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.
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