Resting-state EEG and MEG gamma frequencies in schizophrenia: a systematic review and exploratory power-spectrum metanalysis

The hypoactivity of parvalbumin-containing interneurons (PV-interneurons) is a pathogenetic mechanism of schizophrenia according to the glutamatergic theory, and PV-interneurons are necessary for the generation of EEG/MEG gamma-frequencies (30-100 Hz). The present study aims to a literature synthesis on resting-state gamma-frequency changes in patients with schizophrenia vs healthy controls, and to examine the relationship between these changes and severity of symptoms. A protocol was enregistered in PROSPERO and a systematic search was conducted in PubMed, PsycINFO and Cochrane Database of Systematic Reviews, following PRISMA guidelines. An exploratory metanalysis was realized. Out of 1391 records, 43 were included for a qualitative synthesis (N = 2133 [11-185], females 37.4%, age 33.9 +/- 9.2). Results on power spectra were heterogeneous: in 12 studies gamma power was increased, involving the whole brain (N = 3), multiple regions (N = 6) or only frontal (N = 1), central (n = 1) and temporal (N = 1) areas; in 3 studies gamma power was reduced, involving multiple areas (N = 2) or the right temporal region (N = 1); one study revealed mixed results and 13 studies showed no differences. The meta-analysis on 4 studies (N = 211) showed non-significant differences between patients and controls and a large heterogeneity. The functional connectivity picture consists of sparse patterns of decreases and/or increases, widespread to multiple regions. Relationships emerged between gamma power and connectivity and severity of psychotic and cognitive symptoms. Theta-gamma coupling was increased in patients, with limited evidence for other changes in phase-amplitude coupling. Resting-state gamma-frequencies alterations in schizophrenia were inconsistent across studies; the heterogeneity of patients and methods could partially explain this outcome.