Jan 26 2009

An fMRI Wrinkle

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Functional magnetic resonance imaging, or fMRI, is an extremely useful new technology (created in 1993 and increasingly used over the last decade) to study brain activity. Like any new and complex tool, however, it is critical to understand how the tool works, especially when interpreting research. A new study published today in Nature may cause fMRI researchers to change how they conduct an interpret their research.

fMRI is an application of regular MRI, made possible by advances in computer processing power and researchers finding new ways to exploit how living tissue responds to a powerful magnetic field. In the case of fMRI it was discovered that blood reacts differently when it is highly oxygenated than when it is less oxygenated. This is because oxyhemoglobin (the form of hemoglobin with oxygen) is diamagnetic, while deoxyhemoglobin (the form of hemoglobin without oxygen) is paramagnetic. Most living tissue (and in fact most stuff) is diamagnetic – in response to a strong external magnetic field it creates a weak opposite magnetic field. In superconductors this property can be exploited to create levitation above a strong magnet. A paramagnetic substance, rather, in response to a strong external magnetic field creates an attractive magnetic field. Unlike ferromagnetic materials (like iron), diamagnetic and paramagnetic substances lose their magnetic field as soon as the external field ends – they are not permanent or long-lasting.

All of this means that oxygenated and less oxygenated blood behave differently in the magnetic field of an MRI and this differential response can be exploited to image relative arterial blood flow to different parts of the brain. An entire branch of neuroscientific research has sprung up over this fact – using fMRI to see which parts of the brain are active when subjects are asked to perform a specific task, when they are exposed to external stimuli, or in different disease states.

Of course, using fMRI in such research is based upon the assumption (reasonable, but an assumption none-the-less) that blood flow as imaged by fMRI correlates with brain activity.  This premise is based upon sound physiological knowledge, and also experience from other technologies, such as PET and SPECT scanning, that also image blood flow.

However, it is also this exact premise that is being challenged, at least to a degree, with this new study.

Neuroscientists Yevgeniy Sirotin and Aniruddha Das at Columbia University performed studies on two monkeys. They monitored their brain activity with implanted electrodes and simultaneously monitored their cerebral blood volume and oxygenation with optical methods. They then exposed the monkeys in a dark room to a tiny light at regular intervals and rewarded the monkeys if they fixed their gaze on the light for a few seconds. What they found is that the electrical activity in the visual cortex remained stable (there was not enough light to cause significant activity in the visual cortex),  however the blood flow did rise and fall and peaked a few seconds before the light was to go on.

It seemed in this study that blood flow and cortical activity were not closely correlated. Of course, interpretation is key. As reported in a Science news article:

Although the findings “by no means call into question the whole body of fMRI research,” Das says they should cause fMRI researchers to rethink how they design and interpret their experiments.

I agree this study does not contradict the whole of fMRI research. The usual caveats apply – this was just one study with two subjects, for example. Many studies with various study designs will be necessary to see which variables are important for determining blood flow and cortical activity. But taking these results at face value, what can they mean.

It does not seem as if there was no relationship with blood flow and brain activity. The changes in blood flow were not random – they correlated with the task. One interpretation is that the specific measures of blood flow in this study are more sensitive to changes in brain activity than the electrical recordings.

Another intriguing possibility is that the brain can anticipate its metabolic needs and increase blood flow to parts of the cortex that are about to become active. In this study the light was shown at a regular interval, and the monkeys were being rewarded for fixing their gaze upon it. Perhaps they were anticipating the appearance of the light and priming their visual cortex for the task, but because the light was so small it didn’t actually require that much visual cortical activity.

As is typical for scientific research, this new finding does not so much contradict prior research as add a new level of depth and complexity. There is copious evidence that blood flow tracks with brain activity, but this relationship is probably not as simple as was at first assumed. The good news is that if there in an anticipatory effect, as suggested by this research, then that is something that can be controlled for in the design and interpretation of future fMRI studies.

It also means there is a previously unknown physiological mechanism in the brain for anticipating immediate metabolic needs. This makes sense as the brain is a hungry organ, requiring incredible optimization of delivery of glucose and oxygen as well as a tightly controlled metabolic environment. Even a fleeting drop in blood pressure, or a drop in blood sugar, can cause someone to pass out. Therefore if there were a way to deliver much needed oxygen and glucose to brain tissue just prior to its increased activity, that would be a useful adaptation.

What this study does more than anything else is raise an interesting question, and will likely result in a slew of follow up research. There will likely be criticism and disagreement as well. But that’s the nature of science – it’s all good.

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