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  • Review Article
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Neural mechanisms in Williams syndrome: a unique window to genetic influences on cognition and behaviour

Nature Reviews Neuroscience volume 7, pages 380–393 (2006)Cite this article

Key Points

  • Williams syndrome is a neurodevelopmental disorder with a prevalence of up to 1 in 7,500, caused by a hemizygous deletion of ∼1.6 megabases, containing ∼28 genes, on chromosome 7q11.23 through unequal homologous recombination during meiosis. Williams syndrome is characterized by typical facial features, cardiovascular abnormalities, mild to moderate mental retardation or learning difficulties, and unique neuropsychological and behavioural features that have made it a focus of research in neuroscience and genetics.

  • The neuropsychological profile of Williams syndrome shows a severe weakness in visuospatial construction, combined with relative strength in verbal short-term memory and language. However, neither language production nor verbal short-term memory is typically completely normal. Behaviourally, individuals with Williams syndrome show a striking social fearlessness and gregariousness, combined with strongly increased non-social fear.

  • We review recent advances made in defining the neural substrates of the unique neuropsychiatric features of Williams syndrome and define separable neural subsystems in this syndrome, specifying mechanisms for genetic influences on visuospatial cognition, social behaviour and memory. These results are discussed in the context of emerging data that link dissociable genetic contributions to these phenotypes through the study of knockout mouse models and atypical deletions in humans.

  • The brains of individuals with Williams syndrome are smaller and show regions of reduced grey matter volume, and abnormal gyrus and sulcus configuration. A reduction of grey matter volume and depth has been identified in the intraparietal sulcus, a region that is important for visuospatial constructive function. In addition, functional MRI studies show activation deficits in the adjacent parietal lobe as a functional correlate of a circumscribed dorsal visual stream deficit that can be linked to the structural abnormality and may underlie the severe visuospatial constructive impairment seen in Williams syndrome.

  • Convergent imaging evidence shows abnormal resting blood flow and activation of the anterior hippocampal formation together with only subtly abnormal structure. This might be linked to the severe long-term memory and visual-navigational impairments associated with Williams syndrome.

  • In individuals with Williams syndrome, the amygdala is less active to threatening faces, but shows increased activity to threatening non-social stimuli, mirroring the fear profile in behaviour. Interactions between the amygdala and prefrontal regulatory regions, especially the orbitofrontal cortex, are abnormal, which suggests that the neural systems for social and non-social fear are dissociable and underlie different genetic–developmental trajectories.

  • Knockout mouse models for LIM domain kinase 1 (Limk1) and cytoplasmic linker 2 (C yln2) show similar hippocampal abnormalities to those identified in humans, implicating these genes in hippocampal function. The results of studies of human families with small deletions suggest that LIMK1 is a promising candidate gene for involvement in the severe impairment in visuospatial construction seen in individuals with Williams syndrome, and that GTF2I (general transcription factor II i repeat domain-containing 1) hemideletion is necessary for mental retardation in this syndrome.

Abstract

Williams syndrome, a rare disorder caused by hemizygous microdeletion of about 28 genes on chromosome 7q11.23, has long intrigued neuroscientists with its unique combination of striking behavioural abnormalities, such as hypersociability, and characteristic neurocognitive profile. Williams syndrome, therefore, raises fundamental questions about the neural mechanisms of social behaviour, the modularity of mind and brain development, and provides a privileged setting to understand genetic influences on complex brain functions in a 'bottom-up' way. We review recent advances in uncovering the functional and structural neural substrates of Williams syndrome that provide an emerging understanding of how these are related to dissociable genetic contributions characterized both in special participant populations and animal models.

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Figure 1: Genetics of Williams syndrome.
Figure 2: Structural abnormalities in the brains of individuals with Williams syndrome.
Figure 3: Dorsal visual stream functional deficits in Williams syndrome.
Figure 4: Hippocampal abnormalities in Williams syndrome.
Figure 5: Neural mechanisms of hypersociability in Williams syndrome.

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References

  1. Strømme, P., Bjørnstad, P. G. & Ramstad, K. Prevalence estimation of Williams syndrome. J. Child Neurol. 17, 269–271 (2002).

    Article  PubMed  Google Scholar 

  2. Beuren, A. J., Apitz, J. & Harmjanz, D. Supravalvular aortic stenosis in association with mental retardation and a certain facial appearance. Circulation 26, 1235–1240 (1962).

    Article  CAS  PubMed  Google Scholar 

  3. Williams, J. C., Barratt-Boyes, B. G. & Lowe, J. B. Supravalvular aortic stenosis. Circulation 24, 1311–1318 (1961). The initial description of WS.

    Article  CAS  PubMed  Google Scholar 

  4. American Academy of Pediatrics: Health care supervision for children with Williams syndrome. Pediatrics 107, 1192–1204 (2001).

  5. Morris, C. A. et al. GTF2I hemizygosity implicated in mental retardation in Williams syndrome: genotype–phenotype analysis of five families with deletions in the Williams syndrome region. Am. J. Med. Genet. 123A, 45–59 (2003). Provides evidence that GTF2I is important for normal intellectual ability.

    Article  PubMed  Google Scholar 

  6. Morris, C. A. in Williams–Beuren syndrome: Research, Evaluation, and Treatment (eds Morris, C. A., Lenhoff, H. M. & Wang, P. P.) 3–17 (Johns Hopkins Univ. Press, Baltimore, 2006).

    Google Scholar 

  7. Chapman, C. A., du Plessis, A. & Pober, B. R. Neurologic findings in children and adults with Williams syndrome. J. Child Neurol. 11, 63–65 (1996).

    Article  CAS  PubMed  Google Scholar 

  8. Cherniske, E. M. et al. Multisystem study of 20 older adults with Williams syndrome. Am. J. Med. Genet. 131A, 255–264 (2004).

    Article  Google Scholar 

  9. Marler, J. A., Elfenbein, J. L., Ryals, B. M., Urban, Z. & Netzloff, M. L. Sensorineural hearing loss in children and adults with Williams syndrome. Am. J. Med. Genet. A 138, 318–327 (2005).

