Faulty Brain-Wide Circuitry May Underlie Autism

PITTSBURGH, Aug. 16 -- Autism may be a brain-wide phenomenon caused by poor connections among the brain's parts rather than by defects in one or two areas, according to investigators here.

The finding from an NIH-funded study of autistic children has implications for how those who teach and care for autistic children can help them to learn and function better, reported Nancy J. Minshew, M.D., of the University of Pittsburgh in the August issue of Child Neuropsychology.

The study found that autistic children performed as well as normal children-and sometimes better-when it came to relatively simple cognitive skills such as spelling or vocabulary,

But in tasks requiring multiple domains of the brain to work together, such as reading comprehension or understanding figurative language, autistic children performed worse than their age-matched counterparts, Dr. Minshew and colleagues said.

These results, combined with neuroimaging studies and similar findings in adults, suggest that researchers seeking the fundamental cause of autism may have to step back and look at the big picture, rather than hone in on specific parts of the brain, the investigators said.

Likewise, clinicians' understanding of autism will have to move beyond the standard "diagnostic triad," which defines autism as problems in the areas of social interaction, communication, and reasoning, they added.

The study involved 56 high-functioning autistic children (IQ of 80 or above) who ranged in age from eight to 15. An array of neuropsychological tests assessed these children's ability to perform both simple and complex tasks in various cognitive areas. Test results were compared with those of 56 children without autism.

Overall, the autistic children could handle simple tasks involving sensory perception, language skills, memory, and motor skills as well as the control group.

For example, on a vocabulary test where the mean score was 10, the autistic group scored an average of 11, as did the control group. And on a spelling test with a mean score of 100, the autistic group did somewhat better than the control group, scoring an average of 111 versus 106 for the other children.

But the autistic children's performance began to break down when confronted with more complex tasks in these cognitive domains. On a test where the children had to explain the meaning of figures of speech (mean test score=10), the autistic group scored an average of 7.4 versus 9.9 for the control group.

In the cognitive domain of sensory perception, both groups of children could distinguish equally well between sharp and dull objects. But in a test where the children had to identify a number traced on their backs with a fingertip, the autism group made twice as many errors as the control group (12.7 versus 5.7).

Previous, similar studies in adults yielded largely the same results, the authors said.

Neuroimaging studies have provided biological confirmation of the researcher's new model of autism, which they have termed the "complex information-processing model." The imaging studies "have provided evidence of functional under-connectivity in higher order circuitry and intact lower order circuitry, analogous to the cognitive pattern observed in the present study," the authors said.

In fact, some studies have suggested that in autistic children the brain begins to "overgrow," and this abnormal growth disrupts the development of brain circuitry, the authors added.

For clinicians, "it is important to realize that autism is more than a social disorder," said Diane L. Williams, Ph.D., also of the University of Pittsburgh, a co-author. "Just teaching the children social rules will only deal with a piece of what is going on."

"It really is at the level of how the brain handles incoming information of all types," Dr. Williams said.

Those caring for autistic children "need to mediate the world for these kids," she said. "You need to pre-process information for them, break it down for them, help them to understand what is the most important, and help make the connections for them, because they will not get it themselves."

A chief limitation of the current study was that is included only children eight or older, while a first diagnosis of autism is usually made much earlier, the authors said.

"It is possible that a study of children with autism younger than eight years would reveal involvement of a single domain rather than multiple domains," they said. "However, research to date has not provided support for this hypothesis. Even at first diagnosis, which is about 18 months, there is involvement of multiple domains."

Another limitation is that the study did not evaluate the children in the cognitive domains of social learning and non-verbal communication, two hallmarks of autism, the authors said. However, deficits in these areas have already been well-established, they said.

"The complex information-processing model not only broadens the conceptualization of autism beyond the diagnostic triad, it is also a working concept that facilitates the integration of findings across cognitive and neurobiologic methodologies," the authors concluded. "Such connections are essential in the search for the neural basis and developmental neurobiologic mechanism of autism."

The study was supported by a grant from the National Institute of Child Health and Human Development.