Top

BMC Neurology

Published in:

Open Access 01-12-2012 | Research article

White matter connectivity in children with autism spectrum disorders: a tract-based spatial statistics study

Authors: Lucia Billeci, Sara Calderoni, Michela Tosetti, Marco Catani, Filippo Muratori

Published in: BMC Neurology | Issue 1/2012

Abstract

Background

Autism spectrum disorders (ASD) are associated with widespread alterations in white matter (WM) integrity. However, while a growing body of studies is shedding light on microstructural WM alterations in high-functioning adolescents and adults with ASD, literature is still lacking in information about whole brain structural connectivity in children and low-functioning patients with ASD. This research aims to investigate WM connectivity in ASD children with and without mental retardation compared to typically developing controls (TD).

Methods

Diffusion tensor imaging (DTI) was performed in 22 young children with ASD (mean age: 5.54 years) and 10 controls (mean age: 5.25 years). Data were analysed both using the tract-based spatial statistics (TBSS) and the tractography. Correlations were investigated between the WM microstructure in the identified altered regions and the productive language level.

Results

The TBSS analysis revealed widespread increase of fractional anisotropy (FA) in major WM pathways. The tractographic approach showed an increased fiber length and FA in the cingulum and in the corpus callosum and an increased mean diffusivity in the indirect segments of the right arcuate and the left cingulum. Mean diffusivity was also correlated with expressive language functioning in the left indirect segments of the arcuate fasciculus.

Conclusions

Our study confirmed the presence of several structural connectivity abnormalities in young ASD children. In particular, the TBSS profile of increased FA that characterized the ASD patients extends to children a finding previously detected in ASD toddlers only. The WM integrity abnormalities detected may be relevant to the pathophysiology of ASD, since the structures involved participate in some core atypical characteristics of the disorder.

Available only for authorised users

Belmonte MK, Allen G, Becke-Mitchener A, Boulanger LM, Carper RA, Webb SJ: Autism and abnormal development of brain connectivity. J Neurosci. 2004, 24: 9228-9231. 10.1523/JNEUROSCI.3340-04.2004.CrossRefPubMed

Geschwind DH, Levitt P: Autism spectrum disorders: developmental disconnection syndromes. Curr Opin Neurobiol. 2007, 17: 103-111. 10.1016/j.conb.2007.01.009.CrossRefPubMed

Minshew NJ, Williams DL: The new neurobiology of autism: cortex, connectivity, and neuronal organization. Arch Neurol. 2007, 6: 945-950.CrossRef

Le Bihan D: Looking into the functional architecture of the brain with diffusion MRI. Nat Rev Neurosci. 2003, 4: 469-480. 10.1038/nrn1119.CrossRefPubMed

Beaulieu C: The basis of anisotropic water diffusion in the nervous system - a technical review. NMR Biomed. 2002, 15: 435-455. 10.1002/nbm.782.CrossRefPubMed

Basser PJ: Inferring microstructural features and the physiological state of tissues from diffusion-weighted images. NMR Biomed. 1995, 8: 333-344. 10.1002/nbm.1940080707.CrossRefPubMed

Pierpaoli C, Basser PJ: Toward a quantitative assessment of diffusion anisotropy. Magn Reson Med. 1996, 36: 893-906. 10.1002/mrm.1910360612.CrossRefPubMed

Le Bihan D, Mangin JF, Poupon C, Clark CA, Pappata S, Molko N, Chabriat H: Diffusion tensor imaging: concepts and applications. J Magn Reson Imaging. 2001, 13: 534-546. 10.1002/jmri.1076.CrossRefPubMed

Norris DG: The effects of microscopic tissue parameters on the diffusion weighted magnetic resonance imaging experiment. NMR Biomed. 2001, 14: 77-93. 10.1002/nbm.682.CrossRefPubMed

10.

Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, Watkins KE, Ciccarelli O, Cader MZ, Matthews PM, Behrens TEJ: Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. NeuroImage. 2006, 31: 1487-1505. 10.1016/j.neuroimage.2006.02.024.CrossRefPubMed

11.

Amaral DG, Schumann CM, Nordahl CW: Neuroanatomy of autism. Trends Neurosci. 2008, 31: 137-145. 10.1016/j.tins.2007.12.005.CrossRefPubMed

12.

