Behavior Genetics

, Volume 41, Issue 3, pp 381–393 | Cite as

Relationship Between Brain and Cognitive Processes in Down Syndrome

  • Deny Menghini
  • Floriana Costanzo
  • Stefano VicariEmail author
Original Research


We investigated regional grey matter (GM) density in adolescents with Down syndrome (DS) compared to age-matched controls and correlated MRI data with neuropsychological measures in the DS group. Inter-group comparisons documented several GM concentration abnormalities in the participants with DS compared to controls. In the adolescents with DS, intra-group results also showed associations between regional GM density and the neuropsychological measures considered. In particular, GM density of the cerebellum and middle and inferior temporal gyrus was associated with linguistic measures. Short-term memory performances were correlated with the inferior parietal lobule, insula, superior temporal gyrus, medial occipital lobe, and cerebellum. Long-term memory abilities were correlated with GM density in the orbitofrontal cortex, lateral and medial temporal lobe regions, and anterior cingulum and visuo-perceptual abilities with GM density the left middle frontal gyrus. Results of this preliminary study are consistent with a not always efficient brain organization in DS.


Magnetic resonance Developmental disabilities Cognitive phenotype Voxel-based morphometry 



Authors wish to thank Fabio Cannatà, Elisabetta Genovese, and Daniela Longo for help with images’ acquisition. D.M. gratefully acknowledges financial support from the Jerome Lejeune Foundation.


  1. Abrahamsen A (2000) Explorations of enhanced gestural input to children in the bimodal period. In: Lane H, Emmorey K (eds) The signs of language revisited: an anthology to honor Ursula Bellugi and Edward Klima. Erlbaum, Mahwah, NJ, pp 357–399Google Scholar
  2. Aggleton JP, Neave N, Nagle S, Sahgal A (1995) A comparison of the effects of medial prefrontal, cingulate cortex, and cingulum bundle lesions on tests of spatial memory: evidence of a double dissociation between frontal and cingulum bundle contributions. J Neurosci 15(11):7270–7281PubMedGoogle Scholar
  3. Allen G, Courchesne E (2003) Differential effects of developmental cerebellar abnormality on cognitive and motor functions in the cerebellum: an fMRI study of autism. Am J Psychiatry 160(2):262–273PubMedCrossRefGoogle Scholar
  4. Antonova E, Parslow D, Brammer M, Dawson GR, Jackson SH, Morris RG (2009) Age-related neural activity during allocentric spatial memory. Memory 17(2):125–143PubMedCrossRefGoogle Scholar
  5. Ashburner J, Friston KJ (2000) Voxel-based morphometry—the methods. Neuroimage 11(6):805–821PubMedCrossRefGoogle Scholar
  6. Atkinson J, Anker S, Braddick O, Nokes L, Mason A, Braddick F (2001) Visual and visuospatial development in young children with Williams syndrome. Dev Med Child Neurol 43:330–337PubMedCrossRefGoogle Scholar
  7. Beacher F, Murphy DGM (2006) Neuroimaging studies of individuals with Down syndrome. In: Prasher VP (ed) Alzheimer’s disease and dementia in Down syndrome and intellectual disabilities. Radcliffe, Oxford, pp 157–175Google Scholar
  8. Beery KE, Buktenica NA (2000) VMI, Developmental Test of Visual-Motor Integration. In: Preda C (ed), Il Beery-Buktenica con i test supplementari di Percezione Visiva e Coordinazione Motoria, Manuale (The Beery-Buktenica with the supplementary tests of Visual Perception and Motor Coordination, Manual) Italian adaptation. O.S. Organizzazioni Speciali, FirenzeGoogle Scholar
