Brain Structure and Function

, Volume 218, Issue 3, pp 711–720 | Cite as

Morphometry of corpus callosum in Williams syndrome: shape as an index of neural development

  • Adriana Sampaio
  • Sylvain Bouix
  • Nuno Sousa
  • Cristiana Vasconcelos
  • Montse Férnandez
  • Martha E. Shenton
  • Óscar F. Gonçalves
Original Article


Brain abnormalities in Williams syndrome (WS) have been consistently reported, despite few studies have devoted attention to connectivity between different brain regions in WS. In this study, we evaluated corpus callosum (CC) morphometry: bending angle, length, thickness and curvature of CC using a new shape analysis method in a group of 17 individuals with WS matched with a typically developing group. We used this multimethod approach because we hypothesized that neurodevelopmental abnormalities might result in both volume changes and structure deformation. Overall, we found reduced absolute CC cross-sectional area and volume in WS (mean CC and subsections). In parallel, we observed group differences regarding CC shape and thickness. Specifically, CC of WS is morphologically different, characterized by a larger bending angle and being more curved in the posterior part. Moreover, although CC in WS is shorter, a larger relative thickness of CC was found in all callosal sections. Finally, groups differed regarding the association between CC measures, age, white matter volume and cognitive performance. In conclusions, abnormal patterns of CC morphology and shape may be implicated in WS cognitive and behavioural phenotype.


Corpus callosum MRI Neurodevelopment Williams syndrome 



This research was supported by the grants PIC/IC/83290/2007 and PTDC/PSI-PCL/115316/2009 from Fundação para a Ciência e Tecnologia (Portugal). This study was also supported, in part, by grants from the National Institutes of Health (K05 MH070047).

Conflict of interest

The authors report no conflicts of interest.


