Journal of Neurology

, Volume 255, Issue 3, pp 398–405 | Cite as

Cognitive and social cognitive functioning in spinocerebellar ataxia

A preliminary characterization
  • P. Garrard
  • N. H. Martin
  • P. Giunti
  • L. CipolottiEmail author



The spinocerebellar ataxias (SCAs), are rare neurodegenerative disorders caused by distinct genetic mutations. Clinically, the SCAs are characterised by progressive ataxia and a variety of other features, including cognitive dysfunction. The latter is consistent with a growing body of evidence supporting a cognitive as well as motor role for the cerebellum. Recent suggestions of cerebellar involvement in social cognition have not been extensively explored in these conditions. The availability of definitive molecular diagnosis allows genetically defined subgroups of SCA patients, with distinct patterns of cerebellar and extracerebellar involvement, to be tested comparatively using a common battery of tests of general, social and emotional cognition.


Nine patients with SCA6, and 6 with SCA3 were assessed using a comprehensive battery of neuropsychological instruments, encompassing domains of memory, language, visuo-spatial skills, calculation, attention and executive function, emotional processing and theory of mind (ToM).


There were no deficits in visuo-spatial processing or calculation in either group, while individuals with naming and attentional difficulties were seen in both. Deficits in memory and executive function were present in both conditions, albeit more pronounced in SCA3. By contrast, both groups demonstrated consistently poor performance on ToM tests, and normal attribution of social and emotional responses.


The data support the hypothesis that the cerebellum is important for cognitive as well as motor activity. The pattern of overlap of domain impairments provides tentative preliminary evidence that there is a cerebellar contribution to aspects of memory and executive function and ToM, and that other domains depend more on neural system outside the cerebellum. The findings relating to ToM are relevant to the possibility of cerebellar involvement in autism.