    Article  PubMed  Google Scholar 

  10. Mervis, C. B. & Klein-Tasman, B. P. Williams syndrome: cognition, personality, and adaptive behaviour. Ment. Retard. Dev. Disabil. Res. Rev. 6, 148–158 (2000). Overview of cognition, language and personality in WS.

    Article  CAS  PubMed  Google Scholar 

  11. Mervis, C. B. et al. The Williams syndrome cognitive profile. Brain Cogn. 44, 604–628 (2000).

    Article  CAS  PubMed  Google Scholar 

  12. Farran, E. K. & Jarrold, C. Visuospatial cognition in Williams syndrome: reviewing and accounting for the strengths and weaknesses in performance. Dev. Neuropsychol. 23, 173–200 (2003).

    Article  PubMed  Google Scholar 

  13. Klein-Tasman, B. P. & Mervis, C. B. Distinctive personality characteristics of 8-, 9-, and 10-year-olds with Williams syndrome. Dev. Neuropsychol. 23, 269–290 (2003).

    Article  PubMed  Google Scholar 

  14. Bellugi, U., Adolphs, R., Cassady, C. & Chiles, M. Towards the neural basis for hypersociability in a genetic syndrome. Neuroreport 10, 1653–1657 (1999). A classic paper proposing amygdala involvement in the genesis of the social symptoms of WS.

    Article  CAS  PubMed  Google Scholar 

  15. Dykens, E. M. Anxiety, fears, and phobias in persons with Williams syndrome. Dev. Neuropsychol. 23, 291–316 (2003).

    Article  PubMed  Google Scholar 

  16. Leyfer, O. T., Woodruff-Borden, J., Klein-Tasman, B. P., Fricke, J. S. & Mervis, C. B. Prevalence of psychiatric disorders in 4–16-year-olds with Williams syndrome. Am. J. Med. Genet. B (in the press).

  17. Meyer-Lindenberg, A. et al. Neural basis of genetically determined visuospatial construction deficit in Williams syndrome. Neuron 43, 623–631 (2004). Identification of structural–functional abnormalities in intraparietal sulcus and adjacent parietal areas underlying the visuoconstructive deficit in WS.

    Article  CAS  PubMed  Google Scholar 

  18. Urban, Z. et al. 7q11.23 deletions in Williams syndrome arise as a consequence of unequal meiotic crossover. Am. J. Hum. Genet. 59, 958–962 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Bayes, M., Magano, L. F., Rivera, N., Flores, R. & Perez Jurado, L. A. Mutational mechanisms of Williams–Beuren syndrome deletions. Am. J. Hum. Genet. 73, 131–151 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Korenberg, J. R. et al. VI. Genome structure and cognitive map of Williams syndrome. J. Cogn. Neurosci. 12 (Suppl. 1), 89–107 (2000).

    Article  PubMed  Google Scholar 

  21. Hillier, L. W. et al. The DNA sequence of human chromosome 7. Nature 424, 157–164 (2003).

    Article  CAS  PubMed  Google Scholar 

  22. Hobart, H. H. et al. Heterozygotes for the microinversion of the Williams–Beuren region have an increased risk for affected offspring. Presented at the Annual Meeting of The American Society of Human Genetics, October 2004, Toronto, Ontario, Canada http://genetics.faseb.org/genetics/ashg/annmeet/2004/menu-annmeet-2004.shtml

  23. Osborne, L. R. et al. A 1.5 million-base pair inversion polymorphism in families with Williams–Beuren syndrome. Nature Genet. 29, 321–325 (2001).

    Article  CAS  PubMed  Google Scholar 

  24. Somerville, M. J. et al. Severe expressive-language delay related to duplication of the Williams–Beuren locus. N. Engl. J. Med. 353, 1694–1701 (2005). Describes the first reported case of duplication of the WS region. Documents that the phenotype for duplication of 7q11.23 is very different from the phenotype for hemideletion (WS).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Jernigan, T. L. & Bellugi, U. Anomalous brain morphology on magnetic resonance images in Williams syndrome and Down syndrome. Arch. Neurol. 47, 529–533 (1990).

    Article  CAS  PubMed  Google Scholar 

  26. Mercuri, E. et al. Chiari I malformation in asymptomatic young children with Williams syndrome: clinical and MRI study. Eur. J. Paediatr. Neurol. 1, 177–181 (1997).

    Article  CAS  PubMed  Google Scholar 

  27. Pober, B. R. & Filiano, J. J. Association of Chiari I malformation and Williams syndrome. Pediatr. Neurol. 12, 84–88 (1995).

    Article  CAS  PubMed  Google Scholar 

  28. Schmitt, J. E., Eliez, S., Warsofsky, I. S., Bellugi, U. & Reiss, A. L. Corpus callosum morphology of Williams syndrome: relation to genetics and behavior. Dev. Med. Child Neurol. 43, 155–159 (2001).

    Article  CAS  PubMed  Google Scholar 

  29. Tomaiuolo, F. et al. Morphology and morphometry of the corpus callosum in Williams syndrome: a T1-weighted MRI study. Neuroreport 13, 2281–2284 (2002).

    Article  CAS  PubMed  Google Scholar 

  30. Eckert, M. A. et al. Evidence for superior parietal impairment in Williams syndrome. Neurology 64, 152–153 (2005).

    Article  CAS  PubMed  Google Scholar 

  31. Reiss, A. L. et al. IV. Neuroanatomy of Williams syndrome: a high-resolution MRI study. J. Cogn. Neurosci. 12 (Suppl. 1), 65–73 (2000).

    Article  PubMed  Google Scholar 

  32. Wang, P. P., Hesselink, J. R., Jernigan, T. L., Doherty, S. & Bellugi, U. Specific neurobehavioral profile of Williams' syndrome is associated with neocerebellar hemispheric preservation. Neurology 42, 1999–2002 (1992).

    Article  CAS  PubMed  Google Scholar 

  33. Jones, W. et al. Cerebellar abnormalities in infants and toddlers with Williams syndrome. Dev. Med. Child Neurol. 44, 688–694 (2002).

