Excitation-Inhibition Balance in Schizophrenia Spectrum Disorders: EEG Criticality Reflects Frontal Metabolites and a Potential Compensatory Mechanism

Background The excitation-inhibition (E-I) balance is essential for normal brain functioning, while deviations from this balance have been implicated in several psychiatric disorders. However, the extent to which electroencephalography (EEG) and proton magnetic resonance spectroscopy (1H-MRS) E-I markers are altered in schizophrenia spectrum disorders (SSD), how they converge across modalities, and how they relate to cognitive performance and clinical symptoms remain insufficiently characterized. Methods We recruited 111 healthy controls (HC) and 113 individuals with SSD. All participants underwent resting-state EEG and 1H-MRS. Metabolites were measured either in the anterior cingulate cortex (ACC; NSSD = 63, NHC = 58) or in the left dorsolateral prefrontal cortex (lDLPFC; NSSD = 50, NHC = 53), from which gamma-aminobutyric acid (GABA), glutamate + glutamine (Glx), and the Glx/GABA ratio were extracted. Extracted EEG E-I markers included oscillatory activity, aperiodic activity, functional E-I, microstates, multiscale entropy, and neuronal avalanche criticality. Results MRS results showed no group differences in GABA, Glx, or the Glx/GABA ratio. In contrast, most EEG-derived E-I markers indicated increased cortical inhibition in SSD, including steeper aperiodic exponents, prolonged microstate durations, and greater prevalence of subcritical states. However, functional E-I showed a divergent pattern, suggesting balanced dynamics in SSD and relatively inhibition-weighted dynamics in HC. Across groups, higher ACC and lDLPFC GABA predicted a lower kappa index, whereas a higher lDLPFC Glx/GABA ratio was associated with a higher kappa index. In SSD, reduced avalanche criticality was associated with better cognition and less severe symptoms. Conclusion Several EEG-derived E-I proxies, but not MRS measures, indicate an increased cortical inhibition in SSD. Criticality indices best capture frontal neurochemical metabolites and improvements in clinical symptoms, potentially reflecting inhibitory compensation mechanisms in SSD.