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Impairment in motor reprogramming in Friedreich ataxia reflecting possible cerebellar dysfunction

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Abstract

The cerebellar and spinocerebellar dysfunction seen in Friedreich ataxia (FRDA) has known effects on motor function. Recently, it was suggested that people with FRDA may also have impairment in motor planning, either because of cortical pathology or because of cerebello-cortical projections. Fifteen adults with FRDA and 15 matched controls completed a task requiring reciprocating movements between two buttons on a tapping board. Occasionally there was one of three “oddball” stimuli requiring reprogramming of movement. These were change in (1) direction, (2) extent or (3) direction and extent. We hypothesized that people with FRDA would have prolonged movement times due to their movement disorder, and that changes in preparation time would be affected in a way similar to controls, unless there was impairment in motor planning in FRDA. Movement execution and, to a lesser degree, movement preparation were impaired in individuals with FRDA. We argue this points to disturbed cortical function. There was a significant negative correlation between age of onset and all three reprogramming conditions, suggesting an impact of FRDA on developing motor planning. Future studies will be required to establish whether this dysfunction is due to cerebellar impairment interrupting cerebro-ponto-cerebello-thalamo-cerebral loops, primary cortical pathology or a combination of the two.

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References

  1. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psych 4:561–571

    CAS  Google Scholar 

  2. Botez-Marquard T, Botez MI (1993) Cognitive behavior in heredodegenerative ataxias. Eur Neurol 33:351–357

    Article  CAS  PubMed  Google Scholar 

  3. Botez-Marquard T, Botez MI (1997) Olivopontocerebellar atrophy and Friedreich’s ataxia: neuropsychological consequences of bilateral versus unilateral cerebellar lesions. Int Rev Neurobiol 41:387–410

    Article  CAS  PubMed  Google Scholar 

  4. Botez-Marquard T, Bard C, Leveille J, Botez MI (2001) A severe frontal–parietal lobe syndrome following cerebellar damage. Eur J Neurol 8:347–353

    Article  CAS  PubMed  Google Scholar 

  5. Braver T, Barch D, Gray J, Molfese D, Snyder A (2001) Anterior cingulate cortex and response conflict: effects of frequency, inhibition and errors. Cereb Cortex 11:825–836

    Article  CAS  PubMed  Google Scholar 

  6. Campuzano V, Montermini L, Molto MD, Pianese L, Cossee M, Cavalcanti F et al (1996) Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271:1423–1427

    Article  CAS  PubMed  Google Scholar 

  7. Corben LA, Georgiou-Karistianis N, Fahey MC, Storey E, Churchyard A, Horne MK et al (2006) Towards an understanding of cognitive function in Friedreich Ataxia. Brain Res Bull 70:197–202

    Article  PubMed  Google Scholar 

  8. Courchesne E, Allen G (1997) Prediction and preparation, fundamental functions of the cerebellum. Learn Mem 4:1–35

    Article  CAS  PubMed  Google Scholar 

  9. Delatycki MB, Paris DB, Gardner RJ, Nicholson GA, Nassif N, Storey E et al (1999) Clinical and genetic study of Friedreich ataxia in an Australian population. Am J Med Genet 87:168–174

    Article  CAS  PubMed  Google Scholar 

  10. Delatycki MB, Williamson R, Forrest SM (2000) Friedreich ataxia: an overview. J Med Genet 37:1–8

    Article  CAS  PubMed  Google Scholar 

  11. Della Nave N, Ginestroni A, Giannelli M, Tessa C, Salvatore E, Salvi F, Dotti MT, De Michele G, Piacentini S, Mascalchi M (2008) Brain structural damage in Friedreich’s ataxia. J Neurol Neurosurg Psychiatry 79:82–85

    Article  CAS  PubMed  Google Scholar 

  12. Dove A, Pollmann S, Schubert T, Wiggins CJ, von Cramon DY (2000) Prefrontal cortex activation in task switching: an event-related fMRI study. Brain Res Cogn Brain Res 9:103–109

    Article  CAS  PubMed  Google Scholar 

  13. Drepper J, Timmann D, Kolb FP, Diener HC (1999) Non-motor associative learning in patients with isolated degenerative cerebellar disease. Brain 122:87–97

    Article  PubMed  Google Scholar 

  14. Elliot R (2002) The neuropsychological profile in primary depression. In: Harrison JJ, Owens A (eds) Cognitive deficits in brain disorders. Taylor and Francis, London, pp 273–293

    Google Scholar 

  15. Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Am Soc Psych Res 12:189–198

    CAS  Google Scholar 

  16. Georgiou N, Bradshaw JL, Phillips JG, Chiu E, Bradshaw JA (1995) Reliance on advance information and movement sequencing in Huntington’s disease. Mov Disord 10:472–481