    Article  PubMed  Google Scholar 

  34. Rae, C. et al. Brain biochemistry in Williams syndrome: evidence for a role of the cerebellum in cognition? Neurology 51, 33–40 (1998).

    Article  CAS  PubMed  Google Scholar 

  35. Boddaert, N. et al. Parieto-occipital grey matter abnormalities in children with Williams syndrome. Neuroimage (in the press).

  36. Reiss, A. L. et al. An experiment of nature: brain anatomy parallels cognition and behaviour in Williams syndrome. J. Neurosci. 24, 5009–5015 (2004). A study of structural abnormalities in participants with WS and mental retardation using VBM.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Meyer-Lindenberg, A. et al. Neural correlates of genetically abnormal social cognition in Williams syndrome. Nature Neurosci. 8, 991–993 (2005). Identification of abnormal function in the amygdala and the prefrontal cortical regions that regulate it, suggesting mechanisms for hypersociability and increased non-social fear in WS.

    Article  CAS  PubMed  Google Scholar 

  38. Cammareri, V., Vignati, G., Nocera, G., Beck-Peccoz, P. & Persani, L. Thyroid hemiagenesis and elevated thyrotropin levels in a child with Williams syndrome. Am. J. Med. Genet. 85, 491–494 (1999).

    Article  CAS  PubMed  Google Scholar 

  39. Schmitt, J. E., Eliez, S., Bellugi, U. & Reiss, A. L. Analysis of cerebral shape in Williams syndrome. Arch. Neurol. 58, 283–287 (2001).

    Article  CAS  PubMed  Google Scholar 

  40. Schmitt, J. E. et al. Increased gyrification in Williams syndrome: evidence using 3D MRI methods. Dev. Med. Child Neurol. 44, 292–295 (2002).

    Article  PubMed  Google Scholar 

  41. Thompson, P. M. et al. Abnormal cortical complexity and thickness profiles mapped in Williams syndrome. J. Neurosci. 25, 4146–4158 (2005). Innovative paper showing regionally increased gyrification and cortical thickness in participants with WS.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Jackowski, A. P. & Schultz, R. T. Foreshortened dorsal extension of the central sulcus in Williams syndrome. Cortex 41, 282–290 (2005).

    Article  PubMed  Google Scholar 

  43. Galaburda, A. M. et al. Dorsal forebrain anomaly in Williams syndrome. Arch. Neurol. 58, 1865–1869 (2001).

    Article  CAS  PubMed  Google Scholar 

  44. Kippenhan, J. S. et al. Genetic contributions to human gyrification: sulcal morphometry in Williams syndrome. J. Neurosci. 25, 7840–7846 (2005). An analysis of cortical geometry showing abnormal sulcal depth in the OFC and intraparietal sulcus in WS.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Van Essen, D. C. Towards a quantitative, probabilistic neuroanatomy of cerebral cortex. Cortex 40, 211–212 (2004).

    Article  PubMed  Google Scholar 

  46. Rakic, P. Genetic control of cortical convolutions. Science 303, 1983–1984 (2004).

    Article  CAS  PubMed  Google Scholar 

  47. Van Essen, D. C. A tension-based theory of morphogenesis and compact wiring in the central nervous system. Nature 385, 313–318 (1997).

    Article  CAS  PubMed  Google Scholar 

  48. Mima, T. & Mikawa, T. Folding of the tectal cortex by local remodeling of neural differentiation. Dev. Dyn. 229, 475–479 (2004).

    Article  CAS  PubMed  Google Scholar 

  49. Marenco, S. et al. Preliminary diffusion tensor imaging (DTI) observations in 5 individuals with Williams syndrome (WS). Neuroimage 22 (Suppl. 1), M0363 (2004).

    Google Scholar 

  50. Levitin, D. J. et al. Neural correlates of auditory perception in Williams syndrome: an fMRI study. Neuroimage 18, 74–82 (2003).

    Article  PubMed  Google Scholar 

  51. Winter, M., Pankau, R., Amm, M., Gosch, A. & Wessel, A. The spectrum of ocular features in the Williams–Beuren syndrome. Clin. Genet. 49, 28–31 (1996).

    Article  CAS  PubMed  Google Scholar 

  52. Kapp, M. E., von Noorden, G. K. & Jenkins, R. Strabismus in Williams syndrome. Am. J. Ophthalmol. 119, 355–360 (1995).

    Article  CAS  PubMed  Google Scholar 

  53. Atkinson, J. et al. Visual and visuospatial development in young children with Williams syndrome. Dev. Med. Child Neurol. 43, 330–337 (2001).

    Article  CAS  PubMed  Google Scholar 

  54. Sadler, L. S., Olitsky, S. E. & Reynolds, J. D. Reduced stereoacuity in Williams syndrome. Am. J. Med. Genet. 66, 287–288 (1996).

    Article  CAS  PubMed  Google Scholar 

  55. Grice, S. J. et al. ERP abnormalities of illusory contour perception in Williams syndrome. Neuroreport 14, 1773–1777 (2003).

    Article  PubMed  Google Scholar 

  56. Olsen, R. K. et al. Retinotopic mapping of early visual areas in Williams syndrome. Presented at the Human Brain Mapping Meeting 2003 (New York, USA). Neuroimage 19 (Suppl. 1), 1550 (2003).

    Google Scholar 

  57. Frangiskakis, J. M. et al. LIM-kinase1 hemizygosity implicated in impaired visuospatial constructive cognition. Cell 86, 59–69 (1996). The first study implicating a specific gene in a cognitive characteristic of WS.

    Article  CAS  PubMed  Google Scholar 

  58. Ungerleider, L. G. & Mishkin, M. in Analysis of Visual Behavior (eds Ingle, D. J., Goodale, D. J. & Mansfield, R. J. W.) 549–586 (MIT Press, Cambridge, Massachusetts, 1982).

    Google Scholar 

  59. Van Essen, D. C., Anderson, C. H. & Felleman, D. J. Information processing in the primate visual system: an integrated systems perspective. Science 255, 419–423 (1992).

    Article  CAS  PubMed  Google Scholar 

  60. Landau, B., Hoffman, J. E. & Kurz, N. Object recognition with severe spatial deficits in Williams syndrome: sparing and breakdown. Cognition (in the press).

