Cure Autism Now Science Summary: The White Matter Story

white matter, gray matter

This is Cure Autism Now's Science Director, Sophia Colamarino. Every now and then I will be writing science summaries to help you make sense of important research published about understanding and treating autism. When translating the results I will try not to use those annoying big science-y terms, though I will help you by defining words you may hear thrown around by scientists. However, I will not "dilute down" the science - CAN believes you have every right to know as much as we do!

This first story is long because it is actually a compilation of many important papers published by Dr. Martha Herbert on one very important subject which we call the White Matter Story.

Let us know what you think and stay tuned for future articles...

When first describing autism in 1943, Leo Kanner noted that some autistic children have enlarged heads. Measurements of head circumference have since confirmed that autistic toddlers tend to have greater than normal head size. Images of their brains show that they are indeed bigger, but where does the extra brain come from? The answer is that most of the size increase is accounted for by an enlargement in a part of the brain known as white matter.

In a series of papers released over the past two years, scientist Martha Herbert from Massachusetts General Hospital at the Harvard Medical School measured individual parts of the brain to find out why autistic brains are bigger than normal. Her results have provided a surprising insight into the anatomy of autistic brains - autistic brains are not just bigger versions of normal brains, instead some parts have expanded more than others, resulting in a brain that is no longer to-scale. Using a technique known as Magnetic Resonance Imaging to take detailed pictures of the brain, Dr. Herbert first confirmed earlier studies by Dr. Eric Courchesne showing that the part of the brain that had expanded most in size relative to normal brains is the white matter. White matter consists of the millions of individual nerve fibers that ferry information from one brain region to the next. (The name white matter derives from the color of the fatty material that insulates the nerve cell fibers as they project throughout the brain.)

Examining the white matter enlargement in greater detail, Dr. Herbert discovered that not all white matter is expanded to the same degree. The increase is greatest in the white matter that transmits information between brain regions that are close to each other and on the same side of the brain. In contrast to these local projections, the volume of long-distance white matter projections (which transmit information between regions far from each other or those on opposite sides of the brain) remains relatively unchanged. Even more intriguingly, the increase in locally-projecting white matter is not seen equally throughout the brain. The volume change is biggest in the front of the brain, which is the part of the brain most interconnected with all other brain regions. This area is responsible for integrating information from many other brain regions and is where the most abstract ("higher-order") brain functioning is believed to take place. This white matter area also develops later than many others and doesn't reach maturity until the second year of life, if not later. In the future, this may provide scientists with an important time window for targeting therapies that would protect against the abnormal white matter development.

Dr. Herbert next reasoned that since there is a preferential increase in connections running within each brain half as compared to between brain halves, it may be harder for information on one side of the brain to be shared with the other. In this case, each side may be left to handle information processing on its own. Specialization of function on one side of the brain is called "lateralization," and brain areas are often bigger on the side to which they are lateralized (perhaps to handle their increased work load). For example, language function is lateralized to the left brain, and the areas of the brain which handle language processing are correspondingly bigger on the left than the right side. Dr. Herbert undertook a fine-grained evaluation of brain asymmetry by systematically measuring the sizes of 48 areas on both sides of the brain. Astonishingly, in autistic children she found a reversal of the brain asymmetry - there are more areas that are bigger on the right than the left side of the brain, making the brain size biased overall to the right half. This is opposite of what is found in the brains of typically developing children. Moreover, just as with the white matter increase, the brain areas that show the biggest changes in asymmetry are those higher-order association areas, the ones that tie together information from many different parts of the brain.

According to Dr. Herbert, perhaps the most unexpected finding was that very similar changes are seen in the brains of children with Developmental Language Disorder (also known as Specific Language Impairment), another disorder which involves language impairment and in which Dr. Herbert had earlier also found white matter enlargements. The similarity between the disorders highlights the fact that the anatomical problems may underlie the inability to process complex information such as language, and that the language problems in autism may be part of a much more widespread abnormality.
Overall, Dr. Herbert's discoveries of non-uniform changes in white matter connectivity and abnormal brain asymmetry suggest that in autism parts of the brain may not be talking to each other as normal. Proper brain functioning requires that nerve cells relay information from one part of the brain to another, with information from each brain region becoming integrated with information from others. Complicated thoughts and perceptions are assembled into coherent pictures through the ability of brain cells to speak with each other. This integration is also dependent on good timing, so that the signals arrive in a coordinated fashion rather than helter-skelter. If, in the case of autism, the connections between different brain regions are altered, and not altered evenly, what might this mean to the ability of the brain to process information and function normally? One hypothesis is that the distorted brain wiring might break down coordination and timing, forcing autistic brains to process more information locally rather than globally. This could explain why autistic individuals are much better at processing parts than putting them together into wholes. Altering the network communication might make autistic individuals especially vulnerable to impairments in complex functions that usually depend on multiple brain areas working together, such as social interactions, communication, and adaptability to changing environments.

For years researchers have been puzzled by the fact that the brains of autistic children appear grossly normal even if we know their brains cannot be functioning as normal. Dr. Herbert's thorough analyses have provided us with a long sought after insight into what developmental processes might be going awry. This will allow us to point our radar at something specific and begin to study its mechanism in depth. What is causing the enlargement in a subset of white matter? What are the genes and environmental factors that make someone susceptible to these problems? Do all autistic children have white matter abnormalities, or is this just one way to arrive at some other universal problem that all autistic individuals share? And finally, of highest importance, how can we re-shape the white matter connections by taking advantage of the brain's well-known and rather remarkable ability to continually use experience to alter itself?

For this body of research Dr. Herbert has received a 5-year CAN Innovator Award. Our Science Program is rapidly bringing its resources to bear on this problem and this month will be hosting a White Matter Think Tank. This will allow scientists from many different disciplines, not just autism, to brainstorm about solving the white matter mystery.