Hostname: page-component-8448b6f56d-mp689 Total loading time: 0 Render date: 2024-04-19T06:08:17.952Z Has data issue: false hasContentIssue false
  • English
  • Français

Differential effects on white-matter systems in high-functioning autism and Asperger's syndrome

Published online by Cambridge University Press:  09 April 2009

G. M. McAlonan ,
C. Cheung ,
V. Cheung ,
N. Wong ,
J. Suckling  and
S. E. Chua
G. M. McAlonan*
Affiliation:
State Key Laboratory for Brain and Cognitive Sciences, University of Hong Kong, Pokfulam, Hong Kong SAR China Department of Psychiatry, University of Hong Kong, Pokfulam, Hong Kong SAR China
C. Cheung
Affiliation:
Department of Psychiatry, University of Hong Kong, Pokfulam, Hong Kong SAR China
V. Cheung
Affiliation:
Department of Psychiatry, University of Hong Kong, Pokfulam, Hong Kong SAR China
N. Wong
Affiliation:
Department of Psychiatry, University of Hong Kong, Pokfulam, Hong Kong SAR China
J. Suckling
Affiliation:
Cambridge Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, UK
S. E. Chua
Affiliation:
State Key Laboratory for Brain and Cognitive Sciences, University of Hong Kong, Pokfulam, Hong Kong SAR China Department of Psychiatry, University of Hong Kong, Pokfulam, Hong Kong SAR China
*
*Address for correspondence: G. M. McAlonan, Ph.D., M.B., B.S., Department of Psychiatry, University of Hong Kong, Pokfulam, Hong Kong SAR China. (Email: mcalonan@hkucc.hku.hk)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Whether autism spectrum maps onto a spectrum of brain abnormalities and whether Asperger's syndrome (ASP) is distinct from high-functioning autism (HFA) are debated. White-matter maldevelopment is associated with autism and disconnectivity theories of autism are compelling. However, it is unknown whether children with ASP and HFA have distinct white-matter abnormalities.

Method

Voxel-based morphometry mapped white-matter volumes across the whole brain in 91 children. Thirty-six had autism spectrum disorder. A history of delay in phrase speech defined half with HFA; those without delay formed the ASP group. The rest were typically developing children, balanced for age, IQ, gender, maternal language and ethnicity. White-matter volumes in HFA and ASP were compared and each contrasted with controls.

Results

White-matter volumes around the basal ganglia were higher in the HFA group than ASP and higher in both autism groups than controls. Compared with controls, children with HFA had less frontal and corpus callosal white matter in the left hemisphere; those with ASP had less frontal and corpus callosal white matter in the right hemisphere with more white matter in the left parietal lobe.

Conclusions

HFA involved mainly left hemisphere white-matter systems; ASP affected predominantly right hemisphere white-matter systems. The impact of HFA on basal ganglia white matter was greater than ASP. This implies that aetiological factors and management options for autism spectrum disorders may be distinct. History of language acquisition is a potentially valuable marker to refine our search for causes and treatments in autism spectrum.

