The Conversation
I. Neuroimaging
A transformative technology
HB: Since you kindly gave me a tour of your fMRI facilities here at Stanford, let me just dive in and ask some questions about that. How does functional MRI differ from the normal MRI machine that most people are familiar withâfor medical injuries and so forthâand how does it differ from PET scans which people also might have heard of?
KGS: fMRI has really been a revolution in cognitive neuroscience. It started in the early 90s. Itâs the same machine that does the MRI for a knee scan, for example. The only thing is that, instead of measuring the tissue, weâre measuring changes in brain metabolism.
When you use your brain, to do some sensory processing for example, your brain uses oxygen, and changes in oxygenation levels affect the local magnetic field; this is whatâs picked up by the scanner. The patient is placed inside the scanner, his or her head is placed in a coil, and this coil picks up signals in the brain that are linked to neural activation in the regions that are activated by whatever task the person is doing.
HB: When I first heard about fMRI I was confused about that because I thought, Oh, theyâre measuring the brain, so they must be measuring the electrical signals. Of course what theyâre doing is measuring, just as you said, the oxygen related to the blood supply thatâs flowing into specific brain areas because of neural activity.
KGS: Yes. Weâre not measuring direct neural activity. Weâre measuring a BOLD signal, a blood-oxygen-level-dependent signal. In fact, you might think there would be less oxygen because youâve used it for the metabolism, but the brain overcompensates so you get an overflow of oxygenated haemoglobin. Really what we are picking up with a scanner is the amount of deoxygenated haemoglobin, and that actually gets washed off; this is why the signal goes up. So itâs an indirect measure of brain activity.
The reason that itâs different from PETâpositron emission tomographyâis that itâs non-invasive. For PET you need to inject subjects with a radioactive material. Thatâs an invasive procedure. With fMRI you donât inject anything. This has really been the power of fMRI technology because you can study the same person and run the experiments over and over again, or over time, or over development, or over the lifespan. This has been a really big breakthrough because you can peer into peopleâs brains without doing anything to them invasively.
HB: And this was developed in the early 90s?
KGS: The first fMRI papers were published in Proceedings of the National Academy of Science of the USA in 1992. There were two groups that did this in parallel. One was a group at Bell Labs led by Seiji Ogawa. The other group was at Massachusetts General Hospital and the first author on that paper was Ken Kwong. Basically they conducted the first experiments where they showed people pictures versus no picturesâthey had flashing checkerboardsâand they could see an increase in the back of the brain where the visual cortex is located when people saw stuff versus when they didnât.
HB: So in your own studies, subjects go into this machine and you have them focused on doing particular tasks and thinking about particular things, or seeing particular things. How long do they stay in there for, in general?
KGS: They usually stay between an hour and two. Usually what weâll do is put the subject in the scanner and first run a brain anatomy scan. The reason we want to see their brain anatomy is because we are interested in which part of their brain is involved in what function. This allows us to createâIâll show you laterâthese beautiful cortical reconstructions in which we can see the brain from all three dimensions, because the way we acquire information in the scanner is in slices, like in a CT scan, so we can get the 3D reconstruction. That takes about five to ten minutes. Thatâs called just MRI, anatomical MRI.
HB: Let me just stop you there for a moment. Does this mean that peopleâs brain anatomy differs significantly? I would have thought that this would be relatively constant. But itâs not?
KGS: There are two things to consider here. The first is that, as a field, we are interested in how brain anatomy does change. I, for example, am looking at how it might change from childhood to adulthood. There are some things that will happen as a result of certain diseases, like Alzheimerâs disease for example, where there are actually changes to the brain anatomy because of the disease.
The second point is that we want to look really closely at how function is implemented in each personâs brain. So your brain and my brain have the same general pattern of what we call cortical foldingâthere are hills and valleysâbut there are idiosyncrasies for each brain and we really want to understand the relationship between function and anatomy in each personâs brain. So we want to take a detailed picture of every subjectâs brain.
HB: So there is really significant variation between different people? Thatâs fascinating. I never would have thought that.
KGS: On one hand there is variety; on the other hand there is stability. One of the things weâre trying to figure out is what is stable and what is variable across people. There is more variety than, for example, the hand; there are always five fingers on your hand. There is a little bit more variety in the number of cortical folds, but the big ones are very stable across people.
HB: Rightâbut I had interrupted you. You were telling me that these anatomical scans were the first things that you do.
KGS: Thatâs the first thing we do and that takes between five to ten minutes. Sometimes we do another kind of scan called diffusion tensor imaging or diffusion weighted imaging. That lets us measure how water diffuses in the brain. We do this to look at the wiring of the brainâwhich part of the brain is connected to another part of the brain. There are these really big white matter bundles; theyâre called fascicles. Because they are myelinated, they are very directional, so the water doesnât diffuse in all directions.
HB: Hold on a sec. Where is the water in my brain?
KGS: Your brain is all water.
HB: Thatâs not just my brain presumably?
KGS: Actually, all we are measuring in fMRI is how the magnetic field affects the water molecules. Weâre measuring hydrogen atoms basically. Because the water doesnât propagate freely, most of the direction of diffusion will be parallel to the fascicle, and we can measure the connectivity, the white matter connection, between one part of the brain and another part of the brain. This is another ty...