Global Cerebral Oxidative Metabolism during Hypercapnia and Hypocapnia in Humans: Implications for BOLD fMRI

The effect of carbon dioxide (CO 2 ) 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 (ΔCMRO 2 ), and relies on the assumption of a stable CMRO 2 during CO 2 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 ΔCMRO 2 measurements made noninvasively in humans during graded hypercapnia and hypocapnia. We used computerized end-tidal CO 2 modulation to minimize undesired concurrent changes in oxygen pressure, and our findings suggest that no significant change in global CMRO 2 is expected at the levels of end-tidal CO 2 changes customary to calibrated BOLD.