Mapping the Brain’s Interior Landscape

HealthScienceStories
Rendering of a group connectome based on 20 subjects using TrackVis software by Andreas Horn, M.D., Ph.D.

Like social networks, the brain has a multitude of connections — one hundred trillion of them. As we go through life, the people we meet and our relationships change those networks. Yet little is known about our wiring.

In recent years, however, scientists have gotten much closer to mapping the pathways underlying our mental makeup. The new map, or “connectome,” could shed light on how connections are formed, pruned, and reshaped over our lifetime. Using extraordinarily powerful new technology, researchers have explored every fold and valley in the brain in minute detail. They hope investigating its inner realms will help understand development, aging, and neurological issues related to connectivity such as depression or obsessive-compulsive disorder (OCD).

This three-dimensional, interactive map illustrates the circuitry underpinning how we think, feel, and act. It shows what makes us human and gives us our identities. Some scientists have compared the connectome to a fingerprint. “There are differences across people in connections and, interestingly, that seems stable over time,” says Deanna Barch, Ph.D., a psychologist and chair of the Psychological & Brain Sciences Department at Washington University in St. Louis. “There’s something unique about your individual pattern of connectivity. It’s not that everybody is wildly different, but on top of many commonalities there are differences.”

Barch says the diagram could help reveal how our wiring relates to behavior. For her, the central question is, “Can we use that information to identify atypical patterns in people? ” And, she adds, “If those are linked to mental health or cognitive challenges, can we use that for treatment?” The state-of-the-art technology doesn’t just expand our knowledge of the brain, it takes it to a new level. “The connectome lets us look at the level of relationships between brain regions rather than focusing on a single one,” says Barch.

Barch is part of a team headed by David Van Essen, Ph.D. that worked to map the brain’s connections. The original Human Connectome Project was a five-year, multimillion-dollar study, which was funded by the National Institutes of Health. Using extremely precise magnetic resonance imaging (MRI) scanners, the researchers scanned the brains of 1,200 healthy adults, including 300 sets of twins. The consortium also involves the University of Minnesota and Oxford University.

To create a blueprint of the brain, each of the volunteers spent eight to 10 hours in a scanner. They also underwent behavioral tests and performed computer tasks that measured memory and thinking skills. In addition, they participated in functional MRI testing to observe brain activity and show the relationship between structure and function. The data was also linked to individual characteristics such as IQ, age, and sex.

While the connectome strives for an overall picture of the association between different brain areas, scientists also can use it to pursue deeper questions. “Now we have the tools to measure disconnectedness between brain regions,” says Barch. “That might be relevant for many disorders such as schizophrenia, depression, or OCD.”

Nearly 100 New Brain Regions

Other members of Van Essen’s team have been carefully redefining separate brain regions. They were amazed when they recently discovered nearly 100 new ones.

This is not the first attempt at charting the brain. In the early part of the 20th century, the German neuroscientist Korbinian Brodmann mapped out the cerebral cortex by hand, relying on what he saw under a microscope. He divided it into roughly 50 regions responsible for visual processing, language, memory, attention, sensation, decisionmaking, perception, thought, and consciousness.

Van Essen’s group has been refining that map one millimeter at a time. “We used multiple kinds of information to define brain regions using different types of MRI studies,” says Matthew Glasser, M.D., Ph.D., a neuroanatomist at Washington University in St. Louis. This is an advantage over methods relying on a single feature to characterize brain activity and function. Glasser is also a resident physician at nearby St. Luke’s Hospital.

In hours of tests on 210 adult participants, the researchers tested language, memory, and thought. They also watched the participants’ brains while they listened to stories. Earlier studies had suggested anywhere from 50 to 200 areas in the human cortex. In addition to the known 83 brain regions, their work uncovered 97 new ones. “Sometimes these were brain areas in poorly explored parts of the cortex that hadn’t been mapped out before,” explains Glasser. “Relating this map to previous brain imaging studies is challenging as most are quite blurry.” They often fail to account for individual variation, so it’s not clear whether they’re referring to the same region.

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We believe that neuroscience is the next great scientific frontier, and that advances in understanding the nature of the brain, consciousness, behavior, and health will transform human life in this century.

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