It comes as no big surprise that "no two brains are wired up exactly the same," Michael Huerta, PhD, associate director of the National Institute of Mental Health (NIMH) told Medical Device Daily.

But with the help of a new $30 million project scientists will now have an opportunity to learn more about how the brain is wired, and how many similarities and differences exist between different brains.

Huerta is the lead NIH contact for the Human Connectome Project (HCP) being launched by the National Institutes of Health Blueprint for Neuroscience Research. The HCP will use "cutting-edge" brain imaging technologies to map the circuitry of the healthy adult human brain. According to the NIH, by systematically collecting brain imaging data from hundreds of subjects, the HCP will yield insight into how brain connections underlie brain function, and will open up new lines of inquiry for human neuroscience.

"A major feature of the brain that underlies how it works – or how it doesn't work, very often – is the connectivity of one part of the brain to another part of the brain," Huerta said.

He said scientists have been studying brain connectivity since the 1800s, but until recently it has always required invasive approaches or post-mortem tissue so researchers haven't been able to look at connectivity in healthy, intact human brains because they haven't had the right tools. Within the last five to 10 years, however, Huerta said several different imaging modalities have been developed which the NIMH thinks could be used to start studying the relationship between the structure and function of the human brain.

"These tools are just kind of on the cusp of being able to be used for this so the initiative is bold in that we're asking these people to take these cutting-edge tools and in the first year or two [of the project] to optimize them for this purpose," Huerta said. He added that the organization is asking researchers to use tools that provide complimentary types of data.

Investigators have been invited to submit detailed proposals to carry out the HCP, which will be funded at up to $6 million a year for five years, according to the NIH. The HCP is the first of three Blueprint Grand Challenges, projects that address major questions and issues in neuroscience research, the organization noted.

Unlike a typical NIH grant program that provides a certain amount of money to individual researchers working on separate projects, the HCP will be a "very highly-coordinated, very objective approach," Huerta told MDD. He said the field of human connectomics hasn't really gotten the kickstart that it needs, so that is what the project will hopefully accomplish.

After all the applications are in, only one award will be made, Huerta said. It will probably involve several labs, but they are going to have to work together as a unified team, he added. Rather than being considered a grant program, the HCP is a cooperative agreement, Huerta said, which allows the NIH to be more involved in an ongoing way with the program.

The Blueprint Grand Challenges are intended to promote major leaps in the understanding of brain function, and in approaches for treating brain disorders. The three Blueprint Grand Challenges to be launched in 2009 and 2010 address: the connectivity of the adult, human brain; targeted drug development for neurological diseases; the neural basis of chronic pain disorders.

"The HCP is truly a grand and critical challenge: to map the wiring diagram of the entire, living human brain. Mapping the circuits and linking these circuits to the full spectrum of brain function in health and disease is an old challenge but one that can finally be addressed rigorously by combining powerful, emerging technologies," said Thomas Insel, MD, director of the NIMH, which is part of the NIH Blueprint.

Some parts of the brain serve basic functions such as movement, sensation, emotion, learning and memory. Others are more important for uniquely human functions such as abstract thinking. The connections between brain regions are important for shaping and coordinating these functions, but scientists know little about how different parts of the human brain connect, the NIH says.

"Neuroscientists have only a piecemeal understanding of brain connectivity. If we knew more about the connections within the brain – and especially their susceptibility to change – we would know more about brain dysfunction in aging, mental health disorders, addiction and neurological disease," said Story Landis, PhD, director of the National Institute of Neurological Disorders and Stroke (NINDS), also part of the NIH Blueprint.

For example, there is evidence that the growth of abnormal brain connections during early life contributes to autism and schizophrenia, according to the NIH. Changes in connectivity also appear to occur when neurons degenerate, either as a consequence of normal aging or of diseases such as Alzheimer's.

In addition to brain imaging, the HCP will involve collection of DNA samples, demographic information and behavioral data from the subjects. Together, these data could hint at how brain connectivity is influenced by genetics and the environment, and in turn, how individual differences in brain connectivity relate to individual differences in behavior. Primarily, however, the data will serve as a baseline for future studies. These data will be freely available to the research community.

According to the NIH, the brain is estimated to contain more than 100 billion neurons that form trillions of connections with each other. Neurons can connect across distant regions of the brain by extending long, slender projections called axons – but the trajectories that axons take within the human brain are almost entirely uncharted.

In the HCP, researchers will optimize and combine brain imaging technologies to probe axonal pathways and other brain connections. In recent years, sophisticated versions of MRI have emerged that are capable of looking beyond the brain's gross anatomy to find functional connections. Functional MRI (fMRI), for example, uses changes in blood flow and oxygen consumption within the brain as markers for neuronal activity, and can highlight the brain circuits that become active during different behaviors.

Three imaging techniques are suggested, but are not required, for carrying out the HCP: high angular resolution diffusion imaging with magnetic resonance (HARDI), which detects the diffusion of water along fibrous tissue, and can be used to visualize axon bundles; resting state fMRI (R-fMRI), which detects fluctuations in brain activity while a person is at rest, and can be used to look for coordinated networks within the brain; and electrophysiology and magnetoencephalography (MEG) combined with fMRI (E/M fMRI), which adds information about the brain's electrical activity to the fMRI signal. In this last procedure, the person performs a task so that the brain regions associated with that task become active.

Since this is the first time that researchers will combine these brain imaging technologies to systematically map the brain's connections, the HCP will support development of new data models, informatics and analytic tools to help researchers make the most of the data, the NIH said. Funds will be provided for building an on-line platform to disseminate HCP data and tools, and for engaging and educating the research community about how to use these data and tools.