fMRI In 1000 Words

By Neuroskeptic | May 24, 2010 1:48 pm

I thought I’d write a short and simple intro to how fMRI works. Most such explanations start with the physics of Magnetic Resonance Imaging and eventually explain how it lets you look at brain activity. I’m doing it the other way round, because I like brains more than physics.

So – everyone knows that fMRI is a way of measuring neural activation. But what does it mean for a neuron to be active? All brain cells are “active”: they’re alive, firing electrical action potentials, and sending out neurotransmitters to other cells at synapses. If a certain cell gets more activated, that means that it’s firing action potentials faster, or sending out more chemical signals. It’s mostly synaptic activity which fMRI picks up.

How do you measure neural activation? You can do it directly by sticking in an electrode to measure action potentials, or use a glass tube to measure neurotransmitter levels. You can put electrodes on the scalp to pick up the electrical fields created by lots of neurons firing. But fMRI relies on an indirect approach: when a brain cell is firing hard, it uses more energy than when it’s not.

Cells make energy from sugar and oxygen; oxygen is transported in the blood. So when a given cell is working hard, it uses more oxygen, and the oxygen content of nearby blood falls. Synaptic activity, in particular, uses loads of oxygen. So you might expect that highly active parts of the brain would have less oxygen. Counter-intuitively, they actually show an increase in blood oxygen, which is probably a kind of “overcompensation” for the activity (although there may be an “initial dip” in oxygen, it’s very brief.)

So blood oxygen is a proxy for activation. How do you measure it? Oxygen in blood binds to haemoglobin, a protein that contains iron (which is why blood is red, like rust, and tastes metallic…like iron). By a nice coincidence, haemoglobin with oxygen is red; haemoglobin without oxygen is blueish or purple. This is why your veins, containing deoxygenated blood, are blue and why you turn blue if you’re suffocating.

You could measure neural activity by literally looking to see how red the brain is. This is actually possible, but obviously it’s a bit impractical. Luckily, as well as being blue, deoxygenated haemoglobin acts as a magnet. So blood is magnetic, and the strength of its magnetic field depends on how oxygenated it is. That’s really useful, but how do you measure those magnetic fields?

Using an extremely strong magnet – like the liquid-helium-cooled superconducting coil at the heart of every MRI scanner, for example – you can make some of the protons in the body align in a special way. If you then fire some radio waves at these aligned protons, they can absorb them (“resonate”). As soon as you stop the radio waves, they’ll release them back at you, like an echo – which is why the most common form of fMRI scan is called Echo-Planar Imaging (EPI). All matter contains protons; in the human body, most of them are found in water.

Each proton only responds to a specific frequency of radio waves. This frequency is determined by the strength of the magnetic field in which it sits – stronger fields, higher frequencies. Crucially, the magnetic fields surrounding deoxygenated blood therefore shift the radio frequency at which nearby protons respond. Suppose a certain bit of the brain resonates at frequency X. If some deoxygenated blood appears nearby, it will stop them from responding to that frequency – by making them respond to a different one.

fMRI is essentially a way of measuring the degree to which protons in each part of the brain don’t respond at the “expected” resonant frequency X, due to interference from nearby deoxygenated haemoglobin. But how do you know what resonant frequency to expect? This is the clever bit: simply by varying the magnetic field across different parts of the brain.

Say you make the magnetic field at the left side of the head slightly stronger than the one at the right – a magnetic gradient. The resonant frequency will therefore vary across the head: the further left, the higher the frequency. This is what the “gradient coils” in an MRI machine do.

Gradient coils therefore translate spatial location into magnetic field strength. And as we know, magnetic field strength = resonant frequency. So spatial location = magnetic field strength = resonant frequency. All you then need to do is to hit the brain with a burst of radio waves of all different frequencies – a kind of white noise called the “RF Pulse” – and record the waves you get back.

The strength of the radio waves at a given frequency therefore corresponds to the amount of protons in the appropriate place – so you can work out the density of matter in the brain based on the frequencies you get. Also, different kinds of tissues in the body respond differently to excitation; bone responds differently to brain grey matter, for example. So you can build up an image of brain structure by using magnetic gradients.

Of course you can’t scan the whole brain at once: you scan it in slices, divided up into roughly cubic units called voxels. Typically in fMRI these are 3x3x3 mm or so, but they can be much smaller for specialized applications. The smaller the voxels, the longer the scan takes because it requires more gradient shifting. The loud noises that occur during MRI scans are caused by the gradient coils changing the gradients extremely quickly in order to scan the whole brain. Modern scanners typically image the whole brain once every 3 seconds, but you can go even faster.

