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Altered cingulum bundle microstructure in autism spectrum disorder

Published online by Cambridge University Press:  27 February 2013

Stephanie H. Ameis
Affiliation:
Department of Psychiatry, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
Jin Fan
Affiliation:
Department of Psychology, Queens College, The City University of New York, Flushing, NY, USA Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA
Conrad Rockel
Affiliation:
Department of Psychiatry, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
Latha Soorya
Affiliation:
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA
A. Ting Wang
Affiliation:
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA
Evdokia Anagnostou*
Affiliation:
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA Department of Pediatrics, Holland Bloorview Kids Rehabilitation Hospital, Bloorview Research Institute, University of Toronto, Toronto, ON, Canada
*
Evdokia Anagnostou, Department of Pediatrics, Holland Bloorview Kids Rehabilitation Hospital, Bloorview Research Institute, University of Toronto, 150 Kilgour Road, Toronto, ON, Canada M4G 1R8. Tel: +1 (416) 425-6220 ext. 6005; Fax: +1 (416) 422-7036; E-mail: [email protected]

Abstract

Objective

Here, we examined the cingulum bundle, a long-range white matter tract mediating dorsal limbic connectivity, using diffusion tensor imaging (DTI) tractography, in children and adolescents with autism spectrum disorder (ASD) versus controls. We hypothesised that cingulum bundle microstructure would be altered in ASD, based on evidence implicating abnormal white matter connectivity in this disorder.

Methods

DTI data were acquired for 19 ASD participants (IQ ⩾ 70; 7–18 years; mean = 12.4 ± 3.1) and 16 age-matched controls (7–18 years; mean = 12.3 ± 3.6) on a 3 T magnetic resonance imaging system. Deterministic tractography was used to isolate the cingulum bundle. Left and right cingulum bundles were examined for differences in several DTI metrics in ASD children/adolescents versus controls, including: fractional anisotropy (FA), mean, axial, and radial diffusivity.

Results

Significant age × group interaction effects were found for all DTI metrics (mean diffusivity: F1,28 = 9.5, p = 0.005, radial diffusivity: F1,28 = 7.8, p = 0.009, axial diffusivity: F1,28 = 5.2, p = 0.03, FA: F1,28 = 4.4, p = 0.04). Interaction effects were driven by increases in cingulum bundle diffusivity (mean, radial, and axial diffusivity), and decreased FA, in younger ASD participants within our sample versus controls.

Conclusion

Our results point to immature microstructural organisation of the cingulum bundle in ASD, particularly during the early years of life, with implications for limbic network synchronisation and complex socio-emotional performance.

