Characterising the Neuropathology and Neurobehavioural Phenotype in Friedreich Ataxia

A Systematic Review
  • Louise A. CorbenEmail author
  • Nellie Georgiou-Karistianis
  • John L. Bradshaw
  • Marguerite V. Evans-Galea
  • Andrew J. Churchyard
  • Martin B. Delatycki
Part of the Advances in Experimental Medicine and Biology book series (AEMB)


Friedreich ataxia (FRDA), the most common of the hereditary ataxias, is an autosomal recessive, multisystem disorder characterised by progressive ataxia, sensory symptoms, weakness, scoliosis and cardiomyopathy. FRDA is caused by a GAA expansion in intron one of the FXN gene, leading to reduced levels of the encoded protein frataxin, which is thought to regulate cellular iron homeostasis. The cerebellar and spinocerebellar dysfunction seen in FRDA has known effects on motor function; however until recently slowed information processing has been the main feature consistently reported by the limited studies addressing cognitive function in FRDA. This chapter will systematically review the current literature regarding the neuropathological and neurobehavioural phenotype associated with FRDA. It will evaluate more recent evidence adopting systematic experimental methodologies that postulate that the neurobehavioural phenotype associated with FRDA is likely to involve impairment in cerebello-cortico connectivity.


Dentate Nucleus Superior Cerebellar Peduncle Friedreich Ataxia Tandem Repeat Polymorphism Cellular Iron Homeostasis 
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  1. 1.
    Delatycki MB, Williamson R, Forrest SM. Friedreich ataxia: an overview. J Med Gen 2000; 37(1):1–8.CrossRefGoogle Scholar
  2. 2.
    Friedreich N. Uber degenerative Atrophie der Spinalen Hinterstrange. Virchows Arch Path Anat 1863; 26:433–459.CrossRefGoogle Scholar
  3. 3.
    Harding AE. 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 1981; 104(3):589–620.PubMedCrossRefGoogle Scholar
  4. 4.
    Delatycki MB, Paris DB, Gardner RJ et al. Clinical and genetic study of Friedreich ataxia in an Australian population. Am J Med Gen 1999; 87(2):168–174.CrossRefGoogle Scholar
  5. 5.
    Pandolfo M. Friedreich Ataxia: the clinical picture. J Neurol 2009; 256:3–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Pandolfo M. Friedreich ataxia. Arch Neurol 2008; 65(10):1296–1303.PubMedCrossRefGoogle Scholar
  7. 7.
    Shultz JB, Boesch S, Bürk K et al. Diagnosis and treatment of Friedreich ataxia: a European perspective. Nat Rev Neurol 2009; 5:222–234.CrossRefGoogle Scholar
  8. 8.
    Fahey MC, Cremer PD, Swee TA et al. Vestibular, saccadic and fixation abnormalities in genetically confirmed Friedreich ataxia. Brain 2008; 131:1035–1045.PubMedCrossRefGoogle Scholar
  9. 9.
    Nardulli R, Monitillo V, Losavio E et al. Urodynamic evaluation of 12 ataxic subjects: neurophysiopathologic considerations. Func Neurol 1992; 7(3):223–235.Google Scholar
  10. 10.
    Campanella G, Filla A, DeFalco F et al. Friedreich’s ataxia in the south of Italy: a clinical and biochemical survey of 23 patients. Can J Neurol Sci 1980; 7(4):351–357.PubMedCrossRefGoogle Scholar
  11. 11.
    Shapiro F, Specht L. The diagnosis and orthopaedic treatment of childhood spinal muscular atrophy, peripheral neuropathy, Friedreich ataxia and arthrogryposis. J Bone Joint Surg — Series A 1993; 75(11): 1699–1714.CrossRefGoogle Scholar
  12. 12.
    Labelle H, Tohme S, Duhaime M et al. Natural history of scoliosis in Friedreich’s Ataxia. J Bone Joint Surg 1986; 68:564–572.PubMedCrossRefGoogle Scholar
  13. 13.
