New methods of visualization are revealing surprising patterns within the organization of neurons in the human brain.

The organization of neurons in the brain has been described as a bowl of cooked spaghetti—fibers curving and crossing each other in every direction, forming knots and tangles. But, in a new study published in Science, using a form of magnetic resonance imaging (MRI) to uncover the brain's underlying organization is painting a surprising picture (1). It turns out that raw spaghetti carefully laid out in a grid may be a more apt analogy for how tracts of neurons are arranged.

Sections of DSI images from a rhesus monkey's brain show the grid-like pattern of neuron fibers that crisscross each other in an orderly way. Source: Van Wedeen, MGH Radiology, Harvard Medical School

Neuroscientist Van Wedeen of Harvard Medical School was among the scientists who developed diffusion spectrum imaging (DSI) a decade ago. While standard MRI images show blood flow, DSI uses MRI technology to hone in on water particles. Since water is present in every neuron, DSI can illustrate the direction and placement of precise neurons in the brain.

Although most scientists have applied DSI to human brains, the resolution was limited by how long human test subjects could lie in an MRI machine. So, Wedeen decided to look at primates with similar brains to humans, like rhesus monkeys and marmosets. These high-resolution scans provided the first hint that there was some order to the seemingly chaotic brain.

"The human images that we saw looked a bit like a bad hair day; very complicated," says Wedeen. "But the animal images looked much neater. There was a certain geometric order to them that you couldn't really put your finger on."

Then Wedeen began applying a new analysis technique to the DSI images from both humans and other primates. For these brain images, his team highlighted all neighboring neurons and looked at which direction each neighbor extended in.

"We found that the crossings line up as single woven sheets," says Wedeen, "instead of spreading out into a complicated nest of weirdness in every direction."

Moreover, the scientists found that neuron fibers tended to run in only three directions, and they corresponded to the axes of the body: up and down, side to side, and front to back. The discovery suggests a simplified mechanism for how neurons find their paths in the developing brain, by following chemical gradients. It also suggests how groups of neurons manage to pass along electrical signals simultaneously: if they're parallel, the signal will travel at the same speed along each fiber.

The next step is to find out how much variation in this organization exists between people. Once scientists have a baseline sense of how much variation is normal, they can begin to more easily study deviations from that norm that may be linked to neurological diseases. And new, more powerful MRI machines optimized for DSI will help make this task easier.

"We previously thought that the brain was impossibly complicated," says Wedeen. "But now we've discovered that the large-scale structures in the brain have an extraordinary simple organization. We hope that this will teach us things about how the brain works, evolves, functions, adapts, and more clearly see variations between individual brains."