Key words

cognitive functioning social cognitive functioning spinocerebellar ataxias neurodegenerative disorders genetic mutations 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Abell F, Krams M, Ashburner J, Passingham R, Friston K, Frackowiak R, Happe F, Frith C, Frith U (1999) The neuroanatomy of autism: a voxel-based whole brain analysis of structural scans. Neuroreport 10:1647–1651PubMedCrossRefGoogle Scholar
  2. 2.
    Allen G, Buxton RB, Wong EC, Courchesne E (1997) Attentional activation of the cerebellum independent of motor involvement. Science 275:1940–1943PubMedCrossRefGoogle Scholar
  3. 3.
    Baron-Cohen S (1995) Mind-blindness: an essay on autism and theory of mind. MIT Press, Cambridge (MA)Google Scholar
  4. 4.
    Bauman ML, Kemper TL (1985) Histoanatomic observations of the brain in early infantile autism. Neurology 35:866–874PubMedGoogle Scholar
  5. 5.
    Bauman ML, Kemper TL (1986) Developmental cerebellar abnormalities: a consistent finding in early infantile autism (abstract). Neurology 36(Suppl 1):359Google Scholar
  6. 6.
    Bauman ML, Kemper TL (1990) Limbic and cerebellar abnormalities are also present in an autistic child of normal intelligence (abstract). Neurology 40 (Suppl 1):307Google Scholar
  7. 7.
    Bird C, Castelli F, Malik O, Frith U, Husain M (2004) The impact of extensive medial frontal lobe damage on ‘Theory of Mind’ and cognition. Brain 127:914–928PubMedCrossRefGoogle Scholar
  8. 8.
    Blair J, Cipolotti L (2000) Impaired social response reversal. A case of ‘acquired sociopathy’. Brain 123:1122–1141PubMedCrossRefGoogle Scholar
  9. 9.
    Burgess PW, Shallice T (1997) The Hayling and Brixton Tests. Thames Valley Test Company, Bury St Edmunds UKGoogle Scholar
  10. 10.
    Burk K, Bosch S, Globas C, Zuhlke C, Daum I, Klockgether T, Dichgans J (2001) Executive dysfunction in spinocerebellar ataxia type 1. European Neurology 46:43–48PubMedCrossRefGoogle Scholar
  11. 11.
    Burk K, Globas C, Bosch S, Klockgether T, Zuhlke C, Daum I, Dichgans J (2003) Cognitive deficits in spinocerebellar ataxia type 1:2 and 3. J Neurol 250:207–211PubMedCrossRefGoogle Scholar
  12. 12.
    Cancel G, Abbas N, Stevanin G, Durr A, Chneiweiss H, Neri C, Duyckaerts C, Penet C, Cann HM, Agid Y, Brice A (1995) Marked phenotypic heterogeneity associated with expansion of a CAG repeat sequence at the spinocerebellar ataxia 3/Machado-Joseph disease locus. Am J Hum Genet 57:809–816PubMedGoogle Scholar
  13. 13.
    Courchesne E, Townsend J, Saitoh O (1994) The brain in infantile autism: posterior fossa structures are abnormal. Neurology 44:214–223PubMedGoogle Scholar
  14. 14.
    Fatemi SH, Halt AR, Realmuto G, Earle J, Kist DA, Thuras P, Merz A (2002) Purkinje cell size is reduced in cerebellum of patients with autism. Cell Mol Neurobiol 22:171–175PubMedCrossRefGoogle Scholar
  15. 15.
    Fehlow P, Bernstein K, Tennstedt A, Walther F (1993) Early infantile autism and excessive aerophagy with symptomatic megacolon and ileus in a case of Ehlers-Danlos syndrome. Pädiatr Grenzgeb 31:259–267PubMedGoogle Scholar
  16. 16.
    Fiez JA (1996) Cerebellar contributions to cognition. Neuron 16:13–15PubMedCrossRefGoogle Scholar
  17. 17.
    Fine C, Lumsden J, Blair RJ (2001) Dissociation between ‘theory of mind’ and executive functions in a patient with early left amygdala damage. Brain 124:287–298PubMedCrossRefGoogle Scholar
  18. 18.
    Frith U, Frith CD (2003) Development and neurophysiology of mentalizing. Philosoph Trans R Soc Lond B Biol Sci 358:459–473CrossRefGoogle Scholar
  19. 19.
    Glickstein, M (2006) Thinking about the cerebellum. Brain 129:288–290PubMedCrossRefGoogle Scholar
  20. 20.
    Globas C, Bosch S, Zuhlke C, Daum I, Dichgans J, Burk K (2003) The cerebellum and cognition. Intellectual function in spinocerebellar ataxia type 6 (SCA6). J Neurol 250:1482–1487PubMedCrossRefGoogle Scholar
  21. 21.
    Gottwald B, Wilde B, Mihajlovic Z, Mehdorn HM (2004) Evidence for distinct cognitive deficits after focal cerebellar lesions. J Neurol Neurosurg Psychiatry 75:1524–1531PubMedCrossRefGoogle Scholar
  22. 22.
    Grafman J, Litvan I, Massaquoi S, Stewart M, Sirigu A, Halett M (1992) Cognitive planning deficit in patients with cerebellar atrophy. Neurology 42:1493–1496PubMedGoogle Scholar