  61. Atkinson, J. et al. Neurobiological models of visuospatial cognition in children with Williams syndrome: measures of dorsal-stream and frontal function. Dev. Neuropsychol. 23, 139–172 (2003).

    Article  PubMed  Google Scholar 

  62. Galaburda, A. M., Holinger, D. P., Bellugi, U. & Sherman, G. F. Williams syndrome: neuronal size and neuronal-packing density in primary visual cortex. Arch. Neurol. 59, 1461–1467 (2002).

    Article  PubMed  Google Scholar 

  63. Nakamura, M. et al. Williams syndrome and deficiency in visuospatial recognition. Dev. Med. Child Neurol. 43, 617–621 (2001).

    Article  CAS  PubMed  Google Scholar 

  64. Paul, B. M., Stiles, J., Passarotti, A., Bavar, N. & Bellugi, U. Face and place processing in Williams syndrome: evidence for a dorsal-ventral dissociation. Neuroreport 13, 1115–1119 (2002).

    Article  PubMed  Google Scholar 

  65. Glabus, M. F. et al. Interindividual differences in functional interactions among prefrontal, parietal and parahippocampal regions during working memory. Cereb. Cortex 13, 1352–1361 (2003).

    Article  PubMed  Google Scholar 

  66. McIntosh, A. R. et al. Network analysis of cortical visual pathways mapped with PET. J. Neurosci. 14, 655–666 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Nardini, M., Breckenridge, K. E., Eastwood, R. L., Atkinson, J. & Braddick, O. J. Distinct developmental trajectories in three systems for spatial encoding between the ages of 3 and 6 years. Perception S33, 28b (2004).

    Google Scholar 

  68. O'Hearn, K., Landau, B. & Hoffman, J. E. Multiple object tracking in people with Williams syndrome and in normally developing children. Psychol. Sci. 16, 905–912 (2005).

    Article  PubMed  Google Scholar 

  69. Nichols, S. et al. Mechanisms of verbal memory impairment in four neurodevelopmental disorders. Brain Lang. 88, 180–189 (2004).

    Article  PubMed  Google Scholar 

  70. Vicari, S., Bellucci, S. & Carlesimo, G. A. Visual and spatial long-term memory: differential pattern of impairments in Williams and Down syndromes. Dev. Med. Child Neurol. 47, 305–311 (2005).

    Article  PubMed  Google Scholar 

  71. Meyer-Lindenberg, A. et al. Functional, structural, and metabolic abnormalities of the hippocampal formation in Williams syndrome. J. Clin. Invest. 115, 1888–1895 (2005). Pronounced functional and subtle structural abnormalities in the hippocampal formation in WS.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Pan, J. W. & Takahashi, K. Interdependence of N-acetyl aspartate and high-energy phosphates in healthy human brain. Ann. Neurol. 57, 92–97 (2005).

    Article  CAS  PubMed  Google Scholar 

  73. Izumi, Y. & Zorumski, C. F. Involvement of nitric oxide in low glucose-mediated inhibition of hippocampal long-term potentiation. Synapse 25, 258–262 (1997).

    Article  CAS  PubMed  Google Scholar 

  74. Petroff, O. A., Errante, L. D., Rothman, D. L., Kim, J. H. & Spencer, D. D. Neuronal and glial metabolite content of the epileptogenic human hippocampus. Ann. Neurol. 52, 635–642 (2002).

    Article  CAS  PubMed  Google Scholar 

  75. Preston, A. R., Shrager, Y., Dudukovic, N. M. & Gabrieli, J. D. Hippocampal contribution to the novel use of relational information in declarative memory. Hippocampus 14, 148–152 (2004).

    Article  PubMed  Google Scholar 

  76. Grill-Spector, K. The neural basis of object perception. Curr. Opin. Neurobiol. 13, 159–166 (2003).

    Article  CAS  PubMed  Google Scholar 

  77. Suzuki, W. A. & Amaral, D. G. Perirhinal and parahippocampal cortices of the macaque monkey: cortical afferents. J. Comp. Neurol. 350, 497–533 (1994).

    Article  CAS  PubMed  Google Scholar 

  78. Egan, M. F. et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112, 257–269 (2003).

    Article  CAS  PubMed  Google Scholar 

  79. Bellugi, U., Bihrle, A., Jernigan, T., Trauner, D. & Doherty, S. Neuropsychological, neurological, and neuroanatomical profile of Williams syndrome. Am. J. Med. Genet. Suppl. 6, 115–125 (1990).

    CAS  PubMed  Google Scholar 

  80. Bellugi, U., Sabo, H. & Vaid, J. in Language Development in Exceptional Circumstances (eds Bishop, D. V. M. & Mogford-Bevan, K.) 177–189 (Churchill Livingstone, Edinburgh; New York, 1988). A classic paper that sparked broad interest in WS in the cognitive neurosciences.

    Google Scholar 

  81. Bellugi, U., Wang, P. P. & Jernigan, T. L. in Atypical Cognitive Deficits in Developmental Disorders: Implications for Brain Function (eds Broman, S. H. & Grafman, J.) 23–56 (Erlbaum, Hillsdale, New Jersey, 1994).

    Google Scholar 

  82. Bates, E., Tager-Flusberg, H., Vicari, S. & Volterra, V. Debate over language's link with intelligence. Nature 413, 565–566 (2001).

    Article  CAS  PubMed  Google Scholar 

  83. Mervis, C. B. in Williams–Beuren Syndrome: Research, Evaluation, and Treatment (eds Morris, C. A., Lenhoff, H. M. & Wang, P. P.) 159–206 (Johns Hopkins Univ. Press, Baltimore, 2006).

    Google Scholar 

  84. Dunn, L. M. & Dunn, L. M. Peabody Picture Vocabulary Test (American Guidance Service, 1997).

    Google Scholar 

  85. Bellugi, U., Lichtenberger, L., Jones, W., Lai, Z. & St George, M. I. The neurocognitive profile of Williams Syndrome: a complex pattern of strengths and weaknesses. J. Cogn. Neurosci. 12 (Suppl. 1), 7–29 (2000).