  1. Barnea-Goraly N, Menon V, Eckert M, Tamm L, Bammer R, Karchemskiy A, Dant CC, Reiss AL (2005) White matter development during childhood and adolescence: a cross-sectional diffusion tensor imaging study. Cereb Cortex 15(12):1848–1854PubMedCrossRefGoogle Scholar
  2. Bellugi U, Adolphs R, Cassady C, Chiles M (1999) Towards the neural basis for hypersociability in a genetic syndrome. NeuroReport 10(8):1653PubMedCrossRefGoogle Scholar
  3. Bellugi U, Lichtenberger L, Jones W, Lai Z, St George M (2000) The neurocognitive profile of Williams Syndrome: a complex pattern of strengths and weaknesses. J Cogn Neurosci 12(Suppl 1):7–29PubMedCrossRefGoogle Scholar
  4. Bouix S, Siddiqi K (2005) Optics, mechanics and Hamilton–Jacobi skeletons. Adv Imaging Electron Phys 135:1–39CrossRefGoogle Scholar
  5. Capitao L, Sampaio A, Fernandez M, Sousa N, Pinheiro A, Goncalves OF (2011a) Williams syndrome hypersociability: a neuropsychological study of the amygdala and prefrontal cortex hypotheses. Res Dev Disabilities 32(3):1169–1179CrossRefGoogle Scholar
  6. Capitao L, Sampaio A, Sampaio C, Vasconcelos C, Fernandez M, Garayzabal E, Shenton ME, Goncalves OF (2011b) MRI amygdala volume in Williams syndrome. Res Dev Disabilities 32(6):2767–2772CrossRefGoogle Scholar
  7. Cascio C, Styner M, Smith RG, Poe MD, Gerig G, Hazlett HC, Jomier M, Bammer R, Piven J (2006) Reduced relationship to cortical white matter volume revealed by tractography-based segmentation of the corpus callosum in young children with developmental delay. Am J Psychiatry 163(12):2157–2163PubMedCrossRefGoogle Scholar
  8. Chiang MC, Reiss AL, Lee AD, Bellugi U, Galaburda AM, Korenberg JR, Mills DL, Toga AW, Thompson PM (2007) 3D pattern of brain abnormalities in Williams syndrome visualized using tensor-based morphometry. Neuroimage 36(4):1096–1109PubMedCrossRefGoogle Scholar
  9. Eckert MA, Hu D, Eliez S, Bellugi U, Galaburda A, Korenberg J, Mills D, Reiss AL (2005) Evidence for superior parietal impairment in Williams syndrome. Neurology 64(1):152–153PubMedCrossRefGoogle Scholar
  10. Ewart A, Morris C, Atkinson D, Jin W, Sternes K, Spallone P, Stock AD, Leppert M, Keating M (1993) Hemizygosity at the elastin locus in a developmental disorder. Williams syndrome. Nat Genet 5(1):11–16PubMedCrossRefGoogle Scholar
  11. Frumin M, Golland P, Kikinis R, Hirayasu Y, Salisbury DF, Hennen J, Dickey CC, Anderson M, Jolesz FA, Grimson WE, McCarley RW, Shenton ME (2002) Shape differences in the corpus callosum in first-episode schizophrenia and first-episode psychotic affective disorder. Am J Psychiatry 159(5):866–868PubMedCrossRefGoogle Scholar
  12. Galaburda AM, Holinger DP, Bellugi U, Sherman GF (2002) Williams syndrome: neuronal size and neuronal-packing density in primary visual cortex. Arch Neurol 59(9):1461–1467PubMedCrossRefGoogle Scholar
  13. Gaser C, Luders E, Thompson PM, Lee AD, Dutton RA, Geaga JA, Hayashi KM, Bellugi U, Galaburda AM, Korenberg JR, Mills DL, Toga AW, Reiss AL (2006) Increased local gyrification mapped in Williams syndrome. Neuroimage 33(1):46–54PubMedCrossRefGoogle Scholar
  14. Giedd JN, Blumenthal J, Jeffries N, Rajapakse JC, Vaituzis AC, Liu HG, Berry YC, Tobin M, Nelson J, Castellanos FX (1999a) Development of the human corpus callosum during childhood and adolescence: a longitudinal MRI study. Prog Neuro-Psychopharmacol Biol Psychiatry 23:571–588CrossRefGoogle Scholar
  15. Giedd JN, Blumenthal J, Jeffries NO, Castellanos FX, Liu H, Zijdenbos A, Paus T, Evans AC, Rapoport J (1999b) Brain development during childhood and adolescence: a longitudinal MRI study. Nat Neurosci 2:861–863Google Scholar
  16. Good P (2005) Permutation, parametric, and bootstrap tests of hypotheses, 3rd edn. New YorkGoogle Scholar
