30 April 2012
What can brain scans—functional magnetic resonance imaging (fMRI)—tell us?
To state my biases up front, magnetic resonance is one of my favorite analytical tools.
When I worked in an organic synthesis lab, I used nuclear magnetic resonance at the end of each reaction to identify my compound. I owed a debt to NMR for saving my tail in this regard.
But I also have a fascination with the theory behind magnetic resonance because it was one of the first analytical techniques whose theory was based on quantum mechanical principles.
Magnetic resonance comes in many forms based on the sample type that you wish to study. Nuclear magnetic resonance is used to study molecules and is so named because it is investigating how particular nuclei in particular environments behave in the presence of a magnet.
Usually my work involved looking at hydrogen nuclei; however, there is also carbon-13 NMR as well as fluorine-19. The more common use of magnetic resonance is in the medical field using magnetic resonance imaging (MRI). With MRI, the sample is a human being rather than a small tube of chemicals, and rather than spitting out a series of peaks on a piece of paper, MRI spits out an image of the particular part of the body under investigation.
Functional magnetic resonance imaging specifically looks at the brain and is so named because it is looking at brain activity (function). In this two-part series, we will look at the history of brain scans, and functional magnetic resonance imaging, in particular. Then we will look at how fMRI works, whether it can actually see what you are thinking, and accomplishments and limitations of fMRI. Lastly, we will evaluate the assumptions behind many of the conclusions drawn from fMRI.
History of functional brain scans
Interest in brain scans and the relationship between metabolism and cognitive activity dates back to the mid-nineteenth century. Scientists conducted studies that demonstrated a change in blood volume in specific areas of the brain. In 1890 William James wrote about experiments to determine blood volume in The Principles of Psychology in which he assumed brain activity is related to changes in blood flow.
Charles S. Roy and Charles S. Sherrington (right) are noted for their experiments which attempted to demonstrate that cerebral blood flow not only occurs in the brain but is also locally regulated. This was a debated theory at the time, with the other side assuming that changes in blood flow were due to changes in blood pressure or cardiac output, not from neural activity. Roy and Sherrington’s experiments had several issues that caused people to question their results, including the fact that they were looking at a dog under anesthesia with a portion of his skull removed to observe blood flow—obviously not the brain’s natural environment. However, their work did seem to indicate that cerebral blood flow was independent of blood pressure and other bodily factors outside the brain. Whether cerebral blood flow is a result of cognition or was due to other factors was debated until 1948.
In 1948 Seymour Kety conducted studies with nitrous oxide gas (based on an idea called the Fick Principle) to determine cerebral blood flow in a non-anesthetized patient. Essentially Kety, working with Carl Schmidt, had the patient breath nitrous oxide, and by relating organ metabolism to blood flow was able to quantitatively determine cerebral blood flow as well as quantify the cerebral metabolic rates of oxygen. In follow-up experiments using the same techniques, Kety and Schmidt definitively determined that the brain regulates oxygen metabolism and therefore cerebral blood flow is due to some intrinsic activity of the brain.
At this point in history, scientists were still unable to study localized areas of the brain, but Kety and Schmidt’s studies made this a tantalizing possibility. Scientists conducting earlier studies of patients with brain injuries were suspicious that certain regions of the brain regulated certain functions. For example, a patient who had suffered a brain injury on the left side of the brain may also have difficulty speaking. However, other patients with injuries in other areas of the brain may suffer different losses in function, suggesting that certain regions of the brain control certain functions. Even at this time, though, and as scientists later found, not every patient responded the same way to regional stimulus. (See here for additional background on the history of Kety and Schmidt and here for more information on the history of fMRI.)
What does fMRI do and how does it work?
Enter functional magnetic resonance imaging into the picture.
Magnetic resonance—whether your sample is a vial of unknown chemicals, a leg, or a brain—measures the relaxation of aligned nuclei. This sounds more technical than it has to be. Most of us know what a nucleus of an atom is—it’s the central part of the atom that the electrons orbit, similar to the moon orbiting the Earth. The Earth has a small magnetic field—the same field that causes compasses to point due North. Similarly, nuclei have a very small magnetic field. The difference is that any particular nucleus is surrounded by a bunch of other nuclei so their magnetic fields are pointing in different directions, and they all end up canceling each other out.
Well, what if we place a very strong magnet near those nuclei? Their magnetic field would align with the strong magnet. This is what is happening in magnetic resonance imaging, and this is why you can’t have any metals on you when you get an MRI (including certain colors of tattoo ink).
The nuclei that are being measured in MRI and in fMRI are hydrogen nuclei. The hydrogens are in water (H2O). This is how we get the “magnetic resonance” part of MRI. The “imaging” part comes from the idea that different hydrogens are in different environments. This causes bone, soft tissue, and dense tissue to show up differently in imaging. Sometimes, hydrogens are near paramagnetic or magnetic molecules. These molecules have electrons arranged in such a way that the magnetically aligned hydrogen atoms go back to “normal” much slower than they would if they were not near these electrons. When hydrogen atoms go back to “normal,” this is called “relaxation.”
Functional MRI involves imaging the brain while it is thinking or operating, hence the “functional” part of the name. Based on the assumption that blood flow correlates to the particular part of the brain that is operating, fMRI produces images of where an increase of blood flow occurs.
fMRI still measures hydrogen nuclei, but this time the environmental change is based on whether the hydrogen nuclei are near oxygenated or deoxygenated hemoglobin (i.e., blood). And remember, the theory claims that oxygen is related to metabolism which is related to blood flow which is related to neural activity. There is approximately a six-second delay between neural activity and an fMRI reading because of the lag in the brain’s response to oxygen consumption and subsequent blood flow to re-supply the oxygen.
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Next time we will look at the accomplishments and limitations of fMRI, as well as assess the assumptions behind conclusions from brain scans.