Acute ketamine dysregulates task-related gamma-band oscillations in thalamo-cortical circuits in schizophrenia

  • Hypofunction of the N-methyl-D-aspartate receptor (NMDAR) has been implicated as a possible mechanism underlying cognitive deficits and aberrant neuronal dynamics in schizophrenia. To test this hypothesis, we first administered a sub-anaesthetic dose of S-ketamine (0.006 mg/kg/min) or saline in a single-blind crossover design in 14 participants while magnetoencephalographic data were recorded during a visual task. In addition, magnetoencephalographic data were obtained in a sample of unmedicated first-episode psychosis patients (n = 10) and in patients with chronic schizophrenia (n = 16) to allow for comparisons of neuronal dynamics in clinical populations versus NMDAR hypofunctioning. Magnetoencephalographic data were analysed at source-level in the 1–90 Hz frequency range in occipital and thalamic regions of interest. In addition, directed functional connectivity analysis was performed using Granger causality and feedback and feedforward activity was investigated using a directed asymmetry index. Psychopathology was assessed with the Positive and Negative Syndrome Scale. Acute ketamine administration in healthy volunteers led to similar effects on cognition and psychopathology as observed in first-episode and chronic schizophrenia patients. However, the effects of ketamine on high-frequency oscillations and their connectivity profile were not consistent with these observations. Ketamine increased amplitude and frequency of gamma-power (63–80 Hz) in occipital regions and upregulated low frequency (5–28 Hz) activity. Moreover, ketamine disrupted feedforward and feedback signalling at high and low frequencies leading to hypo- and hyper-connectivity in thalamo-cortical networks. In contrast, first-episode and chronic schizophrenia patients showed a different pattern of magnetoencephalographic activity, characterized by decreased task-induced high-gamma band oscillations and predominantly increased feedforward/feedback-mediated Granger causality connectivity. Accordingly, the current data have implications for theories of cognitive dysfunctions and circuit impairments in the disorder, suggesting that acute NMDAR hypofunction does not recreate alterations in neural oscillations during visual processing observed in schizophrenia.

Download full text files

Export metadata

Metadaten
Author:Tineke Grent-‘t-Jong, Davide Rivolta, Joachim Groß, Ruchika Gajwani, Stephen M. Lawrie, Matthias Schwannauer, Tonio Heidegger, Michael WibralORCiDGND, Wolf SingerORCiDGND, Andreas Sauer, Bertram Scheller, Peter J. Uhlhaas
URN:urn:nbn:de:hebis:30:3-463954
DOI:https://doi.org/10.1093/brain/awy175
ISSN:1460-2156
ISSN:0006-8950
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/30020423
Parent Title (English):Brain
Publisher:Oxford Univ. Press
Place of publication:Oxford
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/08/01
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/08/21
Tag:N-methyl-D-aspartate receptor; functional connectivity; magnetoencephalography; neural oscillations; schizophrenia
Volume:141
Issue:8
Page Number:16
First Page:2511
Last Page:2526
Note:
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
HeBIS-PPN:452426170
Institutes:Medizin / Medizin
Wissenschaftliche Zentren und koordinierte Programme / Frankfurt Institute for Advanced Studies (FIAS)
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0