    Article  PubMed  Google Scholar 

  86. Mervis, C. B., Morris, C. A., Bertrand, J. & Robinson, B. F. in Neurodevelopmental Disorders (ed. Tager-Flusberg, H.) 65–110 (MIT Press, Cambridge, Massacusetts, 1999).

    Google Scholar 

  87. Temple, C. M., Almazan, M. & Sherwood, S. Lexical skills in Williams syndrome: a cognitive neuropsychological analysis. J. Neurolinguistics 15, 463–495 (2002).

    Article  Google Scholar 

  88. Mervis, C. B., Robinson, B. F., Rowe, M. L., Becerra, A. M. & Klein-Tasman, B. P. Language abilities of individuals who have Williams syndrome. Int. Rev. Res. Ment. Retard. 27, 35–81 (2003).

    Article  Google Scholar 

  89. Grant, J., Valian, V. & Karmiloff-Smith, A. A study of relative clauses in Williams syndrome. J. Child Lang. 29, 403–416 (2002).

    Article  PubMed  Google Scholar 

  90. Udwin, O. & Yule, W. Expressive language of children with Williams syndrome. Am. J. Med. Genet. Suppl. 6, 108–114 (1990).

    CAS  PubMed  Google Scholar 

  91. Zukowski, A. Knowledge of constraints on compounding in children and adolescents with Williams syndrome. J. Speech Lang. Hear. Res. 48, 79–92 (2005).

    Article  PubMed  Google Scholar 

  92. Karmiloff-Smith, A. et al. Language and Williams syndrome: how intact is 'intact'? Child Dev. 68, 246–262 (1997).

    Article  CAS  PubMed  Google Scholar 

  93. Levy, Y. & Hermon, S. Morphological abilities of Hebrew-speaking adolescents with Williams syndrome. Dev. Neuropsychol. 23, 59–83 (2003).

    Article  PubMed  Google Scholar 

  94. Laws, G. & Bishop, D. Pragmatic language impairment and social deficits in Williams syndrome: a comparison with Down's syndrome and specific language impairment. Int. J. Lang. Commun. Disord. 39, 45–64 (2004).

    Article  PubMed  Google Scholar 

  95. Robinson, B. F., Mervis, C. B. & Robinson, B. W. The roles of verbal short-term memory and working memory in the acquisition of grammar by children with Williams syndrome. Dev. Neuropsychol. 23, 13–31 (2003).

    Article  PubMed  Google Scholar 

  96. Lukács, A., Racsmány, M. & Pléh, C. Vocabulary and morphological patterns in Hungarian children with Williams syndrome: a preliminary report. Acta Linguistica Hungarica 48, 243–269 (2001).

    Google Scholar 

  97. Karmiloff-Smith, A., Brown, J. H., Grice, S. & Paterson, S. Dethroning the myth: cognitive dissociations and innate modularity in Williams syndrome. Dev. Neuropsychol. 23, 227–242 (2003).

    Article  PubMed  Google Scholar 

  98. Bellugi, U., Lichtenberger, L., Mills, D., Galaburda, A. & Korenberg, J. R. Bridging cognition, the brain and molecular genetics: evidence from Williams syndrome. Trends Neurosci. 22, 197–207 (1999).

    Article  CAS  PubMed  Google Scholar 

  99. Mons, A. W., Wilmowski, W. A. & Detweiler, C. Williams Syndrome: a Highly Musical Species (EO Productions International, 1996).

    Google Scholar 

  100. Levitin, D. J. & Bellugi, U. Musical abilities in individuals with Williams syndrome. Music Percept. 15, 357–389 (1998).

    Article  Google Scholar 

  101. Levitin, D. J. et al. Characterizing the musical phenotype in individuals with Williams Syndrome. Child Neuropsychol. 10, 223–247 (2004).

    Article  PubMed  Google Scholar 

  102. Dykens, E. M., Rosner, B. A., Ly, T. & Sagun, J. Music and anxiety in Williams syndrome: a harmonious or discordant relationship? Am. J. Ment. Retard. 110, 346–358 (2005).

    Article  PubMed  Google Scholar 

  103. Carrasco, X., Castillo, S., Aravena, T., Rothhammer, P. & Aboitiz, F. Williams syndrome: pediatric, neurologic, and cognitive development. Pediatr. Neurol. 32, 166–172 (2005).

    Article  PubMed  Google Scholar 

  104. Gordon, F. E. in Musical Aptitude Profile (Houghton Mifflin, Boston, 1995).

    Google Scholar 

  105. Gordon, F. E. Primary Measures of Music Audiation (G. I. A. Publications, Chicago, 1980).

    Google Scholar 

  106. Don, A. J., Schellenberg, G. & Rourke, B. P. Music and language skills of children with Williams syndrome. Child Neuropsychol. 5, 154–170 (1999).

    Article  Google Scholar 

  107. Hopyan, T., Dennis, M., Weksberg, R. & Cytrynbaum, C. Music skills and the expressive interpretation of music in children with Williams–Beuren syndrome: pitch, rhythm, melodic imagery, phrasing, and musical affect. Child Neuropsychol. 7, 42–53 (2001).

    Article  CAS  PubMed  Google Scholar 

  108. Jones, W. et al. II. Hypersociability in Williams syndrome. J. Cogn. Neurosci. 12 (Suppl. 1), 30–46 (2000).

    Article  PubMed  Google Scholar 

  109. Gosch, A. & Pankau, R. Social–emotional and behavioral adjustment in children with Williams–Beuren syndrome. Am. J. Med. Genet. 53, 335–339 (1994).

    Article  CAS  PubMed  Google Scholar 

  110. Mervis, C. B. Williams syndrome: 15 years of psychological research. Dev. Neuropsychol. 23, 1–12 (2003).

    Article  PubMed  Google Scholar 

  111. Frigerio, E. et al. Is everybody always my friend? Perception of approachability in Williams syndrome. Neuropsychologia 44, 254–259 (2006).