Ben Bashat D, Kronfeld-Duenias V, Zachor DA, Ekstein PM, Hendler T, Tarrasch R, Even A, Levy Y, Ben Sira L: Accelerated maturation of white matter in young children with autism: a high b value dwi study. NeuroImage. 2007, 37: 40-47. 10.1016/j.neuroimage.2007.04.060.CrossRefPubMed

13.

Ke X, Tang T, Hong S, Hang Y, Zou B, Li H, Zhou Z, Ruan Z, Lu Z, Tao G, Liu Y: White matter impairments in autism, evidence from voxel-based morphometry and diffusion tensor imaging. Brain Res. 2009, 1265: 171-177.CrossRefPubMed

14.

Cheung C, Chua SE, Cheung V, Khong PL, Tai KS, Wong TK, Ho TP, McAlonan GM: White matter fractional anisotrophy differences and correlates of diagnostic symptoms in autism. J Child Psychol Psychiatry. 2009, 50: 1102-1112. 10.1111/j.1469-7610.2009.02086.x.CrossRefPubMed

15.

Ingalhalikar M, Parker D, Bloy L, Roberts TP, Verma R: Diffusion based abnormality markers of pathology: toward learned diagnostic prediction of ASD. NeuroImage. 2011, 57: 918-927. 10.1016/j.neuroimage.2011.05.023.CrossRefPubMedPubMedCentral

16.

Kumar A, Sundaram SK, Sivaswamy L, Behen ME, Makki MI, Ager J, Janisse J, Chugani HT, Chugani DC: Alterations in frontal lobe tracts and corpus callosum in young children with autism spectrum disorder. Cereb Cortex. 2010, 20: 2103-2113. 10.1093/cercor/bhp278.CrossRefPubMed

17.

Weinstein M, Ben-Sira L, Levy Y, Zachor DA, Ben Itzhak E, Artzi M, Tarrasch R, Eksteine PM, Hendler T, Ben Bashat D: Abnormal white matter integrity in young children with autism. Hum Brain Mapp. 2011, 32: 534-543. 10.1002/hbm.21042.CrossRefPubMed

18.

Tager-Flusberg H: Understanding the language and communicative impairments in autism. Intl Rev Res Ment Retard. 2001, 23: 185-205.CrossRef

19.

Fletcher PT, Whitaker RT, Tao R, DuBray MB, Froehlich A, Ravichandran C, Alexander AL, Bigler ED, Lange N, Lainhart JE: Microstructural connectivity of the arcuate fasciculus in adolescents with high-functioning autism. NeuroImage. 2010, 51: 1117-1125. 10.1016/j.neuroimage.2010.01.083.CrossRefPubMedPubMedCentral

20.

Lord C, Risi S, Lambrecht L, Cook E, Leventhal BL, DiLavore PC, Pickles A, Rutter M: 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: 205-223. 10.1023/A:1005592401947.CrossRefPubMed

21.

Schopler E, Reichler RJ, Renner BR: Western Psychological Services. The Childhood Autism Rating Scale. 1988, Los Angeles, CA

22.

Roid GH, Miller LJ: Psychological Assessment Resources. The Leiter International Performance Scale-revised Edition. 1997, Lutz, FL

23.

Griffiths R: A.R.I.C.D. The Test Agency Limited. The abilities of young children: a comprehensive system of mental measurement for the first eight years of life, Revised ed. 1984, Bucks, U.K

24.

Wechsler D: Organizzazioni Speciali. Wechsler Preschool and Primary Scale of Intelligence (WWPSI). 1973, Firenze (Italy)

25.

Wechsler D: Organizzazioni Speciali. Wechsler Intelligence Scale for Children-Revised (WISC-R). 1986, Firenze (Italy)

26.

Tager-Flusberg H, Rogers S, Cooper J, Landa R, Lord C, Paul R, Rice M, Stoel-Gammon C, Wetherby A, Yoder P: Defining spoken language benchmarks and selecting measures of expressive language development for young children with autism spectrum disorders. J Speech Lang Hear Res. 2009, 52: 643-652. 10.1044/1092-4388(2009/08-0136).CrossRefPubMedPubMedCentral

27.

Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TEJ, Johansen-Berg H, Bannister PR, De Luca M, Drobnjak I, Flitney DE, Niazy R, Saunders J, Vickers J, Zhang Y, De Stefano N, Brady JM, Matthews PM: Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage. 2004, 23 (S1): 208-219.CrossRef

28.

Behrens TE, Woolrich MW, Jenkinson M, Johansen-Berg H, Nunes RG, Clare S, Matthews PM, Brady JM, Smith SM: Characterization and propagation of uncertainty in diffusion-weighted MR imaging. Magn Reson Med. 2003, 50: 1077-1088. 10.1002/mrm.10609.CrossRefPubMed

29.

Smith SM: Fast robust automated brain extraction. Hum Brain Mapp. 2002, 17: 143-155. 10.1002/hbm.10062.CrossRefPubMed

30.

Andersson LR, Jenkinson M, Smith SM: Non-linear optimisation, FMRIB technical report TR07JA1. http://www.fmrib.ox.ac.uk/analysis/techrep,

31.

Andersson JLR, Jenkinson M, Smith S: Non-linear registration, aka Spatial normalisation, FMRIB technical report TR07JA2. http://www.fmrib.ox.ac.uk/analysis/techrep,

32.

Rueckert D, Sonoda LI, Hayes C, Hill DLG, Leach MO, Hawkes DJ: Non-rigid registration using free-form deformations: Application to breast MR images. IEEE Trans Med Imaging. 1999, 18: 712-721. 10.1109/42.796284.CrossRefPubMed

33.

Nichols TE, Holmes AP: Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp. 2002, 15: 1-25. 10.1002/hbm.1058.CrossRefPubMed

34.

Catani M, Thiebaut De Schotten M: A diffusion tensor imaging tractography atlas for virtual in vivo dissections. Cortex. 2008, 44: 1105-1132. 10.1016/j.cortex.2008.05.004.CrossRefPubMed

35.

Rothman KJ: No adjustments are needed for multiple comparisons. Epidemiology. 1990, 1: 43-46. 10.1097/00001648-199001000-00010.CrossRefPubMed

36.

Saville DJ: Multiple Comparison Procedures: The Practical Solution. Am Stat. 1990, 44: 174-180.

37.

Gelman A, Hill J, Yajima M: Why We (Usually) Don’t Have to Worry About Multiple Comparisons. J Res Educational Effectiveness. 2012, 2012 (5): 189-211.CrossRef

38.

Alexander AL, Lee JE, Lazar M, Boudos R, DuBray MB, Oakes TR, Miller JN, Lu J, Jeong E, McMahon WM, Bigler ED, Lainhart JE: Diffusion tensor imaging of the corpus callosum in autism. NeuroImage. 2007, 34: 61-73. 10.1016/j.neuroimage.2006.08.032.CrossRefPubMed

39.

Keller TA, Kana RK, Just MA: A developmental study of the structural integrity of white matter in autism. NeuroReport. 2007, 18: 23-27. 10.1097/01.wnr.0000239965.21685.99.CrossRefPubMed

40.

Barnea-Goraly N, Kwon H, Menon V, Eliez S, Lotspeich L, Reiss AL: White matter structure in autism: preliminary evidence from diffusion tensor imaging. Biol Psychiatry. 2004, 55: 323-326. 10.1016/j.biopsych.2003.10.022.CrossRefPubMed

41.

Lee JE, Bigler ED, Alexander AL, Lazar M, DuBray MB, Chung MK, Johnson M, Morgan J, Miller JN, McMahon WM, Lu J, Jeong E, Lainhart JE: Diffusion tensor imaging of white matter in the superior temporal gyrus and temporal stem in autism. Neurosci Lett. 2007, 424: 127-132. 10.1016/j.neulet.2007.07.042.CrossRefPubMed

42.

Shukla DK, Keehna B, Smyliea DM, Müllera R: Microstructural abnormalities of short-distance white matter tracts in autism spectrum disorder. Neuropsychologia. 2011, 49: 1378-1382. 10.1016/j.neuropsychologia.2011.02.022.CrossRefPubMedPubMedCentral

43.

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: 873-882. 10.1016/j.neuroimage.2010.01.011.CrossRefPubMed

44.

Courchesne E, Carper R, Akshoomoff N: Evidence of brain overgrowth in the first year of life in autism. JAMA. 2003, 290: 337-344. 10.1001/jama.290.3.337.CrossRefPubMed

45.

