The influence of moderate hypercapnia on neural activity in the anesthetized nonhuman primate

Hypercapnia is often used as vasodilatory challenge in clinical applications and basic research. In functional magnetic resonance imaging (fMRI), elevated CO(2) is applied to derive stimulus-induced changes in the cerebral rate of oxygen consumption (CMRO(2)) by measuring cerebral blood flow and blood-oxygenation-level-dependent (BOLD) signal. Such methods, however, assume that hypercapnia has no direct effect on CMRO(2). In this study, we used combined intracortical recordings and fMRI in the visual cortex of anesthetized macaque monkeys to show that spontaneous neuronal activity is in fact significantly reduced by moderate hypercapnia. As expected, measurement of cerebral blood volume using an exogenous contrast agent and of BOLD signal showed that both are increased during hypercapnia. In contrast to this, spontaneous fluctuations of local field potentials in the beta and gamma frequency range as well as multiunit activity are reduced by approximately 15% during inhalation of 6% CO(2) (pCO(2) = 56 mmHg). A strong tendency toward a reduction of neuronal activity was also found at CO(2) inhalation of 3% (pCO(2) = 45 mmHg). This suggests that CMRO(2) might be reduced during hypercapnia and caution must be exercised when hypercapnia is applied to calibrate the BOLD signal.