  9. 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(1):7–29PubMedCrossRefGoogle Scholar
  10. Ben-Yehudah G, Fiez JA (2008) Impact of cerebellar lesions on reading and phonological processing. Ann N Y Acad Sci 1145:260–274PubMedCrossRefGoogle Scholar
  11. Bozzo MT, Mansueto Zecca G (1993) Adattamento italiano della Scala d’intelligenza Stanford-Binet Forma L-M, III revisione di Terman LM e Merril MA (Italian adaptation of the Stanford-Binet Intelligence Scale, Form L-M, III revision of Terman LM and Merril MA). Organizzazioni Speciali, FirenzeGoogle Scholar
  12. Campbell LE, Daly E, Toal F, Stevens A, Azuma R, Karmiloff-Smith A, Murphy DG, Murphy KC (2009) Brain structural differences associated with the behavioural phenotype in children with Williams syndrome. Brain Res 1258:96–107PubMedCrossRefGoogle Scholar
  13. Carlesimo GA, Marotta L, Vicari S (1997) Long-term memory in mental retardation: evidence for a specific impairment in subjects with Down’s syndrome. Neuropsychologia 35(1):71–79PubMedCrossRefGoogle Scholar
  14. Carr J (1985) The development of intelligence. In: Lane D, Stratford B (eds) Current approaches to Down syndrome. Holt, Rinehart and Winston, LondonGoogle Scholar
  15. Caselli MC, Vicari S, Longobardi E, Lami L, Pizzoli C, Stella G (1998) Gestures and words in early development of children with Down syndrome. J Speech Lang Hear Res 41:1125–1135PubMedGoogle Scholar
  16. Chan J, Iacono T (2001) Gesture and word production in children with Down syndrome. Altern Augment Commun 17:73–87Google Scholar
  17. Clark D, Wilson GN (2003) Behavioral assessment of children with Down syndrome using the Reiss psychopathology scale. Am J Med Genet A 118(3):210–216CrossRefGoogle Scholar
  18. Colom R, Jung RE, Haier RJ (2007) General intelligence and memory span: evidence for a common neuroanatomic framework. Cogn Neuropsychol 24(8):867–878PubMedCrossRefGoogle Scholar
  19. Courtney SM, Petit L, Maisog JM, Ungerleider LG, Haxby JV (1998) An area specialized for spatial working memory in human frontal cortex. Science 279(5355):1347–1351PubMedCrossRefGoogle Scholar
  20. de Ribaupierre S, Ryser C, Villemure J-G, Clarke S (2008) Cerebellar lesions: is there a lateralisation effect on memory deficits? Acta Neurochir (Wien) 150(6):545–550CrossRefGoogle Scholar
  21. Dogil G, Ackermann H, Grodd W, Haider H, Kamp H, Mayer H, Riecker H, Wildgruber D (2002) The speaking brain: a tutorial introduction to fMRI experiments in the production of speech, prosody and syntax. J Neurolinguist 15(1):59–90CrossRefGoogle Scholar
  22. Dulaney CL, Raz N, Devine C (1996) Effortful and automatic processes associated with Down syndrome and nonspecific mental retardation. Am J Ment Retard 100(4):418–423PubMedGoogle Scholar
  23. Dunn LM, Dunn LM (1981) Peabody Picture Vocabulary Test—revised. American Guidance Service, Circle Pines, MNGoogle Scholar
  24. Ellison A, Schindler I, Pattison LL, Milner AD (2004) An exploration of the role of the superior temporal gyrus in visual search and spatial perception using TMS. Brain 127(10):2307–2315PubMedCrossRefGoogle Scholar
  25. Ennaceur A, Neave N, Aggleton JP (1997) Spontaneous object recognition and object location memory in rats: the effects of lesions in the cingulate cortices, the medial prefrontal cortex, the cingulum bundle and the fornix. Exp Brain Res 113(3):509–519PubMedCrossRefGoogle Scholar
