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Brain lumps and bumps A neural risk for autism.

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EDITORIAL
Brain Lumps and Bumps: A Neural Risk
for Autism
Autism and specific language impairment (SLI) are
neurodevelopmental disorders that differ on many cognitive and behavioral dimensions. For example, a hallmark of autism is the deficient processing of emotionally laden stimuli including language, gesture, and
facial expression. In contrast, SLI is characterized by
impaired language functions but is not specifically
linked to emotional processing deficits. Both disorders
share deficits in language, although the nature and degree of deficits may differ. Given the common involvement of language systems in these two clinical disorders, it is most interesting to study the anatomy of
language-related cortex to see whether these two disorders are similar or dissimilar in brain morphology. The
study by De Fosse and colleagues1 utilizes advanced
magnetic resonance imaging (MRI) methods to study
frontal language regions in boys with autism and SLI.
The anatomy of the language-related cortex has been
studied using MRI methods with evidence that approximately 70% of individuals with normal language function have a larger substrate in the left cerebral hemisphere (leftward asymmetry). The regions that
consistently show a robust leftward asymmetry include
the pars triangularis (Brodmann’s area 45) within the
inferior frontal gyrus and the planum temporale (Brodmann’s area 22) within the superior temporal gyrus.2
In addition, a significant relationship has been found
between these anatomical asymmetries and language
laterality.3,4 Individuals with a larger left pars triangularis and larger left planum temporale have been found
to have language lateralized to the left cerebral hemisphere (left hemispheric dominant for language), and
individuals with a larger right pars triangularis and
larger right planum temporale have language lateralized
to the right. Thus, there is direct support for a structure–function relationship. In addition, atypical asymmetry (rightward or no interhemispheric size
difference-symmetry) of these language-related regions
has been found more commonly in individuals with
neurodevelopmental speech (developmental stuttering)5
and language disorders (dyslexia, SLI).6,7 Thus, atypical
asymmetry seems to be a neural risk for atypical function.
The study by De Fosse and colleagues1 is timely and
important for a number of reasons. First, subjects were
carefully screened and then divided into diagnostic
groups that differed on some levels, and important subject variables were controlled across the groups. The
groups included two autistic subgroups, one with intact language function and the other with language
deficits. The SLI group had language deficits and the
control group had normal language function. Sex and
handedness were controlled in the study subjects because all subjects were right-handed boys. Thus, important confounds were controlled. Second, the brain
regions of interest were measured in a reliable way and
were selected because of the well-known structure–
function relationships. Finally, the hypothesis that
some aspects of brain anatomy may dissociate clinical
groups that differ on one level (language) but not another (emotional processing) is intriguing and is supported by the results of the study, which showed that
the two language-impaired groups (autistic and SLI)
had atypical rightward asymmetry of frontal language
areas, whereas the non–language-impaired autistic
group and the controls had typical leftward asymmetry
of frontal language areas. The notion that structural
and functional relationships are biologically linked is
further bolstered by the contention that autism and
SLI may share genetic aspects as well.
It is important to speculate about specific features of
the anatomical group differences. Of greatest significance may be the evolving notion that “bigger is not
always better.” That is, in several anatomical studies of
a variety of neurodevelopmental disorders, structures
that are implicated behaviorally are not smaller but are
larger in the affected group. Similar to the study by De
Fosse and colleagues,1 in which the asymmetries were
atypical and the size of the regions and total brain volumes were larger, our research group has found a different brain region, the planum temporale, to be both
atypical in asymmetry patterns (ie, more symmetric)
and larger in size in adults with developmental stuttering. What does it mean to have atypical asymmetry?
What does it mean when the brain region is larger in
size in a group with functional deficits? It may be easier to explain atypical asymmetry first. Atypical asymmetry of language-related cortical areas seems to be a
neural risk for atypical function, and atypical asymmetries in specific regions seem to dissociate specific neurodevelopmental disorders. Frontal language areas are
atypical in autism and SLI, and posterior language areas are atypical in developmental stuttering. Larger size
is more difficult to explain. A larger size of a brain
region may be because of a greater number of neurons
in the region of interest, a larger neuropil, more con-
© 2004 American Neurological Association
Published by Wiley-Liss, Inc., through Wiley Subscription Services
755
nections or a combination of alterations in these basic
structural elements. Furthermore, the potential alterations in cellular morphology may be specific to a single cortical layer or may be more extensive and may be
associated with minor heterotopias. All of these possibilities require further study, and the potential linkage
of brain anatomy at the cellular and subcellular level
up to the gross morphological level needs to be systematically examined.
Although direct structure-function relationships are
not necessarily one-to-one, and some individuals with
atypical anatomical features seem to have normal language development, the overall hypothesis that atypical
anatomy is associated with atypical function has been
replicated across many studies using different methodologies and in different neurodevelopmental disorders.
A common thread, as identified by De Fosse and colleagues,1 in these language-related developmental disorders relates to the presence of atypical anatomy in
language-related cortical regions. The argument that
autism and SLI also share a common genetic linkage
makes these results even more compelling. The molecular biology of genetics represents a new frontier in
cognitive and behavioral neurology. Researchers need
to directly probe the potentially important relationships between brain morphology, behavior, and genetic
susceptibility to neural syndromes that may converge
on some cognitive, behavioral and anatomical measures
and diverge on others. De Fosse and colleagues1 have
provided robust data in a small sample of carefully selected subjects, and have provided a model for future
756
Annals of Neurology
Vol 56
No 6
December 2004
studies to examine these complex but important relationships.
Anne L. Foundas, MD
Department of Psychiatry and Neurology
Tulane University Health Sciences Center
and Neurology Service
Department of Veterans Affairs Medical Center
New Orleans, LA
References
1. De Fosse L, Hodge SM, Makris N, et al. Language association
cortex asymmetry in autism and specific language impairment.
Ann Neurol 2004;56:757–766.
2. Jancke L, Steinmetz H. Anatomical brain asymmetries and their
relevance for functional asymmetries. In: Hugdahl K, Davidson
RJ, eds. The asymmetrical brain. Cambridge, MA: MIT Press,
2003:187–229.
3. Foundas AL, Leonard CM, Gilmore R, et al. Planum temporale
asymmetry and language dominance. Neuropsychologia 1994;10:
1225–1231.
4. Foundas AL, Leonard CM, Gilmore R, et al. Pars triangularis
asymmetry and language dominance. Proc Natl Acad Sci USA
1996;93:719 –722.
5. Foundas AL, Bollich AB, Corey DM, et al. Anomalous anatomy
in adults with persistent developmental stuttering: a volumetric
MRI study of cortical speech-language areas. Neurology 2001;57:
207–215.
6. Clark MM, Plante E. Morphology of the inferior frontal gyrus in
developmentally language-disordered adults. Brain Lang 1998;
61:288 –303.
7. Gauger LM, Lombardino LJ, Leonard CM. Brain morphology in
children with specific language impairment. J Speech Lang Hear
Res 1997;40:1272–1284.
DOI: 10.1002/ana.20344
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