Do NMDA-R antagonists re-create patterns of spontaneous gamma-band activity in schizophrenia? A systematic review and perspective

Bianciardi, B. and Uhlhaas, P. J. (2021) Do NMDA-R antagonists re-create patterns of spontaneous gamma-band activity in schizophrenia? A systematic review and perspective. Neuroscience and Biobehavioral Reviews, 124, pp. 308-323. (doi: 10.1016/j.neubiorev.2021.02.005) (PMID:33581223)

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NMDA-R hypofunctioninig is a core pathophysiological mechanism in schizophrenia. However, it is unclear whether the physiological changes observed following NMDA-R antagonist administration are consistent with gamma-band alterations in schizophrenia. This systematic review examined the effects of NMDA-R antagonists on the amplitude of spontaneous gamma-band activity and functional connectivity obtained from preclinical (n = 24) and human (n = 9) studies and compared these data to resting-state EEG/MEG-measurements in schizophrenia patients (n = 27). Overall, the majority of preclinical and human studies observed increased gamma-band power following acute administration of NMDA-R antagonists. However, the direction of gamma-band power alterations in schizophrenia were inconsistent, which involved upregulation (n = 10), decreases (n = 7), and no changes (n = 8) in spectral power. Five out of 6 preclinical studies observed increased connectivity, while in healthy controls receiving Ketamine and in schizophrenia patients the direction of connectivity results was also inconsistent. Accordingly, the effects of NMDA-R hypofunctioning on gamma-band oscillations are different than pathophysiological signatures observed in schizophrenia. The implications of these findings for current E/I balance models of schizophrenia are discussed.

Item Type:Articles
Keywords:E/I imbalance, EEG/MEG-recordings, ketamine, MK-801, PCP, resting-state, schizophrenia, spontaneous gamma-band activity.
Glasgow Author(s) Enlighten ID:Uhlhaas, Professor Peter and Bianciardi, Miss Bianca
Authors: Bianciardi, B., and Uhlhaas, P. J.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Neuroscience and Biobehavioral Reviews
ISSN (Online):1873-7528
Published Online:10 February 2021
Copyright Holders:Copyright © 2021 Elsevier Ltd.
First Published:First published in Neuroscience and Biobehavioral Reviews 124: 308-323
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
306543Identifying Neural Signatures of Auditory-Predictive Processing in Schizophrenia: A Multi-Modal Imaging ApproachPeter UhlhaasMedical Research Council (MRC)MR/T003138/1NP - Centre for Neuroscience