  23. 23.
    Grasby PM, Frith CD, Friston KJ, Bench C, Frackowiak RS, Dolan RJ (1993) Functional mapping of brain areas implicated in auditory-verbal memory function. Brain 116:1–20PubMedCrossRefGoogle Scholar
  24. 24.
    Ishikawa K, Watanabe M, Yoshizawa K, Nakamagoe K, Satoh A, Shoji S (1999) Clinical, neuropathological and molecular study in two families with spinocerebellar ataxia type 6 (SCA6). J Neurol Neurosurg Psychiatry 67:86–89PubMedCrossRefGoogle Scholar
  25. 25.
    Jackson M, Warrington E (1986) Arithmetic skills in patients with unilateral cerebral lesions. Cortex 22:610–620Google Scholar
  26. 26.
    Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, Kawakami H, Nakamura S, Nishimura M, Akiguchi I, Kimura J, Naramiya S, Kakizuka A (1994) CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32. 1. Nat Genet 8:221–227PubMedCrossRefGoogle Scholar
  27. 27.
    Kawai Y, Takeda A, Abe Y, Washimi Y, Tanaka F, Sobue G (2004) Cognitive impairments in Machado-Joseph disease. Arch Neurol 61:1757–1760PubMedCrossRefGoogle Scholar
  28. 28.
    Khan NL, Giunti P, Sweeney MB, Scherfler C, O’Brien M, Piccini P, Wood NW, Lees AJ (2005) Parkinsonism nigrostriatal dysfunction are associated with spinocerebellar ataxia type 6 (SCA6). Movement Disorders 20:1115–1119PubMedCrossRefGoogle Scholar
  29. 29.
    Kim SG, Ugurbil K, Strick PL (1994) Activation of a cerebellar output nucleus during cognitive processing. Science 265:949–951PubMedCrossRefGoogle Scholar
  30. 30.
    Klein D, Milner B, Zatorre RJ, Meyer E, Evans AC (1995) The neural substrates underlying word generation: a bilingual functional-imaging study. Proc Natl Acad Sci USA 92:2899–2903PubMedCrossRefGoogle Scholar
  31. 31.
    Koob MD, Moseley ML, Schut LJ, Benzow KA, et al. (1999) An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nat Genet 21:379–384PubMedCrossRefGoogle Scholar
  32. 32.
    La Pira F, Zappala G, Saponara R, Domina E, Restivo DA, Reggio E, Nicoletti A, Giuffrida S (2002) Cognitive findings in spinocerebellar ataxia type 2: relationship to genetic and clinical variables. J Neurol Sci 201:53–57CrossRefGoogle Scholar
  33. 33.
    Manto MU (2005) The wide spectrum of spinocerebellar ataxias (SCAs). Cerebellum 4:2–6PubMedCrossRefGoogle Scholar
  34. 34.
    Maruff P, Tyler P, Burt T, Currie B, Burns C, Currie J (1996) Cognitive deficits in Machado-Joseph Disease. Ann Neurol 40:421–427PubMedCrossRefGoogle Scholar
  35. 35.
    McKenna P, Warrington E (1980) The Graded Naming Test. NFER-Nelson, Windsor UKGoogle Scholar
  36. 36.
    Muller U, Mottweiler E, Bublak P (2005) Noradrenergical blockade and numeric working memory in humans. J Psychopharmacol 19:21–28PubMedCrossRefGoogle Scholar
  37. 37.
    Murata Y, Tamaguchi S, Kawakami H, et al. (1998a) Characteristic magnetic resonance imaging findings in Machado-Joseph disease. Arch Neurol 55:33–37CrossRefGoogle Scholar
  38. 38.
    Murata Y, Kawakami H, Yamaguchi S, et al. (1998b) Characteristic magnetic resonance imaging findings in spinocerebellar ataxia 6. Arch Neurol 55:1348–1352CrossRefGoogle Scholar
  39. 39.
    Nelson HE (1976) A modified card sorting test sensitive to frontal lobe defects. Cortex 12:313–324PubMedGoogle Scholar
  40. 40.
    Nelson HE (1982) The National Adult Reading Test. NFER-Nelson, Windsor UKGoogle Scholar
  41. 41.
    Paulson H, Ammache Z (2001) Ataxia and hereditary disorders. Neurol Clin 19:759–782PubMedCrossRefGoogle Scholar
  42. 42.
    Petersen SE, Fox PT, Posner MI, Minten M, Raichle ME (1989) Positron emission tomographic studies of the processing of single words. J Cog Neurosci 1:153–170CrossRefGoogle Scholar
  43. 43.
    Radvany J, Camargo CHP, Costa ZM, Fonseca NC, Nascimento ED (1993) Machado-Joseph Disease of Azorean ancestry in Brazil: The Catarina Kindred. Arquivos de Neuropsiquiatria 51:21–30Google Scholar
  44. 44.
    Ritvo ER, Freeman BJ, Scheibel AB, Duong T, Robinson H, Guthrie D, Ritvo A (1986) Lower Purkinje cell counts in the cerebella of four autistic subjects: initial findings of the UCLA-NSAC autopsy research report. Am J Psychiatry 143:862–866PubMedGoogle Scholar
  45. 45.