  17. Hardan AY, Pabalan M, Gupta N, Bansal R, Melhem NM, Fedorov S, Keshavan MS, Minshew NJ (2009) Corpus callosum volume in children with autism. Psychiatry Res 174(1):57–61PubMedCrossRefGoogle Scholar
  18. Hines RJ, Paul LK, Brown WS (2002) Spatial attention in agenesis of the corpus callosum: shifting attention between visual fields. Neuropsychologia 40(11):1804–1814PubMedCrossRefGoogle Scholar
  19. Hoeft F, Barnea-Goraly N, Haas BW, Golarai G, Ng D, Mills D, Korenberg J, Bellugi U, Galaburda A, Reiss AL (2007) More is not always better: increased fractional anisotropy of superior longitudinal fasciculus associated with poor visuospatial abilities in Williams syndrome. J Neurosci 27(44):11960–11965PubMedCrossRefGoogle Scholar
  20. Hofer S, Frahm J (2006) Topography of the human corpus callosum revisited-comprehensive fiber tractography using diffusion tensor magnetic resonance imaging. Neuroimage 32(3):989–994PubMedCrossRefGoogle Scholar
  21. Holinger DP, Bellugi U, Mills DL, Korenberg JR, Reiss AL, Sherman GF, Galaburda AM (2005) Relative sparing of primary auditory cortex in Williams Syndrome. Brain Res 1037(1–2):35–42PubMedCrossRefGoogle Scholar
  22. Johansen-Berg H, Della-Maggiore V, Behrens TE, Smith SM, Paus T (2007) Integrity of white matter in the corpus callosum correlates with bimanual co-ordination skills. Neuroimage 36(Suppl 2):T16–T21PubMedCrossRefGoogle Scholar
  23. Karmiloff-Smith A, Brown JH, Grice S, Paterson S (2003) Dethroning the myth: cognitive dissociations and innate modularity in Williams syndrome. Dev Neuropsychol 23(1–2):227–242PubMedGoogle Scholar
  24. Keshavan MS, Diwadkar VA, DeBellis M, Dick E, Kotwal R, Rosenberg DR, Sweeney JA, Minshew N, Pettegrew JW (2002) Development of the corpus callosum in childhood, adolescence and early adulthood. Life Sci 70(16):1909–1922PubMedCrossRefGoogle Scholar
  25. Klein-Tasman B, Mervis C (2003) Distinctive personality characteristics of 8-, 9-, and 10-year-olds with Williams syndrome. Dev Neuropsychol 23(1):269–290PubMedCrossRefGoogle Scholar
  26. LaMantia AS, Rakic P (1990) Axon overproduction and elimination in the corpus callosum of the developing rhesus monkey. J Neurosci 10(7):2156–2175PubMedGoogle Scholar
  27. Lenroot RK, Giedd JN (2006) Brain development in children and adolescents: insights from anatomical magnetic resonance imaging. Neurosci Biobehav Rev 30:718–729PubMedCrossRefGoogle Scholar
  28. Lindwall C, Fothergill T, Richards LJ (2007) Commissure formation in the mammalian forebrain. Curr Opin Neurobiol 17(1):3–14PubMedCrossRefGoogle Scholar
  29. Luders E, Di Paola M, Tomaiuolo F, Thompson PM, Toga AW, Vicari S, Petrides M, Caltagirone C (2007a) Callosal morphology in Williams syndrome: a new evaluation of shape and thickness. NeuroReport 18(3):203–207PubMedCrossRefGoogle Scholar
  30. Luders E, Narr KL, Bilder RM, Thompson PM, Szeszko PR, Hamilton L, Toga AW (2007b) Positive correlations between corpus callosum thickness and intelligence. Neuroimage 37(4):1457–1464PubMedCrossRefGoogle Scholar
  31. Luders E, Cherbuin N, Thompson PM, Gutman B, Anstey KJ, Sachdev P, Toga AW (2010) When more is less: associations between corpus callosum size and handedness lateralization. Neuroimage 52(1):43–49PubMedCrossRefGoogle Scholar
  32. Luders E, Thompson PM, Narr KL, Zamanyan A, Chou YY, Gutman B, Dinov ID, Toga AW (2011) The link between callosal thickness and intelligence in healthy children and adolescents. Neuroimage 54(3):1823–1830PubMedCrossRefGoogle Scholar
  33. Marenco S, Siuta MA, Kippenhan JS, Grodofsky S, Chang WL, Kohn P, Mervis CB, Morris CA, Weinberger DR, Meyer-Lindenberg A, Pierpaoli C, Berman KF (2007) Genetic contributions to white matter architecture revealed by diffusion tensor imaging in Williams syndrome. Proc Natl Acad Sci USA 104(38):15117–15122PubMedCrossRefGoogle Scholar
