Origins of the Resting-State Functional MRI Signal: Potential Limitations of the “Neurocentric” Model

Resting-state functional connectivity (rsFC) is emerging as a research tool for systems and clinical neuroscience. The mechanism underlying resting-state functional MRI (rsfMRI) signal, however, remains incompletely understood. A widely held assumption is that the spontaneous fluctuations in blood oxygenation level-dependent (BOLD) signal reflect ongoing neuronal processes (herein called “neurocentric” model). In support of this model, evidence from human and animal studies collectively reveals that the spatial synchrony of spontaneously occurring electrophysiological signal recapitulates BOLD rsFC networks. Two recent experiments from independent labs designed to specifically examine neuronal origins of rsFC, however, suggest that spontaneously occurring neuronal events, as assessed by multiunit activity or local field potential (LFP), although statistically significant, explain only a small portion (∼10%) of variance in resting-state BOLD fluctuations. These two studies, although each with its own limitations, suggest that the spontaneous fluctuations in rsfMRI, may have complex cellular origins, and the “neurocentric” model may not apply to all brain regions.