A hypercapnia-based normalization method for improved spatial localization of human brain activation with fMRI

An issue in blood oxygenation level dependent contrast-based functional MRI is the accurate interpretation of the activation-induced signal changes. Hemodynamic factors other than activation-induced changes in blood oxygenation are known to contribute to the signal change magnitudes and dynamics, and therefore need to be accounted for or removed. In this paper, a general method for removal of effects other than activation-induced blood oxygenation changes from fMRI brain activation maps by the use of hypercapnic stress normalization is introduced. First, the effects of resting blood volume distribution across voxels on activation-induced BOLD-based fMRI signal changes are shown to be significant. Second, the effects of hypercapnia and hypoxia on resting and activation-induced signal changes are demonstrated. These results suggest that global hemodynamic stresses may be useful for non-invasive mapping of blood volume. Third, the normalization technique is demonstrated.