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Functional connectivity

Can BOLD go up when the brain uses less oxygen?

Epp SM, Castrillón G, Yuan B, et al. · Nature neuroscience · 2026

Open access · cc by · source: Europe PMC

In 40 healthy adults, about 40% of voxels with significant BOLD changes—especially in default-mode network—showed oxygen metabolism moving the opposite way.

Study at a glance

Design
Human experiment — BOLD plus quantitative fMRI (CBF/CBV/OEF/CMRO2) during calculation, memory, control, and rest tasks in healthy adults
N
N=40 · 47 enrolled; 40 analysed (22 women, 18 men; mean age 32.1±9.2); CBV subset n=10; control study n=18
Population
Healthy right-handed adults performing cognitive tasks in the scanner
Outcome
Whether BOLD signal direction matches oxygen-metabolism (CMRO2) changes across cortex, especially default-mode network

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Key findings

~40% of significant BOLD voxels were discordant, often in DMN. Discordant voxels had different baseline OEF and used OEF changes to meet oxygen demand; concordant voxels relied mainly on CBF. Authors argue quantitative fMRI better tracks neuronal activity.

Methodology

Collected BOLD and quantitative fMRI while people did calculation, autobiographical memory, control, and rest tasks, then classified voxels as concordant or discordant for ΔBOLD vs ΔCMRO2.

Limitations

Healthy-adult task fMRI does not rewrite every clinical BOLD study; it shows canonical neurovascular coupling is not uniform across cortex.

How this study connects

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