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Brain Advance Access published online on November 24, 2004

Brain, doi:10.1093/brain/awh330
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Received April 2, 2004
Revised July 27, 2004
Accepted September 27, 2004

Article

Brain asymmetries in autism and developmental language disorder: a nested whole-brain analysis

M. R. Herbert 1*, D. A. Ziegler 2, C. K. Deutsch 3, L. M. O'Brien 4, D. N. Kennedy 5, P. A. Filipek 6, A. I. Bakardjiev 7, J. Hodgson 8, M. Takeoka 9, N. Makris 10, and V. S. Caviness Jr10

1 Center for Morphometric Analysis, Massachusetts General Hospital, Harvard Medical School, Boston, USA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, USA; Department of Neurology, McLean Hospital, Belmont, USA
2 Center for Morphometric Analysis, Massachusetts General Hospital, Harvard Medical School, Boston, USA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, MA, USA
3 Department of Psychiatry, Harvard Medical School, Boston, USA; Psychobiology and Medical Genetics Programs, Eunice Kennedy Shriver Center, Waltham, USA; Mailman Research Center, McLean Hospital, Belmont, USA
4 Department of Mathematics, Colby College, Waterville, ME, USA
5 Center for Morphometric Analysis, Massachusetts General Hospital, Harvard Medical School, Boston, USA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, USA
6 Department of Pediatrics, University of California, Irvine, USA
7 Department of Infectious Diseases, Children's Hospital Oakland, CA, USA
8 Tennessee Center for the Study and Treatment of Dyslexia, Middle Tennessee State University, Murfreesboro, TN, USA
9 Children's Hospital, Boston, USA
10 Center for Morphometric Analysis, Massachusetts General Hospital, Harvard Medical School, Boston, USA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, USA

* To whom correspondence should be addressed.
M. R. Herbert, E-mail: mherbert1{at}partners.org


   Abstract

Summary We report a whole-brain MRI morphometric survey of asymmetry in children with high-functioning autism and with developmental language disorder (DLD). Subjects included 46 boys of normal intelligence aged 5.7-11.3 years (16 autistic, 15 DLD, 15 controls). Imaging analysis included grey-white segmentation and cortical parcellation. Asymmetry was assessed at a series of nested levels. We found that asymmetries were masked with larger units of analysis but progressively more apparent with smaller units, and that within the cerebral cortex the differences were greatest in higher-order association cortex. The larger units of analysis, including the cerebral hemispheres, the major grey and white matter structures and the cortical lobes, showed no asymmetries in autism or DLD and few asymmetries in controls. However, at the level of cortical parcellation units, autism and DLD showed more asymmetry than controls. They had a greater aggregate volume of significantly asymmetrical cortical parcellation units (leftward plus rightward), as well as a substantially larger aggregate volume of right-asymmetrical cortex in DLD and autism than in controls; this rightward bias was more pronounced in autism than in DLD. DLD, but not autism, showed a small but significant loss of leftward asymmetry compared with controls. Right : left ratios were reversed, autism and DLD having twice as much right- as left-asymmetrical cortex, while the reverse was found in the control sample. Asymmetry differences between groups were most significant in the higher-order association areas. Autism and DLD were much more similar to each other in patterns of asymmetry throughout the cerebral cortex than either was to controls; this similarity suggests systematic and related alterations rather than random neural systems alterations. We review these findings in relation to previously reported volumetric features in these two samples of brains, including increased total brain and white matter volumes and lack of increase in the size of the corpus callosum. Larger brain volume has previously been associated with increased lateralization. The sizeable right-asymmetry increase reported here may be a consequence of early abnormal brain growth trajectories in these disorders, while higher-order association areas may be most vulnerable to connectivity abnormalities associated with white matter increases.

Keywords: association cortex; connectivity; lateralization; neural systems development; specific language impairment.
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