  34. Martens MA, Wilson SJ, Chen J, Wood A, Reutens D (2012) Handedness and corpus callosum morphology in Williams syndrome. Dev Psychopathol (in press)Google Scholar
  35. McLaughlin NC, Paul RH, Grieve SM, Williams LM, Laidlaw D, DiCarlo M, Clark CR, Whelihan W, Cohen RA, Whitford TJ, Gordon E (2007) Diffusion tensor imaging of the corpus callosum: a cross-sectional study across the lifespan. Int J Dev Neurosci 25(4):215–221PubMedCrossRefGoogle Scholar
  36. Meyer-Lindenberg A, Kohn P, Mervis CB, Kippenhan JS, Olsen RK, Morris CA, Berman KF (2004) Neural basis of genetically determined visuospatial construction deficit in Williams syndrome. Neuron 43(5):623–631PubMedCrossRefGoogle Scholar
  37. Meyer-Lindenberg A, Mervis CB, Sarpal D, Koch P, Steele S, Kohn P, Marenco S, Morris CA, Das S, Kippenhan S, Mattay VS, Weinberger DR, Berman KF (2005) Functional, structural, and metabolic abnormalities of the hippocampal formation in Williams syndrome. J Clin Investig 115(7):1888–1895PubMedCrossRefGoogle Scholar
  38. Mobbs D, Eckert MA, Mills D, Korenberg J, Bellugi U, Galaburda AM, Reiss AL (2007) Frontostriatal dysfunction during response inhibition in Williams syndrome. Biol Psychiatry 62(3):256–261PubMedCrossRefGoogle Scholar
  39. Nichols H (2003) Controlling the familywise error rate in functional neuroimaging: a comparative review. Stat Methods Med Res 12(5):419–446PubMedCrossRefGoogle Scholar
  40. Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9(1):97–113PubMedCrossRefGoogle Scholar
  41. Paul LK, Brown WS, Adolphs R, Tyszka JM, Richards LJ, Mukherjee P, Sherr EH (2007) Agenesis of the corpus callosum: genetic, developmental and functional aspects of connectivity. Nat Rev Neurosci 8(4):287–299PubMedCrossRefGoogle Scholar
  42. Pinheiro AP, Galdo-Alvarez S, Sampaio A, Niznikiewicz M, Goncalves OF (2010) Electrophysiological correlates of semantic processing in Williams syndrome. Res Dev Disabil 31(6):1412–1425PubMedCrossRefGoogle Scholar
  43. Plessen KJ, Wentzel-Larsen T, Hugdahl K, Feineigle P, Klein J, Staib LH, Leckman JF, Bansal R, Peterson BS (2004) Altered interhemispheric connectivity in individuals with Tourette’s disorder. Am J Psychiatry 161(11):2028–2037PubMedCrossRefGoogle Scholar
  44. Pohl K, Bouix S, Nakamura M, Rohlfing T, McCarley R, Kikinis R, Grimson W, Shenton ME, Wells W (2007) A hierarchical algorithm for MR brain image parcellation. IEEE Trans Med Imaging 26(9):1201–1212PubMedCrossRefGoogle Scholar
  45. Porter MA, Coltheart M, Langdon R (2007) The neuropsychological basis of hypersociability in Williams and Down syndrome. Neuropsychologia 45(12):2839–2849PubMedCrossRefGoogle Scholar
  46. Raine A, Lencz T, Taylor K, Hellige JB, Bihrle S, Lacasse L, Lee M, Ishikawa S, Colletti P (2003) Corpus callosum abnormalities in psychopathic antisocial individuals. Arch Gen Psychiatry 60(11):1134–1142PubMedCrossRefGoogle Scholar
  47. Reiss AL, Abrams MT, Singer HS, Ross JL, Denckla MB (1996) Brain development, gender and IQ in children. A volumetric imaging study. Brain 119(Pt 5):1763–1774PubMedCrossRefGoogle Scholar
  48. Reiss AL, Eckert MA, Rose FE, Karchemskiy A, Kesler S, Chang M, Reynolds MF, Kwon H, Galaburda A (2004) An experiment of nature: brain anatomy parallels cognition and behavior in Williams syndrome. J Neurosci 24(21):5009–5015PubMedCrossRefGoogle Scholar
  49. Sampaio A, Sousa N, Fernandez M, Vasconcelos C, Shenton ME, Goncalves OF (2008) MRI assessment of superior temporal gyrus in Williams syndrome. Cognitive and behavioral neurology. J Soc Behav Cogn Neurol 21(3):150–156CrossRefGoogle Scholar
  50. Sampaio A, Sousa N, Fernandez M, Vasconcelos C, Shenton ME, Goncalves OF (2010) Williams syndrome and memory: a neuroanatomic and cognitive approach. J Autism Dev Disord 40(7):870–877PubMedCrossRefGoogle Scholar
