title: On the origins of the 'global signal' determined by functional magnetic resonance imaging in the resting state.
abstract: OBJECTIVE
  Functional magnetic resonance imaging blood oxygen level dependent (BOLD) determinations of correlations between 'resting-state' neuronal activity in different regions of cortex have generated much interest. Determination of these correlations requires regressing out signals that are correlated in all parts of the cortex and are taken to be artefactual, such as those due to movement, respiration and cardiovascular activity. However when these are removed there still remains a 'global signal' (GS), which is taken to be of unknown physiological origin, and is regressed out by some researchers but not by others.
  
  
  METHODS
  We have investigated the origin of this GS using cortical models consisting of coupled networks of modules representing regions of interest.
  
  
  RESULTS
  We show that the GS has an amplitude that is linearly related to the average correlation between the modules/voxels in the network over a large range of such correlations. The GS arises as a consequence of feedback between the modules/voxels leading to correlations in their BOLD signals. Given the relationship between the GS and the average correlations it might be anticipated that regressing out the GS during preprocessing will significantly modify the correlations subsequently determined. This is shown to be the case when comparing the connections of individual modules with that predicted by the correlations.
  
  
  CONCLUSIONS
  The present model shows that such correlations can arise as a consequence of the intermodular feedback connectivity without recourse to imposing a GS independent of the connectivity. Our model indicates that the GS reflects the extent of feedback pathways provided by the intermodular/inter-regional connections and hence the average correlation between modules or regions of cortex. However the model has not been used to elucidate the possible contributions of a GS independent of the connectivity, which might indeed contribute to the GS of the cortex.
authors.affiliation: The Brain and Mind Research Institute, University of Sydney, Sydney, NSW, Australia. The Centre for Mathematical Biology, University of Sydney, Sydney, NSW, Australia.
authors.forename: Maxwell R
authors.initials: MR
authors.lastname: Bennett
authors.forename: Les
authors.initials: L
authors.lastname: Farnell
authors.forename: William
authors.initials: W
authors.lastname: Gibson
authors.forename: Jim
authors.initials: J
authors.lastname: Lagopoulos
mesh_terms: D000465:Algorithms; D001931:Brain Mapping / Q000379:methods*; D002540:Cerebral Cortex / Q000502:physiology*; D003198:Computer Simulation; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology*; D010363:Pattern Recognition, Automated / Q000379:methods; D015203:Reproducibility of Results; D012146:Rest / Q000502:physiology; D012680:Sensitivity and Specificity