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.
Similar content being viewed by others
References
Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psych 4:561–571
Botez-Marquard T, Botez MI (1993) Cognitive behavior in heredodegenerative ataxias. Eur Neurol 33:351–357
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
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
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
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
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
Courchesne E, Allen G (1997) Prediction and preparation, fundamental functions of the cerebellum. Learn Mem 4:1–35
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
Delatycki MB, Williamson R, Forrest SM (2000) Friedreich ataxia: an overview. J Med Genet 37:1–8
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
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
Drepper J, Timmann D, Kolb FP, Diener HC (1999) Non-motor associative learning in patients with isolated degenerative cerebellar disease. Brain 122:87–97
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
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
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
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
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
Golden CJ (2002) Stroop color and word test. A manual for clinical and experimental uses. Stoelting, Illinois
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
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
Hart RP, Kwentus JA, Leshner RT, Frazier R (1985) Information processing speed in Friedreich’s ataxia. Ann Neurol 17:612–614
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
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
Ito M (1993) Movement and thought: identical control mechanisms by the cerebellum. Trends Neurosci 16:448–450
Ito M (2005) Bases and implications of learning in the cerebellum—adaptive control and internal model mechanism. Prog Brain Res 148:95–109
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
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
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
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
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
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
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
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
Pandolfo M (2003) Friedreich ataxia. Sem Ped Neurol 10:163–172
Pandolfo M (2008) Friedreich ataxia. Arch Neurol 65:1296–1303
Ramani N (2006) The primate cortico-cerebellar system: anatomy and function. Nat Rev Neurosci 7:511–522
Reitan MN (1955) The relation of the trail making test to organic brain damage. J Consult Psychol 19:393–394
Riva D, Giorgi C (2000) The cerebellum contributes to higher functions during development. Brain 123:1051–1061
Rosenbaum DA (1980) Human movement initiation: specification of arm, direction, and extent. J Exp Psychol 109:444–474
Schmahmann JD (1991) An emerging concept. The cerebellar contribution to higher function. Arch Neurol 48:1178–1187
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
Schmahmann JD, Pandya DN (1997) The cerebrocerebellar system. Int Rev Neurobiol 41:31–60
Schmahmann JD, Sherman JC (1998) The cerebellar cognitive affective syndrome. Brain 121:561–579
Schmahmann JD (2004) Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. J Neuropsych Clin Neurosci 16:367–378
Schweizer TA, Oriet C, Meiran N, Alexander MP, Cusimano M, Struss DT (2007) The cerebellum mediates conflict resolution. J Cogn Neurosci 19:1974–1982
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
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
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
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
Tipper SP, Lortie C, Baylis GC (1992) Selective reaching: evidence for action-centered attention. J Exp Psychol Hum Percept Perform 18:891–905
Voncken M, Ioannou P, Delatycki MB (2004) Friedreich ataxia-update on pathogenesis and possible therapies. Neurogenetics 5:1–8
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
White M, Lalonde R, Botez-Marquard T (2000) Neuropsychologic and neuropsychiatric characteristics of patients with Friedreich’s ataxia. Acta Neurol Scand 102:222–226
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
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
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.
Conflict of interest statement
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-009-5410-1