In a pharmacological study recently published in "Schizophrenia Research" Dr Davide Rivolta adopted advanced neuroimaging tools to investigate the validity of the N-methyl-D-aspartate receptor (NMDAR)-hypofunction model for the pathophysiology of schizophrenia.
In particular, the 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 (0.006 mg/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, results 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.
You can read the article here
Rivolta, D, Heidegger, T., Scheller, B., Sauer, A., Schaum, M., Birkner, K., Singer, W., Wibral, M. & Uhlhaas, P. (in press). Ketamine dysregulates the amplitude and connectivity of high-frequency oscillations in cortical-subcortical networks in Humans: Evidence from resting-state MEG-recordings. Schizophrenia Bulletin
