Can BOLD go up when the brain uses less oxygen?

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

Source

BOLD signal changes can oppose oxygen metabolism across the human cortex

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

doi.org/10.1038/s41593-025-02132-9 Read the full paper ↗16 citationscc by

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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What they did

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.

What they found

~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.

The limits

What it doesn't show

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

Key terms

BOLD: Blood-oxygenation-level-dependent fMRI signal from deoxyhemoglobin, not neurons directly.
CMRO2: Cerebral metabolic rate of oxygen—how much oxygen tissue actually uses.
OEF: Oxygen extraction fraction; how much oxygen is pulled from blood.
Discordant voxels: Places where BOLD direction opposes oxygen-metabolism direction.
Default mode network (DMN): Network where many discordant BOLD–metabolism mismatches appeared.
Neurovascular coupling: Assumed link from neuronal activity to blood-flow/BOLD changes.

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BOLD directly measures:

Common questions

Analytic N?

40 right-handed adults (22 women, 18 men; mean age 32.1).

How often did BOLD oppose metabolism?

About 40% of voxels with significant BOLD changes.

Where was discordance common?

Especially in the default mode network.

What did concordant voxels depend on?

Mainly cerebral blood flow changes.