General Hospital (MGH) has identified specific portions of the brain's whitematter that are abnormally large in children with autism and developmentallanguage disorder (DLD). The findings confirm that the previously observedovergrowth of white matter occurs after birth and suggest that it may berelated to the process of myelination, in which portions of nerve cellscalled axons are covered with a material called myelin. The report appearsin the April issue of Annals of Neurology.

The researchers noted that the factor most closely associated with the areasshowing the greatest volume increase is when the axons in those areasmyelinate, a key step in maturation that allows nerve impulses to betransmitted properly. In both autistic and DLD patients, the most enlargedareas were those that myelinate latest in normal development and wheremyelination takes a longer period of time.

"Knowing that white matter is most enlarged in the area that develops myelinlatest will help us narrow the time window in which to look for the cause ofthese problems and should help focus future research," says Martha Herbert,MD, PhD, of MGH Neurology and the Center for Morphometric Analysis, thepaper's lead author.

Autism is a serious developmental disorder characterized by a lack of normalsocial interaction, language abnormalities and repetitive, ritualisticbehavior. Many earlier studies have shown that autistic children often haveunusually large brains and experience rapid brain growth in the first yearsof life. This increased brain volume appears to be concentrated in the whitematter. Primarily made up of axons - long processes that extend out frombrain or other nerve cells - the white matter is located in the interior ofthe brain, beneath the cerebral cortex which contains the bodies of braincells.

The same white matter abnormality is found in developmental languagedisorder, a condition in which language is abnormal but intelligence andbehavior are normal. Few studies have measured brain volume in DLD patients,and some have shown increased brain volume in these children as well.

The current study used advanced techniques for analyzing magnetic resonanceimaging(MRI) studies to subdivide white matter into distinct regions related to thepathways taken by axon fibers. Imaging studies were made on 63 children - 13with autism (all boys), 24 with DLD (14 boys, 7 girls), and 29 normalcontrols (15 boys, 14 girls). The participants were about ages 8 and 9, andall were high functioning, with IQs over 80.

The results showed that in both the autistic and DLD participants, the outerlayer of white matter was significantly larger than among controls, whilethe inner areas were no different from controls. While all portions of theouter layer of white matter were enlarged in autistic participants, thefrontal lobe area (behind the forehead) showed the greatest enlargement.White-matter enlargement in the DLD participants was seen in the frontal,temporal (behind the temples) and occipital (back of brain) areas, but notin the parietal lobe (upper, lateral area). Both groups of children showedthe greatest white matter enlargement in the prefrontal area, the very frontof the brain. Of particular interest, white matter in the corpus callosum,which connects the right and left hemispheres, showed no volume increase.

"Finding a change in these children's brains that occurs after birth maygive us better targets for preventing and treating these disorders. If wedevelop methods for early detection, we may be able to treat theseconditions before they get too advanced," says Herbert, an instructor inNeurology at Harvard Medical School.

Herbert's co-authors are senior author Verne Caviness, MD, DPhil, DavidZiegler, Nikos Makris, MD, PhD, Joseph Normandin, and David Kennedy, PhD, ofthe MGH; Pauline Filipek, MD, University of California at Irvine; ThomasKemper, MD, Boston University School of Medicine; and Heather Sanders,University of Pittsburgh School of Medicine.

The research was supported by grants from the National Institute ofNeurological Disorders and Stroke, the Cure Autism Now Foundation, theNational Institutes of Health, the Human Brain Project, the Fairway Trust,and the Giovanni Armenise-Harvard Foundation for Advanced ScientificResearch.Massachusetts General Hospital, established in 1811, is the original andlargest teaching hospital of Harvard Medical School. The MGH conducts thelargest hospital-based research program in the United States, with an annualresearch budget of more than $400 million and major research centers inAIDS, cardiovascular research, cancer, cutaneous biology, medical imaging,neurodegenerative disorders, transplantation biology and photomedicine. In1994, MGH and Brigham and Women's Hospital joined to form PartnersHealthCare System, an integrated health care delivery system comprising thetwo academic medical centers, specialty and community hospitals, a networkof physician groups, and nonacute and home health services.

This story has been adapted from a news release issued by Massachusetts General Hospital.
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