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Brain Imaging: The Way We’re Wired

Two major research efforts are helping scientists view the brain’s trillions of connections with unprecedented clarity, opening a window on neurological disorders.

By Anita Slomski // The MGH Research Issue 2011
the way we're wired

Adam Voorhes for Proto

Dissecting a monkey’s brain reveals a complex mesh of nerve fibers that crisscross and interlock, providing passage for scores of electrical impulses. Yet, while the human brain is likely to have a vastly richer, still more complicated wiring system, tracing the trajectories of white matter tracts—the bundles of long, thin nerve-cell projections, called axons, that connect brain regions—has been impossible. Conventional brain imaging has shown only the largest cables, leaving unmapped thousands of miles of axons that branch into the inner recesses of the brain’s gray matter, where they form trillions of connections with billions of neurons to generate abstract thought, memory, learning, emotions and movement.

Now scientists at Massachusetts General Hospital are working with other researchers on two ambitious initiatives—the Human Connectome Project and the Brain Genomics Superstruct Project—that will provide remarkably detailed information about the ways neural circuitry differs from one person to another based on experiences, behavioral traits and genetic makeup.

Learning what constitutes normal variability will help researchers understand how brain wiring goes awry in psychiatric and neurological disorders. Diseases such as schizophrenia, depression and multiple sclerosis are all thought to be caused by abnormal connections, “but we’ve never had great tools to test that theory,” says Bruce Rosen, director of the Athinoula A. Martinos Center for Biomedical Imaging at MGH. Changes also occur when neurons degenerate through normal aging or through such disorders as Alzheimer’s disease. “If we can take a better picture of the brain, it may show those abnormalities just as the Hubble telescope revealed things we couldn’t see from earth,” Rosen says.

Those clearer images will come from the centerpiece of the $40 million Human Connectome Project—an ultra-high-resolution scanner—which also involves collaborators at the University of California, Los Angeles. The new superscanner uses the technology of diffusion MRI—which brings white matter tracts into sharp relief by mapping the way water molecules move in the brain—but ramps up the power. The 8.3-ton machine’s gradient magnets are eight times the size of those in conventional MRI scanners, and it uses as much as 24 megawatts of peak power, four times more than a typical MRI.

The connectome scanner was built by Siemens Medical Systems in Germany. Delivered to MGH in August, it is slated to provide images of the identical and fraternal twins and their siblings recruited for the study. The images will be added to ones supplied by researchers at Washington University in St. Louis and the University of Minnesota, who last year began mapping the twins’ brains using customized MRIs and functional MRIs (fMRIs). Studying the brains of twins and their siblings will help researchers understand genetic contributions to brain differences, while accompanying behavioral data about the volunteers is expected to reveal clues about the ways environment shapes the brain’s circuits.

Judging from scans of cats and monkeys already tested in the connectome scanner, brain wiring may be more similar to a two-dimensional grid that connects large segments of the brain like a woven cloth, according to Rosen, than the linear point-by-point connections that scientists saw with less sensitive imaging. “We’ve never seen this grid before, and if it’s in people too, it will change the way we think about how the brain is wired, how it develops and the forces that shape it,” he says. “This could lead to the most important neuroanatomy discoveries in 100 years.”

The Superstruct Project is also collecting data on white matter architecture, but its strength lies in its numbers of images rather than in their detail. Since 2009, Superstruct has scanned 3,200 adults in identical scanners at numerous facilities in Boston, and it’s scheduled to provide images of 1,800 more by next year. That will make the project one of the largest repositories of functional and structural brain images in the world. “By using uniform sets of brain images and behavioral measures on thousands of people that are available today, we can work out important features of the architecture of the cognitive brain system,” says neuroscientist Randy Buckner, director of the Psychiatric Neuroimaging Research Program at MGH.

The Superstruct Project builds on recent engineering innovations, several of which came from MGH’s Martinos Center, to speed up the imaging process. “We can now take a picture of the structure of the brain in two minutes, vs. the eight to 10 minutes it normally takes,” says Buckner, whose team has already mapped the organization of the neural circuits in the cerebellum, a large brain region involved in motor control and probably cognition as well. “This is the first time we’ve been able to look at the brain with such clarity. At first, the patterns looked very complicated, but the wealth of images ultimately revealed an organized pattern connecting the cere­bellum to the cerebral cortex, which is involved in higher cognition,” he explains. “Cerebrocerebellar circuits seem to be disrupted in a number of psychiatric illnesses, and having this map will allow us to see how that happens.”

Analyzing this huge collection of images is also helping researchers answer questions about how genetic factors change the brain’s architecture. “Several genetic studies have identified risk factors for such psychiatric illnesses as bipolar disease and schizophrenia, but we haven’t known how they affect the brain,” Buckner says. Ultimately, researchers may see not only how particular genes alter brain structure and function, but also how brain architecture produces specific types of behavioral tendencies, such as anxiety. “So many of these illnesses have been invisible because they’re caused by subtle disruptions to the wiring and function of the brain,” he explains. “We hope to be able to use information from this project to identify who’s at risk so we can intervene early, as well as identify targets for therapy.”

Scientists also think the trove of more revealing images may show the way the brain rewires itself after a stroke and other neurodegenerative illnesses. “We don’t think the brain grows many new white matter axons, yet we see changes in connectivity even in older people,” Rosen says. If the connectome scanner uncovers how the brain redirects nerve fibers to compensate for an injury, “maybe we can find ways to support those changes. At the very least we’ll have extremely sensitive tools that let us compare treatments and see which ones seem to promote new connections.”

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