April 9, 2012

Complex Brain Has Simple Grid Structure

Wiring diagram of the human brain shows curvature of 2-D sheets of parallel neuronal fibers crossing paths at right angles. Source: Van Wedeen, M.D., Martinos Center and Dept. of Radiology, Massachusetts General Hospital and Harvard University Medical School.

A landmark study revealed that nerve cells in the brain form a simple checkerboard grid pattern. The new technique will help researchers better understand how the brain develops and may give insights into disorders like epilepsy, autism and schizophrenia.

A new field of research called connectomics aims to understand the connections between neurons (nerve cells) in the brain. This type of wiring diagram can provide useful information about the healthy and diseased brain. However, analyzing these connections is extremely complex and time-consuming. The wiring diagram of a roundworm brain with 300 neurons took almost 10 years to complete. Mapping of the human brain, with 100 billion neurons, is daunting. The highly folded structure of the cortex (gray matter) makes it difficult to follow neurons and their connections. Added to the complexity is the fact that connections in the brain are continuously changing with age and in response to environment and experiences.

Traditionally, brain connections have been visualized by injecting dyes into nerve fibers and tracing them. However, this technique doesn't provide very detailed structures, and it's unsafe for use in humans. To address these problems, researchers developed a technique called diffusion MRI. Scanners detect the movement of water inside nerve fibers, which is then used to assess their location. Diffusion MRI can visualize the networks of crisscrossing fibers with 10 times greater detail than conventional MRI. Diffusion MRI is also harmless, so it can be used in humans.

In the new study, a research team led by Dr. Van J. Wedeen of Massachusetts General Hospital and the Harvard Medical School used diffusion MRI to obtain detailed wiring diagrams of the brain. They studied the postmortem brains of 4 primates—rhesus monkey, owl monkey, marmoset and galago (bushbabies)—and of living humans. The work was funded in part by NIH's National Institute of Mental Health (NIMH).

In the March 30, 2012, issue of Science, the scientists reported that the nerve fibers of the brain aren't just a crisscross tangle of wires. Rather, they form a highly structured geometrical pattern that looks like a curved 3-D grid. The nerve pathways run parallel to each other and cross each other at right angles.

The brain's grid structure appears to guide connectivity like lane markers on a highway, limiting options for growing nerve fibers to change direction during development. Instead of randomly changing paths while growing, the fibers have just 4 options: up, down, left or right. This would enforce a more efficient, orderly way for the fibers to find their proper connections—and for the structure to adapt through evolution, the researchers say.

“Far from being just a tangle of wires, the brain's connections turn out to be more like ribbon cables—folding 2-D sheets of parallel neuronal fibers that cross paths at right angles, like the warp and weft of a fabric,” Wedeen says. “This grid structure is continuous and consistent at all scales and across humans and other primate species.”

“Getting a high-resolution wiring diagram of our brains is a landmark in human neuroanatomy,” says NIMH Director Dr. Thomas R. Insel. “This new technology may reveal individual differences in brain connections that could aid diagnosis and treatment of brain disorders.”

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Reference: Science. 2012 Mar 30;335(6076):1634-6.