    Article  CAS  PubMed  Google Scholar 

  17. Georgiou-Karistianis N, Sritharan A, Farrow M, Cunnington R, Stout J, Bradshaw J et al (2007) Increased cortical recruitment in Huntington’s disease using a Simon task. Neuropsychologia 45:1791–1800

    Article  PubMed  Google Scholar 

  18. Goh MYA, Bradshaw JL, Bradshaw JA, Georgiou-Karistianis N (2002) Inhibition of expected movements in Tourette’s syndrome. J Clin Exp Neuropsychol 24:1017–1031

    Article  Google Scholar 

  19. Golden CJ (2002) Stroop color and word test. A manual for clinical and experimental uses. Stoelting, Illinois

    Google Scholar 

  20. Grafman J, Litvan I, Massaquoi S, Stewart M, Sirigu A, Hallett M (1992) Cognitive planning deficit in patients with cerebellar atrophy. Neurology 42:1493–1496

    CAS  PubMed  Google Scholar 

  21. Harding AE (1981) Friedreich’s ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. Brain 104:589–620

    Article  CAS  PubMed  Google Scholar 

  22. Hart RP, Kwentus JA, Leshner RT, Frazier R (1985) Information processing speed in Friedreich’s ataxia. Ann Neurol 17:612–614

    Article  CAS  PubMed  Google Scholar 

  23. Hart RP, Henry GK, Kwentus JA, Leshner RT (1986) Information processing speed of children with Friedreich’s ataxia. Dev Med Child Neurol 28:310–313

    Article  CAS  PubMed  Google Scholar 

  24. Huettel SA, McCarthy G (2004) What is odd in the oddball task? Prefrontal cortex is activated by dynamic changes in response strategy. Neuropsychologia 42:379–386

    Article  PubMed  Google Scholar 

  25. Ito M (1993) Movement and thought: identical control mechanisms by the cerebellum. Trends Neurosci 16:448–450

    Article  CAS  PubMed  Google Scholar 

  26. Ito M (2005) Bases and implications of learning in the cerebellum—adaptive control and internal model mechanism. Prog Brain Res 148:95–109

    Article  PubMed  Google Scholar 

  27. Junck L, Gilman S, Gebarski SS, Koeppe RA, Kluin KJ, Markel DS (1994) Structural and functional brain imaging in Friedreich’s ataxia. Arch Neurol 51:349–355

    CAS  PubMed  Google Scholar 

  28. Levisohn L, Cronin-Golomb A, Schmahmann JD (2000) Neuropsychological consequences of cerebellar tumour resection in children. Cerebellar cognitive affective syndrome in a paediatric population. Brain 123:1041–1050

    Article  PubMed  Google Scholar 

  29. Linden DEJ, Prulovic D, Formisano E, Vollinger M, Zanella FE, Goebel R et al (1999) The functional neuroanatomy of target detection: An fMRI study of visual and auditory oddball tasks. Cereb Cortex 9:815–823

    Article  CAS  PubMed  Google Scholar 

  30. Loose R, Kaufmann C, Tucha O, Auer DP, Lange KW (2006) Neural networks of response shifting: influence of task speed and stimulus material. Brain Res 1090:146–155

    Article  CAS  PubMed  Google Scholar 

  31. Lynch DR, Farmer JM, Balcer LJ, Wilson RB (2002) Friedreich ataxia: effects of genetic understanding on clinical evaluation and therapy. Arch Neurol 59:743–747

    Article  PubMed  Google Scholar 

  32. Mantovan M, Martinuzzi A, Squarzanti F, Bolla A, Silvestri I, Liessi G et al (2006) Exploring mental status in Friedreich’s ataxia: a combined neuropsychological, behavioural and neuroimaging study. Eur J Neurol 13:827–835

    Article  CAS  PubMed  Google Scholar 

  33. Mattingley JB, Corben LA, Bradshaw JL, Bradshaw JA, Phillips JG, Horne MK (1998) The effects of competition and motor reprogramming on visuomotor selection in unilateral neglect. Exp Brain Res 120:243–256

    Article  CAS  PubMed  Google Scholar 

  34. Montermini L, Richter A, Morgan K, Justice CM, Julien D, Castellotti B et al (1997) Phenotypic variability in Friedreich ataxia: role of the associated GAA triplet repeat expansion. Ann Neurol 41:675–682

    Article  CAS  PubMed  Google Scholar 

  35. Pandolfo M (2003) Friedreich ataxia. Sem Ped Neurol 10:163–172

    Article  Google Scholar 

  36. Pandolfo M (2008) Friedreich ataxia. Arch Neurol 65:1296–1303

    Article  PubMed  Google Scholar 

  37. Ramani N (2006) The primate cortico-cerebellar system: anatomy and function. Nat Rev Neurosci 7:511–522

    Article  CAS  Google Scholar 

  38. Reitan MN (1955) The relation of the trail making test to organic brain damage. J Consult Psychol 19:393–394

    Article  CAS  PubMed  Google Scholar 

  39. Riva D, Giorgi C (2000) The cerebellum contributes to higher functions during development. Brain 123:1051–1061

    Article  PubMed  Google Scholar 

  40. Rosenbaum DA (1980) Human movement initiation: specification of arm, direction, and extent. J Exp Psychol 109:444–474

