Ketamine dysregulates the amplitude and connectivity of high-frequency oscillations in cortical–subcortical networks in humans: evidence from resting-state magnetoencephalography-recordings

Rivolta, D., Heidegger, T., Scheller, B., Sauer, A., Schaum, M., Birkner, K., Singer, W., Wibral, M. and Uhlhaas, P. (2015) Ketamine dysregulates the amplitude and connectivity of high-frequency oscillations in cortical–subcortical networks in humans: evidence from resting-state magnetoencephalography-recordings. Schizophrenia Bulletin, 41(5), pp. 1105-1114. (doi:10.1093/schbul/sbv051) (PMID:25987642)

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Abstract

Hypofunctioning of the N-methyl-D-aspartate receptor (NMDA-R) has been prominently implicated in the pathophysiology of schizophrenia (ScZ). The current study tested the effects of ketamine, a dissociative anesthetic and NMDA-R antagonist, on resting-state activity recorded with magnetoencephalography (MEG) in healthy volunteers. In a single-blind cross-over design, each participant (n = 12) received, on 2 different sessions, a subanesthetic dose of S-ketamine (0.006mg/Kg) and saline injection. MEG-data were analyzed at sensor- and source-level in the beta (13–30 Hz) and gamma (30–90 Hz) frequency ranges. In addition, connectivity analysis at source-level was performed using transfer entropy (TE). Ketamine increased gamma-power while beta-band activity was decreased. Specifically, elevated 30–90 Hz activity was pronounced in subcortical (thalamus and hippocampus) and cortical (frontal and temporal cortex) regions, whilst reductions in beta-band power were localized to the precuneus, cerebellum, anterior cingulate, temporal and visual cortex. TE analysis demonstrated increased information transfer in a thalamo-cortical network after ketamine administration. The findings are consistent with the pronounced dysregulation of high-frequency oscillations following the inhibition of NMDA-R in animal models of ScZ as well as with evidence from electroencephalogram-data in ScZ-patients and increased functional connectivity during early illness stages. Moreover, our data highlight the potential contribution of thalamo-cortical connectivity patterns towards ketamine-induced neuronal dysregulation, which may be relevant for the understanding of ScZ as a disorder of disinhibition of neural circuits.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Uhlhaas, Professor Peter
Authors: Rivolta, D., Heidegger, T., Scheller, B., Sauer, A., Schaum, M., Birkner, K., Singer, W., Wibral, M., and Uhlhaas, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Schizophrenia Bulletin
Publisher:Oxford University Press
ISSN:0586-7614
ISSN (Online):1745-1701
Copyright Holders:Copyright © 2015 Oxford University Press
First Published:First published in Schizophrenia Bulletin 41(5):1105-1114
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.

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