Rethinking Thought

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More Than a Delivery Service

"The old-school view is, blood is the pizza delivery man," says Moore. "It's delivering food to the hardworking neurons, and then it leaves. It doesn't even say hello." But the volume of blood flowing to active areas of the brain far outstrips neurons' metabolic needs: it's bringing a large meat-lover's pizza when a slice of cheese would do. Blood flow in other parts of the body is much less profligate; active muscles, for example, get only the blood they need, and sometimes less (which explains that burning sensation in your quads when you take a longer-than-usual run). "The rest of the body doesn't have a hyperflow of blood to an area," says Moore. "Only the brain does that."

That's why Kenneth Kwong, the father of fMRI, thinks Moore's radical hypothesis is plausible. Kwong, who is now a physicist at Harvard Medical School, demonstrated in 1990 that fluctuations in blood flow as measured by fMRI are correlated with the brain's response to stimuli such as viewing a checkerboard pattern. Since blood does feed neurons, neuroscientists assumed that the fluctuations occurred in response to the neuronal activity. "A neuron fires first, then blood flow changes," Kwong says, summarizing that view. "Chris says, That's true, but maybe blood flow has a bigger role to play. Maybe it's more than a passive reflector." After all, biological systems are often characterized by two-way feedback: if one cell talks to another, the second cell typically talks back. Initially the blood responds to the call of the neurons, feeding them the glucose and oxygen they need. But Moore believes that the neurons respond to the blood in turn.

In Moore's theory, called the hemo-neural hypothesis, "blood doesn't direct the neuronal circuitry," Kwong says: it isn't what kicks a neuron into gear in the first place. But once the blood arrives, it might fine-tune the circuitry by changing a neuron's sensitivity from one second to the next, which in turn determines its ­activity level. A relatively sensitive neuron will fire off a relatively large number of electrical signals called action potentials--the basic unit of communication in the brain--in response to stimulation by another neuron. This cell-level activity is what makes a thought. If changes in blood flow cause a neuron to fire more or fewer action potentials, then changes in blood flow influence thought.

This fine-tuning might take place by chemical or mechanical means. Brain tissue is interlaced with blood vessels that expand and shrink in response to the contractions of the smooth muscle surrounding them, causing blood volume to increase or decrease. This exerts physical pressure on neurons and the cells, called glia, that support them. And of course, the blood itself carries any number of chemical compounds beyond oxygen and glucose that might affect neuronal sensitivity.

Moore believes that the hemo-­neural hypothesis provides a more biologically satisfying explanation for how the brain works, and one that fits better with fMRI data. But the idea is new, so "people are having a hard time grokking this," he says. To him, it's intuitive. It just seems right when he looks at a microscope image of a neuron, its armlike extensions wrapped around a blood vessel in a cellular embrace. It seems right when he watches fMRI scans produced in his studies of sensory perception. But now he's got to prove it in the lab, to himself and to the neuroscience community.