    CAS  Google Scholar 

  41. Schmahmann JD (1991) An emerging concept. The cerebellar contribution to higher function. Arch Neurol 48:1178–1187

    CAS  PubMed  Google Scholar 

  42. Schmahmann JD, Pandya DN (1995) Prefrontal cortex projections to the basilar pons in rhesus monkey: implications for the cerebellar contribution to higher function. Neurosci Lett 199:175–178

    Article  CAS  PubMed  Google Scholar 

  43. Schmahmann JD, Pandya DN (1997) The cerebrocerebellar system. Int Rev Neurobiol 41:31–60

    Article  CAS  PubMed  Google Scholar 

  44. Schmahmann JD, Sherman JC (1998) The cerebellar cognitive affective syndrome. Brain 121:561–579

    Article  PubMed  Google Scholar 

  45. Schmahmann JD (2004) Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. J Neuropsych Clin Neurosci 16:367–378

    Google Scholar 

  46. Schweizer TA, Oriet C, Meiran N, Alexander MP, Cusimano M, Struss DT (2007) The cerebellum mediates conflict resolution. J Cogn Neurosci 19:1974–1982

    Article  PubMed  Google Scholar 

  47. Sohn M-H, Ursu S, Anderson J, Stenger A, Carter C (2000) The role of prefrontal cortex and posterior parietal cortex in task switching. Proc Natl Acad Sci USA 97:13448–13453

    Article  CAS  PubMed  Google Scholar 

  48. Subramony SH, May W, Lynch D, Gomez C, Fischbeck K, Hallett M et al (2005) Measuring Friedreich ataxia: interrater reliability of a neurologic rating scale. Neurology 64:1261–1262

    CAS  PubMed  Google Scholar 

  49. Sylvester C, Wager T, Lacey SC, Hernandez L, Nichols TE, Smith EE et al (2003) Switching attention and resolving interference: fMRI measures of executive functions. Neuropsychologia 41:357–370

    Article  PubMed  Google Scholar 

  50. Thiruvady D, Georgiou-Karistianis N, Egan G, Ray S, Sritharan A, Farrow M et al (2007) Functional connectivity of the prefrontal cortex in Huntington’s disease. J Neurol Neurosurg Psychiatry 78:127–133

    Article  CAS  PubMed  Google Scholar 

  51. Tipper SP, Lortie C, Baylis GC (1992) Selective reaching: evidence for action-centered attention. J Exp Psychol Hum Percept Perform 18:891–905

    Article  CAS  PubMed  Google Scholar 

  52. Voncken M, Ioannou P, Delatycki MB (2004) Friedreich ataxia-update on pathogenesis and possible therapies. Neurogenetics 5:1–8

    Article  PubMed  Google Scholar 

  53. Waldvogel D, van Gelderen P, Hallett M (1999) Increased iron in the dentate nucleus of patients with Friedrich’s ataxia. Ann Neurol 46(1):123–125

    Article  CAS  PubMed  Google Scholar 

  54. White M, Lalonde R, Botez-Marquard T (2000) Neuropsychologic and neuropsychiatric characteristics of patients with Friedreich’s ataxia. Acta Neurol Scand 102:222–226

    Article  CAS  PubMed  Google Scholar 

  55. Wollmann T, Barroso J, Monton FI, Nieto A (2002) Neuropsychological test performance of patients with Friedreich’s ataxia. J Clin Exp Neuropsychol 24:677–686

    Article  PubMed  Google Scholar 

  56. Wollmann T, Nieto-Barco A, Monton-Alvarez F, Barroso-Ribal J (2004) Ataxia de Friedreich: analisis de parametros de resonancia magnetica y correlatos con el enlentecimiento cognitivo y motor. Rev Neurol 38:217–222

    CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to express our appreciation to the participants in this study who gave their time so willingly and continue to support our research. We would also like to thank Dr. Roger Peverill, Dr. Veronica Collins and Dr. Simon Moss for their valuable statistical advice. We would also like to thank the Friedreich Ataxia Research Association (Australasia) and the Friedreich Ataxia Research Alliance (USA) for their ongoing financial support of our research programme. MBD is a NHMRC Practitioner Fellow.

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Correspondence to Martin B. Delatycki.

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Corben, L.A., Delatycki, M.B., Bradshaw, J.L. et al. Impairment in motor reprogramming in Friedreich ataxia reflecting possible cerebellar dysfunction. J Neurol 257, 782–791 (2010). https://doi.org/10.1007/s00415-009-5410-1

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