Abstract
INTRODUCTION: Global signal regression (GSR) is widely used in functional magnetic resonance imaging (fMRI) analysis, yet its effects on anesthetic-related brain activity are not well understood. METHODS: Using fMRI data from patients under general anesthesia, we analyzed temporal variability indices, amplitude of low-frequency fluctuations, functional connectivity, and graph theoretical measures with and without GSR. RESULTS: Here we show that GSR differentially affects brain activity patterns during propofol- and sevoflurane-induced unconsciousness. While temporal variability indices decreased similarly between conscious and unconscious states regardless of GSR, functional connectivity analyses revealed anesthetic-specific effects: GSR altered specific network connections under propofol but broadly reduced connectivity differences under sevoflurane. Network topology analyses demonstrated that GSR minimally affected propofol-induced changes in graph theoretical measures but significantly diminished sevoflurane-related network alterations. DISCUSSION: These findings reveal that GSR's impact on functional brain organization is anesthetic-specific, with sevoflurane-induced changes being particularly sensitive to global signal removal. Our results suggest that GSR should be applied cautiously when comparing different anesthetic agents and highlight the importance of considering drug-specific effects when analyzing consciousness-related brain activity.