Two distinct modes of hemodynamic responses in the human brain

Abstract

ABSTRACTFunctional magnetic resonance imaging (fMRI) detects changes in brain activity by measuring fluctuations in blood oxygenation. While fMRI assumes a fixed relationship between changes in cerebral blood flow (CBF) and metabolic activity, its uniform application across the human cortex lacks complete validation. We used quantitative fMRI together with blood oxygenation level-dependent (BOLD) fMRI to assess oxygen metabolism against both positive and negative BOLD signal changes. We found a surprising mismatch between changes in oxygen consumption and the direction of BOLD signal changes (ΔBOLD) in 14-33% of voxels with significant positive, and in 50-66% of voxels with significant negative ΔBOLD. This implies that a substantial number of voxels with negative ΔBOLD actually demonstrate increased metabolic activity, and vice versa. Contrary to the canonical hemodynamic response model, discordant voxels cover their oxygen demand predominantly via changes in the oxygen extraction fraction (ΔOEF) and not via ΔCBF. This coincides with a higher vascular density and a lower OEF during baseline that we identified in discordant voxels. In summary, we identified a second type of hemodynamic response mechanism for regulating oxygen supply in the human brain. Our results suggest that the classical interpretation of positive and negative BOLD signal changes in terms of increased or decreased neural activity may be too simplistic and we recommend incorporating quantitative MRI or additional CBF measurements for a more accurate assessment of neuronal activity.