Scientists Provide First Detailed Maps Of Wiring Circuitry In The Living Human Brain

"This technique will enable scientists to make more detailed maps of connections between different parts of the brain. In particular, this technique can provide diagrams of how the brain is wired and which parts of the brain talk to which other parts," says Thomas E. Conturo, M.D., Ph.D., assistant professor of radiology at Washington University School of Medicine in St. Louis. "By knowing that, scientists may be able to identify abnormal connections between brain areas that might be important in diseases such as schizophrenia."

The study, published in today's issue of Proceedings of the National Academy of Sciences, also may provide a way to tell if behavioral differences among people partly result from differences in the way their brains are wired. Conturo, the lead author, also notes that wiring diagrams could be used to study how the recently recognized process of "re-wiring" occurs in brain ailments such as stroke.

Scientists' understanding of the wiring of the human brain has come primarily from studies of animals, which lack many of the higher brain functions of humans. A nine-member team of physicists, computer scientists, neuroscientists, radiologists and anatomists spent three years developing the variation of magnetic resonance imaging (MRI) and analyzing data to provide detailed maps of brain wiring in living humans.

The MRI fiber tracking method monitors the random movements of water inside and around nerve cells. The cells have long fiber extensions that transmit electrical impulses to communicate with other nerve cells. These fibers are arranged in parallel bundles like cables in a telephone line. Water tends to move more easily along the length of these cables. Using an MRI method that has high sensitivity to water movements, the researchers traced these cables by following the preferred direction of water movement.

The research team studied four volunteers and determined the wiring layout of fiber bundles throughout the brain, which primarily were found in white matter regions where a white fatty substance insulates the bundles. The researchers then selected certain areas for closer evaluation.

They first studied fiber bundles in the back of the head that cross between the two sides of the brain. One group of the crossing fibers went forward and to the top of the brain, whereas another group went to the back of the brain where visual information is processed. The two groups of fibers came very close together to run side-by-side when crossing to the other side of the brain, but their wires did not intermix.

Next, the researchers traced longer fiber bundles that transmit visual information from the eyes to the brain. Fibers that are used for seeing different parts of the visual world were identified. The researchers note that such detailed 3-D information on human brain wiring could guide surgery in the future. "For example, a surgeon might want to use these data when deciding how to remove a cancer without cutting cables that are used for vision," Conturo says.

The research team then showed that MRI fiber tracking could reveal which parts of the brain work together to perform a specific task. Using functional MRI, the researchers determined what brain areas are activated when a person is watching a flashing light. Then, using MRI fiber tracking, they determined that the brain areas joined together and that direct fiber connections exist between the areas.

Finally, the researchers identified complicated connections between several brain areas involved in higher level thinking skills such as speaking, paying attention, and multiplying numbers. The fiber bundles that connected to different brain areas often ran side-by-side to form larger cables without mixing their wires, like driving onto a highway from an on-ramp having its own lane. "We were surprised and excited to find that the brain circuitry was wired in such an orderly fashion," Conturo says.

###GRAPHICS: A high-resolution, color image of a fiber tract positioned on a 3-D model of the human head is available from the Office of Medical Public Affairs upon request. Copies of the article are available from the PNAS News Office 202-334-2138, or email pnasnews@nas.edu.

Conturo TE, Lori NF, Cull TS, Akbudak E, Snyder AZ, Shimony JS, McKinstry RC, Burton H, Raichle ME. Tracking neuronal fiber pathways in the living human brain. Proceedings of the National Academy of Sciences, 96, 10422-10427, Aug. 31, 1999.

Nicolas F. Lori, a predoctoral physics candidate, developed the computer graphics algorithms and fiber tract selection methods, analyzed data, and assisted with development of algorithms for computing fiber tracts. Erbil Akbudak, Ph.D., research instructor in radiology, developed the MRI scanning methods and data collection algorithms. Abraham Z. Snyder, Ph.D., M.D., research scientist in radiology, developed algorithms for image processing and fiber tract computation. Joshua S. Shimony, M.D., Ph.D., clinical fellow in radiology, developed the data analysis to compute the direction of water movement. Harold Burton, Ph.D., professor of neurobiology and radiology, provided anatomical expertise and assisted with the interpretation of results. Marcus E. Raichle, M.D., professor of radiology and neurology and co-director of the Division of Radiological Sciences, suggested that data on nerve fiber directions could be used to study interactions among brain areas, and assisted with the interpretation of results.

This research was funded by the McDonnell Center for Higher Brain Function, the Charles A. Dana Foundation Consortium on Neuroimaging Leadership Training, and the National Institutes of Health.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC Health System.