Ketamine Dysregulates the Amplitude and Connectivity of High-Frequency Oscillations in Cortical-Subcortical Networks in Humans: Evidence From Resting-State Magnetoencephalography-Recordings

Article


Rivolta, D., Heidegger, T., Scheller, B., Sauer, A., Schaum, M., Birkner, K., Singer, W., Wibral, M. and Uhlhaas, P. J. 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.
AuthorsRivolta, D., Heidegger, T., Scheller, B., Sauer, A., Schaum, M., Birkner, K., Singer, W., Wibral, M. and Uhlhaas, P. J.
Abstract

Hypofunctioning of the N-methyl-D-aspartate (NMDA)-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 two different sessions, a subanesthetic
dose of S-ketamine (0.006 mg/Kg) and saline injection. MEG-data were analyzed at sensorand
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 highfrequency
oscillations following the inhibition of NMDA-R in animal models of ScZ as well as
with evidence from EEG-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 schizophrenia as a disorder of disinhibition of neural circuits.

JournalSchizophrenia Bulletin
ISSN1745-1701
0586-7614
Year2015
PublisherOxford University Press
Accepted author manuscript
License
CC BY
Web address (URL)http://dx.doi.org/10.1093/schbul/sbv051
Publication dates
Print18 May 2015
Publication process dates
Deposited17 Jun 2015
Accepted18 May 2015
Copyright information© 2015 The Authors This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Schizophrenia Bulletin following peer review. The definitive publisher-authenticated version of Ketamine Dysregulates the Amplitude and Connectivity of High-Frequency Oscillations in Cortical–Subcortical Networks in Humans: Evidence From Resting-State Magnetoencephalography-Recordings is available online at: http://dx.doi.org/10.1093/schbul/sbv051
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