Keywords

AspergerautismMRI
Type
Original Articles
Information
Psychological Medicine , Volume 39 , Issue 11 , November 2009 , pp. 1885 - 1893
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alexander, GE, Crutcher, MD, DeLong, MR (1990). Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, ‘prefrontal’ and ‘limbic’ functions. Progress in Brain Research 85, 119–146.CrossRefGoogle ScholarPubMed
Barnea-Goraly, N, Kwon, H, Menon, V, Eliez, S, Lotspeich, L, Reiss, AL (2004). White matter structure in autism: preliminary evidence from diffusion tensor imaging. Biological Psychiatry 55, 323–326.CrossRefGoogle ScholarPubMed
Baron-Cohen, S, Ring, HA, Bullmore, ET, Wheelwright, S, Ashwin, C, Williams, SC (2000). The amygdala theory of autism. Neuroscience and Biobehavioural Reviews 24, 355–364.CrossRefGoogle ScholarPubMed
Ben Bashat, D, Kronfeld-Duenias, V, Zachor, DA, Ekstein, PM, Hendler, T, Tarrasch, R, Even, A, Levy, Y, Ben Sira, L (2007). Accelerated maturation of white matter in young children with autism: a high b value DWI study. Neuroimage 37, 40–47.CrossRefGoogle Scholar
Boger-Megiddo, I, Shaw, DW, Friedman, SD, Sparks, BF, Artru, AA, Giedd, JN, Dawson, G, Dager, SR (2006). Corpus callosum morphometrics in young children with autism spectrum disorder. Journal of Autism and Developmental Disorders 36, 733–739.CrossRefGoogle ScholarPubMed
Brambilla, P, Hardan, A, di Nemi, SU, Perez, J, Soares, JC, Barale, F (2003). Brain anatomy and development in autism: review of structural MRI studies. Brain Research Bulletin 61, 557–569.CrossRefGoogle ScholarPubMed
Bullmore, ET, Suckling, J, Overmeyer, S, Rabe-Hesketh, S, Taylor, E, Brammer, MJ (1999). Global, voxel, and cluster tests, by theory and permutation, for a difference between two groups of structural MR images of the brain. IEEE Transactions on Medical Imaging 18, 32–42.CrossRefGoogle ScholarPubMed
Carper, RA, Moses, P, Tigue, ZD, Courchesne, E (2002). Cerebral lobes in autism: early hyperplasia and abnormal age effects. Neuroimage 16, 1038–1051.CrossRefGoogle ScholarPubMed
Castelli, F, Frith, C, Happe, F, Frith, U (2002). Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes. Brain 125, 1839–1849.CrossRefGoogle ScholarPubMed
Chandana, SR, Behen, ME, Juhasz, C, Muzik, O, Rothermel, RD, Mangner, TJ, Chakraborty, PK, Chugani, HT, Chugani, DC (2005). Significance of abnormalities in developmental trajectory and asymmetry of cortical serotonin synthesis in autism. International Journal of Developmental Neuroscience 23, 171–182.CrossRefGoogle ScholarPubMed
Cheung, C, Chua, SE, Cheung, V, Khong, PL, Tai, KS, Wong, TKW, Ho, TP, McAlonan, GM (in press). White matter fractional anisotrophy differences and correlates of diagnostic symptoms in autism. Journal of Child Psychology and Psychiatry.Google Scholar
Chua, SE, Cheung, C, Cheung, V, Tsang, JT, Chen, EY, Wong, JC, Cheung, JP, Yip, L, Tai, KS, Suckling, J, McAlonan, GM (2007). Cerebral grey, white matter and CSF in never-medicated, first-episode schizophrenia. Schizophrenia Research 89, 12–21.CrossRefGoogle ScholarPubMed
Courchesne, E (2002). Abnormal early brain development in autism. Molecular Psychiatry 7 (Suppl. 2), S21–S23.CrossRefGoogle ScholarPubMed
Courchesne, E (2004). Brain development in autism: early overgrowth followed by premature arrest of growth. Mental Retardation and Developmental Disability Research Review 10, 106–111.CrossRefGoogle ScholarPubMed
Courchesne, E, Carper, R, Akshoomoff, N (2003). Evidence of brain overgrowth in the first year of life in autism. Journal of the American Academy of Medicine 290, 337–344.Google ScholarPubMed