    Folker J, Murdoch B, Cahill L et al. Dysarthria in Friedreich’s Ataxia: a perceptual analysis. Folia Phon Log 2010; 62:97–103.CrossRefGoogle Scholar
  14. 14.
    Ribaï P, Pousset F, Tanguy M et al. Neurological, cardiological and oculomotor progression in 104 patients with Friedreich ataxia during long-term follow-up. Arch Neurol 2007; 64:558–564.PubMedCrossRefGoogle Scholar
  15. 15.
    Dutka DP, Donnelly JE, Palka P et al. Echocardiographic characterization of cardiomyopathy in Friedreich’s ataxia with tissue Doppler echocardiographically derived myocardial velocity gradients. Circulation 2000; 102(11):1276–1282.PubMedCrossRefGoogle Scholar
  16. 16.
    Mottram PM, Delatycki MB, Donelan L et al. Early changes in left ventricular long axis function in Friedreich ataxia — relation with the FXN gene mutation and cardiac structural change. J Am Soc Echo 2011;24(7):782–789.CrossRefGoogle Scholar
  17. 17.
    Rance G, Fava R, Baldock H et al. Speech perception ability in individuals with Friedreich ataxia. Brain 2008; 131:2002–2012.PubMedCrossRefGoogle Scholar
  18. 18.
    Rance G, Corben L, Barker E et al. Auditory perception in individuals with Friedreich’s ataxia. Audiol Neurotol 2010; 15:229–240.CrossRefGoogle Scholar
  19. 19.
    Meyer C, Schmid G, Görlitz S et al. Cardiomyopathy in Friedreich ataxia: Assessment by cardiac MRI. Mov Dis 2007; 22(11):1615–1622.CrossRefGoogle Scholar
  20. 20.
    Tsou AY, Paulsen EK, Lagedrost SJ et al. Mortality in Friedreich ataxia. J Neurol Sci 2011; 307:46–49.PubMedCrossRefGoogle Scholar
  21. 21.
    Campuzano V, Montermini L, Molto MD et al. Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 1996; 271(5254):1423–1427.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Voncken M, Ioannou P, Delatycki MB. Friedreich ataxia-update on pathogenesis and possible therapies. Neurogenetics 2004; 5(1):1–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Evans-Galea MV, Corben LA, Hasell J et al. A novel deletion-insertion mutation identified in exon 3 of FXN in two siblings with a severe Friedreich ataxia phenotype. Neurogenetics 2011.Google Scholar
  24. 24.
    Forrest SM, Knight M, Delatycki MB et al. The correlation of clinical phenotype in Friedreich ataxia with the site of point mutations in the FRDA gene. Neurogenetics 1998; l(4):253–257.CrossRefGoogle Scholar
  25. 25.
    Cossée M, Dürr A, Schmitt M et al. Friedreich’s ataxia: point mutations and clinical presentation of compound heterozygotes. Ann Neurol 1999; 45(2):200–206.PubMedCrossRefGoogle Scholar
  26. 26.
    Schmucker S, Reutenauer L, Devos et al. Identification of an atypical Friedreich ataxia patient with no GAA expansion but with a homozygous point mutation in the mitochondrial targeting sequence of frataxin. Presented at the Friedreich ataxia scientific meeting; Strasbourg, France. 2011Google Scholar
  27. 27. Boehm T, Scheiber-Mojdehkar B, Kluge B et al. Variations of frataxin protein levels in normal individuals. Neurol Sci 2010:327–330.PubMedCrossRefGoogle Scholar
  28. 28.
    Delatycki MB, Paris D, Gardner RJ et al. Sperm DNA analysis in a Friedreich ataxia premutation carrier suggests both meiotic and mitotic expansion in the FRDA gene. J Med Gen 1998; 35(9):713–716.CrossRefGoogle Scholar
  29. 29.
