Global signal regression acts as a temporal downweighting process in resting-state fMRI.
UNLABELLED Spontaneous activity observed with resting-state fMRI is used widely to uncover the brain's intrinsic functional networks in health and disease. Although many networks appear modular and specific, global and nonspecific fMRI fluctuations also exist and both pose a challenge and present an opportunity for characterizing and understanding brain networks. Here, we used a multimodal approach to investigate the neural correlates to the global fMRI signal in the resting state. Like fMRI, resting-state power fluctuations of broadband and arrhythmic, or scale-free, macaque electrocorticography and human magnetoencephalography activity were correlated globally. The power fluctuations of scale-free human electroencephalography (EEG) were coupled with the global component of simultaneously acquired resting-state fMRI, with the global hemodynamic change lagging the broadband spectral change of EEG by ∼5 s. The levels of global and nonspecific fluctuation and synchronization in scale-free population activity also varied across and depended on arousal states. Together, these results suggest that the neural origin of global resting-state fMRI activity is the broadband power fluctuation in scale-free population activity observable with macroscopic electrical or magnetic recordings. Moreover, the global fluctuation in neurophysiological and hemodynamic activity is likely modulated through diffuse neuromodulation pathways that govern arousal states and vigilance levels. SIGNIFICANCE STATEMENT This study provides new insights into the neural origin of resting-state fMRI. Results demonstrate that the broadband power fluctuation of scale-free electrophysiology is globally synchronized and directly coupled with the global component of spontaneous fMRI signals, in contrast to modularly synchronized fluctuations in oscillatory neural activity. These findings lead to a new hypothesis that scale-free and oscillatory neural processes account for global and modular patterns of functional connectivity observed with resting-state fMRI, respectively.