  26. Fowler A (1990) Language abilities in children with Down syndrome: evidence for a specific syntactic delay. In: Cicchetti D, Beeghly M, Cambridge UK (eds) Down syndrome: a developmental perspective. University Press, Cambridge, pp 302–328CrossRefGoogle Scholar
  27. Gerton BK, Brown TT, Meyer-Lindenberg A, Kohn P, Holt JL, Olsen RK, Berman KF (2004) Shared and distinct neurophysiological components of the digits forward and backward tasks as revealed by functional neuroimaging. Neuropsychologia 42(13):1781–1787PubMedCrossRefGoogle Scholar
  28. Glabus MF, Horwitz B, Holt JL, Kohn PD, Gerton BK, Callicott JH, Meyer-Lindenberg A, Berman KF (2003) Interindividual differences in functional interactions among prefrontal, parietal and parahippocampal regions during working memory. Cereb Cortex 13(12):1352–1361PubMedCrossRefGoogle Scholar
  29. Good CD, Johnsrude IS, Ashburner J, Henson RN, Friston KJ, Frackowiak RS (2001) A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage 14:21–36PubMedCrossRefGoogle Scholar
  30. Haier RJ, Jung RE, Yeo RA, Head K, Alkire MT (2005) The neuroanatomy of general intelligence: sex matters. Neuroimage 25(1):320–327PubMedCrossRefGoogle Scholar
  31. Haier RJ, Head K, Head E, Lott IT (2008) Neuroimaging of individuals with Down’s syndrome at-risk for dementia: evidence for possible compensatory events. Neuroimage 39(3):1324–1332PubMedCrossRefGoogle Scholar
  32. Hammill DD, Pearson NA, Voress JK (1994) TPV, Test di percezione visiva e integrazione visuo-motoria. In: Janes D (ed) Visual perception and visual-motor coordination test (Italian edition). Erickson, TrentoGoogle Scholar
  33. Ikeda M, Arai Y (2002) Longitudinal changes in brain CT scans and development of dementia in Down’s syndrome. Eur Neurol 47(4):205–208PubMedCrossRefGoogle Scholar
  34. Iverson J, Longobardi E, Caselli MC (2003) The relationship between gestures and words in children with Down syndrome and typically-developing children in the early stages of communicative development. Int J Lang Commun Disord 38:179–197PubMedCrossRefGoogle Scholar
  35. Jansen A, Liuzzi G, Deppe M, Kanowski M, Olschläger C, Albers JM, Schlaug G, Knecht S (2010) Structural correlates of functional language dominance: a voxel-based morphometry study. J Neuroimaging 20(2):148–156PubMedCrossRefGoogle Scholar
  36. Jarrold C, Baddeley AD (1997) Short-term memory for verbal and visuo-spatial information in Down’s syndrome. Cogn Neuropsychiatry 2(2):101–122CrossRefGoogle Scholar
  37. Jarrold C, Baddeley AD, Hewes AK (2000) Verbal short-term memory deficits in Down syndrome: a consequence of problems in rehearsal? J Child Psychol Psychiatry 40:233–244CrossRefGoogle Scholar
  38. Jarrold C, Baddeley A, Phillips CE (2002) Verbal short-term memory in Down syndrome: a problem of memory, audition, or speech? J Speech Lang Hear Res 45:531–544PubMedCrossRefGoogle Scholar
  39. Jernigan TL, Bellugi U, Sowell E, Doherty S, Hesselink JR (1993) Cerebral morphologic distinctions between Williams and Down syndromes. Arch Neurol 50(2):186–191PubMedGoogle Scholar
  40. Johnson MK, Mitchell KJ, Raye CL, Greene EJ (2004) An age-related deficit in prefrontal cortical function associated with refreshing information. Psychol Sci 15(2):127–132PubMedCrossRefGoogle Scholar
  41. Kaplan E, Goodglass H, Weintraub S (1983) The Boston naming test. L & Febiger, PhiladelphiaGoogle Scholar
  42. Karnath H-O, Ferber S, Himmelbach M (2001) Spatial awareness is a function of the temporal not the posterior parietal lobe. Nature 41:950–953CrossRefGoogle Scholar
