The Cure Autism Now Foundation's newest major project, the Brain Development Initiative, aims to bring together many methods and scientists to capitalize on the findings of regional abnormalities in the development of white matter in the autistic brain. Lead by Dr. Martha Herbert of Massachusetts General Hospital, this initiative will explore the possible causes and consequences of white matter changes, relating measures of brain structure and function to neurochemistry and genetics. This work continues Cure Autism Now's focus on bridging research disciplines to fund innovative work that approaches autism in ways not previously contemplated.
Martha Herbert knows exactly what spurred her to work on autism. "It got under my skin," she explained. "I began to realize that this problem contained everything I've ever been interested in." For Herbert, "everything I've ever been interested in" is a lot of ground to cover. Specializing in pediatric neurology with a background in anthropology, she is fascinated by pure science, the culture that drives it and the application of scientific discoveries to alleviate human suffering.
Dr. Herbert's project is a perfect choice for Cure Autism Now in that her work not only promises to advance science and eventually the clinical treatment of autism, but it also has the potential to change the entire culture of autism research. From the beginning, CAN has worked to address the scientific culture and to breach barriers between institutions and disciplines that often threaten to block science from realizing its full potential. Cure Autism Now sees its role as not to simply supplement existing research approaches but to complement them, to identify the new strategies and sometimes risky investments whose payoff will allow treatments and prevention for autism to be discovered today rather than tomorrow.
Science is by nature a cautious and conservative discipline, and can sometimes be its own worst enemy when it comes to considering new ways of thinking. "There is no time to be conservative," says Dr. Herbert, when it comes to exploring these new paradigms.
The Brain Development Initiative takes its impetus from a confluence of recent findings on the timing of brain development in autism. Although it's become well known during the past few years that children with autism have abnormally large brains in early childhood, it's still unclear just what this observation may be telling us. Is it the brain overgrowth that causes development to go haywire, or is the overgrowth itself a response to some other, less obvious problem? In other words, is an overgrown brain a cause or an effect? And just what part or parts of the brain are abnormal?
In order to gather some more specific information on these problems, Dr. Herbert has spent the past several years meticulously measuring MRI scans of people with autism in her laboratory. This work began with a pilot research grant from Cure Autism Now. Her recently published findings show that the white matter of the brain accounts for a great deal of the overgrowth, and that it's specifically the later-developing parts of this white matter that are most affected.
White matter contains fibers that connect neurons in separate areas of the brain. Gray matter contains the neurons themselves. You can think of this distinction as analogous to that between the cables (white matter) and circuit boards (gray matter) inside a computer: even though each individual circuit board may be intact, if the cables are disrupted then the computer can't function.
Dr. Herbert suspects that the her findings of abnormal white matter may be related to abnormally sized regions of gray matter that she's found in people with autism. These gray-matter abnormalities are most pronounced in areas of the brain that integrate inputs from many sources -- for example, areas that put together information from many sensory inputs rather than dealing with only a single source of input. It's exactly these regions that mature latest in development and that depend on properly structured input in order to mature correctly. If the white matter isn't providing the proper inputs to these areas, their maturation will end up skewed. White and gray matter may distort each other's development in a vicious circle, with effects that are greatest in the most complex, latest-developing regions of the brain. This emerging theme of greater abnormality in later-maturing parts of the brain suggests that perhaps the bulk of autism's difficulties arise as secondary consequences and that if we can understand what it is that sets them off, then we can intervene at an early enough stage to prevent them from going so far off track.
Dr. Herbert describes her discoveries about white matter as a "hook." Even though abnormal white matter may not be a direct cause of autism, it gives scientists an entry point to autism's complex web of inter-related abnormalities. By exploring the causes and consequences of white-matter overgrowth, we can advance fronts of inquiry through this web of relationships. Using techniques such as magnetic resonance spectroscopy and positron emission tomography to examine the brain's chemical composition, Cure Autism Now's Brain Development Initiative will explore at cellular and molecular levels what may be causing these abnormal patterns of brain growth. Studies of EEG coherence will relate brain structure to brain function by investigating how brain regions that are abnormally connected during development communicate with each other. Finally, the detailed analyses that Dr Herbert conducted in her earlier studies can be combined with genetic information. This bridging of levels of investigation -- between brain structure, brain function, brain chemistry, and genetics -- is what will allow us to connect the dots and to see how abnormalities in all these aspects relate to each other.
What people see is in great measure limited by what they're interested in seeing. Perhaps this truth is best appreciated by those of us who know people with autism. A person with autism may be able to memorize the arrangement of freckles on a person's face, yet unable to recall whether the face was smiling or frowning. In the same way, we scientists tend to zero in on the details with which we're most concerned; the observations that we choose to collect and the interpretations that we choose to construct around them depend very strongly on what we expect to find.
For many years, neuroscientists tried to understand autism as we had understood other disorders of the brain: by trying to find some particular bit of brain tissue in which autism was localized. Historically this approach had brought great success in understanding conditions in which an adult brain was damaged by a stroke or a tumor. What this lesion approach failed to appreciate fully, though, is that abnormalities in a developing brain aren't circumscribed in the same way as an injury to a fully developed brain. What makes autism such a difficult and fascinating problem is the very complexity of interplay amongst the developing brain's many subsystems and regions. Autism's solution cannot come from just one approach or one focus, but must depend on integrating findings on many levels. In order to bridge these levels, says Dr Herbert, "We need to nurture people into thinking collaboratively."
The Brain Development Initiative continues Cure Autism Now's tradition of focusing on promising but undeveloped scientific questions, and bringing together scientists from different backgrounds and disciplines so that they can work towards a synthesis of ideas.
Cure Autism Now would like to recognize the Autism Coalition for Research and Education (ACRE) as a Research Partner on the Brain Development Initiative.