pharmaceutical Biotechnology June 21, 2018
- Preclinical models of antipsychotic drug action The International Journal of Neuropsychopharmacology June 10, 2013
and 11 more in the library
Cites 9
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans Pharmacopsychiatry July 1, 1998
- Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Archives of General Psychiatry December 1, 2000
- From drugs to deprivation: a Bayesian framework for understanding models of psychosis Psychopharmacology May 27, 2009
and 4 more in the library