In the first three pioneer studies, the BOLD-contrast fMRI has been independently demonstrated in noninvasively mapping in vivo neurophysiologic changes due to either visual stimulation [3, 4] or motor tasks [5]. In all these three experiments as well as numerous fMRI studies that followed, the brain regions engaged in performing a task or processing a stimulus demonstrate increased BOLD signals relative to the resting state, namely the positive BOLD response (PBR). The PBR is widely believed to result from the over-compensation of oxygen usage by the cerebrovascular system, which causes a regional hemodynamic influx in excess of the oxygen consumption of the activated neuronal tissue [6, 7]. In fact, the BOLD signal reflects the combined effect of CBF, CBV and CMRO2 [30]. Several models have been proposed to describe the BOLD signal as a function of the neural activity-induced changes in CBF, CBV and CMRO2 [30–35]. Qualitatively, the CBF contributes positively to the BOLD signal while the CBV and CMRO2 have negative contributions; yet such relationships are not necessarily linear.