Dementieva YA, Vance DD, Donnelly SL, Elston LA, Wolpert CM, Ravan SA, DeLong GR, Abramson RK, Wright HH, Cuccaro ML: Accelerated head growth in early development of individuals with autism. Pediatr Neurol. 2005, 32: 102-108. 10.1016/j.pediatrneurol.2004.08.005.CrossRefPubMed

46.

Muratori F, Calderoni S, Apicella F, Filippi T, Santocchi E, Calugi S, Cosenza A, Tancredi R, Narzisi A: Tracing back to the onset of abnormal head circumference growth in Italian children with autism spectrum disorder. Res Autism Spectr Disord. 2012, 6: 442-449. 10.1016/j.rasd.2011.07.004.CrossRef

47.

Wolff JJ, Gu H, Gerig G, Elison JT, Styner M, Gouttard S, Botteron KN, Dager SR, Dawson G, Estes AM, Evans AC, Hazlett HC, Kostopoulos P, McKinstry RC, Paterson SJ, Schultz RT, Zwaigenbaum L, Piven J, IBIS Network: Differences in white matter fiber tract development present from 6 to 24 months in infants with autism. Am J Psychiatry. 2012, 169: 589-600.CrossRefPubMedPubMedCentral

48.

Walker L, Gozzi M, Lenroot R, Thurm A, Behseta B, Swedo S, Pierpaoli C: Diffusion Tensor Imaging in Young Children with Autism: Biological Effects and Potential Confounds. Biol Psychiatry. 2012, 72: 1043-1051. 10.1016/j.biopsych.2012.08.001.CrossRefPubMedPubMedCentral

49.

Badaruddin DH, Andrews GL, Bölte S, Schilmoeller KJ, Schilmoeller G, Paul LK, Brown WS: Social and behavioral problems of children with agenesis of the corpus callosum. Child Psychiatry Hum Dev. 2007, 38: 287-302. 10.1007/s10578-007-0065-6.CrossRefPubMed

50.

Brown WS, Paul LK, Symington M, Dietrich R: Comprehension of humor in primary agenesis of the corpus callosum. Neuropsychologia. 2005, 43: 906-916. 10.1016/j.neuropsychologia.2004.09.008.CrossRefPubMed

51.

Brown WS, Symingtion M, VanLancker-Sidtis D, Dietrich R, Paul LK: Paralinguistic processing in children with callosal agenesis: emergence of neurolinguistic deficits. Brain Lang. 2005, 93: 135-139. 10.1016/j.bandl.2004.09.003.CrossRefPubMed

52.

Noriuchi M, Kikuchi Y, Yoshiura T, Kira R, Shigeto H, Hara T, Tobimatsu S, Kamio Y: Altered white matter fractional anisotropy and social impairment in children with autism spectrum disorder. Brain Res. 2010, 1362: 141-149.CrossRefPubMed

53.

Jou RJ, Jackowski AP, Papademetris X, Rajeevan N, Staib LH, Volkmar FR: Diffusion tensor imaging in autism spectrum disorders: preliminary evidence of abnormal neural connectivity. Aust N Z J Psychiatry. 2011, 45: 153-162. 10.3109/00048674.2010.534069.CrossRefPubMed

54.

Di Martino A, Ross K, Uddin LQ, Sklar AB, Castellanos FX, Milham MP: Functional brain correlates of social and nonsocial processes in autism spectrum disorders: an activation likelihood estimation meta-analysis. Biol Psychiatry. 2009, 65: 63-74. 10.1016/j.biopsych.2008.09.022.CrossRefPubMed

55.

Thakkar KN, Polli FE, Joseph RM, Tuch DS, Hadjikhani N, Barton JJ, Manoach DS: Response monitoring, repetitive behaviour and anterior cingulate abnormalities in autism spectrum disorders (ASD). Brain. 2008, 131: 2464-2478. 10.1093/brain/awn099.CrossRefPubMedPubMedCentral

56.

Pugliese L, Catani M, Ameis S, Dell’Acqua F, Thiebaut De Schotten M, Murphy C, Robertson D, Deeley Q, Daly E, Murphy DG: The anatomy of extended limbic pathways in Asperger syndrome: a preliminary diffusion tensor imaging tractography study. NeuroImage. 2009, 47: 427-434. 10.1016/j.neuroimage.2009.05.014.CrossRefPubMed

57.