    Pianese L, Cavalcanti F, De Michele G et al. The effect of parental gender on the GAA dynamic mutation in the FRDA gene. Am J Hum Gen 1997; 60(2):460–463.Google Scholar
  30. 30.
    Campuzano V, Montermini L, Lutz Y et al. Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes. Hum Mol Gen 1997; 6(11): 1771–1780.PubMedCrossRefGoogle Scholar
  31. 31.
    Santos R, Lefevre S, Sliwa S et al. Friedreich Ataxia: Molecular mechanisms, redox considerations and therapeutic opportunities. Ant Red Sig 2010; 13(5):651–690.Google Scholar
  32. 32.
    Al-Mahdawi S, Pinto RM, Ismail O et al. The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues. Hum Mol Gen 2008; 17(5):735–746.PubMedCrossRefGoogle Scholar
  33. 33.
    Punga T, Bühler M. Long intronic GAA repeats causing Friedreich ataxia impede transcription elongation. EMBO Mol Med 2010; 2:120–129.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Herman D, Jenssen K, Burnett R et al. Histone deacetylase inhibitors reverse gene silencing in Friedreich’s ataxia. Nat Chem Biol 2007; 2(10):551–558.CrossRefGoogle Scholar
  35. 35.
    Rai M, Soragni E, Jenssen K et al. HD AC inhibitors correct frataxin deficiency in a Friedreich ataxia mouse model. PloS One 2008; 3:el958.CrossRefGoogle Scholar
  36. 36.
    Evans-Galea MV, Carrodus N, Rowley SN et al. FXN methylation predicts expression and clinical outcome in Friedreich ataxia. Ann Neurol 2011 In press.Google Scholar
  37. 37.
    Cossee M, Puccio H, Gansmuller A et al. Inactivation of the Friedreich ataxia mouse gene leads to early embryonic lethality without iron accumulation. Hum Mol Gen 2000; 9(8):1219–1226.PubMedCrossRefGoogle Scholar
  38. 38.
    Pandolfo M, Pastore A. The pathogenesis of Friedreich ataxia and the structure and function of frataxin. JNeurol 2009; 256(Suppl 1):9–17.Google Scholar
  39. 39.
    Calabrese V, Lodi R, Tonon C et al. Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich’s Ataxia. J Neurol Sci 2005; 233(1–2): 145–162.PubMedCrossRefGoogle Scholar
  40. 40.
    Koeppen AH. Friedreich’s ataxia: pathology, pathogenesis and molecular genetics. J Neurol Sci 2011; 303(1–2):l–12.Google Scholar
  41. 41.
    Junck L, Gilman S, Gebarski SS et al. Structural and functional brain imaging in Friedreich’s ataxia. Arch Neurol 1994; 51(4):349–355.PubMedCrossRefGoogle Scholar
  42. 42.
    Koeppen AH. Neuropathology of the inherited ataxias. In: Manto U-M, Pandolfo M, eds. The Cerebellum and its Disorders. Cambridge: Cambridge University Press, 2002: 387–409.Google Scholar
  43. 43.
    Koeppen AH, Morral JA, Davis AN et al. The dorsal root ganglion in Friedreich’s ataxia. Acta Neuropath 2009; 118(6):763–776.PubMedCrossRefGoogle Scholar
  44. 44.
    Koeppen AH, Morral JA, McComb RD et al. The neuropathology of late-onset Friedreich’s ataxia. Cerebellum 2011; 10(1):96–103.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Botez MI, Leveille J, Lambert R et al. Single photon emission computed tomography (SPECT) in cerebellar disease: cerebello-cerebral diaschisis. Eur Neurol 1991; 31(6):405–412.PubMedCrossRefGoogle Scholar
  46. 46.
    Ormerod IE, Harding AE, Miller DH et al. Magnetic resonance imaging in degenerative ataxic disorders. J Neurol Neurosurg Psych 1994; 57(1):51–57.CrossRefGoogle Scholar
  47. 47.