Damasio, AR, Maurer, RG (1978). A neurological model for childhood autism. Archives of Neurology 35, 777–786.CrossRefGoogle ScholarPubMed
De Fosse, L, Hodge, SM, Makris, N, Kennedy, DN, Caviness, VS Jr., McGrath, L, Steele, S, Ziegler, DA, Herbert, MR, Frazier, JA, Tager-Flusberg, H, Harris, GJ (2004). Language-association cortex asymmetry in autism and specific language impairment. Annals of Neurology 56, 757–766.CrossRefGoogle ScholarPubMed
Egaas, B, Courchesne, E, Saitoh, O (1995). Reduced size of corpus callosum in autism. Archives of Neurology 52, 794–801.CrossRefGoogle ScholarPubMed
Ellis, HD, Gunter, HL (1999). Asperger syndrome: a simple matter of white matter? Trends in Cognitive Science 3, 192–200.CrossRefGoogle ScholarPubMed
Freitag, CM, Kleser, C, Schneider, M, von Gontard, A (2007). Quantitative assessment of neuromotor function in adolescents with high functioning autism and Asperger syndrome. Journal of Autism and Developmental Disorders 37, 948–959.CrossRefGoogle ScholarPubMed
Gilchrist, A, Green, J, Cox, A, Burton, D, Rutter, M, Le Couteur, A (2001). Development and current functioning in adolescents with Asperger syndrome: a comparative study. Journal of Child Psychology and Psychiatry 42, 227–240.CrossRefGoogle ScholarPubMed
Gunter, HL, Ghaziuddin, M, Ellis, HD (2002). Asperger syndrome: tests of right hemisphere functioning and interhemispheric communication. Journal of Autism and Developmental Disorders 32, 263–281.CrossRefGoogle ScholarPubMed
Happe, F, Ehlers, S, Fletcher, P, Frith, U, Johansson, M, Gillberg, C, Dolan, R, Frackowiak, R, Frith, C (1996). ‘Theory of mind’ in the brain. Evidence from a PET scan study of Asperger syndrome. Neuroreport 8, 197–201.CrossRefGoogle ScholarPubMed
Hazlett, HC, Poe, M, Gerig, G, Smith, RG, Provenzale, J, Ross, A, Gilmore, J, Piven, J (2005). Magnetic resonance imaging and head circumference study of brain size in autism: birth through age 2 years. Archives of General Psychiatry 62, 1366–1376.CrossRefGoogle ScholarPubMed
Herbert, MR (2005). Large brains in autism: the challenge of pervasive abnormality. Neuroscientist 11, 417–440.CrossRefGoogle ScholarPubMed
Herbert, MR, Harris, GJ, Adrien, KT, Ziegler, DA, Makris, N, Kennedy, DN, Lange, NT, Chabris, CF, Bakardjiev, A, Hodgson, J, Takeoka, M, Tager-Flusberg, H, Caviness, VS Jr. (2002). Abnormal asymmetry in language association cortex in autism. Annals of Neurology 52, 588–596.CrossRefGoogle ScholarPubMed
Herbert, MR, Ziegler, DA, Deutsch, CK, O'Brien, LM, Kennedy, DN, Filipek, PA, Bakardjiev, AI, Hodgson, J, Takeoka, M, Makris, N, Caviness, VS Jr. (2005). Brain asymmetries in autism and developmental language disorder: a nested whole-brain analysis. Brain 128, 213–226.CrossRefGoogle ScholarPubMed
Herbert, MR, Ziegler, DA, Deutsch, CK, O'Brien, LM, Lange, N, Bakardjiev, A, Hodgson, J, Adrien, KT, Steele, S, Makris, N, Kennedy, D, Harris, GJ, Caviness, VS Jr. (2003). Dissociations of cerebral cortex, subcortical and cerebral white matter volumes in autistic boys. Brain 126, 1182–1192.CrossRefGoogle ScholarPubMed
Herbert, MR, Ziegler, DA, Makris, N, Filipek, PA, Kemper, TL, Normandin, JJ, Sanders, HA, Kennedy, DN, Caviness, VS Jr. (2004). Localization of white matter volume increase in autism and developmental language disorder. Annals of Neurology 55, 530–540.CrossRefGoogle ScholarPubMed
Horwitz, B, Rumsey, JM, Grady, CL, Rapoport, SI (1988). The cerebral metabolic landscape in autism. Intercorrelations of regional glucose utilization. Archives of Neurology 45, 749–755.CrossRefGoogle ScholarPubMed
