An unprecedented five-year, $30-million effort to generate a first-of-its kind map of all the major circuits in the human brain is being led by Washington University School of Medicine in St. Louis and the University of Minnesota's Center for Magnetic Resonance Research (CMRR).

Thirty-three researchers at nine institutions will contribute to the Human Connectome Project. Using powerful, custom-built brain scanners, a supercomputer, new brain analysis techniques and other state-of-the-art resources, they will trace the anatomical 'wires' that interconnect thousands of different regions of the human brain's gray matter.

A second Human Connectome Project grant for $8.5 million has been awarded to a consortium led by investigators at Harvard and UCLA to develop a new brain scanner with improved sensitivity and spatial resolution.

"This effort will have a major impact on our understanding of the healthy adult human brain," says lead investigator David Van Essen, PhD, the Edison Professor and head of the Department of Anatomy and Neurobiology at Washington University. "It will also enable future projects that probe what changes in brain circuits underlie a broad variety of disorders, such as autism and schizophrenia."

The project is funded by 16 components of the National Institutes of Health via its Blueprint for Neuroscience Research.

"In the last two decades, scientists have developed a fantastic number of tools for non-invasive study of the human brain," says lead investigator Kamil Ugurbil, PhD, director of the CMRR and the McKnight Presidential Chair Professor of Radiology, Neurosciences and Medicine at the University of Minnesota. "The connectome project will significantly advance these techniques, many of which are based on magnetic resonance imaging (MRI), and apply them to generate unprecedented insights into the connectivity and function of the brain."

"On a scale never before attempted, this highly coordinated effort will use state-of-the-art imaging instruments, analysis tools and informatics technologies – and all of the resulting data will be freely shared with the research community," said Dr. Michael Huerta of the National Institute of Mental Health, who directs the NIH Connectome initiative. "Individual variability in brain connections underlies the diversity of our thinking, perception and motor skills, so understanding these networks promises advances in brain health."

Brain scans of volunteer subjects for the connectome project will be carried out at Washington University, the University of Minnesota and Saint Louis University. Scientists will use instrumentation and methods developed at the CMRR with the participation of researchers at Advanced MRI Technologies. Powerful new methods for analyzing these extremely complex datasets will be developed by investigators from Oxford University, Indiana University, University of California at Berkeley, Warwick University, University d'Annunzio, and the Ernst Strungmann Institute.

The brain is among the most complex structures known. Each human brain contains approximately 90 billion neurons (more than 10 times the number of people on Earth), which transmit information across roughly 150 trillion cell-to-cell connections known as synapses.

"These cells and synapses form the circuits that underlie all our thinking and emotion – everything that makes each of us a unique individual," Van Essen says.

The project will limit the resolution of its map of the brain to voxels, small patches of brain tissue, 1 to 2 millimeters on a side, that each contain as many as one million neurons. Bundles of long nerve cell branches from each voxel extend in complex trajectories, connecting cells in one voxel to those in others.

"At its essence, the human connectome is a description of the full pattern of connections between each brain region and every other brain region," says Van Essen.

Much of the project will focus on the cerebral cortex, the wrinkled sheets of gray matter on both sides of the brain where the most complex mental functions are carried out. If spread out flat, the cerebral cortex of each brain hemisphere would be about 14 inches across, or the size of a medium pizza.

The wrinkles and folds of each person's cortex, the shape and size of other brain structures, and the wiring of individual brain circuits vary significantly. To better understand this variability and its genetic underpinnings, Van Essen and his colleagues plan to recruit and study 1,200 twins and siblings of twins.

"This lets us look at the heritability of different brain circuits by comparing identical twins to non-identical twins and siblings," he explains. "It will also let us start linking various genes to specific aspects of brain circuitry."

Subjects for the research will first come to Washington University for a comprehensive battery of behavioral tests and brain scans. Some will also be scanned at the University of Minnesota or St. Louis University. Scanning techniques will include:

* diffusion imaging, a new form of magnetic resonance imaging (MRI) that produces detailed information on cell structure by tracking the random movements of water molecules;

* resting state functional MRI, which monitors brain activity while subjects relax, to reveal which brain regions work in sync with each other via brain networks;

* task-related functional MRI, which helps associate particular capabilities with specific brain regions by tracking brain activity as subjects perform visual, motor, cognitive, and other tasks; and

* magnetoencephalography, which can monitor very rapid patterns of activity involving millions of brain cells but provides less specific spatial data.

The information gathered via the scanning will allow scientists to map the brain's connections, track how the connections transmit information and identify how brain regions work together in dozens of networks and sub-networks.

Van Essen estimates the project will produce about 1 petabyte, or 1 quadrillion (1,000,000,000,000,000) bytes of data. The sophisticated analyses performed to produce this data will require the processing power of a newly acquired supercomputer at Washington University's High Performance Computing Center.

Van Essen says rapid and open data sharing will be a hallmark of the federally funded connectome project. As they gather and analyze results, the team will quickly make the data available to other neuroscientists for use in their own research.

"We're already working to create a well-organized data platform and tools that will allow scientists to drill down into the massive amounts of data the connectome project will produce and to efficiently extract the information they need to make exciting discoveries," he says.

According to Van Essen, as information about how brain circuits are normally connected reaches a critical mass, scientists can begin to use that data to study how differences in those connections contribute to differences in human behavior.

"In the future, this will enable studies of abnormal brain circuits in complex disorders such as autism and schizophrenia," he says. "It may also help us understand why treatments for those disorders work or fail."