Origin of the Time Lag Phenomenon and the Global Signal in Resting-State fMRI.

The global mean signal of resting-state fMRI (rs-fMRI) shows a characteristic spatiotemporal pattern that is closely related to the pattern of vascular perfusion. Although being increasingly adopted in the mapping of the flow of neural activity, the mechanism that gives rise to the BOLD signal time lag remains controversial. In the present study, we compared the time lag of the global mean signal with those of the local network components obtained by applying temporal independent component analysis to the resting-state fMRI data, as well as by using simultaneous wide-field visual stimulation, and demonstrated that the time lag patterns are highly similar across all types of data. These results suggest that the time lag of the rs-fMRI signal reflects the local variance of the hemodynamic responses rather than the arrival or transit time of the stimulus, whether the trigger is neuronal or non-neuronal in origin as long as it is mediated by local hemodynamic responses. Examinations of the internal carotid artery signal further confirmed that the arterial signal is tightly inversely coupled with the global mean signal in accordance with previous studies, presumably reflecting the blood flow or blood pressure changes that are occurring almost simultaneously in the internal carotid artery and the cerebral pial/capillary arteries, within the low-frequency component in human rs-fMRI.