Casanova MF, Buxhoeveden DP, Brown C: Clinical and macroscopic correlates of mini-columnar pathology in autism. J Child Neurol. 2002, 17: 692-695. 10.1177/088307380201700908.CrossRefPubMed

58.

Herbert MR, Ziegler DA, Makris N, Filipek PA, Kemper TL, Normandin JJ, Sanders HA, Kennedy DN, Caviness VS: Localization of white matter volume increase in autism and developmental language disorder. Ann Neurol. 2004, 55: 530-540. 10.1002/ana.20032.CrossRefPubMed

59.

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: Dissociations of cerebral cortex, subcortical and cerebral white matter volumes in autistic boys. Brain. 2003, 126 (Pt 5): 1182-1192.CrossRefPubMed

60.

Sundaram SK, Kumar A, Makki MI, Behen ME, Chugani HT, Chugani DC: Diffusion tensor imaging of frontal lobe in autism spectrum disorder. Cereb Cortex. 2008, 18: 2659-2665. 10.1093/cercor/bhn031.CrossRefPubMedPubMedCentral

61.

Lauder JM: Ontogeny of the serotonergic system in the rat: serotonin as a developmental signal. Ann N Y Acad Sci. 1990, 600: 297-313. 10.1111/j.1749-6632.1990.tb16891.x. discussion 314CrossRefPubMed

62.

van Kesteren RE, Spencer GE: The role of neurotransmitters in neurite outgrowth and synapse formation. Rev Neurosci. 2003, 14: 217-231.CrossRefPubMed

63.

Croen LA, Grether JK, Yoshida CK, Odouli R, Hendrick V: Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry. 2011, 68: 1104-1112. 10.1001/archgenpsychiatry.2011.73.CrossRefPubMed

64.

Nagae LM, Zarnow DM, Blaskey L, Dell J, Khan SY, Qasmieh S, Levy SE, Roberts TP: Elevated mean diffusivity in the left hemisphere superior longitudinal fasciculus in autism spectrum disorders increases with more profound language impairment. AJNR. 2012, 10.3174/ajnr.A3037.

65.

Catani M, Jones DK, Ffytche DH: Perisylvian language networks of the human brain. Ann Neurol. 2005, 57: 8-16. 10.1002/ana.20319.CrossRefPubMed

66.

Schmithorst VJ, Wilke M, Dardzinski BJ, Holland SK: Correlation of white matter diffusivity and anisotropy with age during childhood and adolescence: a cross-sectional diffusion-tensor MR imaging study. Radiology. 2002, 222: 212-218.CrossRefPubMedPubMedCentral

67.

Hermoye L, Saint-Martin C, Cosnard G, Lee SK, Kim J, Nassogne MC, Menten R, Clapuyt P, Donohue PK, Hua K, Wakana S, Jiang H, van Zijl PC, Mori S: Pediatric diffusion tensor imaging: normal database and observation of the white matter maturation in early childhood. NeuroImage. 2006, 29: 493-504. 10.1016/j.neuroimage.2005.08.017.CrossRefPubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2377/12/148/prepub

Title: White matter connectivity in children with autism spectrum disorders: a tract-based spatial statistics study
Authors: Lucia Billeci
Sara Calderoni
Michela Tosetti
Marco Catani
Filippo Muratori
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: BMC Neurology / Issue 1/2012
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/1471-2377-12-148

Keynote webinar | Spotlight on medication adherence

Springer Medicine

White matter connectivity in children with autism spectrum disorders: a tract-based spatial statistics study

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2012

Pregnancy and fetal outcomes after Glatiramer Acetate exposure in patients with multiple sclerosis: a prospective observational multicentric study

Comparison of gait in progressive supranuclear palsy, Parkinson’s disease and healthy older adults

Exploring the predictive value of the evoked potentials score in MS within an appropriate patient population: a hint for an early identification of benign MS?

Sparse learning and stability selection for predicting MCI to AD conversion using baseline ADNI data

Recurrent aseptic meningitis in association with Kikuchi-Fujimoto disease: case report and literature review

Eye movement impairments in Parkinson's disease: possible role of extradopaminergic mechanisms