Hospital (MGH) has identified specific portions
of the brain's white matter that are abnormally
large in children with autism and developmental language
disorder (DLD). The findings confirm that the
previously observed overgrowth of white matter
occurs after birth and suggest that it may be related
to the process of myelination, in which portions
of nerve cells called axons are covered with a
material called myelin. The report appears in the
April issue of Annals of Neurology.
The researchers noted that the factor most closely
associated with the areas showing the greatest
volume increase is when the axons in those areas myelinate,
a key step in maturation that allows nerve impulses
to be transmitted properly. In both autistic and
DLD patients, the most enlarged areas were those
that myelinate latest in normal development and
where myelination takes a longer period of time.
"Knowing that white matter is most enlarged
in the area that develops myelin latest will help
us narrow the time window in which to look for
the cause of these problems and should help focus
future research," says Martha Herbert, MD,
PhD, of MGH Neurology and the Center for Morphometric
Analysis, the paper's lead author.
Autism is a serious developmental disorder characterized
by a lack of normal social interaction, language
abnormalities and repetitive, ritualistic behavior.
Many earlier studies have shown that autistic
children often have unusually large brains and
experience rapid brain growth in the first years of
life. This increased brain volume appears to be
concentrated in the white matter. Primarily made
up of axons - long processes that extend out from brain
or other nerve cells - the white matter is located
in the interior of the brain, beneath the cerebral
cortex which contains the bodies of brain cells.
The same white matter abnormality is found in
developmental language disorder, a condition in
which language is abnormal but intelligence and behavior
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 resonance imaging(MRI) studies
to subdivide white matter into distinct regions
related to the pathways taken by axon fibers. Imaging
studies were made on 63 children - 13 with autism
(all boys), 24 with DLD (14 boys, 7 girls), and
29 normal controls (15 boys, 14 girls). The participants
were about ages 8 and 9, and all were high functioning,
with IQs over 80.
The results showed that in both the autistic
and DLD participants, the outer layer of white
matter was significantly larger than among controls,
while the inner areas were no different from controls.
While all portions of the outer layer of white
matter were enlarged in autistic participants,
the frontal 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 not in the parietal lobe (upper, lateral
area). Both groups of children showed the greatest
white matter enlargement in the prefrontal area,
the very front of the brain. Of particular interest,
white matter in the corpus callosum, which connects
the right and left hemispheres, showed no volume
"Finding a change in these children's brains
that occurs after birth may give us better targets
for preventing and treating these disorders. If
we develop methods for early detection, we may
be able to treat these conditions before they get
too advanced," says Herbert, an instructor
in Neurology at Harvard Medical School.
Herbert's co-authors are senior author Verne
Caviness, MD, DPhil, David Ziegler, Nikos Makris,
MD, PhD, Joseph Normandin, and David Kennedy,
PhD, of the MGH; Pauline Filipek, MD, University
of California at Irvine; Thomas Kemper, 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 of Neurological Disorders and
Stroke, the Cure Autism Now Foundation, the National
Institutes of Health, the Human Brain Project,
the Fairway Trust, and the Giovanni Armenise-Harvard
Foundation for Advanced Scientific Research. Massachusetts
General Hospital, established in 1811, is the
original and largest teaching hospital of Harvard
Medical School. The MGH conducts the largest hospital-based
research program in the United States, with an
annual research budget of more than $400 million
and major research centers in AIDS, cardiovascular
research, cancer, cutaneous biology, medical imaging, neurodegenerative
disorders, transplantation biology and photomedicine.
In 1994, MGH and Brigham and Women's Hospital joined
to form Partners HealthCare System, an integrated
health care delivery system comprising the two
academic medical centers, specialty and community
hospitals, a network of physician groups, and nonacute
and home health services.
This story has been adapted from a news release
issued by Massachusetts General Hospital.