Functional MRI in Brain Research

Animal rights groups, along with Dr. Greek, continue to argue that new imaging technologies, such as fMRI, provide an alternative to invasive brain research in animals, accusing those doing animal work of failing to adopt these modern methods. Such a position reflects a misunderstanding of what these instruments measure and their limitation in studying how the brain works.

Our perceptions, thoughts, speech and decisions are carried out by a complex network of neurons that communicate through brief electrical impulses about one millisecond in duration (so called action potentials or ‘spikes’). These electrical impulses allows the brain to perform all its amazing computations in real time, such as recognizing faces, keeping your balance, and understanding speech. In other words, spikes are the currency of computation in the brain. To study how the brain is capable of these feats we need, therefore, to measure directly how populations of neurons communicate with each other by means of spiking activity.

A key challenge in this work is that neurons are very small (cell bodies are about 25 micrometer in diameter) and they are tightly packed together. As an analogy, consider a football stadium full of spectators. The problem is akin to developing a method to listen to the conversation between two individuals in the middle of this noisy crowd. Clearly, without getting a microphone close enough to them, the background noise would make the measurement nearly impossible. You cannot listen to an individual conversation with a microphone hanging in the middle of the stadium. The micro-electrode, an insulated wire with a diameter smaller than a human hair, is such a “microphone” that allows us to record the spikes of individual cells in the working brain by getting close enough to the individual cells.

Is there a way to measure the activity of single neurons non-invasively in humans? The answer is no. So what about functional MRI? fMRI does not measure neural activity directly, but instead relies on indirect changes in blood flow and volume triggered by modulation in neural activity. To begin with, it turns out that we we still do not know how fMRI measurements relate to neural activity. Clearly, to be able to understand how fMRI signals relate to neural activity we need to measure both simultaneously, work that will also require the use of animals. Importantly, fMRI has a limited spatial resolution of about a cubic millimeter. In such a volume, one can find in the order of 100,000 neurons. In other words, the ‘fMRI microphone’ cannot listen to individual cells, but to a whole stadium full of them. Finally, we already know that fMRI signals are much slower than neuronal activity, as the time course of hemodynamic signals is in the order of 5 seconds. As neurons work hundreds of of times faster (you can recognize an image in less than 150 ms), the dynamics of fMRI signals are too slow to understand how brains compute in real time. Instead, fMRI provides useful information about what brain areas might be involved in certain tasks. After these areas are identified, electrophysiological measurements with micro-electrodes can be used to measure the activity of single neurons in those areas. The combination of such tools is proving extremely useful in neuroscience research.

A couple of weeks ago animal right activists marched through UCLA carrying a sign saying “Support alternatives to animal research”. I was unsure whether to join them or not. After all, we fully support and work towards the development of alternative, non-invasive methods. Their sign, of course, is designed to suggest to the public that such methods currently exist and scientists refuse to use them. This is just not the case. Functional MRI is am extremely useful research useful tool, but not a replacement for electrophysiological work that requires measurement at micrometer scales.

In addition, Dr. Greek's claims that functional MRI and other imaging technologies were developed without the use of animals is simply untrue. In the case of functional MRI, it was the groundbreaking work of Owaga and colleagues at Bell Labs using rodents that showed that changes in the levels of deoxygenated haemoglobin in blood vessels changed the MR signal from water molecules surrounding them. Neural activity in the brain affects the the relative concentration of oxy- and deoxy-haemoglobin which then gives rise to an indirect measurement of neural activity through the the T2* weighted image intensity. They subsequently showed functional signals in human visual cortex based on the animal studies.