Howlin, P (2003). Outcome in high-functioning adults with autism with and without early language delays: implications for the differentiation between autism and Asperger syndrome. Journal of Autism and Developmental Disorders 33, 3–13.CrossRefGoogle ScholarPubMed
Just, MA, Cherkassky, VL, Keller, TA, Kana, RK, Minshew, NJ (2007). Functional and anatomical cortical underconnectivity in autism: evidence from an fMRI study of an executive function task and corpus callosum morphometry. Cerebral Cortex 17, 951–961.CrossRefGoogle ScholarPubMed
Just, MA, Cherkassky, VL, Keller, TA, Minshew, NJ (2004). Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity. Brain 127, 1811–1821.CrossRefGoogle ScholarPubMed
Keller, TA, Kana, RK, Just, MA (2007). A developmental study of the structural integrity of white matter in autism. Neuroreport 18, 23–27.CrossRefGoogle ScholarPubMed
Klin, A, Volkmar, FR (2003). Asperger syndrome: diagnosis and external validity. Child and Adolescent Psychiatry Clinics of North America 12, 1–13, v.CrossRefGoogle ScholarPubMed
Koshino, H, Carpenter, PA, Minshew, NJ, Cherkassky, VL, Keller, TA, Just, MA (2005). Functional connectivity in an fMRI working memory task in high-functioning autism. Neuroimage 24, 810–821.CrossRefGoogle Scholar
Kwon, H, Ow, AW, Pedatella, KE, Lotspeich, LJ, Reiss, AL (2004). Voxel-based morphometry elucidates structural neuroanatomy of high-functioning autism and Asperger syndrome. Developmental Medicine and Child Neurology 46, 760–764.CrossRefGoogle ScholarPubMed
Lebel, C, Walker, L, Leemans, A, Phillips, L, Beaulieu, C (2008). Microstructural maturation of the human brain from childhood to adulthood. Neuroimage 40, 1044–1055.CrossRefGoogle ScholarPubMed
Loh, A, Soman, T, Brian, J, Bryson, SE, Roberts, W, Szatmari, P, Smith, IM, Zwaigenbaum, L (2007). Stereotyped motor behaviors associated with autism in high-risk infants: a pilot videotape analysis of a sibling sample. Journal of Autism and Developmental Disorders 37, 25–36.CrossRefGoogle ScholarPubMed
Lotspeich, LJ, Kwon, H, Schumann, CM, Fryer, SL, Goodlin-Jones, BL, Buonocore, MH, Lammers, CR, Amaral, DG, Reiss, AL (2004). Investigation of neuroanatomical differences between autism and Asperger syndrome. Archives of General Psychiatry 61, 291–298.CrossRefGoogle ScholarPubMed
McAlonan, GM, Cheung, V, Cheung, C, Chua, SE, Murphy, DG, Suckling, J, Tai, KS, Yip, LK, Leung, P, Ho, TP (2007). Mapping brain structure in attention deficit-hyperactivity disorder: a voxel-based MRI study of regional grey and white matter volume. Psychiatry Research 154, 171–180.CrossRefGoogle ScholarPubMed
McAlonan, GM, Cheung, V, Cheung, C, Suckling, J, Lam, GY, Tai, KS, Yip, L, Murphy, DG, Chua, SE (2005). Mapping the brain in autism. A voxel-based MRI study of volumetric differences and intercorrelations in autism. Brain 128, 268–276.CrossRefGoogle ScholarPubMed
McAlonan, GM, Daly, E, Kumari, V, Critchley, HD, van Amelsvoort, T, Suckling, J, Simmons, A, Sigmundsson, T, Greenwood, K, Russell, A, Schmitz, N, Happe, F, Howlin, P, Murphy, DG (2002). Brain anatomy and sensorimotor gating in Asperger's syndrome. Brain 125, 1594–1606.CrossRefGoogle ScholarPubMed
McAlonan, GM, Suckling, J, Wong, N, Cheung, V, Lienenkaemper, N, Cheung, C, Chua, SE (2008). Distinct patterns of grey matter abnormality in high-functioning autism and Asperger's syndrome. Journal of Child Psychology and Psychiatry 49, 1287–1295.CrossRefGoogle ScholarPubMed
Nordahl, CW, Dierker, D, Mostafavi, I, Schumann, CM, Rivera, SM, Amaral, DG, Van Essen, DC (2007). Cortical folding abnormalities in autism revealed by surface-based morphometry. Journal of Neuroscience 27, 11725–11735.CrossRefGoogle ScholarPubMed