    Article  PubMed  Google Scholar 

  112. Davies, M., Udwin, O. & Howlin, P. Adults with Williams syndrome. Preliminary study of social, emotional and behavioural difficulties. Br. J. Psychiatry 172, 273–276 (1998).

    Article  CAS  PubMed  Google Scholar 

  113. Greer, M. K., Brown, F. R., Pai, G. S., Choudry, S. H. & Klein, A. J. Cognitive, adaptive, and behavioral characteristics of Williams syndrome. Am. J. Med. Genet. 74, 521–525 (1997).

    Article  CAS  PubMed  Google Scholar 

  114. Gagliardi, C. et al. Facial expression recognition in Williams syndrome. Neuropsychologia 41, 733–738 (2003).

    Article  PubMed  Google Scholar 

  115. Tager-Flusberg, H. & Sullivan, K. A componential view of theory of mind: evidence from Williams syndrome. Cognition 76, 59–90 (2000). Relates cognitive subcomponents of theory of mind to social function in WS.

    Article  CAS  PubMed  Google Scholar 

  116. Plesa Skwerer, D., Faja, S., Schofield, C., Verbalis, A. & Tager-Flusberg, H. Perceiving facial and vocal expressions of emotion in Williams syndrome. Am. J. Ment. Retard. (in the press).

  117. Udwin, O. & Yule, W. A cognitive and behavioural phenotype in Williams syndrome. J. Clin. Exp. Neuropsychol. 13, 232–244 (1991).

    Article  CAS  PubMed  Google Scholar 

  118. Davies, M., Howlin, P. & Udwin, O. Independence and adaptive behavior in adults with Williams syndrome. Am. J. Med. Genet. 70, 188–195 (1997).

    Article  CAS  PubMed  Google Scholar 

  119. Levine, K. & Wharton, R. Williams syndrome and happiness. Am. J. Ment. Retard. 105, 363–371 (2000).

    Article  CAS  PubMed  Google Scholar 

  120. LeDoux, J. The emotional brain, fear, and the amygdala. Cell. Mol. Neurobiol. 23, 727–738 (2003).

    Article  PubMed  Google Scholar 

  121. Amaral, D. G. The primate amygdala and the neurobiology of social behavior: implications for understanding social anxiety. Biol. Psychiatry 51, 11–17 (2002).

    Article  PubMed  Google Scholar 

  122. Hariri, A. R., Tessitore, A., Mattay, V. S., Fera, F. & Weinberger, D. R. The amygdala response to emotional stimuli: a comparison of faces and scenes. Neuroimage 17, 317–323 (2002).

    Article  PubMed  Google Scholar 

  123. Dilger, S. et al. Brain activation to phobia-related pictures in spider phobic humans: an event-related functional magnetic resonance imaging study. Neurosci. Lett. 348, 29–32 (2003).

    Article  CAS  PubMed  Google Scholar 

  124. Kringelbach, M. L. & Rolls, E. T. The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology. Prog. Neurobiol. 72, 341–372 (2004).

    Article  PubMed  Google Scholar 

  125. Pears, A., Parkinson, J. A., Hopewell, L., Everitt, B. J. & Roberts, A. C. Lesions of the orbitofrontal but not medial prefrontal cortex disrupt conditioned reinforcement in primates. J. Neurosci. 23, 11189–11201 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Adolphs, R. Cognitive neuroscience of human social behaviour. Nature Rev. Neurosci. 4, 165–178 (2003). An excellent and inspiring synthesis of social cognitive neuroscience.

    Article  CAS  Google Scholar 

  127. Rolls, E. T., Hornak, J., Wade, D. & McGrath, J. Emotion-related learning in patients with social and emotional changes associated with frontal lobe damage. J. Neurol. Neurosurg. Psychiatry 57, 1518–1524 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Stone, V. E., Baron-Cohen, S. & Knight, R. T. Frontal lobe contributions to theory of mind. J. Cogn. Neurosci. 10, 640–656 (1998).

    Article  CAS  PubMed  Google Scholar 

  129. Bauman, M. D., Lavenex, P., Mason, W. A., Capitanio, J. P. & Amaral, D. G. The development of social behaviour following neonatal amygdala lesions in rhesus monkeys. J. Cogn. Neurosci. 16, 1388–1411 (2004). Dissociation of social/non-social fears in the primate after neonatal lesions.

    Article  CAS  PubMed  Google Scholar 

  130. Meyer-Lindenberg, A. et al. Neural mechanisms for genetic risk for violence and impulsivity in humans. Proc. Natl Acad. Sci. USA (in the press).

  131. Fodor, J. A. The Modularity of Mind: an Essay on Faculty Psychology (MIT Press, Cambridge, Massachusetts, 1983).

    Google Scholar 

  132. Paterson, S. J., Brown, J. H., Gsödl, M. K., Johnson, M. H. & Karmiloff-Smith, A. Cognitive modularity and genetic disorders. Science 286, 2355–2358 (1999).

    Article  CAS  PubMed  Google Scholar 

  133. Pinker, S. Words and Rules: The Ingredients of Language (Basic Books, New York, 1999).

    Google Scholar 

  134. Piattelli-Palmarini, M. Speaking of learning: how do we acquire our marvellous facility for expressing ourselves in words? Nature 411, 887–888 (2001).

    Article  Google Scholar 

  135. Karmiloff-Smith, A. Beyond Modularity: a Developmental Perspective on Cognitive Science (MIT Press, Cambridge, Massachusetts, 1992).

    Google Scholar 

  136. Hoogenraad, C. C. et al. Targeted mutation of Cyln2 in the Williams syndrome critical region links CLIP-115 haploinsufficiency to neurodevelopmental abnormalities in mice. Nature Genet. 32, 116–127 (2002). A key paper that shows the effects of Cyln2 hemi-insufficiency on hippocampal function in mice.

    Article  CAS  PubMed  Google Scholar 

  137. Meng, Y. et al. Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice. Neuron 35, 121–133 (2002). Abnormal microstructure and hippocampal function in Limk1 null knockouts.

    Article  CAS  PubMed  Google Scholar 

  138. Zhao, C. et al. Hippocampal and visuospatial learning defects in mice with a deletion of frizzled 9, a gene in the Williams syndrome deletion interval. Development 132, 2917–2927 (2005).

