Beyond noise to function: reframing the global brain activity and its dynamic topography

Abstract

How global and local activity interact with each other is a common question in complex systems like climate and economy. Analogously, the brain too displays 'global' activity that interacts with local-regional activity and modulates behavior. The brain's global activity, investigated as global signal in fMRI, so far, has mainly been conceived as non-neuronal noise. We here review the findings from healthy and clinical populations to demonstrate the neural basis and functions of global signal to brain and behavior. We show that global signal (i) is closely coupled with physiological signals and modulates the arousal level; and (ii) organizes an elaborated dynamic topography and coordinates the different forms of cognition. We also postulate a Dual-Layer Model including both background and surface layers. Together, the latest evidence strongly suggests the need to go beyond the view of global signal as noise by embracing a dual-layer model with background and surface layer.

Fig. 1. GS topography during resting state.

A reliable relationship between GS and cortical regions has been observed across various studies^,,–,–. In general, the primary sensory regions (i.e., sensorimotor and visual cortex) show higher correlations with GS (as indicated by the more yellow color), and the higher-order cortical regions show low correlations with GS (as indicated by the red color).

Fig. 2. Altered GS topography in different psychiatric disorders.

The GS topography is significantly altered in the different phases of bipolar disorder, with increased GSCORR in hippocampus (and parahippocampus/fusiform gyrus) in bipolar depression and motor cortex in bipolar mania (from Zhang et al.). In major depressive disorder, the GS topography is increased in default-mode regions that shows abnormally strong global functional connectivity with all other regions, i.e., non-DMN in the rest of the brain (from Scalabrini et al.). GS Global signal, GSCORR Global signal correlation, C Control group, D Depression, M Mania, E Euthymic, MDD Major depressive disorder, HC Healthy control, GSR Global signal regression.

Fig. 3. Two interpretations of GS topography.

Interpretation 1 suggests that the GS topography is the degree of the phase coherence between global and local activity. Interpretation 2 suggests that the GS topography is constituted by the co-activation patterns (CAPs) of different networks as being phase-locked to the peak of GS, i.e., the instantaneous CAPs with zero-phase lag to GS. Global signal GS; Co-activation patterns CAPs.

Fig. 4. Single-layer model (SLM) vs. Dual-layer model (DLM) of GS.

a The SLM of GS suggests that the GS stems from physiological signal like respiration and cardiac activity, or subcortical areas like basal forebrain. The cortical topography of GS is a consequence of the representation of these subcortical-cortical sources in the brain. Therefore, cortical GS topography is considered to be a mere manifestation of the subcortical-cortical GS itself with both standing in a one-to-one correspondence. b The DLM of GS suggests that GS is a constellation of neural activities at both a more spatially extended global background layer and a more spatially restricted surface layer featuring co-activation pattern of different networks. The background layer is the global brain activity whose neural signals, through its subcortical-cortical phase-based infraslow fluctuations, are closely coupled with the fluctuations of the bodily physiological signals like respiration, cardiac activity, and are projected from subcortical to whole brain cortical regions. That, in turn, allows for (1) regulating the level of arousal, and (2) the structuring of the dynamic topography of the cortical instantaneous brain networks/co-activation patterns (CAPs) at the surface layer as basis for coordinating different forms of cognition. Co-activation patterns CAPs; Global signal GS.