A Systematic Analysis of the Impact of Hemodynamic, Metabolic and Vascular Factors on the BOLD Signal

In fMRI studies changes in BOLD signal intensities during task activation are related to multiple physiological parameters such as cerebral blood flow (CBF), cerebral blood volume (CBV), and oxidative metabolism (CMRO2), as well as to the regional microvascular anatomy. The aim of the present studies was to systematically analyze the contribution of these factors to BOLD signal changes during neuronal activation. Assuming similarities between the mechanisms responsible for the coupling of CBF to neuronal activation and the increase of CBF during hypercapnia, a global hypercapnic challenge was used to indirectly investigate the regional sensitivity of the BOLD contrast to neuronal activation, which is mainly influenced by the microvascular system and basal CBV. Moreover, a hypercapnic calibration procedure was employed to determine CMRO2 changes during functional activation. Finally, a combined CBF-sensitized and BOLD fMRI technique was used to obtain activation-induced CBF and BOLD signal changes simultaneously. In the first study BOLD signal changes during hypercapnia were significantly different in various cortical regions. The highest BOLD signal changes were found in those regions with dense capillary networks and large basal CBV values, indirectly suggesting that that these factors will also influence the regional sensitivities of the BOLD responses to neuronal activation. A linear relationship between CBF and BOLD signal intensity changes during bilateral finger tapping with 6 different frequencies (0.5–3Hz), as well as significant increases in CMRO2 were found in the second study, supporting the notion that the magnitudes of activation-induced BOLD signal changes are appreciably determined by these two hemodynamic and metabolic factors. In the last study a significantly reduced activation pattern in the primary sensorimotor cortex during finger tapping in a group of old (n=6; mean age 65 years) compared with a group of young subjects (n=6; mean age 27 years) could be put down to the fact that age-dependent changes of the cerebral vasculature alter the neuronal-vascular coupling leading to attenuated BOLD responses in spite of similar neuronal activation. The results of these systematic studies clearly demonstrate that activation-induced BOLD signal changes are determined by several physiological parameters. Potential alterations of these variables, especially in patients with neurological disorders, must be considered to acquire valid data.