    Klockgether T, Zuhlke C, Schulz JB et al. Friedreich’s ataxia with retalned tendon reflexes: molecular genetics, clinical neurophysiology and magnetic resonance imaging. Neurology 1996; 46(1): 118–121.PubMedCrossRefGoogle Scholar
  48. 48.
    Delia Nave R, Ginestroni A, Giannelli M et al. Brain structural damage in Friedreich’s ataxia. J Neurol, Neurosurg, Psych 2008; 79:82–85.CrossRefGoogle Scholar
  49. 49.
    De Michele G, Mainenti PP, Soricelli A et al. Cerebral blood flow in spinocerebellar degenerations: a single photon emission tomography study in 28 patients. J Neurol 1998; 245(9):603–608.PubMedCrossRefGoogle Scholar
  50. 50.
    Gilman S, Junck L, Markel DS et al. Cerebral glucose hypermetabolism in Friedreich’s ataxia detected with positron emission tomography. Ann Neurol 1990; 28(6):750–757.PubMedCrossRefGoogle Scholar
  51. 51.
    Brighina F, Scalia S, Gennuso M et al. Hypo-excitability of cortical areas in patients affected by Friedreich ataxia: A TMS study. J Neurol Sci 2005; 235:19–22.PubMedCrossRefGoogle Scholar
  52. 52.
    DellaNave R, Ginestroni A, Tessa C et al. Brain white mattertracts degeneration in Friedreich ataxia. An in vivo MRI study usingtract-based spatial statistics and voxel-based morphometry Neurolmage 2008; 40(1): 19–35.Google Scholar
  53. 53.
    Akhlaghi H, Corben LA, Georgiou-Karistianis N et al. Superior cerebellar peduncle atrophy in Friedreich’s Ataxia correlates with disease symptoms. Cerebellum 2011; 10:81–87.PubMedCrossRefGoogle Scholar
  54. 54.
    Synofzik M, Godau J, Lindig T et al. Transcranial sonography reveals cerebellar, nigral and forebrain abnormalities in Friedreich’s ataxia. Neurodeg Dis 2011; 8(6):470–475.CrossRefGoogle Scholar
  55. 55.
    França AE, D’Abreu A, Yasuda CL et al. A combined voxel-based morphometry and 1H-MRS study in patients with Friedreich’s ataxia. J Neurol 2009; 256:1114–1120.PubMedCrossRefGoogle Scholar
  56. 56.
    Pagani E, Ginestroni A, Delia Nave R et al. Assessment of brain white matter fiber bundle atrophy in patients with Friedreich ataxia. Radiology 2010; 255(3):882–889.PubMedCrossRefGoogle Scholar
  57. 57.
    Koeppen AH, Michael SC, Knutson MD et al. The dentate nucleus in Friedreich’s ataxia: the role of nonresponsive proteins. Acta Neuropath 2007; 114:163–173.PubMedCrossRefGoogle Scholar
  58. 58.
    Koeppen AH, Davis AN, Morral JA. The cerebellar component of Friedreich’s ataxia. Acta Neuropath 2011; 122(3):323–330.PubMedCrossRefGoogle Scholar
  59. 59.
    Middleton FA, Strick PL. Basal ganglia and cerebellar loops: motor and cognitive circuits. Brain Res Rev 2000; 31:236–250.PubMedCrossRefGoogle Scholar
  60. 60.
    Bidichandani SI, Ashizawa T, Patel PI. The GAA triplet-repeat expansion in Friedreich ataxia interferes with transcription and may be associated with an unusual DNA structure. Am J Hum Gen 1998; 62(1): 111–121.CrossRefGoogle Scholar
  61. 61.
    De Michele G, Filla A, Criscuolo C et al. Determinants of onset age in Friedreich’s ataxia. J Neurol 1998; 245(3):166–168.PubMedCrossRefGoogle Scholar
  62. 62.
