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BOLD signal changes can oppose oxygen metabolism across the human cortex

Samira Epp, Gabriel Castrillón, Beijia Yuan, Jessica R. Andrews‐Hanna, Christine Preibisch, Valentin Riedl

2025Nature Neuroscience20 citationsDOIOpen Access PDF

Abstract

Functional magnetic resonance imaging measures brain activity indirectly by monitoring changes in blood oxygenation levels, known as the blood-oxygenation-level-dependent (BOLD) signal, rather than directly measuring neuronal activity. This approach crucially relies on neurovascular coupling, the mechanism that links neuronal activity to changes in cerebral blood flow. 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 and regulated oxygen demand via oxygen extraction fraction changes, whereas 'concordant' voxels depended mainly on cerebral blood flow changes. Our findings challenge the canonical interpretation of the BOLD signal, indicating that quantitative functional magnetic resonance imaging provides a more reliable assessment of both absolute and relative changes in neuronal activity.

Topics & Concepts

Functional magnetic resonance imagingVoxelNeuroscienceHuman brainPremovement neuronal activityBlood-oxygen-level dependentCerebral blood flowChemistryBlood oxygenationOxygenationMagnetic resonance imagingSIGNAL (programming language)OxygenNeuroimagingFunctional imagingCerebral cortexBrain mappingSomatosensory systemCortex (anatomy)Human bloodFunctional magnetic resonance spectroscopy of the brainNuclear magnetic resonanceElectrophysiologyBlood flowResting state fMRIOxygen metabolismBrain activity and meditationNeurovascular bundleVisual cortexAdvanced MRI Techniques and ApplicationsFunctional Brain Connectivity StudiesOptical Imaging and Spectroscopy Techniques
BOLD signal changes can oppose oxygen metabolism across the human cortex | Litcius