Nordahl, CW, Simon, TJ, Zierhut, C, Solomon, M, Rogers, SJ, Amaral, DG (2008). Brief report: methods for acquiring structural MRI data in very young children with autism without the use of sedation. Journal of Autism and Developmental Disorders 38, 1581–1590.CrossRefGoogle ScholarPubMed
Rinehart, NJ, Bellgrove, MA, Tonge, BJ, Brereton, AV, Howells-Rankin, D, Bradshaw, JL (2006 a). An examination of movement kinematics in young people with high-functioning autism and Asperger's disorder: further evidence for a motor planning deficit. Journal of Autism and Developmental Disorders 36, 757–767.CrossRefGoogle ScholarPubMed
Rinehart, NJ, Bradshaw, JL, Brereton, AV, Tonge, BJ (2002 a). Lateralization in individuals with high-functioning autism and Asperger's disorder: a frontostriatal model. Journal of Autism and Developmental Disorders 32, 321–331.CrossRefGoogle ScholarPubMed
Rinehart, NJ, Bradshaw, JL, Tonge, BJ, Brereton, AV, Bellgrove, MA (2002 b). A neurobehavioral examination of individuals with high-functioning autism and Asperger's disorder using a fronto-striatal model of dysfunction. Behavioural and Cognitive Neuroscience Review 1, 164–177.Google ScholarPubMed
Rinehart, NJ, Tonge, BJ, Bradshaw, JL, Iansek, R, Enticott, PG, Johnson, KA (2006 b). Movement-related potentials in high-functioning autism and Asperger's disorder. Developmental Medicine and Child Neurology 48, 272–277.CrossRefGoogle ScholarPubMed
Rinehart, NJ, Tonge, BJ, Bradshaw, JL, Iansek, R, Enticott, PG, McGinley, J (2006 c). Gait function in high-functioning autism and Asperger's disorder: evidence for basal-ganglia and cerebellar involvement? European Child and Adolescent Psychiatry 15, 256–264.CrossRefGoogle ScholarPubMed
Schultz, RT (2005). Developmental deficits in social perception in autism: the role of the amygdala and fusiform face area. International Journal of Developmental Neuroscience 23, 125–141.CrossRefGoogle ScholarPubMed
Suckling, J, Brammer, MJ, Lingford-Hughes, A, Bullmore, ET (1999 a). Removal of extracerebral tissues in dual-echo magnetic resonance images via linear scale-space features. Magnetic Resonance Imaging 17, 247–256.CrossRefGoogle ScholarPubMed
Suckling, J, Sigmundsson, T, Greenwood, K, Bullmore, ET (1999 b). A modified fuzzy clustering algorithm for operator independent brain tissue classification of dual echo MR images. Magnetic Resonance Imaging 17, 1065–1076.CrossRefGoogle ScholarPubMed
Sundaram, SK, Kumar, A, Makki, MI, Behen, ME, Chugani, HT, Chugani, DC (2008). Diffusion tensor imaging of frontal lobe in autism spectrum disorder. Cerebral Cortex 18, 2659–2665.CrossRefGoogle ScholarPubMed
Talairach, J, Tournoux, P (1988). Co-planar Stereotaxic Atlas of the Human Brain. Thieme, Stuttgart, Germany.Google Scholar
Utter, AA, Basso, MA (2008). The basal ganglia: an overview of circuits and function. Neuroscience and Biobehavioural Reviews 32, 333–342.CrossRefGoogle ScholarPubMed
Vilensky, JA, Damasio, AR, Maurer, RG (1981). Gait disturbances in patients with autistic behavior: a preliminary study. Archives of Neurology 38, 646–649.CrossRefGoogle ScholarPubMed
Waiter, GD, Williams, JH, Murray, AD, Gilchrist, A, Perrett, DI, Whiten, A (2005). Structural white matter deficits in high-functioning individuals with autistic spectrum disorder: a voxel-based investigation. Neuroimage 24, 455–461.CrossRefGoogle ScholarPubMed
Zilbovicius, M, Meresse, I, Chabane, N, Brunelle, F, Samson, Y, Boddaert, N (2006). Autism, the superior temporal sulcus and social perception. Trends in Neurosciences 29, 359–366.CrossRefGoogle ScholarPubMed