    Mateo I, Llorca J, Volpini V et al. Expanded GAA repeats and clinical variation in Friedreich’s ataxia. Acta Neurol Scand 2004; 109(1):75–78.PubMedCrossRefGoogle Scholar
  63. 63.
    Montermini L, Richter A, Morgan K et al. Phenotypic variability in Friedreich ataxia: role of the associated GAA triplet repeat expansion. Ann Neurol 1997; 41(5):675–682.PubMedCrossRefGoogle Scholar
  64. 64.
    Montermini L, Andermann E, Labuda M et al. The Friedreich ataxia GAA triplet repeat: premutation and normal alleles. Hum Mol Gen 1997; 6(8):1261–1266.PubMedCrossRefGoogle Scholar
  65. 65.
    La Pean A, Jeffries N, Grow C et al. Predictors of progression in patients with Friedreich ataxia. Mov Dis 2008; 23(14):2026–2032.Google Scholar
  66. 66.
    Maione S, Giunta A, Filla A et al. May age onset be relevant in the occurrence of left ventricular hypertrophy in Friedreich’s ataxia? Clin Cardiol 1997; 20(2):141–145.PubMedCrossRefGoogle Scholar
  67. 67.
    Montermini L, Kish SJ, Jiralerspong S et al. Somatic mosaicism for Friedreich’s ataxia GAA triplet repeat expansions in the central nervous system. Neurology 1997; 49(2):606–610.PubMedCrossRefGoogle Scholar
  68. 68.
    Sandi C, Pinto RM, Al-Mahdawi S et al. Prolongedtreatment with pimelic o-aminobenzamide HD AC inhibitors ameliorates the disease phenotype of a Friedreich ataxia mouse model. Neurobiol Dis 2011; 42:496–505.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Castaldo I, Pinelli M, Monticelli A et al. DNA methylation in intron 1 of the frataxin gene is related to GAA repeat length and age of onset in Friedreich ataxia patients. J Med Gen 2008; 45(12):808–812.CrossRefGoogle Scholar
  70. 70.
    Dürr A, Cossee M, Agid Y et al. Clinical and genetic abnormalities in patients with Friedreich’s ataxia. New Eng J Med 1996; 335(16): 1169–1175.PubMedCrossRefGoogle Scholar
  71. 71.
    Filla A, De Michele G, Coppola G et al. Accuracy of clinical diagnostic criteria for Friedreich’s ataxia. Mov Dis 2000; 15(6):1255–1258.CrossRefGoogle Scholar
  72. 72.
    Bidichandani SI, Garcia CA, Patel PI et al. Very late-onset Friedreich ataxia despite large GAA triplet repeat expansions. Arch Neurol 2000; 57(2):246–251.PubMedCrossRefGoogle Scholar
  73. 73.
    Bhidayasiri SP, P Stefan, D Geschwind. Late onset Friedreich Ataxia. Phenotypic analysis, magnetic resonance imaging findings and review of the literature. Arch Neurol 2005; 62:1865–1869.PubMedCrossRefGoogle Scholar
  74. 74.
    De Michele G, Filla A, Cavalcanti F et al. Late onset Friedreich’s disease: clinical features and mapping of mutation to the FRDA locus. J Neurol Neurosurg Psych 1994; 57(8):977–979.CrossRefGoogle Scholar
  75. 75.
    Palau F, De Michele G, Vilchez JJ et al. Early-onset ataxia with cardiomyopathy and ret alned tendon reflexes maps to the Friedreich’s ataxia locus on chromosome 9q. Ann Neurol 1995; 37(3):359–362.PubMedCrossRefGoogle Scholar
  76. 76.
    Barbeau A, Roy M, Sadibelouiz M et al. Recessive ataxia in Acadians and “Cajuns”. Can J Neurol Sci 1984; 11(4 Suppl):526–533.PubMedCrossRefGoogle Scholar
  77. 77.
