Ketamine effects on default mode network activity and vigilance: A randomized, placebo‐controlled crossover simultaneous fMRI/EEG study

In resting‐state functional connectivity experiments, a steady state (of consciousness) is commonly supposed. However, recent research has shown that the resting state is a rather dynamic than a steady state. In particular, changes of vigilance appear to play a prominent role. Accordingly, it is cri...

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Bibliographic Details
Published in:Human brain mapping 2020-01, Vol.41 (1), p.107-119
Main Authors: Zacharias, Norman, Musso, Francesco, Müller, Felix, Lammers, Florian, Saleh, Andreas, London, Markus, Boer, Peter, Winterer, Georg
Format: Article
Language:English
Subjects:
Adult
antidepressant action
Antidepressants
Antidepressive Agents - pharmacology
Arousal - drug effects
Brain Waves - drug effects
Cerebral Cortex - diagnostic imaging
Cerebral Cortex - drug effects
Connectome - methods
Cross-Over Studies
Default Mode Network - diagnostic imaging
Default Mode Network - drug effects
depression
Double-Blind Method
EEG
EEG‐fMRI
Electroencephalography
Functional magnetic resonance imaging
Humans
Ketamine
Ketamine - pharmacology
Magnetic Resonance Imaging
Male
Multimodal Imaging
Neural networks
Neuroimaging
Pharmacodynamics
Prefrontal cortex
Randomization
Steady state
Vigilance
vigilance control
Young Adult
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Summary:In resting‐state functional connectivity experiments, a steady state (of consciousness) is commonly supposed. However, recent research has shown that the resting state is a rather dynamic than a steady state. In particular, changes of vigilance appear to play a prominent role. Accordingly, it is critical to assess the state of vigilance when conducting pharmacodynamic studies with resting‐state functional magnetic resonance imaging (fMRI) using drugs that are known to affect vigilance such as (subanesthetic) ketamine. In this study, we sought to clarify whether the previously described ketamine‐induced prefrontal decrease of functional connectivity is related to diminished vigilance as assessed by electroencephalography (EEG). We conducted a randomized, double‐blind, placebo‐controlled crossover study with subanesthetic S‐Ketamine in N = 24 healthy, young subjects by simultaneous acquisition of resting‐state fMRI and EEG data. We conducted seed‐based default mode network functional connectivity and EEG power spectrum analyses. After ketamine administration, decreased functional connectivity was found in medial prefrontal cortex whereas increased connectivities were observed in intraparietal cortices. In EEG, a shift of energy to slow (delta, theta) and fast (gamma) wave frequencies was seen in the ketamine condition. Frontal connectivity is negatively related to EEG gamma and theta activity while a positive relationship is found for parietal connectivity and EEG delta power. Our results suggest a direct relationship between ketamine‐induced functional connectivity changes and the concomitant decrease of vigilance in EEG. The observed functional changes after ketamine administration may serve as surrogate end points and provide a neurophysiological framework, for example, for the antidepressant action of ketamine (trial name: 29JN1556, EudraCT Number: 2009‐012399‐28).
ISSN:1065-9471
1097-0193
DOI:10.1002/hbm.24791