🩸 Oxygen and the BOLD signal

Follow the chain from active neurons to blood flow to a brighter MR signal.

Runs in real time: watch how late the signal follows.

1. Neurons more active
2. Blood flow rises, more than oxygen use
3. Deoxyhemoglobin falls in the veins
4. Magnetic field less disturbed
5. MR signal slightly brighter

oxyhemoglobin (carries oxygen) deoxyhemoglobin (oxygen given up) active neuron

BOLD signal change, last 40 seconds

Shaded: stimulus on. The size (about 1 %) is typical for 3 T; the model is simplified (see below).

Oxyhemoglobin

Haemoglobin carrying oxygen; bright red.
Diamagnetic: almost no effect on the magnetic field, like the tissue around it.
More of it in a voxel: the signal fades a little more slowly.

Deoxyhemoglobin

Haemoglobin that has given up its oxygen; darker.
Paramagnetic: makes small field distortions around vessels, so nearby protons fall out of step faster (shorter T2*).
It is the body's own contrast agent: less of it, brighter BOLD signal.

How to read this

Switch the stimulus on (think of a flickering checkerboard in front of the visual cortex) and follow the five steps:

The neurons become more active straight away and need more energy.
Over the next seconds, oxygen use rises a little and local blood flow rises much more (roughly 2–4 times more, in relative terms).
So fresh, oxygen-rich blood washes out the deoxyhemoglobin: the veins end up less deoxygenated than at rest.
Deoxyhemoglobin is what disturbs the magnetic field, so there is less disturbance.
Protons stay in step a little longer (longer T2*), and the MR signal gets about 1 % brighter, peaking about 5 s after the change.

The key point: fMRI measures this blood oxygen change, an indirect and slow proxy for neural activity, not the neurons firing themselves.

What is simplified: oxygen use (20 % above rest) and blood flow (60 % above rest) both follow the canonical HRF, and the signal is taken as proportional to the drop in venous deoxyhemoglobin. So the model shows no initial dip (small and debated in real data). Real responses also involve changes in blood volume, and vary by region and person.

Key terms

BOLD: Blood-oxygen-level-dependent contrast: the MR signal change caused by changes in deoxyhemoglobin.
Neurovascular coupling: The link between neural activity and local changes in blood flow.
CBF: Cerebral blood flow: how much blood passes through the tissue per minute.
CMRO2: Cerebral metabolic rate of oxygen: how much oxygen the tissue uses.
Paramagnetic: Slightly attracted by a magnetic field and distorting it nearby (deoxyhemoglobin).
Diamagnetic: Very slightly repelled; little effect on the field (oxyhemoglobin, most tissue).

Sources

Ogawa S., Lee T. M., Kay A. R., Tank D. W. (1990). Brain magnetic resonance imaging with contrast dependent on blood oxygenation. PNAS 87(24): 9868–9872.
Fox P. T., Raichle M. E. (1986). Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. PNAS 83(4): 1140–1144.
Buxton R. B. (2013). The physics of functional magnetic resonance imaging (fMRI). Reports on Progress in Physics 76(9): 096601.

Used in lesson 4 of fMRI from zero.