AUTHOR=Lu Fa , Li Lunxu , Wang Juan , Chen Xuanling , Yang Ho-Ching , Li Xiaoli , Yao Lan , Liang Zhenhu 

TITLE=Distinct effects of global signal regression on brain activity during propofol and sevoflurane anesthesia

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 19 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1576535

DOI=10.3389/fnins.2025.1576535

ISSN=1662-453X

ABSTRACT=IntroductionGlobal 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.MethodsUsing 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.ResultsHere 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.DiscussionThese 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.