  43. Kesslak JP, Nagata BS, Lott I, Nalcioglu O (1994) MRI analysis of age-related changes in the brains of individuals with DS. Neurology 44(6):1039–1045PubMedGoogle Scholar
  44. Krasuski JS, Alexander GE, Horwitz B, Rapoport SI, Schapiro MB (2002) Relation of medial temporal lobe volumes to age and memory function in nondemented adults with Down’s syndrome: implications for the prodromal phase of Alzheimer’s disease. Am J Psychiatry 159(1):74–81PubMedCrossRefGoogle Scholar
  45. Kringelbach ML (2005) The orbitofrontal cortex: linking reward to hedonic experience. Nat Rev Neurosci 6:691–702PubMedCrossRefGoogle Scholar
  46. Lanfranchi S, Cornoldi C, Vianello R (2004) Verbal and visuospatial working memory deficits in children with Down syndrome. Am J Ment Retard 109(6):456–466PubMedCrossRefGoogle Scholar
  47. Lanfranchi S, Jerman O, Dal Pont E, Alberti A, Vianello R (2010) Executive function in adolescents with Down syndrome. J Intellect Disabil Res 54(4):308–319PubMedCrossRefGoogle Scholar
  48. Laws G, Bishop DV (2004) Verbal deficits in Down’s syndrome and specific language impairment: a comparison. Int J Lang Commun Disord 39(4):423–451PubMedCrossRefGoogle Scholar
  49. Leung HC, Gore JC, Goldman-Rakic PS (2002) Sustained mnemonic response in the human middle frontal gyrus during on-line storage of spatial memoranda. J Cogn Neurosci 14(4):659–671PubMedCrossRefGoogle Scholar
  50. Mandolesi L, Leggio MG, Graziano A, Neri P, Petrosini L (2001) Cerebellar contribution to spatial event processing: involvement in procedural and working memory components. Eur J Neurosci 14(12):2011–2022PubMedCrossRefGoogle Scholar
  51. Marien P, Engelborghs S, De Deyn PP (2001) Cerebellar neurocognition: a new avenue. Acta Neurol Belg 101(2):96–109PubMedGoogle Scholar
  52. Martin A (2007) The representation of object concepts in the brain. Annu Rev Psychol 58:25–45PubMedCrossRefGoogle Scholar
  53. Martin LA, Escher T, Goldowitz D, Mittleman G (2004) A relationship between cerebellar Purkinje cells and spatial working memory demonstrated in a lurcher/chimera mouse model system. Genes Brain Behav 3(3):158–166PubMedCrossRefGoogle Scholar
  54. Martin GE, Klusek J, Estigarribia B, Roberts JE (2009) Language characteristics of individuals with Down syndrome. Top Lang Disord 29(2):112–132PubMedCrossRefGoogle Scholar
  55. Matsui M, Suzuki M, Zhou SY, Takahashi T, Kawasaki Y, Yuuki H, Kato K, Kurachi M (2008) The relationship between prefrontal brain volume and characteristics of memory strategy in schizophrenia spectrum disorders. Prog Neuropsychopharmacol Biol Psychiatry 32(8):1854–1862PubMedCrossRefGoogle Scholar
  56. McGaugh JL (2000) Memory—a century of consolidation. Science 287(5451):248–251PubMedCrossRefGoogle Scholar
  57. Menghini D, Di Paola M, Federico F, Vicari S, Petrosini L, Caltagirone C, Bozzali M (2010) Relationship between brain abnormalities and cognitive profile in Williams syndrome. Behav Genet. doi: 10.1007/s10519-010-9419-0
  58. Müller NG, Knight RT (2006) The functional neuroanatomy of working memory: contributions of human brain lesion studies. Neuroscience 139(1):51–58PubMedCrossRefGoogle Scholar
  59. Pasupathy A (2006) Neural basis of shape representation in the primate brain. In: Martinez-Conde S, Macknik SL, Martinez LM, Alonso J-M, Tse PU (eds) Visual perception—fundamentals of vision: low and mid-level processes in perception. Prog Brain Res 154(1):293–313Google Scholar
