Global cerebral oxidative metabolism during hypercapnia and hypocapnia in humans: implications for BOLD fMRI

The effect of carbon dioxide (CO2) on cerebral metabolism is of tremendous interest to functional imaging. In particular, mild-to-moderate hypercapnia is routinely used in calibrated blood oxygen-level dependent (BOLD)-functional magnetic resonance imaging (fMRI)-based quantification of cerebral oxidative metabolism changes (ΔCMRO2), and relies on the assumption of a stable CMRO2 during CO2 challenges. However, this assumption has been challenged by certain animal studies, necessitating its verification in humans and under conditions customary to fMRI. We report, for the first time, on global ΔCMRO2 measurements made noninvasively in humans during graded hypercapnia and hypocapnia. We used computerized end-tidal CO2 modulation to minimize undesired concurrent changes in oxygen pressure, and our findings suggest that no significant change in global CMRO2 is expected at the levels of end-tidal CO2 changes customary to calibrated BOLD.