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

摘要

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