As we’ve seen, deoxygenated blood degrades the image nearby, in what’s called the Blood Oxygenation Level Dependent (BOLD) response. Neural activation increases oxygen and literally makes the brain light up; you could, in theory, see the changes with the naked eye. In fact, they’re tiny, and there is always a lot of background noise as well, so you need statistical analysis to determine which parts light up, and then map this onto the brain as colored blobs. But that’s another story…

  • petrossa

    Still all that does is show level of activity. It doesn't tell you anything about what that activity is busy doing. Even when it happens in a well mapped part of the brain, you still don't know what the activity is doing there. It might be busy inhibiting other activity, which you can't see because that falls below the threshold due to the focal area you chose, or as a direct effect of the inhibition.
    So, to me, it seems the fMRI in it's current state is only good for very coarse deductions, and nowhere near good enough to make anything more then educated guesses as to higher functions.

    But then again, i not a neurophysicist

  • BrianW

    “It's mostly synaptic activity which fMRI picks up.”

    This sentence sounds strange to me. Synaptic activity correlates well with the BOLD signals from fMRI, though it isn't picked up directly. Also, if it's “mostly” synaptic activity being picked up, what else is picked up?

  • Ori

    Thanks for this! It was probably trivial for many of your readers, but it wasn't for me.

  • Neuroskeptic

    Ori: Thanks!

    BrianW: That was a bit of a clumsy phrase… I meant that the main driver of energy use in neurons is synaptic activity, as opposed to action potential spiking. So fMRI mainly (although not entirely) picks up synaptic activity. Which is, AFAIK, the current opinion among people who study the physiology of BOLD. (Although in fact BOLD measures the body's reaction to the increased energy i.e. the increase in blood O2).

  • Anonymous

    Sorry guys and gals. fMRI = Modern Day Phrenology.

  • David
  • George Larson

    Fascinating stuff! Great write up. The most thorough explanation of fMRI that I've read.

    This week I've been reading a lot about the possibility of information processing taking place in glial cells. Would that be visible with an fMRI?

  • Neuroskeptic

    Well… if glia use oxygen (which they do, being cells) they'll affect the MRI signal. However whether they can “activate” and “deactivate” like neurons can, and thereby drive differences in BOLD that show up on fMRI, I don't know.

  • Patrick Hurley, PhD

    Thanks for the really clear explanation. Do you ever delve into other types of neuroimaging techniques? I know that fMRI is heavy in terms of use in the basic side, but what about clinical applications?

  • Michael Meadon

    Excellent post, thanks.

  • peard33

    Here's a look at some of the real-life applications of fMRI technology in court cases.

    Paresh Dave, executive producer of USC Anennberg's Neon Tommy

  • Anonymous

    Very nice article, but there are a few inaccuracies:

    * Deoxygenated blood is not blue, as pointed out above. It's dark red.

    * Deoxygenated hemoglobin does not act as a magnet, any more than your refrigerator door does. Like steel, it is paramagnetic, which means it can concentrate magnetic fields.

    * Protons do not produce “echoes” spontaneously when radio waves are turned off. They will store energy until they are again stimulated to produce an echo. The sequence of stimulation determines the type of echo, which is why echoes can convey different types of information about the proton depending on the sequence used.

    * Protons near deoxygenated hemoglobin resonate like their neighbors when an RF pulse is applied, and many MRI sequences have no problem detecting their signal. fMRI exploits their faster rate of signal decay, essentially letting those protons escape undetected.

    * Gradients switch very fast, and they are not usually rate-limiting. The relationship between voxel size and scan time is like the relationship between shutter duration and film speed. It only take a few mouse clicks to acquire MRI in a very short time with very small voxels, but the result will always be very noisy – just like a picture snapped with a fast shutter and large film grains (high ISO). Typically, fMRI is designed to sacrifice spatial resolution for very high temporal resolution and adequate signal/noise ratios.

  • Anonymous

    Above you say that increased cell energy consumption leads to a local increase in blood oxygenation. While this may often be the case, a paper by Devor and colleagues a few years ago showed that the opposite can happen (i.e., increased energy consumption can lead to a decrease in blood oxygenation/flow). See

    Thanks for the nice write up.

  • muebles

    I believe everyone must look at this.


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About Neuroskeptic

Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.


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