  51. Schmitt JE, Eliez S, Bellugi U, Reiss AL (2001a) Analysis of cerebral shape in Williams syndrome. Arch Neurol 58(2):283–287PubMedCrossRefGoogle Scholar
  52. Schmitt JE, Eliez S, Warsofsky IS, Bellugi U, Reiss AL (2001b) Corpus callosum morphology of Williams syndrome: relation to genetics and behavior. Dev Med Child Neurol 43(3):155–159PubMedGoogle Scholar
  53. Schulte T, Sullivan EV, Muller-Oehring EM, Adalsteinsson E, Pfefferbaum A (2005) Corpus callosal microstructural integrity influences interhemispheric processing: a diffusion tensor imaging study. Cereb Cortex 15(9):1384–1392PubMedCrossRefGoogle Scholar
  54. Strømme P, Bjømstad P, Ramstad K (2002) Prevalence estimation of Williams syndrome. J Child Neurol 17(4):269PubMedCrossRefGoogle Scholar
  55. Thompson PM, Giedd JN, Woods RP, MacDonald D, Evans AC, Toga AW (2000) Growth patterns in the developing brain detected by using continuum mechanical tensor maps. Nature 404(6774):190–193PubMedCrossRefGoogle Scholar
  56. Thompson PM, Lee AD, Dutton RA, Geaga JA, Hayashi KM, Eckert MA, Bellugi U, Galaburda AM, Korenberg JR, Mills DL, Toga AW, Reiss AL (2005) Abnormal cortical complexity and thickness profiles mapped in Williams syndrome. J Neurosc Off J Soc Neurosci 25(16):4146–4158CrossRefGoogle Scholar
  57. Tomaiuolo F, Di Paola M, Caravale B, Vicari S, Petrides M, Caltagirone C (2002) Morphology and morphometry of the corpus callosum in Williams syndrome: a T1-weighted MRI study. NeuroReport 13(17):2281–2284PubMedCrossRefGoogle Scholar
  58. Van Essen DC (1997) A tension-based theory of morphogenesis and compact wiring in the central nervous system. Nature 385:313–318PubMedCrossRefGoogle Scholar
  59. Van Essen DC, Drury HA (1997) Structural and functional analyses of human cerebral cortex using a surface-based atlas. J Neurosci 17(18):7079–7102PubMedGoogle Scholar
  60. Van Essen DC, Drury HA, Joshi S, Miller MI (1998) Functional and structural mapping of human cerebral cortex: solutions are in the surfaces. Proc Natl Acad Sci USA 95(3):788–795PubMedCrossRefGoogle Scholar
  61. Vidal CN, Nicolson R, DeVito TJ, Hayashi KM, Geaga JA, Drost DJ, Williamson PC, Rajakumar N, Sui Y, Dutton RA, Toga AW, Thompson PM (2006) Mapping corpus callosum deficits in autism: an index of aberrant cortical connectivity. Biol Psychiatry 60(3):218–225PubMedCrossRefGoogle Scholar
  62. Wechsler D (1991) Wechsler Intelligence Scale for Children. Manual, 3rd edn. Psychological Corporation, San AntonioGoogle Scholar
  63. Wechsler D (1997) Wechsler Adult Intelligence Scale. Manual, 3rd edn. Psychological Corporation, San AntonioGoogle Scholar
  64. Witelson SF (1989) Hand and sex differences in the isthmus and genu of the human corpus callosum. A postmortem morphological study. Brain 112(Pt 3):799–835PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Adriana Sampaio
    • 1
  • Sylvain Bouix
    • 3
  • Nuno Sousa
    • 2
  • Cristiana Vasconcelos
    • 4
  • Montse Férnandez
    • 5
  • Martha E. Shenton
    • 3
    • 6
  • Óscar F. Gonçalves
    • 1
  1. 1.Neuropsychophysiology Laboratory, CiPsi, School of PsychologyUniversity of MinhoBragaPortugal
  2. 2.Life and Health Sciences Research InstituteUniversity of MinhoBragaPortugal
  3. 3.Psychiatry Neuroimaging Laboratory, Department of PsychiatryBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  4. 4.Department of NeuroradiologyHospital de Santo AntónioPortoPortugal
  5. 5.Genetic Molecular Unit, Galician Public Foundation of Genomic Medicine, University of Santiago de CompostelaSantiago de CompostelaSpain
  6. 6.Laboratory of Neuroscience, Clinical Neuroscience Division, Department of PsychiatryVA Boston Healthcare System, and Harvard Medical SchoolBrocktonUSA

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