Neuroscientists at Washington University School of Medicine in St. Louis have assembled a first-of-its kind atlas of the folds of the cerebral cortex, the wrinkled surface layer of the brain credited with many of the higher cognitive functions that make us human. The atlas, known as the Population-Average, Landmark and Surface-based (PALS) Atlas, links brain functions to the various peaks and valleys of the cortex.
PALS is the first brain atlas that accurately portrays the complex folds of the cerebral cortex not just from a single individual but from a group of individuals. It is available online (http://sumsdb.wustl.edu:8081/sums/) both to provide a resource for neuroscientists seeking to determine the functions of an interesting brain area and as a repository for adding new data that expand and fine-tune the atlas’ maps.
The creators hope it will be useful in a wide variety of research projects. Among other studies, PALS is already helping scientists understand how an inherited disorder changes the brain and how brain function adjusts in response to blindness.
A paper on the creation of PALS appears online this week in the journal Neuroimage.
Senior investigator David Van Essen, Ph.D., the Edison Professor of Neurobiology and head of the Department of Anatomy and Neurobiology, has been compiling cortical cartography for two decades. He compares scientists’ current knowledge of the details of human brain structure to 17th-century mapmakers’ grasp of the surface of the Earth.
“We know a lot, and we’re learning much more all the time, but some features that we would like to be able to definitively pinpoint are actually rife with uncertainty,” he says. “And large fractions of the cortex have areas of controversy or outright error.”
In all fairness to cortical cartographers, Van Essen notes, mapmakers charting the Earth never had to deal with the tremendous variability found in billions of individual human brains. Genetic and environmental differences, reactions to injury, and inherited disorders can all change the topography of the brain in minor and major ways.
To compensate for these variations, neuroscientists have developed a process called registration that lets them mathematically adjust the results of a brain scan to either match it with an atlas or enter it into the atlas. This approach previously has been used to assemble atlases based on study of the volume of different brain areas.
“The cerebral cortex has been crumpled up so that it can fit snugly inside the skull, like a beach ball crumpled to fit inside a cardboard box,” Van Essen explains. “Volume-based registration is like squeezing and twisting each cardboard box so that they all end up the same size. That’s a good start, but it doesn’t allow us to bring different folds from the individual beach balls into alignment.”
Surface-based registration sets the box aside, according to Van Essen.
“That lets us inflate each cortex into a perfectly spherical shape, and then it becomes much easier to rotate and locally deform each beach ball so that they are all consistently aligned to the target atlas,” he explains. “We can do this with much more accuracy than is possible when both the atlas and the individual brain are in the crumpled state, and this leads to a dramatic improvement in the quality of the results.”
Initially based on MRI scans of 12 healthy people gathered by Randy Buckner, Ph.D., associate professor of neurobiology and of radiology in the School of Medicine and associate professor of psychology in Arts & Sciences, PALS now includes data from 60 additional scans. To give the atlas its first test run, Van Essen conducted a study of the structural differences between the left and right hemispheres of the brain.
“In addition to being functionally different, it’s been known for decades that the left and right hemisphere are also subtly different in structural ways,” Van Essen explains. “And we were able to use PALS to characterize some of these differences in greater detail than has previously been possible.”
For example, Van Essen’s study showed that a fold in the temporal lobe is deeper in the right hemisphere than it is in the left. The fold is involved in such tasks as combining information from vision and hearing.
Van Essen’s lab is currently using PALS in studies of Williams syndrome, an unusual genetic disorder that produces some cognitive deficits but also makes children hyper-social.
“Kids with this condition are very gregarious, and we have previously shown some dramatic differences in the shapes of their brains,” Van Essen says.
One example of these differences is found in the parietal lobe, a region located near the top of the head that, among other functions, helps the brain track where objects are in space. In Williams syndrome patients, a valley in the parietal lobe known as the intra-parietal sulcus is typically shallower.
A colleague, Harold Burton, Ph.D., professor of neurobiology, of radiology and of cell biology and physiology, will use PALS to aid his studies of how the brain adapts to blindness.
“PALS allows us to link the areas of changes in brain function in the blind to known functional areas identified in normally sighted people,” Burton explains. “It’s probably one of the most useful tools that have come around in recent years.”
Van Essen envisions continued expansion and adjustment of the atlas through online contributions of data from researchers whose studies have benefited from the atlas.
“After they publish their results, we’ll encourage the investigators to display those results on the database and to place their data into a common repository,” he explains. “This will allow neuroscientists to have access to many sources and types of data through the common framework of the online PALS atlas.”
Van Essen, DC. A Population-Average, Landmark- and Surface-based (PALS) atlas of human cerebral cortex. Neuroimage, September 2005.
Funding from the National Institute of Mental Health, the National Institute for Biomedical Imaging and Bioengineering and the National Science Foundation supported this research.
Washington University School of Medicine’s full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.