    Richter A, Poirier J, Mercier J et al. Friedreich ataxia in Acadian families from eastern Canada: clinical diversity with conserved haplotypes. Am J Med Gen 1996; 64(4):594–601.CrossRefGoogle Scholar
  78. 78.
    Wollmann T, Barroso J, Monton F et al. Neuropsychological test performance of patients with Friedreich’s ataxia. J Clin Exp Neuropsych 2002; 24(5):677–686.CrossRefGoogle Scholar
  79. 79.
    Holmes G. The cerebellum of man (The Hughlings Jackson memorial lecture). Brain 1939; 62:1–30.CrossRefGoogle Scholar
  80. 80.
    Schmahmann JD. An emerging concept. The cerebellar contribution to higher function. Arch Neurol 1991; 48(11):1178–1187.PubMedCrossRefGoogle Scholar
  81. 81.
    Grafman J, Litvan I, Massaquoi S et al. Cognitive planning deficit in patients with cerebellar atrophy. Neurology 1992; 42(8): 1493–1496.PubMedCrossRefGoogle Scholar
  82. 82.
    Schmahmann JD, Sherman JC. The cerebellarcognitive affective syndrome. Brain 1998; 121(Pt 4):561–579.PubMedCrossRefGoogle Scholar
  83. 83.
    Botez-Marquard T, Bard C, Leveille J et al. A severe frontal-parietal lobe syndrome following cerebellar damage. Eur J Neurol 2001; 8(4):347–353.PubMedCrossRefGoogle Scholar
  84. 84.
    Thach WT. On the mechanism of cerebellar contributions to cognition. Cerebellum 2007;6:163–167.PubMedCrossRefGoogle Scholar
  85. 85.
    Baillieux H, De Smet HJ, Paquier PF et al. Cerebellar neurocognition: Insights into the bottom of the brain. Clin Neurol Neurosurg 2008; 110:763–773.PubMedCrossRefGoogle Scholar
  86. 86.
    Strick PL, Dum RP, Fiez JA. Cerebellum and nonmotor function. Ann Rev Neurosci 2009; 32:413–434.PubMedCrossRefGoogle Scholar
  87. 87.
    Timmann D, Drepper J, Frings M et al. The human cerebellum contributes to motor, emotional and cognitive associative learning. A review. Cortex 2010; 46(7):845–857.PubMedCrossRefGoogle Scholar
  88. 88.
    Dum RP, Strick PL. An unfolded map of the cerebellar dentate nucleus and its projections to the cerebral cortex. J Neurophysiol 2003; 89(1):634–639.PubMedCrossRefGoogle Scholar
  89. 89.
    Stoodley CJ, Schmahmann JD. Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex 2010; 46(7):831–844.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Flood MK, Perlman SL. The mental status of patients with Friedreich’s ataxia. J Neurosci Nurs 1987; 19(5):251–255.PubMedCrossRefGoogle Scholar
  91. 91.
    Giordani B, Boivan M, Berent S et al. Cognitive and emotional function in Friedreich’s Ataxia. J Clin Expl Neuropsychol 1989; 11:53–54.Google Scholar
  92. 92.
    Botez-Marquard T, Botez MI. Cognitive behavior in heredodegenerative ataxias. Eur Neurol 1993; 33(5):351–357.PubMedCrossRefGoogle Scholar
  93. 93.
    Botez-Marquard T, Botez MI. Olivopontocerebellar atrophy and Friedreich’s ataxia: neuropsychological consequences of bilateral versus unilateral cerebellar lesions. Int Rev Neurobiol 1997; 41:387–410.PubMedCrossRefGoogle Scholar
  94. 94.
    Hart RP, Henry GK, Kwentus JA et al. Information processing speed of children with Friedreich’s ataxia. Dev Med Child Neurol 1986; 28(3):310–313.PubMedCrossRefGoogle Scholar
  95. 95.
