EXPRESS: Baseline Electrophysiology versus Oxidative Metabolism as Traits of Inter-Network Differences in Neurometabolic Association.

Electrophysiological recordings such as electroencephalogram (EEG) are gold standards for measuring neuronal activity, which requires substantial oxidative metabolism (CMRO2) for support. Although EEG-CMRO2 links have long been assumed or measured qualitatively, quantitative characterization in humans remains limited, hindering our understanding of neurometabolic mechanisms and the utility of electrophysiological biomarkers in brain disease. Given that the neurometabolic process is sensitive to baseline perfusion and aerobic glycolysis, we hypothesized EEG-CMRO2 associations would show strong network and sex dependence, as these factors strongly influence perfusion and glycolytic activity. Here, we quantified EEG-CMRO2 associations and their underlying profiles (with cerebral blood flow and oxygen extraction fraction) across brain networks and between sexes. We further investigated how the EEG-CMRO2 association influenced resting-state functional magnetic resonance imaging (rs-fMRI) measurements. Our main findings suggest: (1) globally, CMRO2 only partially mediated EEG-fMRI relationships, revealing O2-independent coupling pathways; (2) EEG-CMRO2 associations varied significantly across functional networks; (3) sex differences in EEG-CMRO2 associations showed minimal network dependence; (4) high-frequency and low-frequency EEG bands exhibited opposite-polarities CMRO2 associations between males and females. These findings demonstrate that neurometabolic coupling differs across functional networks, frequency bands, and importantly, across biological sexes, with important implications for interpreting developing electrophysiological biomarkers and rs-fMRI measurements.