Removal of Confounding Effects of Global Signal in Functional MRI Analyses

doi:10.1006/nimg.2000.0719

NeuroImage

Volume 13, Issue 4, April 2001, Pages 751-758

https://doi.org/10.1006/nimg.2000.0719 Get rights and content

Abstract

Local signals obtained from BOLD fMRI are generally confounded by global effects. In this paper, we make an essential distinction between global effects and the global signal. Global effects have a similar influence on local signals from a large proportion of cerebral voxels. They may reflect diffuse physiological processes or variations in scanner sensitivity and are difficult to measure directly. Global effects are often estimated from the global signal, which is the spatial average of local signals from all cerebral voxels. If the global signal is strongly correlated with experimental manipulations, meaningfully different results may be obtained whether or not global effects are modeled (G. K. Aguirre et al., 1998, NeuroImage, 8, 302–306). In particular, if local BOLD signals make a significant contribution to the global signal, analyses using ANCOVAor proportional scaling models may yield artifactual deactivations. In this paper, we present a modification to the proportional scaling model that accounts for the contribution of local BOLD signals to the global signal. An event-related oddball stimulus paradigm and a block design working memory task were used to illustrate the efficacy of our model.

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Functional ultrasound imaging (fUSI) is an appealing method for measuring blood flow and thus infer brain activity, but it relies on the physiology of neurovascular coupling and requires extensive signal processing. To establish to what degree fUSI trial-by-trial signals reflect neural activity, we performed simultaneous fUSI and neural recordings with Neuropixels probes in awake mice. fUSI signals strongly correlated with the slow (<0.3 Hz) fluctuations in the local firing rate and were closely predicted by the smoothed firing rate of local neurons, particularly putative inhibitory neurons. The optimal smoothing filter had a width of ∼3 s, matched the hemodynamic response function of awake mice, was invariant across mice and stimulus conditions, and was similar in the cortex and hippocampus. fUSI signals also matched neural firing spatially: firing rates were as highly correlated across hemispheres as fUSI signals. Thus, blood flow measured by ultrasound bears a simple and accurate relationship to neuronal firing.
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Citation Excerpt :
In rs-fMRI studies a common preprocessing step before estimating FC is global signal regression (GSR), where a global time course is regressed out of the data. The global signal (GS) is obtained by averaging the resting-state time courses over the entire brain (Desjardins et al., 2001). The GS is often thought of as a mixture of processes that confound the BOLD fMRI signals (artifacts).
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^☆: The code for implementing adjusted proportional scaling in SPM 99 analyses is available on request from Peter F. Liddle, 2255 Wesbrook Mall, Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada, V6T 2A1. Fax: (604) 822-7756. E-mail: [email protected].

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Regular ArticleRemoval of Confounding Effects of Global Signal in Functional MRI Analyses☆

Abstract

NeuroImage

NeuroImage

NeuroImage

NeuroImage

Electroencephalogr. Clin. Neurophysiol.

Electroencephalogr. Clin. Neurophysiol.

Electroencephalogr. Clin. Neurophysiol.

Electroencephalogr. Clin. Neurophysiol.

NeuroImage

NeuroImage

Temporal dynamics of brain activation during a working memory task

Nature

Human Brain Function

Regular Article
Removal of Confounding Effects of Global Signal in Functional MRI Analyses☆