  60. Pinter JD, Eliez S, Schmitt JE, Capone GT, Reiss AL (2001a) Neuroanatomy of Down’s syndrome: a high-resolution MRI study. Am J Psychiatry 158(10):1659–1665PubMedCrossRefGoogle Scholar
  61. Pinter JD, Brown WE, Eliez S, Schmitt JE, Capone GT, Reiss AL (2001b) Amygdala and hippocampal volumes in children with Down syndrome: a high-resolution MRI study. Neurology 56:972–974PubMedGoogle Scholar
  62. Price JR, Roberts JE, Hennon EA, Berni MC, Anderson KL, Sideris J (2008) Syntactic complexity during conversation of boys with fragile X syndrome and Down syndrome. J Speech Lang Hear Res 51(1):3–15PubMedCrossRefGoogle Scholar
  63. Rigoldi C, Galli M, Condoluci C, Carducci F, Onorati P, Albertini G (2009) Gait analysis and cerebral volumes in Down’s syndrome. Funct Neurol 24(3):147–152PubMedGoogle Scholar
  64. Riva D, Nichelli F, Devoti M (2000) Developmental aspects of verbal fluency and confrontation naming in children. Brain Lang 71:267–284PubMedCrossRefGoogle Scholar
  65. Rondal JA (1998) Exceptional language development in Down syndrome. University Press, CambridgeGoogle Scholar
  66. Rowe JB, Toni I, Josephs O, Frackowiak RS, Passingham RE (2000) The prefrontal cortex: response selection or maintenance within working memory? Science 288(5471):1656–1660PubMedCrossRefGoogle Scholar
  67. Rustioni D. (1994). Prove di valutazione della comprensione linguistica (Linguistic comprehension evaluation tests). Organizzazioni Speciali, FirenzeGoogle Scholar
  68. Schapiro MB, Luxenberg JS, Kaye JA, Haxby JV, Friedland RP, Rapoport SI (1989) Serial quantitative CT analysis of brain morphometrics in adult Down’s syndrome at different ages. Neurology 39(10):1349–1353PubMedGoogle Scholar
  69. Schmidt-Sidor B, Wisniewski KE, Shepard TH, Sersen EA (1990) Brain growth in Down syndrome subjects 15 to 22 weeks of gestational age and birth to 60 months. Clin Neuropathol 9(4):181–190PubMedGoogle Scholar
  70. Shin M, Besser LM, Kucik JE, Lu C, Siffel C, Correa A (2009) Congenital anomaly multistate prevalence and survival collaborative prevalence of Down syndrome among children and adolescents in 10 regions of the United States. Pediatrics 124(6):1565–1571PubMedCrossRefGoogle Scholar
  71. Silverman W (2007) Down syndrome: cognitive phenotype. Ment Retard Dev Disabil Res Rev 13(3):228–236PubMedCrossRefGoogle Scholar
  72. Singer Harris NG, Bellugi U, Bates E, Jones W, Rossen M (1997) Contrasting profiles of language development in children with Williams and Down syndromes. Dev Neuropsychol 13:345–370CrossRefGoogle Scholar
  73. Spiers HJ, Maguire EA (2007) The neuroscience of remote spatial memory: a tale of two cities. Neuroscience 149(1):7–27PubMedCrossRefGoogle Scholar
  74. Steinmetz H, Rademacher J, Jäncke L, Huang YX, Thron A, Zilles K (1990) Total surface of temporoparietal intrasylvian cortex: diverging left-right asymmetries. Brain Lang 39(3):357–372PubMedCrossRefGoogle Scholar
  75. Stella G, Pizzoli C, Tressoldi P (2000) Peabody Picture Vocabulary Test-Revised: adattamento Italiano e standardizzazione (Peabody Picture Vocabulary Test-Revised: Italian adaptation and standardization). Omega Edizioni, TorinoGoogle Scholar
  76. Strick PL, Dum RP, Fiez JA (2009) Cerebellum and nonmotor function. Annu Rev Neurosci 32:413–434PubMedCrossRefGoogle Scholar
  77. Teipel SJ, Hampel H (2006) Neuroanatomy of Down syndrome in vivo: a model of preclinical Alzheimer’s disease. Behav Genet 36(3):405–415PubMedCrossRefGoogle Scholar
