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Does autism start as a glitch in one area of the brain--the brainstem, perhaps--and then radiate out to affect others? Or is it a widespread problem that becomes more pronounced as the brain is called upon to set up and utilize increasingly complex circuitry? Either scenario is plausible, and experts disagree as to which is more probable. But one thing is clear: very early on, children with autism have brains that are anatomically different on both microscopic and macroscopic scales.
For example, Dr. Margaret Bauman, a pediatric neurologist at Harvard Medical School, has examined postmortem tissue from the brains of nearly 30 autistic individuals who died between the ages of 5 and 74. Among other things, she has found striking abnormalities in the limbic system, an area that includes the amygdala (the brain's primitive emotional center) and the hippocampus (a seahorse-shaped structure critical to memory). The cells in the limbic system of autistic individuals, Bauman's work shows, are atypically small and tightly packed together, compared with the cells in the limbic system of their normal counterparts. They look unusually immature, comments University of Chicago psychiatrist Dr. Edwin Cook, "as if waiting for a signal to grow up."
An intriguing abnormality has also been found in the cerebellum of both autistic children and adults. An important class of cells known as Purkinje cells (after the Czech physiologist who discovered them) is far smaller in number. And this, believes neuroscientist Eric Courchesne, of the University of California at San Diego, offers a critical clue to what goes so badly awry in autism. The cerebellum, he notes, is one of the brain's busiest computational centers, and the Purkinje cells are critical elements in its data-integration system. Without these cells, the cerebellum is unable to do its job, which is to receive torrents of information about the outside world, compute their meaning and prepare other areas of the brain to respond appropriately.
Several months ago, Courchesne unveiled results from a brain-imaging study that led him to propose a provocative new hypothesis. At birth, he notes, the brain of an autistic child is normal in size. But by the time these children reach 2 to 3 years of age, their brains are much larger than normal. This abnormal growth is not uniformly distributed. Using MRI-imaging technology, Courchesne and his colleagues were able to identify two types of tissue where this mushrooming in size is most pronounced.
These are the neuron-packed gray matter of the cerebral cortex and white matter, which contains the fibrous connections projecting to and from the cerebral cortex and other areas of the brain, including the cerebellum. Perhaps, Courchesne speculates, it is the signal overload caused by this proliferation of connections that injures the Purkinje cells and ultimately kills them. "So now," says Courchesne, "a very interesting question is, What's driving this abnormal brain growth? If we could understand that, then we might be able to slow or stop it."