Save the Global: Global Signal Connectivity as a Tool for Studying Clinical Populations with Functional Magnetic Resonance Imaging

Abstract

The global signal is commonly removed from resting-state data, as it was presumed to reflect physiological noise. However, removal of the global signal is now under debate, as this signal may reflect important neuronal components, and its removal may introduce artifacts into the data. Here, we show that the functional connectivity (FC) of the global signal is of functional relevance, as it differentiates between schizophrenia patients and healthy controls during rest. We also demonstrate that other reported findings related to various clinical populations may actually reflect alternations in global signal FC. The evidence of the clinical relevance of the global signal propose its usage as a research tool, and extend previously reported perils of global signal removal in resting-state data of clinical populations.

Functional hierarchy underlies preferential connectivity disturbances in schizophrenia

“…6 F-I, brown vs. cyan), suggesting that differences in recurrent local self-excitation (implemented by setting network-specific scalar multipliers of E-E weights: w A > w S ) drove these effects, rather than differences in anatomical connectivity. Critically, these additional model-generated effects extend predictions to another functional measure, namely BOLD signal variance, previously implicated in SCZ (18,59). Consequences of functional differentiation on model baseline activity are presented in SI Appendix, Fig.…”

“…This does not include the variance of the region itself. Although the maximum covariance necessarily places a lower bound on the variance of each region, there could be important differences in the BOLD signal variance between SCZ and HCS, as implicated in previous studies (18,59). We therefore repeated our analysis, replacing the GBC with local variance, finding comparable results.…”

The Whole-Brain “Global” Signal from Resting State fMRI as a Potential Biomarker of Quantitative State Changes in Glucose Metabolism

“…They observed greater variance in the eyes closed state, which may correspond to the lower mean correlation observed here. Schizophrenia shows increased cortical power and variance across the whole brain (Yang et al, 2014) and lower global brain connectivity overall (Hahamy et al, 2014). Obsessive-compulsive disorder shows changes in local areas in terms of how closely they relate to the global signal (Anticevic et al, 2014).…”

Increased short-range and long-range functional connectivity in first-episode, medication-naive schizophrenia at rest

“…Several nuisance signals, along with their temporal derivatives, including six head motion parameters obtained by rigid body correction, the signal from a ventricular ROI, and the signal from a region centered in white matter, were regressed out from the data (Fox et al, 2005;Liu et al, 2015). However, the global mean signal was not regressed out for the reason that it is suggested to be saved in analyzing the FC data (Hahamy et al, 2014).…”