This article first appeared in the St. Louis Beacon, April 5, 2011 - Washington University's David van Essen is working on a $30-million project that he says is essentially a matter of "the human brain trying to understand the human brain." And thanks to cutting-edge technology, the brains at nine institutions nationwide are making substantial progress.
Van Essen is the lead investigator for the Human Connectome project that is aimed at creating a wiring diagram for the brain in the next five years. The hope is that the research could someday lead to therapies for neurological and psychological disorders.
The Connectome project is the work of a consortium of nine institutions led by Washington University and the University of Minnesota's Center for Magnetic Resonance Research. St. Louis University will also play a role in the research that will make a road map showing how each small area of the cerebral cortex connects to the rest of the brain. The map will give detailed information down to a resolution of 1-2 cubic millimeters.
The brain contains about 90 billion nerve cells (neurons) that make approximately 150 trillion synapses (connections) with each other. Trying to untangle such a vast network seems dazzling in its audacity. However, the Human Genome Project seemed like an impossible dream at one point. Today geneticists know the exact sequence of every bit of DNA in the normal human chromosome, and are using that information to compare genes in healthy and abnormal situations.
The imaging technologies that will be used to draw the brain map are non-invasive and safe, allowing investigators to explore both function and structure in the living normal brain. Benefits will surely follow. With the map in hand, neuroscientists in the future will be able to see how the brain structure of patients with diseases like Alzheimer's, Parkinson's and autism differs from normal brain structure.
For example, explains St. Louis University neurosurgeon Richard Bucholz, deep brain stimulation with an electrode surgically implanted into certain regions can relieve many of the symptoms of Parkinson's. But the treatment often has serious side effects. A detailed map should allow the surgeon to pinpoint the areas where stimulation will help and avoid the areas where stimulation will cause undesirable side effects.
This study is not simply updated textbook anatomy. One of the new imaging techniques will generate a high-resolution representation of the physical wiring that traverses the brain as white matter. (White matter consists of bundles of axons -- the long processes that carry impulses from the cell body to synapses with other cells. These processes are protected with a sheath that is white in color. Grey matter consists mostly of nerve cell bodies. The cerebral cortex that lies under the skull is grey matter.)
In addition, the Connectome will map functional connections. Whether at rest or while performing mental tasks, discrete areas across the brain fire off impulses that are synchronized in time and pattern. These synchronized areas are said to have functional connectivity.
The Brains of Twins and Their Siblings
Twelve hundred subjects will participate in the Connectome project: 150 pairs of identical twins, 150 pairs of fraternal twins and 600 siblings of those twins. All will be healthy young adults with no known neurological problems.
This distribution should shed light on the influence of environment and genetics in individual brain wiring. Van Essen points out that environmental influence begins in the womb. Even identical twins have unique wrinkling patterns on the surface of the brain, almost as different from each other as from strangers.
Washington University will scan each subject's brain in a number of ways to give a complete picture of both structural and functional connections. The data from all the scans will be processed by the university's supercomputer. Some subjects will also go to St. Louis University for another type of imaging, and some will travel to the University of Minnesota, where a more powerful scanner can generate images with finer detail.
Between imaging sessions, the subjects will be given a battery of tests including IQ, personality profile and a short neurological work-up.
The acquisition of data from brain imaging and testing is just the beginning. As stated by Dan Marcus of Washington University, "Imaging data is a stack of 2-D pictures on the supercomputer, but integrating all into the connectivity information -- how point A is connected to point B -- will generate up to a petabyte of data." A petabyte is 1 quadrillion bytes of information.
Communicating the Results
All the raw data and analysis from this NIH funded project will be made available to the entire scientific community. Marcus, who is in charge of the informatics, is working with partners at the eight other institutions of the consortium to develop analysis and imaging methods.
The van Essen lab is developing a downloadable desktop application for visualizing the data and navigating through it, called the Connectome Workbench. Marcus' lab is developing the database that will feed into the Workbench.
Marcus compares the computational side to Google Earth. They are building an atlas of connections in the human brain that people will be able to explore visually. A scientist can go into the human brain atlas, click on a point and see what is connected to both functionally and physically. The click will bring them into the database on the supercomputer at Washington University for answers.
This database is more complicated than Google Earth. There is only one earth, but data from 1,200 brains will be in this system at the beginning. They will try to synthesize these 1,200 brains into one representative "normal brain" reference.
At the same time they want to understand the variability among brains. An investigator may want to compare high IQ to low IQ brains or optimists to pessimists. Because each individual brain, its cognitive profile and its analysis will be on the database, comparisons should be meaningful and accurate.
The project will have a strong outreach program to help train investigators how to capitalize on the Connectome data. They will provide tutorials, seminars and webinars.
Lots of questions will be answered as this project progresses, and likely more will be raised. One question is just how much agreement will be found between structural connectivity and functional connectivity. Studies to date have shown a great deal of overlap in many areas, but less in other areas. However, as Shimony point out about a study he participated in, many of the differences can be explained by limitations in the methods.
Finally, the 1 cubic mm "voxels" that will be the building blocks of the map can contain up to a million neurons. It is certainly possible that this level of detail will not be able to answer all questions. Maybe, for example, personality traits are defined by smaller groups of cells. But in five years time, it is also certainly possible that more powerful imaging techniques will be applicable to the involved areas pointed out by the Connectome project.
Jo Seltzer is a freelance writer with more than 30 years on the research faculty at the Washington University School of Medicine and seven years teaching technical writing at WU's engineering school.