Brain Architecture and Williams Syndrome

Charlie is thirteen. He has Williams syndrome (WS). When either his mother's egg or his father's sperm were forming, about 20 genes were dropped from chromosome seven. Those 20 might not seem like many out of the 25,000 that make a human being, but they made a big difference in who Charlie is, what he loves, and what he can do. He can neither read nor write, probably never will learn say the doctors, although his vocabulary is large and he speaks with clarity and expression.

His IQ has been measured at 60, but his social graces show no impairment. He's charming with people: bubbly, sociable, trusting—perhaps indiscriminately trusting—with everyone he meets, and he remembers everyone's face. Charlie can't button his shirt and manipulating a fork at the dinner table is tough, but his motor coordination is excellent when he engages in his favorite activity: playing the drum. Charlie goes to a special school and loves the people there. When he's not in school or playing the drums, he's listening to music on his iPod.

Neuroscientists have studied the brains of children like Charlie in the hope of better understanding not only Williams syndrome but also the structure and development of the normal brain. Compared to children in a control group, kids like Charlie tend to have a small volume when both overall brain size and the size of the cerebrum are measured, but the volume of the cerebellum is no different, although the brainstem is disproportionately small. Relative to typically developing kids, Charlie probably has less white matter in his cerebrum and less gray matter in his right occipital lobe. (The gray matter is composed primarily of the bodies of neurons. It's found mostly in the brain's outer layer, the cerebral cortex. The white matter lies beneath the cortex. It's made mostly of axons, thin projections from neurons that carry impulses away from the cell body.)

Charlie's brain is convoluted into folded gyri and sulci like everybody else's, but not everywhere in the normal way. The central sulcus, the large deep groove that runs across the top of the head separating the frontal and parietal lobes, is abnormally shaped, as if it failed sometime during development to twist back on itself. In the right hemisphere, the Sylvian fissure (also called the lateral sulcus), which is a prominent valley in the temporal lobe, cuts horizontally and fails to ascend into the parietal lobe the way it should. Studies have also revealed an abnormality of the planum temporale, a region of the auditory cortex known to play a role in musical learning and processing. In most people, it's larger in the left hemisphere than in the right, but in kids like Charlie, it's the same on both sides, because the right is greatly expanded.

As brain studies continue, we are learning more about the neurological basis of Williams syndrome. This week, an important new report was published in the Proceedings of the National Academy of Sciences. A team of scientists led by the National Institutes of Health has now found in such cases changes in the connectivity and volume of gray matter in a brain region called the anterior insula (AI), which is thought to control emotion and personality.

The researchers found an overall decrease in gray-matter volume in one region of the AI, along with locally increased volume in another area; compromised white-matter integrity of the structure that connects the insula with some other brain regions; and disturbed neuron interactions between the AI and limbic regions known to be involved in processing emotions. Perhaps most important, the team found that differences in the AI correlate with the extent of WS characteristics. The greater the number and degree of the AI changes, the more of the typical WS behaviors that can be observed and measured in the person.

I sometimes hear criticism of brain mapping studies such as these. Critics say, "But knowing where changes happen in the brain has no practical use. It doesn't lead to treatment or prevention." In the short term, that's true. But in the longer view, if we can learn how changes in a gene lead to structural changes in the brain (or any other body part), we can—in theory—tailor-make interventions, either preventative or palliative. Granted, such advances will be a long time in coming, but they will never come if we don't first understand how a tiny change in the structure of a protein can lead to both anatomical and behavioral differences.

I also hear criticisms of studies on rare disorders, which WS certainly is. But this point, also, requires us to think long-term. Say the authors of the new study: "The present observations, in a rare population of individuals with well known genetic architecture and unique personality features, not only provide a deeper understanding of WS, but also inform the search for neural mechanisms by which genetic features contribute to complex behavior, both in the general population and in neuropsychiatric disorders."