Type
Original Articles
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2013 

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References

1.American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th edn, text revision. Washington, DC: American Psychiatric Association, 2000.Google Scholar
2.Belmonte, MK, Allen, G, Beckel-Mitchener, A, Boulanger, LM, Carper, RA, Webb, SJ. Autism and abnormal development of brain connectivity. J Neurosci 2004;24:92289231.CrossRefGoogle ScholarPubMed
3.Catani, M, Thiebaut de Schotten, M. Limbic pathways. In: Atlas of human brain connections. New York: Oxford University Press, 2012;439–451.Google Scholar
4.Voineagu, I, Wang, X, Johnston, Pet al. Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature 2011;474:380384.CrossRefGoogle ScholarPubMed
5.Wicker, B, Fonlupt, P, Hubert, B, Tardif, C, Gepner, B, Deruelle, C. Abnormal cerebral effective connectivity during explicit emotional processing in adults with autism spectrum disorder. Soc Cogn Affect Neurosci 2008;3:135143.CrossRefGoogle ScholarPubMed
6.Schumann, CM, Bloss, CS, Barnes, CCet al. Longitudinal magnetic resonance imaging study of cortical development through early childhood in autism. J Neurosci 2010;30:44194427.CrossRefGoogle ScholarPubMed
7.Zikopoulos, B, Barbas, H. Changes in prefrontal axons may disrupt the network in autism. J Neurosci 2010;30:1459514609.CrossRefGoogle Scholar
8.Ciccarelli, O, Catani, M, Johansen-Berg, H, Clark, C, Thompson, A. Diffusion-based tractography in neurological disorders: concepts, applications, and future developments. Lancet Neurol 2008;7:715727.CrossRefGoogle ScholarPubMed
9.Beaulieu, C. The basis of anisotropic water diffusion in the nervous system – a technical review. NMR Biomed 2002;15:435455.CrossRefGoogle ScholarPubMed
10.Ameis, SH, Fan, J, Rockel, Cet al. Impaired structural connectivity of socio-emotional circuits in autism spectrum disorders: a diffusion tensor imaging study. PLoS One 2011;6:e28044.CrossRefGoogle ScholarPubMed
11.Barnea-Goraly, N, Lotspeich, LJ, Reiss, AL. Similar white matter aberrations in children with autism and their unaffected siblings: a diffusion tensor imaging study using tract-based spatial statistics. Arch Gen Psychiatry 2010;67:10521060.CrossRefGoogle ScholarPubMed
12.Shukla, DK, Keehn, B, Muller, RA. Tract-specific analyses of diffusion tensor imaging show widespread white matter compromise in autism spectrum disorder. J Child Psychol Psychiatry 2011;52:286295.CrossRefGoogle ScholarPubMed
13.Cheng, Y, Chou, KH, Chen, IY, Fan, YT, Decety, J, Lin, CP. Atypical development of white matter microstructure in adolescents with autism spectrum disorders. Neuroimage 2010;50:873882.CrossRefGoogle ScholarPubMed
14.Sahyoun, CP, Belliveau, JW, Mody, M. White matter integrity and pictorial reasoning in high-functioning children with autism. Brain Cogn 2010;73:180188.CrossRefGoogle ScholarPubMed
15.Mori, S, Crain, BJ, Chacko, VP, van Zijl, PC. Three-dimensional tracking of axonal projections in the brain by magnetic resonance imaging. Ann Neurol 1999;45:265269.3.0.CO;2-3>CrossRefGoogle ScholarPubMed
16.Kumar, A, Sundaram, SK, Sivaswamy, Let al. Alterations in frontal lobe tracts and corpus callosum in young children with autism spectrum disorder. Cereb Cortex 2010;20:21032113.CrossRefGoogle ScholarPubMed
17.Lo, YC, Soong, WT, Gau, SSet al. The loss of asymmetry and reduced interhemispheric connectivity in adolescents with autism: a study using diffusion spectrum imaging tractography. Psychiatry Res 2011;192:6066.CrossRefGoogle ScholarPubMed
18.Weinstein, M, Ben-Sira, L, Levy, Yet al. Abnormal white matter integrity in young children with autism. Hum Brain Mapp 2011;32:534543.CrossRefGoogle ScholarPubMed
19.Wechsler, D. The Wechsler Intelligence Scale for Children, 4th edn. London: Pearson Assessment, 2004.Google Scholar
20.Lord, C, Risi, S, Lambrecht, Let al. The Autism Diagnostic Observation Schedule-Generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord 2000;30:205223.CrossRefGoogle ScholarPubMed
21.Lord, C, Rutter, M, Le Couteur, A. Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord 1994;24:659685.CrossRefGoogle ScholarPubMed
