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Autistic individuals have a fundamental structural difference in the alignment and wiring of their brain cells, a difference that explains these individuals' proclivity to live in their own world, according to researchers.
"The fundamental structure by which they think and process information is different," said Dr. Manuel F. Casanova, neurologist and neuropathologist at the Medical College of Georgia and lead author on research findings published in the Feb. 12 issue of Neurology. The structural difference they have found would result in too much communication, too little inhibition and a tendency to shut out much of the world around them, the researchers said.
Dr. Casanova's research team members examined the brain tissue of nine autistic people with a mean age of 12 and found to their surprise that not only do they have smaller minicolumns – a basic organizational unit of 80 to100 brain cells and their connective wiring – they have more of them. The team reproduced its findings using a different method of microscopic analysis before submitting them for publication.
"We believe that we have uncovered a major source of pathology that has been untouched before because no one looked at minicolumns," Dr. Casanova said. "I pray we are correct because this is standing on the verge of something that could be very important to many people."
The team previously published studies indicating that microscopic differences in the minicolumns of man and non-human primates help explain man's capacity for complex communication. They also postulated that differences in the minicolumns might hold clues to conditions such as autism and schizophrenia in which communication is dramatically impacted. "Intelligence is not the property of single cells, it's in the circuitry," Dr. Casanova said, referring to the minicolumns where cells take in information, process it and respond.
Despite the general observation that autistic individuals tend to have unusually large brains, the researchers found throughout those brains smaller units of circuitry and many more of them. Everyone has millions of minicolumns yet their presence cannot be detected grossly with even the most sophisticated brain-imaging equipment. A microscope is needed to detect the structures that are about forty-millionth of a meter in diameter (a meter is 39.37 inches).
In autistic individuals, often defined as non-communicative and self-centered, these microscopic structures are even tinier and more numerous so the individuals are literally bombarded with communication and stimulation from the environment. "Even the flickering of a fluorescent light can interfere with an autistic person's concentration," Dr. Casanova said.
Computer modeling of their tiny minicolumns indicates excess signaling between cells along with too little inhibition, he said, noting that about one third of the people with autism also develop seizures, another condition in which signaling and inhibition are out of balance. In fact, case reports have shown that anti-seizure medications – which limit the flood of signals reaching the brain – have reduced the autistic symptoms of those who also have epilepsy. Dr. Casanova theorizes that if inhibitory medications, such as anti-seizure medications, were given early enough to an autistic child, in the first few years of life while their brains are being hard-wired, they could help normalize the flow of stimulation reaching the minicolumns. The Augusta researchers already have begun studying the minicolumns of people with epilepsy to determine their pathology as well.
This peculiar pathology linked to autism begins during early development when germinal cells, which have great potential for developing into different types of cells, start dividing to form the brain's major component, the cortex. "In the cortex, the germinal cells continue to migrate. This provides for progressive layering of cells into minicolumns, almost like rainbow Jell-O," Dr. Casanova said. "So autism results from a defect during creation of the cortex."
But, based on his group's research, Dr. Casanova suggests that these microscopic differences in cell organization may not be a defect at all but a step in brain evolution that enables people to truly focus on complex issues facing today's society, such as technology and science.
"Evolution is usually depicted as a ladder where one rung follows the next," he said. "It is really more of a bush with sideway branches or improvisations. Variation in the size and number of minicolumns may represent one such improvisation." Today, less than 1 percent of the population is autistic but the numbers have steadily increased since the 1940s when the first figures began being gathered.
Co-authors on the Neurology article include Dr. Daniel P. Buxhoeveden, research associate, MCG; Andrew E. Switala, computer programmer and mathematician, and Dr. Emil Roy, computer applications expert at the Augusta Department of Veterans Affairs Medical Center.
Brain tissue used in the study came from the Autism Research Foundation in Boston and funding was provided by grants from the Theodore and Vada Stanley Foundation and the VA Merit Review Board. "We are grateful to the Autism Research Foundation and to the families who donated brain tissue for study," Dr. Casanova said. "Without the generosity of both, this type of research would not be possible."
Journal
Neurology