Modeling ketamine effects on synaptic plasticity during the mismatch negativity.
Cereb Cortex
; 23(10): 2394-406, 2013 Oct.
Article
em En
| MEDLINE
| ID: mdl-22875863
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.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Receptores de N-Metil-D-Aspartato
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Antagonistas de Aminoácidos Excitatórios
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Potenciais Evocados
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Ketamina
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Plasticidade Neuronal
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Cereb Cortex
Assunto da revista:
CEREBRO
Ano de publicação:
2013
Tipo de documento:
Article