    Hart RP, Kwentus JA, Leshner RT et al. Information processing speed in Friedreich’s ataxia. Ann Neurol 1985; 17(6):612–614.PubMedCrossRefGoogle Scholar
  96. 96.
    White M, Lalonde R, Botez-Marquard T. Neuropsychologic and neuropsychiatric characteristics of patients with Friedreich’s ataxia. Acta Neurol Scand 2000; 102(4):222–226.PubMedCrossRefGoogle Scholar
  97. 97.
    Wollmann T, Nieto-Barco A, Monton-Alvarez F et al. Ataxia de Friedreich: analisis de parametres de resonancia magnetica y correlates con el enlentecimiento cognitivo y motor. Rev Neurol 2004; 38(3):217–222.PubMedGoogle Scholar
  98. 98.
    Corben LA, Georgiou-Karistianis N, Fahey MC et al. Towards an understanding of cognitive function in Friedreich Ataxia. Brain Res Bull 2006; 70:197–202.PubMedCrossRefGoogle Scholar
  99. 99.
    Manto M, Lorivel T. Cognitive repercussions of hereditary cerebellar disorders. Cortex 2011;47(1):81–100.PubMedCrossRefGoogle Scholar
  100. 100.
    Lynch DR, Farmer JM, Balcer LJ et al. Friedreich ataxia: effects of genetic understanding on clinical evaluation and therapy. Arch Neurol 2002; 59(5):743–747.PubMedCrossRefGoogle Scholar
  101. 101.
    Mantovan MC, Martinuzzi A, Squarzanti F et al. Exploring mental status in Friedreich’s ataxia: a combined neuropsychological, behavioural and neuroimaging study. Eur J Neurol 2006; 13:827–835.PubMedCrossRefGoogle Scholar
  102. 102.
    Lalonde R, Botez T, Botez MI. Methodologic considerations in neuropsychologic testing of ataxic patients. Arch Neurol 1992; 49(3):218–219.PubMedCrossRefGoogle Scholar
  103. 103.
    de Nóbrega E, Nieto A, Barrosso J et al. Differential impairment in semantic, phonemic and action fluency performance in Friedreich’s ataxia: Possible evidence of prefrontal dysfunction. J Int Neuropsych Soc 2007; 13:944–952.CrossRefGoogle Scholar
  104. 104.
    Ciancarelli I, Cofini V, Carolei A. Evaluation of neuropsychological functions in patients with Friedreich ataxia before and after cognitive therapy. Func Neurol 2010; 25(2):81–85.Google Scholar
  105. 105.
    Bürk K. Cognition in hereditary ataxia. Cerebellum 2007; 6:280–286.PubMedCrossRefGoogle Scholar
  106. 106.
    Corben LA, Delatycki MB, Bradshaw JL et al. Impairment in motor reprogramming in Friedreich ataxia reflecting possible cerebellar dysfunction. J Neurol 2010; 257(5):782–791.PubMedCrossRefGoogle Scholar
  107. 107.
    Corben LA, Akhlaghi H, Georgiou-Karistianis N et al. Impaired inhibition of prepotent motor tendencies in Friedreich ataxia demonstrated by the Simon interference task. Brain Cog 2011; 76(1): 140–145.CrossRefGoogle Scholar
  108. 108.
    Corben LA, Georgiou-Karistianis N, Bradshaw JL et al. The Fitts task reveals impairments in planning and online control of movement in Friedreich ataxia: reduced cerebellar-cortico connectivity? Neuroscience 2011; 192:382–390.PubMedCrossRefGoogle Scholar
  109. 109.
    Corben LA, Delatycki MB, Bradshaw JL et al. Utilisation of advance motor information is impaired in Friedreich ataxia. Cerebellum 2011: June 2. DOI 10.1007/s12311-011-0289-7.Google Scholar
  110. 110.
    Salthouse TA, Heddon T. Interpreting reaction time measures in between-group comparisons. J Clin Exp Neuropsychol 2002; 24(7):858–872.PubMedCrossRefGoogle Scholar
  111. 111.