    Article  CAS  PubMed  Google Scholar 

  139. Durkin, M. E., Keck-Waggoner, C. L., Popescu, N. C. & Thorgeirsson, S. S. Integration of a c-myc transgene results in disruption of the mouse Gtf2ird1 gene, the homologue of the human GTF2IRD1 gene hemizygously deleted in Williams–Beuren syndrome. Genomics 73, 20–27 (2001).

    Article  CAS  PubMed  Google Scholar 

  140. Tassabehji, M. et al. GTF2IRD1 in craniofacial development of humans and mice. Science 310, 1184–1187 (2005).

    Article  CAS  PubMed  Google Scholar 

  141. Bayarsaihan, D. et al. Genomic organization of the genes Gtf2ird1, Gtf2i, and Ncf1 at the mouse chromosome 5 region syntenic to the human chromosome 7q11.23 Williams syndrome critical region. Genomics 79, 137–143 (2002).

    Article  CAS  PubMed  Google Scholar 

  142. DeSilva, U. et al. Generation and comparative analysis of approximately 3.3 Mb of mouse genomic sequence orthologous to the region of human chromosome 7q11.23 implicated in Williams syndrome. Genome Res. 12, 3–15 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Proschel, C., Blouin, M. J., Gutowski, N. J., Ludwig, R. & Noble, M. Limk1 is predominantly expressed in neural tissues and phosphorylates serine, threonine and tyrosine residues in vitro. Oncogene 11, 1271–1281 (1995).

    CAS  PubMed  Google Scholar 

  144. Hoogenraad, C. C., Akhmanova, A., Galjart, N. & De Zeeuw, C. I. LIMK1 and CLIP-115: linking cytoskeletal defects to Williams syndrome. Bioessays 26, 41–150 (2004).

    Article  CAS  Google Scholar 

  145. Franke, Y., Peoples, R. J. & Francke, U. Identification of GTF2IRD1, a putative transcription factor within the Williams–Beuren syndrome deletion at 7q11.23. Cytogenet. Cell Genet. 86, 296–304 (1999).

    Article  CAS  PubMed  Google Scholar 

  146. Wang, Y. K., Perez-Jurado, L. A. & Francke, U. A mouse single-copy gene, Gtf2i, the homolog of human GTF2I, that is duplicated in the Williams–Beuren syndrome deletion region. Genomics 48, 163–170 (1998).

    Article  CAS  PubMed  Google Scholar 

  147. Cairo, S., Merla, G., Urbinati, F., Ballabio, A. & Reymond, A. WBSCR14, a gene mapping to the Williams–Beuren syndrome deleted region, is a new member of the Mlx transcription factor network. Hum. Mol. Genet. 10, 617–627 (2001).

    Article  CAS  PubMed  Google Scholar 

  148. Botta, A. et al. Expression analysis and protein localization of the human HPC-1/syntaxin 1A, a gene deleted in Williams syndrome. Genomics 62, 525–528 (1999).

    Article  CAS  PubMed  Google Scholar 

  149. Botta, A. et al. Detection of an atypical 7q11.23 deletion in Williams syndrome patients which does not include the STX1A and FZD3 genes. J. Med. Genet. 36, 478–480 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Heller, R., Rauch, A., Luttgen, S., Schroder, B. & Winterpacht, A. Partial deletion of the critical 1.5 Mb interval in Williams–Beuren syndrome. J. Med. Genet. 40, E99 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Karmiloff-Smith, A. et al. Using case study comparisons to explore genotype–phenotype correlations in Williams–Beuren syndrome. J. Med. Genet. 40, 136–140 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Tassabehji, M. et al. Williams syndrome: use of chromosomal microdeletions as a tool to dissect cognitive and physical phenotypes. Am. J. Hum. Genet. 64, 118–125 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Donnai, D. & Karmiloff-Smith, A. Williams syndrome: from genotype through to the cognitive phenotype. Am. J. Med. Genet. 97, 164–171 (2000).

    Article  CAS  PubMed  Google Scholar 

  154. Hirota, H. et al. Williams syndrome deficits in visual spatial processing linked to GTF2IRD1 and GTF2I on chromosome 7q11.23. Genet. Med. 5, 311–321 (2003).

    Article  CAS  PubMed  Google Scholar 

  155. Elliott, C. D. Differential Ability Scales (Psychological Corporation, San Antonio, Texas, 1990).

    Google Scholar 

  156. Kaufman, A. S. & Kaufman, N. L. Kaufman Brief Intelligence Test (American Guidance Services, Pines, Minnesota, 1990).

    Google Scholar 

  157. American Psychiatric Association Task Force on DSM-IV. Diagnostic and statistical manual of mental disorders: DSM-IV (American Psychiatric Association, Washington, DC, 1994).

  158. Pelphrey, K., Adolphs, R. & Morris, J. P. Neuroanatomical substrates of social cognition dysfunction in autism. Ment. Retard. Dev. Disabil. Res. Rev. 10, 259–271 (2004).

    Article  PubMed  Google Scholar 

  159. Reiss, A. L., Feinstein, C., Rosenbaum, K. N., Borengasser-Caruso, M. A. & Goldsmith, B. M. Autism associated with Williams syndrome. J. Pediatr. 106, 247–249 (1985).

    Article  CAS  PubMed  Google Scholar 

  160. Gillberg, C. & Rasmussen, P. Brief report: four case histories and a literature review of Williams syndrome and autistic behavior. J. Autism Dev. Disord. 24, 381–393 (1994).

    Article  CAS  PubMed  Google Scholar 

  161. Baron-Cohen, S. & Belmonte, M. K. Autism: a window onto the development of the social and the analytic brain. Annu. Rev. Neurosci. 28, 109–126 (2005).

    Article  CAS  PubMed  Google Scholar 

  162. Bauman, M. L. & Kemper, T. L. Neuroanatomic observations of the brain in autism: a review and future directions. Int. J. Dev. Neurosci. 23, 183–187 (2005).

