Mapping the Brain on a Massive Scale

A massive new project to scan the brains of 1,200 volunteers could finally give scientists a picture of the neural architecture of the human brain and help them understand the causes of certain neurological and psychological diseases.

The National Institutes of Health announced $40 million in funding this month for the five-year effort, dubbed the Human Connectome Project. Scientists will use new imaging technologies, some still under development, to create both structural and functional maps of the human brain.

The project is novel in its size; most brain-imaging studies have looked at tens to hundreds of brains. Scanning so many people will shed light on the normal variability within the brain structure of healthy adults, which will in turn provide a basis for examining how neural “wiring” differs in such disorders as autism and schizophrenia.

The researchers also plan to collect genetic and behavioral data, testing participants’ sensory and motor skills, memory, and other cognitive functions, and deposit this information along with brain scans in a public database (although the patients’ personal information will be stripped out). Scientists around the world can then use the database to search for the genetic and environmental factors that influence the structure of the brain.

“We want to learn as much as we can, not only about the typical patterns of brain connectivity, but also about the differences in wiring that make each of us a unique individual,” says David Van Essen, a neuroscientist at Washington University in St. Louis, who is one of the project leaders. “If you’re good at math, and I’m better at certain types of memory, can we identify some of the wiring characteristics that account for those differences?”

The most detailed studies to date of the neural circuits that connect one brain cell to another have focused on animal brains, because scientists can examine the animals’ living tissue cells and their networks under a microscope. “We don’t know how our species specifically is wired up,” says Michael Huerta, associate director of the Division of Neuroscience and Basic Behavioral Science at the National Institute of Mental Health, and director of the Connectome project. “There is an entire class of data that is missing from neuroscience that is fundamentally important for how the brain works and how it breaks down in different disorders.” And because researchers will be scanning only identical and fraternal twins and their siblings, the scientists can get a sense of the role that genetics and environment play in shaping brain structure. Structures of the brain that are highly dictated by genes will be more similar in identical twins than in fraternal twins, for example.

Most human brain imaging studies have employed magnetic resonance imaging (MRI) to examine the gross anatomy of the brain or functional MRI to detect which regions are active during specific tasks. But advances in brain imaging technologies in recent years, as well as growing computing power, have made it possible to look at the fine wiring connecting brain regions. “If we want to understand the brain, we need to know what individual areas are doing and how they talk to each other,” says Russell Poldrack, director of the Imaging Research Center at the University of Texas at Austin. “Moving from examining how 120 brain areas operate on their own to determining how those 120 areas interact with each other increases the complexity by an order of magnitude, and the scale you need to address the problem also goes up.”

Van Essen and his collaborators plan to scan participants using two relatively recent variations on MRI. Diffusion imaging, which detects the flow of water molecules down insulated neural wires, indirectly measures the location and direction of the fibers that connect one part of the brain to another. Functional connectivity, in contrast, examines whether activity in different parts of the brain fluctuates in synchrony. The regions that are highly correlated are most likely to be connected, either directly or indirectly. Combining both approaches will give scientists a clearer picture. Collaborators at the University of Minnesota and Massachusetts General Hospital are optimizing existing scanners with new magnets and custom analysis programs so that they are better suited to detecting these circuits.

“This will be a landmark study,” says Robert Williams, a neuroscientist at the University of Tennessee, in Memphis. “I think it will have the same kind of impact on neuroscience that the Human Genome Project had on human genetics, providing a strong foundation for other work.”