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

Article, Other literature type English OPEN
Rivolta, Davide ; Heidegger, T. ; Scheller, B. ; Sauer, A. ; Schaum, M. ; Birkner, K. ; Singer, W. ; Wibral, M. ; Uhlhaas, P. J. (2015)

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