ORIGINAL RESEARCH article
Front. Neuroimaging
Sec. Brain Imaging Methods
Global signal regression reduces connectivity patterns related to physiological signals and does not alter EEG-derived connectivity
Provisionally accepted
- McGill University, Montreal, Canada
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Functional brain connectivity measures extracted from resting-state functional magnetic resonance imaging (fMRI) scans have generated wide interest as potential noninvasive biomarkers. In this context, performing global signal regression (GSR) as a preprocessing step remains controversial. Specifically, while it has been shown that a considerable fraction of global signal variations is associated with physiological and motion sources, GSR may also result in removing neural activity. Here, we address this question by examining the fundamental sources of resting global signal fluctuations using simultaneous electroencephalography (EEG)-fMRI data combined with cardiac and breathing recordings. Our results suggest that systemic physiological fluctuations account for a significantly larger fraction of global signal variability compared to electrophysiological fluctuations. Furthermore, we show that GSR reduces artifactual connectivity due to heart rate and breathing fluctuations, but preserves connectivity patterns associated with electrophysiological activity within the alpha and beta frequency ranges. Overall, these results provide evidence that the neural component of resting-state fMRI-based connectivity is preserved after the global signal is regressed out.
Keywords: Global signal, simultaneous EEG-fMRI, Physiological confounds, functional connectivity, fMRI preprocessing, brain networks
Received: 24 Jun 2025; Accepted: 24 Nov 2025.
Copyright: © 2025 Xifra Porxas, Kassinopoulos, Prokopiou, Boudrias and Mitsis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Georgios D Mitsis
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