TY  - JOUR
A1  - Grent-'t-Jong, Tineke
A1  - Rivolta, Davide
A1  - Groß, Joachim
A1  - Gajwani, Ruchika
A1  - Lawrie, Stephen M.
A1  - Schwannauer, Matthias
A1  - Heidegger, Tonio
A1  - Wibral, Michael
A1  - Singer, Wolf
A1  - Sauer, Andreas
A1  - Scheller, Bertram
A1  - Uhlhaas, Peter J.
T1  - Acute ketamine dysregulates task-related gamma-band oscillations in thalamo-cortical circuits in schizophrenia
T2  - Brain
N2  - 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.
KW  - schizophrenia
KW  - magnetoencephalography
KW  - N-methyl-D-aspartate receptor
KW  - neural oscillations
KW  - functional connectivity
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46395
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-463954
SN  - 1460-2156
SN  - 0006-8950
N1  - 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.
VL  - 141
IS  - 8
SP  - 2511
EP  - 2526
PB  - Oxford Univ. Press
CY  - Oxford
ER  -