    Fielding J, Corben L, Cremer P et al. Disruption to higher order processes in Friedreich ataxia. Neuropsychologia 2010; 48(1):235–42.PubMedCrossRefGoogle Scholar
  112. 112.
    Hocking DR, Fielding J, Corben L A et al. Ocular Motor Fixation Deficits in Friedreich Ataxia. Cerebellum 2010; 9:411–418.PubMedCrossRefGoogle Scholar
  113. 113.
    Liu X, Banich M, Jacobson B et al. Common and distinct neural substrates of attentional control in an integrated Simon and spatial Stroop task as assessed by event-related fMRI. Neuroimage 2004; 22(3):1097–1106.PubMedCrossRefGoogle Scholar
  114. 114.
    Klopper F, Delatycki M.B, Corben LA et al. The test of everyday attention reveals significant sustained volitional attention and working memory deficits in Friedreich Ataxia. J Int Neuropsy Soc 2011; 17:196–200.CrossRefGoogle Scholar
  115. 115.
    Timmann D, Drepper J, Maschke M et al. Motor deficits cannot explain impaired cognitive associative learning in cerebellar patients. Neuropsychologia 2002; 40(7):788–800.PubMedCrossRefGoogle Scholar
  116. 116.
    Koziel LF, Budding DE. The cerebellum: Quality control, creativity, intuition and unconscious working memory. Subcortical structures and cognition: Implicationforneuropsychological assessment. New York: Springer; 2009; pp.124–65.CrossRefGoogle Scholar
  117. 117.
    Ito M. Control ofmental activities by internal models in the cerebellum. Nat Rev Neurosci2008;9(4):304–313.PubMedCrossRefGoogle Scholar
  118. 118.
    Courchesne E, Allen G. Prediction and preparation, fundamental functions of the cerebellum. Learn Mem 1997; 4(1):1–35.PubMedCrossRefGoogle Scholar
  119. 119.
    Leggio MG, Chiricozzi FR, Clausi S et al. The neuropsychological profile of cerebellar damage: the sequencing hypothesis. Cortex 2011; 47(1):137–144.PubMedCrossRefGoogle Scholar
  120. 120.
    Ebner TJ, Pasalar S. Cerebellum predicts the future motor state. Cerebellum 2008; 7:583–588.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Thiruvady D, Georgiou-Karistianis N, Egan G et al. Functional connectivity of the prefrontal cortex in Huntington’s disease. JNeurol, Neurosurg, Psych 2007; 78(2):127–133.CrossRefGoogle Scholar
  122. 122.
    Medina FJ, Tunez I. Huntington’s disease: the value of transcranial meganetic stimulation. Curr Med Chem 2010; 17(23):2482–2491.PubMedCrossRefGoogle Scholar
  123. 123.
    Stagg CJ, O’Shea J, Johansen-Berg H. Imaging the effects of rTMS-induced cortical plasticity. Res Neurol Neurosci 2010; 28(4):425–436.Google Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  • Louise A. Corben
    • 1
    Email author
  • Nellie Georgiou-Karistianis
    • 2
  • John L. Bradshaw
    • 2
  • Marguerite V. Evans-Galea
    • 1
  • Andrew J. Churchyard
    • 3
  • Martin B. Delatycki
    • 1
    • 4
    • 5
  1. 1.Bruce Lefroy Centre for Genetic Health ResearchMurdoch Childrens Research Institute, The Royal Children’s HospitalParkvilleAustralia
  2. 2.Experimental Neuropsychology Research Unit, School of Psychology and PsychiatryMonash UniversityClaytonAustralia
  3. 3.Monash NeurologyMonash Medical CentreClaytonAustralia
  4. 4.Department of Clinical GeneticsAustin HealthHeidelbergAustralia
  5. 5.Department of MedicineUniversity of Melbourne at Austin HealthHeidelbergAustralia

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