Tuesday, July 28, 2009

The National Institutes of Health Blueprint for Neuroscience Research is launching a $30 million project that will use cutting-edge brain imaging technologies to map the circuitry of the healthy adult human brain. By systematically collecting brain imaging data from hundreds of subjects, the Human Connectome Project (HCP) will yield insight into how brain connections underlie brain function, and will open up new lines of inquiry for human neuroscience.

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

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 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," says Thomas Insel, M.D., director of the National Institute of Mental Health (NIMH), which is part of the NIH Blueprint.

Scientists have studied the relationship between the structure and function of the human brain since the 1800s. 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.

"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," says Story Landis, Ph.D., 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. 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.

The complexity of the brain and a lack of adequate imaging technology have hampered past research on human brain connectivity. 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 state-of-the-art brain imaging technologies to probe axonal pathways and other brain connections. In recent years, sophisticated versions of magnetic resonance imaging (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.-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 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. 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.

"Human connectomics has been gaining momentum in the research community for a few years," says Michael Huerta, Ph.D., associate director of NIMH and the lead NIH contact for the HCP. "The data, the imaging tools and the analytical tools produced through the HCP will play a major role in launching connectomics as a field."

The field of neuroscience emerged in the late 19th century, when scientists observed individual brain cells for the first time. Since then, researchers have made breathtaking progress in understanding the anatomy, cell biology, physiology and chemistry of the brain in both health and disease. Yet many fundamental questions remain unanswered, including how brain function translates into mental function and why brain function declines with age. Advances in neuroimaging, genomics, computational neuroscience and engineering have put us on the brink of another great era in neuroscience, when we can expect to make unprecedented discoveries regarding normal brain activity, disorders of the brain and our very sense of self.