  78. Teipel SJ, Alexander GE, Schapiro MB, MoÈller H, Rapoport SI, Hampel H (2004) Age-related cortical grey matter reductions in nondemented Down’s syndrome adults determined by MRI with voxel-based morphometry. Brain 127:811–824PubMedCrossRefGoogle Scholar
  79. Terman LM, Merrill MA (1960) Stanford–Binet intelligence scale: manual for the third revision form L–M with revised IQ tables by Samuel R. Pinneau. Houghton Mifflin, Boston, MAGoogle Scholar
  80. Vallar G, Papagno C (1993) Preserved vocabulary acquisition in Down’s syndrome: the role of phonological short-term memory. Cortex 29(3):467–483PubMedGoogle Scholar
  81. Vandenberghe R, Nobre AC, Price CJ (2002) The response of left temporal cortex to sentences. J Cogn Neurosci 14:550–560PubMedCrossRefGoogle Scholar
  82. Vender C, Borgia R, Bruno S, Freo P, Zardini G (1981) Un test di ripetizione di frasi. Analisi delle performances in bambini normali (A test of sentence repetition. Analysis of performance in normal children). Neuropsichiatria Infantile 243:819–831Google Scholar
  83. Vicari S (2006) Motor development and neuropsychological patterns in persons with Down syndrome. Behav Genet 36:355–364PubMedCrossRefGoogle Scholar
  84. Vicari S (2007) Promea, Prove Di Memoria e Apprendimento per L’età Evolutiva (Memory and learning tests in developmental age). Organizzazioni Speciali, FirenzeGoogle Scholar
  85. Vicari S, Carlesimo GA (2006) Short-term memory deficits are not uniform in Down and Williams syndromes. Neuropsychol Rev 16(2):87–94PubMedCrossRefGoogle Scholar
  86. Vicari S, Caselli MC, Gagliardi C, Tonucci F, Volterra V (2002) Language acquisition in special populations: a comparison between Down and Williams syndromes. Neuropsychologia 40(13):2461–2470PubMedCrossRefGoogle Scholar
  87. Vicari S, Marotta L, Carlesimo GA (2004) Verbal short-term memory in Down’s syndrome: an articulatory loop deficit? J Intell Disabil Res 48:80–92CrossRefGoogle Scholar
  88. Vicari S, Bellucci S, Carlesimo GA (2005) Visual and spatial long-term memory: differential pattern of impairments in Williams and Down syndromes. Dev Med Child Neurol 47(5):305–311PubMedCrossRefGoogle Scholar
  89. Vicari S, Verucci L, Carlesimo GA (2007) Implicit memory is independent from IQ and age but not from etiology: evidence from Down and Williams syndromes. J Intell Disabil Res 51:932–941CrossRefGoogle Scholar
  90. Wang P (1996) A neuropsychological profile of Down syndrome: cognitive skills and brain morphology. Ment Retard Dev Disabil Res Rev 2:102–108CrossRefGoogle Scholar
  91. White NS, Alkire MT, Haier RJ (2003) A voxel-based morphometric study of nondemented adults with Down syndrome. Neuroimage 20(1):393–403PubMedCrossRefGoogle Scholar
  92. Williams KR, Wishart JG, Pitcairn TK, Willis DS (2005) Emotion recognition by children with Down syndrome: investigation of specific impairments and error patterns. Am J Ment Retard 110(5):378–392PubMedCrossRefGoogle Scholar
  93. Wishart JG (2007) Socio-cognitive understanding: a strength or weakness in Down’s syndrome? J Intellect Disabil 51(12):996–1005CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Deny Menghini
    • 1
  • Floriana Costanzo
    • 1
  • Stefano Vicari
    • 1
    • 2
    Email author
  1. 1.Department of NeuroscienceChildren’s Hospital Bambino GesùRomeItaly
  2. 2.Child Neuropsychiatry Unit, Department of NeuroscienceChildren’s Hospital Bambino GesùRomeItaly

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