Thinking with Blood
A New View of Information Processing in the Brain

Christopher Moore proposes that changes in blood flow in the brain affects how neurons function. Photo courtesy Donna Coveney, MIT

Cambridge, Mass, October 11, 2007 -- Most people have seen jazzy pictures of the brain from functional magnetic resonance imaging (fMRI) experiments. The brain looks like a cauliflower with patches of bright color - hot spots of activity that come and go as different brain regions engage in seeing, moving and thinking.

These bright spots represent places in the brain where there is a transient increase in blood volume. Until now, scientists have presumed that this blood flow is to deliver fuel and oxygen, serving only a metabolic role.

Christopher Moore at MIT proposes a new view. "We hypothesize that blood actively modulates how neurons process information," explains Moore, a principle investigator in the McGovern Institute for Brain Research at MIT, in an invited review in the Journal of Neurophysiology published this week. "Many lines of evidence suggest that blood does something more interesting than just delivering supplies. If it does modulate how neurons relay signals, that changes how we think the brain works."

According to Moore's Hemo-Neural Hypothesis, blood is not just a physiological support system but actually helps control brain activity. Specifically, localized changes in blood flow affect the activity of nearby neurons, changing how they transmit signals to each other and hence regulating information flow throughout the brain. Ongoing studies in Moore's laboratory support this view, showing that blood flow does modulate individual neurons.

Moore's theory has implications for understanding brain diseases such as Alzheimer's disease, schizophrenia, multiple sclerosis and epilepsy. "Many neurological and psychiatric diseases have associated changes in the vasculature," Moore says. "Most people assume the symptoms of these diseases are a secondary consequence of damage to the neurons. But we propose that they may also be a causative factor in the disease process, and that insight suggests entirely new treatments." For example, in epilepsy people often have abnormal vessels in the brain region where the seizures occur, and the hypothesis suggests this abnormal flow may induce epileptic onset. If so, drugs that affect blood flow may provide an alternative to current therapies.

The hypothesis also has important implications for fMRI, a widely used brain scanning method that indicates local changes in blood flow. "Scientists looking at fMRI currently regard blood flow and volume changes as a secondary process that only provides read out of neural activity," explains Rosa Cao, a graduate student in Moore's lab and co-author of the paper. "If blood flow shapes neural activity and behavior, then fMRI is actually imaging a key contributor to information processing."

Again, studies in Moore's lab support this interpretation. For example, his fMRI studies of the sensory homunculus - the brain's detailed map of body parts like fingers, toes, arms, legs, etc. - show that when more blood flows to the area representing the fingertip, people more readily perceive a light tap on the finger. This suggests that blood affects the function of this brain region and that information about blood flow can predict future brain activity. This finding does not undermine prior studies, but adds another, richer layer to their interpretation and makes it an even more useful tool than it already is.

How could blood flow affect brain activity? Blood contains diffusible factors that could leak out of vessels to affect neural activity, and changes to blood volume could affect the concentration of these factors. Also, neurons and support cells called glia may react to the mechanical forces of blood vessels expanding and contracting. In addition, blood influences the temperature of brain tissue, which affects neural activity.

To Moore's knowledge, the Hemo-Neural Hypothesis offers an entirely new way of looking at the brain. "No one ever includes blood flow in models of information processing in the brain," he asserts. One historical exception is the philosopher Aristotle, who thought the circulatory system was responsible for thoughts and emotions. Perhaps the ancient Greeks were on to something.

Figure: How Do Hemodynamics Impact Neural Excitability?

Light gray arrows: Accepted theory of the one-way influence of neurons directly on blood vessels and indirectly on astrocytes (a type of glia) that in turn modulate blood vessels, increasing blood volume locally. The activity-driven increase in blood volume, or functional hyperemia, is detected by fMRI.

Darker arrows The new hypothesis predicts a two-way street between blood vessels and both neurons and glia. Increased blood flow and volume could directly modulate neurons (black arrow) by opening mechanically sensitive ion channels that are in high concentration in brain areas such as the sensory cortex, increasing concentration of diffusible messengers from vessels, and causing thermal effects. Darker gray arrows indicate that modulation of glia by hemodynamics could in turn impact neuronal activity.

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