    Robertson IH, Ward T, Ridgeway V, Nimmo-Smith I (1994) The Test of Everyday Attention. Thames Valley Test Company, Bury St Edmunds UKGoogle Scholar
  46. 46.
    Salmond CH, de Haan M, Friston KJ, Gadian DG, Varga-Khadem F (2003) Investigating individual differences in brain abnormalities in autism. Phil Trans R Soc Lond B 358:405–413CrossRefGoogle Scholar
  47. 47.
    Sasaki H, Kojima H, Yabe I, Tashiro K, Hamada T, Sawa H, Hiraga H, Nagashima K (1998) Neuropathological and molecular studies of spinocerebellar ataxia type 6 (SCA6). Acta Neuropathol 95:199–204PubMedCrossRefGoogle Scholar
  48. 48.
    Saver JL, Damasio AR (1991) Preserved access and processing of social knowledge in a patient with acquired sociopathy due to ventromedial frontal damage. Neuropsychologia 29:1241–1249PubMedCrossRefGoogle Scholar
  49. 49.
    Schmahmann JD (1991) An emerging concept: The cerebellar contribution to higher function. Arch Neurol 48:1178–1187PubMedGoogle Scholar
  50. 50.
    Schmahmann JD, Sherman JC (1998) The cerebellar cognitive affective syndrome. Brain 121:561–579PubMedCrossRefGoogle Scholar
  51. 51.
    Spreen O, Strauss E (1998) A compendium of neuropsychological tests (2nd edition). Oxford University Press, New YorkGoogle Scholar
  52. 52.
    Takiyama Y, Igarashi S, Rogaeva EA Endo K, Rogaev EI, Tanaka H, Sherrington R, Sanpei K, Liang Y, Saito M, Tsuda T, Takano H, Ikeda M, Lin C, Chi H, Kennedy JL, Lang AE, Wherrett JR, Segawa M, Nomura Y, Yuasa T, Weissenbach J, Yoshida M, Nishizawa M, Kidd KK, Tsuji S, St George-Hyslop PH (1995) Evidence for inter-generational instability in the CAG repeat in the MJD1 gene and for conserved haplotypes at flanking markers amongst Japanese and Caucasian subjects with Machado-Joseph disease. Hum Molec Genet 4:1137–1146PubMedCrossRefGoogle Scholar
  53. 53.
    Trenerry MR, Crossen B, DeBoe J, Leber WR (1989) Stroop Neuropsychological Screening Test (SNST). NFER-Nelson Publishing Co. Ltd, Windsor UKGoogle Scholar
  54. 54.
    Van Harskamp NJ, Rudge P, Cipolotti L (2005) Cognitive and social impairments in patients with superficial siderosis. Brain 128:1082–1092PubMedCrossRefGoogle Scholar
  55. 55.
    Warrington E (1984) The Recognition Memory Test. NFER-Nelson, Windsor UKGoogle Scholar
  56. 56.
    Warrington E, James M (1991) The Visual Object and Space Perception Battery. Thames Valley Test Company, Bury St Edmonds UKGoogle Scholar
  57. 57.
    Wechsler D (1981) Wechsler Adult Intelligence Scale-Revised:Manual. Psychological Corporation, New YorkGoogle Scholar
  58. 58.
    Wechsler D (1997) Wechsler Memory Scale-Revised. Psychological Corporation, LondonGoogle Scholar
  59. 59.
    Yu GY, Howell MJ, Roller MJ, Xie TD, Gomez CM (2005) Spinocerebellar ataxia type 26 maps to chromosome 19p13. 3 adjacent to SCA6. Ann Neurol 57:349–354PubMedCrossRefGoogle Scholar
  60. 60.
    Zawacki TM, Grace J, Friedman JH, Sudarsky L (2002) Executive emotional dysfunction in Machado-Joseph Disease. Movement Disorders 17:1004–1010PubMedCrossRefGoogle Scholar
  61. 61.
    Zeman A, Stone J, Porteus M, Burns E, Barron L, Warner J (2004) Spinocerebellar ataxia type 8 in Scotland: genetic and clinical features in seven unrelated cases and a review of published reports. J Neurol Neurosurg Psychiatry 75:459–465PubMedCrossRefGoogle Scholar
  62. 62.
    Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton DW, Amos C, Dobyns WB, Subramony SH, Zoghbi HY, Lee CC (1997) Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the α–1A-voltage-dependent calcium channel. Nat Genet 15:62–69PubMedCrossRefGoogle Scholar

Copyright information

© Steinkopff-Verlag 2008

Authors and Affiliations

  • P. Garrard
    • 1
    • 2
  • N. H. Martin
    • 3
  • P. Giunti
    • 4
  • L. Cipolotti
    • 5
    • 6
    Email author
  1. 1.Institute of Cognitive NeuroscienceLondonUK
  2. 2.Dept. of Clinical NeurosciencesRoyal Free HospitalLondonUK
  3. 3.Dept. of NeuropsychologyNational Hospital for Neurology and NeurosurgeryLondonUK
  4. 4.Institute of NeurologyLondonUK
  5. 5.Dept. of NeuropsychologyNational Hospital for Neurology and NeurosurgeryLondonUK
  6. 6.Dipartimento Di PsicologiaUniversita Degli Studi di PalermoItaly

Personalised recommendations