Paul M. Thompson,1 Agatha D. Lee,1 Rebecca A. Dutton,1 Jennifer A. Geaga,1 Kiralee M. Hayashi,1 Mark A. Eckert,2Ursula Bellugi,3 Albert M. Galaburda,4 Julie R. Korenberg,5 Debra L. Mills,6 Arthur W. Toga,1 and Allan L. Reiss 2

1Laboratory of Neuroimaging, Brain Mapping Division, Department of Neurology, University of California Los Angeles School of Medicine, Los Angeles, California 90095, 2Stanford Psychiatry Neuroimaging Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305, 3Salk Institute Laboratory for Cognitive Neuroscience, La Jolla, California 92037, 4Department of Neurology, Harvard Medical School, Boston, Massachusetts 02215, 5Department of Pediatrics, University of California Los Angeles, Los Angeles, California 90095, and 6Department of Psychology, Emory University, Atlanta, Georgia 30322 4146

• The Journal of Neuroscience, April 20, 2005 • 25(16):4146–4158

A review for interested parents, by Paul. P. Wang, M. D.

Studies of brain anatomy in Williams syndrome started in the early 1990s, and the sophistication of their methods has increased rapidly. The earliest studies were limited by the MRI methods that were available at the time. These studies could only measure the size of relatively large parts of the brain. The newer studies can look much more closely at specific regions of the brain, with a resolution down to about 1 millimeter.

The most recent study, by Prof. Paul Thompson and colleagues at UCLA, used MRI to examine the brains of 42 teens and adults who have Williams syndrome, in comparison to 40 volunteers who were roughly of the same age, but do not have any genetic diagnosis. Thompson and his colleagues used state-of-the-art methods to identify specific regions of the brain (we've all seen pictures of the complex folds and crevices on the surface of the human brain). In addition, their methods allowed the identification of brain grey matter (where the "bodies" of the neurons are concentrated) and brain white matter (where the long "axons" of the neurons are found). Gray matter is on the surface of the brain, like a layer of gray icing over the white matter, which is under the surface.

Similar to previous studies, Thompson et al. found that the overall volume of the brain in Williams syndrome tends to be about 10-15% smaller than in volunteers who are the same age but who don't have WS. There was no important difference between the left and right hemispheres of the brain in the reduction of volume. Taking a closer look at their images, it was found that the volume of white matter was decreased much more (15-20%) than the volume of gray matter (5-10%). It was also found that the pattern of folds and crevices in the WS brains was more complex than in the comparison group. The study team reasoned that this is because relatively more gray matter has to be spread across the surface of relatively less white matter, resulting in more bumps and folds in the gray matter "icing."

Going a step further than any other investigators have gone, Thompson et al. looked at the thickness of the gray matter layer in the brain. They found that in the right hemisphere of the brain, in the regions that are important for processing sounds and language, the layer of gray matter was actually thicker in Williams syndrome than in the comparison subjects. Other regions showing thicker gray matter in WS included the areas of the brain that are important for recognizing and interpreting faces and facial expressions. Still other regions had a thinner gray matter layer in WS than in the comparison subjects, but statistical analysis showed that these results are uncertain. Finally, the thickness of the gray matter layer decreased with age, which is believed to be true regardless of the diagnosis of WS.

Unfortunately, our ability to interpret MRI results like these is still very poor. We still don't know whether a thicker gray matter layer is helpful or not. Perhaps the neurons are not working well, so that is why more cells in a thicker layer are needed, or perhaps they work in a different way because the layer of cells is thicker than usual. These new findings are definitely helpful, nonetheless, because they will help us to understand how the development of the brain is different in WS, which may ultimately allow us to understand how therapies for WS should be designed.

To read the complete text of the study (in Adobe .pdf format), please click here.