BOLD signal changes can oppose oxygen metabolism across the human cortex

Abstract

Functional MRI measures brain activity by monitoring changes in blood oxygen levels, known as the blood-oxygen-level-dependent (BOLD) signal, rather than measuring neuronal activity directly. This approach crucially relies on neurovascular coupling, the mechanism that links neuronal activity to changes in cerebral blood flow (CBF). However, it remains unclear whether this relationship is consistent for both positive and negative BOLD responses across the human cortex. Here we found that about 40% of voxels with significant BOLD signal changes during various tasks showed reversed oxygen metabolism, particularly in the default mode network. These "discordant" voxels differed in baseline oxygen extraction fraction (OEF) and regulated oxygen demand via OEF changes, while "concordant" voxels depended mainly on CBF changes. Our findings challenge the canonical interpretation of the BOLD signal, indicating that quantitative fMRI provides a more reliable assessment of both absolute and relative changes in neuronal activity.