1Christine N. Vidal, 3Timothy J. DeVito, 1Kiralee M. Hayashi, 3Dick J. Drost PhD, 2,3Peter C. Williamson MD, 2Beth Craven-Thuss, 1David Herman, 1Yihong Sui, 1Arthur W. Toga PhD, 2,3Rob Nicolson MD, 1Paul M. Thompson PhD
1Laboratory of Neuro Imaging, Dept. Neurology, UCLA School of Medicine, Los Angeles, CA, USA
2Dept. Psychiatry, University of Western Ontario, London, Canada
3Dept. of Medical Biophysics, University of Western Ontario, London, Canada
Fig. 1: (a): Witelson Partitioning Scheme; (b),(c): Significant Anatomical Differences (Autistics vs. Controls); (d) Percentage Thickness Reduction in Autism.
35 T1-weighted 3D MP-RAGE 3T MRI volumes (1.2-mm isotropic) were acquired from 15 autistic children (age: 9.9 yrs.+/-3.2SD), 7 matched Tourette syndrome subjects (10.5 yrs.+/-2.8SD), and 13 controls (10.0 yrs.+/-2.1SD) matched for age, height, and sex. In ICBM space, the CC was delineated as a surface extending 4 mm either side of the interhemispheric fissure. Traces were converted into 3D parametric surface meshes. Group average shape models were overlaid. A medial surface equidistant between each subjectís upper and lower surfaces was derived, and its distance to each boundary point was mapped. Group differences in the resulting thickness maps were assessed at each surface location, by ANOVA and permutation testing. Mean group differences in callosal anatomy were plotted as a percentage reduction in local thickness (see Fig. 1).
Average maps in autism revealed reduced callosal thickness in the genu, midbody and splenium (p<0.0002); midsagittal callosal area was 13.7% smaller, overall (604.8+/-37.2mm2 versus 700.7+/-21.8mm2 in controls; p<0.021). The Witelson partition, which divides the callosum into fifths (see Fig. 1a), identified similar reductions in the genu (14.8%; p<0.016), midbody (13.3%; p<0.047), and splenium (14.9%; p<0.036). No overall brain volume differences were detected (p>0.38). No shape or thickness differences were found in Tourette patients.
These anomalies suggest impaired frontal and occipital connectivity in autism. The fluctuating effect size, and lower power, of volumetric measures may explain why some prior studies have found anatomical reductions only in the genu and rostrum , or most prominent in the body or posterior sectors [3-5]. Here, shape mapping discriminates groups better (p<0.0002) than volumetry (p<0.02). Visualization of these deficit profiles may provide an MRI-based biomarker of autism, for genetic and behavioral studies.
References: . Witelson S (1989). Brain 112:799-835. . Hardan A (2000). Neurology 55:1033-1036. . Egaas B et al. (1995). Arch. Neurol. 52:794-801. . Piven J et al. (1997). Am. J. Psychiatry 154:1051-1056. . Manes F et al. (1999). J Neuropsych. Clin. Neurosci. 11(4):470-4.
Paul Thompson, Ph.D.
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