22.Smith, SM, Jenkinson, M, Woolrich, MWet al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 2004;23(Suppl. 1):S208S219.CrossRefGoogle ScholarPubMed
23.Jenkinson, M, Bannister, P, Brady, M, Smith, S. Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage 2002;17:825841.CrossRefGoogle ScholarPubMed
24.Wang, RBT, Sorensen, AG, Wedeen, VJ. Diffusion toolkit: a software package for Ddffusion imaging data processing and tractography. Proc Intl Soc Mag Reson Med 2007:3720.Google Scholar
25.Wheeler-Kingshott, CA, Cercignani, M. About ‘axial’ and ‘radial’ diffusivities. Magn Reson Med 2009;61:12551260.CrossRefGoogle ScholarPubMed
26.Catani, M, Thiebaut de Schotten, M. A diffusion tensor imaging tractography atlas for virtual in vivo dissections. Cortex 2008;44:11051132.CrossRefGoogle ScholarPubMed
27.Faria, AV, Zhang, J, Oishi, Ket al. Atlas-based analysis of neurodevelopment from infancy to adulthood using diffusion tensor imaging and applications for automated abnormality detection. Neuroimage 2010;52:415428.CrossRefGoogle Scholar
28.Huppi, PS, Dubois, J. Diffusion tensor imaging of brain development. Semin Fetal Neonatal Med 2006;11:489497.CrossRefGoogle ScholarPubMed
29.Fields, RD. White matter in learning, cognition and psychiatric disorders. Trends Neurosci 2008;31:361370.CrossRefGoogle ScholarPubMed
30.Fields, RD. White matter matters. Sci Am 2008;298:4249.Google ScholarPubMed
31.Starr, E, Szatmari, P, Bryson, S, Zwaigenbaum, L. Stability and change among high-functioning children with pervasive developmental disorders: a 2-year outcome study. J Autism Dev Disord 2003;33:1522.CrossRefGoogle ScholarPubMed
32.Thakkar, KN, Polli, FE, Joseph, RMet al. Response monitoring, repetitive behaviour and anterior cingulate abnormalities in autism spectrum disorders (ASD). Brain 2008;131(Pt 9):24642478.CrossRefGoogle ScholarPubMed
33.Pugliese, L, Catani, M, Ameis, Set al. The anatomy of extended limbic pathways in Asperger syndrome: a preliminary diffusion tensor imaging tractography study. Neuroimage 2009;47:427434.CrossRefGoogle ScholarPubMed
34.Gao, W, Lin, W, Chen, Yet al. Temporal and spatial development of axonal maturation and myelination of white matter in the developing brain. AJNR Am J Neuroradiol 2009;30:290296.CrossRefGoogle ScholarPubMed
35.Klawiter, EC, Schmidt, RE, Trinkaus, Ket al. Radial diffusivity predicts demyelination in ex-vivo multiple sclerosis spinal cords. Neuroimage 2011;55:14541460.CrossRefGoogle ScholarPubMed
36.Song, SK, Sun, SW, Ramsbottom, MJ, Chang, C, Russell, J, Cross, AH. Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage 2002;17:14291436.CrossRefGoogle ScholarPubMed
37.Wolff, JJ, Gu, H, Gerig, Get al. Differences in white matter fiber tract development present from 6 to 24 months in infants with autism. Am J Psychiatry 2012;169:589600.CrossRefGoogle ScholarPubMed
38.Marshall, CR, Scherer, SW. Detection and characterization of copy number variation in autism spectrum disorder. Methods Mol Biol 2012;838:115135.CrossRefGoogle ScholarPubMed
39.Casanova, MF. White matter volume increase and minicolumns in autism. Ann Neurol 2004;56:453.CrossRefGoogle ScholarPubMed
40.Casanova, MF, Buxhoeveden, DP, Switala, AE, Roy, E. Minicolumnar pathology in autism. Neurology 2002;58:428432.CrossRefGoogle ScholarPubMed
41.Bava, S, Boucquey, V, Goldenberg, Det al. Sex differences in adolescent white matter architecture. Brain Res 2011;1375:4148.CrossRefGoogle ScholarPubMed
42.Menzler, K, Belke, M, Wehrmann, Eet al. Men and women are different: diffusion tensor imaging reveals sexual dimorphism in the microstructure of the thalamus, corpus callosum and cingulum. Neuroimage 2011;54:25572562.CrossRefGoogle ScholarPubMed
43.Zwicker, JG, Missiuna, C, Harris, SR, Boyd, LA. Developmental coordination disorder: a pilot diffusion tensor imaging study. Pediatr Neurol 2012;46:162167.CrossRefGoogle ScholarPubMed
44.Gotham, K, Pickles, A, Lord, C. Standardizing ADOS scores for a measure of severity in autism spectrum disorders. J Autism Dev Disord 2009;39:693705.CrossRefGoogle ScholarPubMed