Relationship Between Replay-Associated Ripples and Hippocampal N-Methyl-D-Aspartate Receptors: Preliminary Evidence From a PET-MEG Study in Schizophrenia. Issue 1 (7th July 2022)

• Record Type: Journal Article
• Authors: Nour, Matthew M; Beck, Katherine; Liu, Yunzhe; Arumuham, Atheeshaan; Veronese, Mattia; Howes, Oliver D; Dolan, Raymond J
• Is Part Of: Schizophrenia bulletin open. Volume 3:Issue 1(2022)
• Publication Date: 2022-07-07
• Subjects: Psychosis -- inference -- sharp wave ripple -- excitation-inhibition balance -- replay; Schizophrenia -- Periodicals; Schizophrenia -- Research -- Periodicals; Psychoses -- Periodicals; 616.898005
• DOI: 10.1093/schizbullopen/sgac044
• Languages: English
• ISSNs: 2632-7899

Abstract

Abstract: Background and Hypotheses: Hippocampal replay and associated high-frequency ripple oscillations are among the best-characterized phenomena in resting brain activity. Replay/ripples support memory consolidation and relational inference, and are regulated by N -methyl-D-aspartate receptors (NMDARs). Schizophrenia has been associated with both replay/ripple abnormalities and NMDAR hypofunction in both clinical samples and genetic mouse models, although the relationship between these 2 facets of hippocampal function has not been tested in humans. Study Design: Here, we avail of a unique multimodal human neuroimaging data set to investigate the relationship between the availability of (intrachannel) NMDAR binding sites in hippocampus, and replay-associated ripple power, in 16 participants (7 nonclinical participants and 9 people with a diagnosis of schizophrenia, PScz). Each participant had both a [ 18 F]GE-179 positron emission tomography (PET) scan (to measure NMDAR availability, V T ) and a magnetoencephalography (MEG) scan (to measure offline neural replay and associated high-frequency ripple oscillations, using Temporally Delayed Linear Modeling). Study Results: We show a positive relationship between hippocampal NMDAR availability and replay-associated ripple power. This linkage was evident across control participants ( r (5) = .94, P = .002) and PScz ( r (7) = .70, P = .04), with no group difference. Conclusions: Our findings provide preliminary evidence for a relationship between hippocampal NMDAR availability and replay-associated ripple power in humans, and haverelevance for NMDAR hypofunction theories of schizophrenia.