    Article  PubMed  Google Scholar 

  163. Baron-Cohen, S. et al. Social intelligence in the normal and autistic brain: an fMRI study. Eur. J. Neurosci. 11, 1891–1898 (1999).

    Article  CAS  PubMed  Google Scholar 

  164. Critchley, H. D. et al. The functional neuroanatomy of social behaviour: changes in cerebral blood flow when people with autistic disorder process facial expressions. Brain 123, 2203–2212 (2000).

    Article  PubMed  Google Scholar 

  165. Wang, A. T., Dapretto, M., Hariri, A. R., Sigman, M. & Bookheimer, S. Y. Neural correlates of facial affect processing in children and adolescents with autism spectrum disorder. J. Am. Acad. Child Adolesc. Psychiatry 43, 481–490 (2004).

    Article  PubMed  Google Scholar 

  166. Schultz, R. T. et al. Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome. Arch. Gen. Psychiatry 57, 331–340 (2000).

    Article  CAS  PubMed  Google Scholar 

  167. Pierce, K., Muller, R. A., Ambrose, J., Allen, G. & Courchesne, E. Face processing occurs outside the fusiform 'face area' in autism: evidence from functional MRI. Brain 124, 2059–2073 (2001).

    Article  CAS  PubMed  Google Scholar 

  168. Dalton, K. M. et al. Gaze fixation and the neural circuitry of face processing in autism. Nature Neurosci. 8, 519–526 (2005).

    Article  CAS  PubMed  Google Scholar 

  169. Adolphs, R. The neurobiology of social cognition. Curr. Opin. Neurobiol. 11, 231–239 (2001).

    Article  CAS  PubMed  Google Scholar 

  170. Martin, J. H. Neuroanatomy: Text and Atlas 2nd edn (Appleton & Lange, Stamford, Connecticut, 1996).

    Google Scholar 

  171. Galaburda, A. M., Holinger, D. P., Bellugi, U. & Sherman, G. F. Williams syndrome: neuronal size and neuronal-packing density in primary visual cortex. Arch. Neurol. 59, 1461–1467 (2002).

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the National Institute of Mental Health (NIMH) Intramural Research Program (IRP), a grant from the National Institute of Neurological Disorders and Stroke (C.B.M.) and a grant from the National Institute of Child Health and Human Development (C.B.M.). We thank C. Rainey for help with figure preparation, L. Kempf for preparation of the supplementary table and S. Kippenhan, P. Kohn and C. Morris for their ongoing collaboration on our neuroimaging work.

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Authors and Affiliations

  1. Unit for Systems Neuroscience in Psychiatry, National Institute of Mental Health, NIH, DHHS, 9000 Rockville Pike, Bethesda, 20892-1365, Maryland, USA

    Andreas Meyer-Lindenberg

  2. Neuroimaging Core Facility, National Institute of Mental Health, NIH, DHHS, 9000 Rockville Pike, Bethesda, 20892-1365, Maryland, USA

    Andreas Meyer-Lindenberg

  3. Genes, Cognition and Psychosis Program, National Institute of Mental Health, NIH, DHHS, 9000 Rockville Pike, Bethesda, 20892-1365, Maryland, USA

    Andreas Meyer-Lindenberg & Karen Faith Berman

  4. Department of Psychological and Brain Sciences, Neurodevelopmental Sciences Laboratory, University of Louisville, Louisville, 40292, Kentucky, USA

    Carolyn B. Mervis

  5. Section on Integrative Neuroimaging, National Institute of Mental Health, NIH, DHHS, 9000 Rockville Pike, Bethesda, 20892-1365, Maryland, USA

    Karen Faith Berman

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Correspondence to Andreas Meyer-Lindenberg.

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DATABASES

OMIM

Down syndrome

Williams syndrome

FURTHER INFORMATION

Meyer-Lindenberg's laboratory

Glossary

Haploinsufficiency

Presence of only a single functional copy of a gene that does not provide sufficient transcript or protein production to assure normal function.

Hypercalcaemia

Abnormally high calcium concentration in the blood.

Hyperreflexia

Exaggerated deep tendon reflexes.

Strabismus

Eye misalignment; also known as 'crossed eyes'.

Nystagmus

Involuntary and often rapid and repetitive oscillatory movements of the eyeballs.

Homologous recombination

Exchange of DNA segments of similar sequence. Occurs by breakage and reunion in paired chromosomes during meiosis.

(Arnold-)Chiari malformations

A group of disorders characterized by protrusion of the cerebellum through the large opening in the base of the skull into the spinal canal.

Differential Ability Scales-School Age

(DAS-School Age). A standardized assessment of general intellectual functioning designed to provide specific information about an individual's strengths and weaknesses across a wide range of intellectual abilities. It is particularly appropriate for assessing individuals with WS because it yields separate standard scores for verbal, nonverbal reasoning and spatial abilities, as well as an overall standard score (general conceptual ability (GCA), which is similar to IQ).

Voxel-based morphometry

(VBM). A widely used method for the analysis of imaging data that enables a statistically principled voxel-wise between-groups comparison of local grey matter volume, unconstrained by anatomical landmarks.

Retinotopic mapping

A functional imaging technique that can be used to delineate the extent of visual brain areas by capitalizing on the fact that they represent retinal information in a consistent spatial map.

Long-term potentiation

(LTP). Enduring increase in the amplitude of excitatory postsynaptic potentials as a result of high-frequency stimulation of afferent pathways; LTP has been most studied in the hippocampus.

Theory of mind

The ability to interpret people's behaviour in terms of their mental states. Includes both social–perceptual (capacity to distinguish between people and objects, and to infer mental disposition from facial, prosodic and body expressions) and social–cognitive (explicit representation of and reasoning about others' beliefs and intentions) components.

Endophenotype

A quantitative biological trait associated with a complex genetic disorder that is hoped to more directly index the underlying pathophysiology, facilitating efforts to find or characterize contributing genes.

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Meyer-Lindenberg, A., Mervis, C. & Faith Berman, K. Neural mechanisms in Williams syndrome: a unique window to genetic influences on cognition and behaviour. Nat Rev Neurosci 7, 380–393 (2006). https://doi.org/10.1038/nrn1906

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