Hostname: page-component-586b7cd67f-g8jcs Total loading time: 0 Render date: 2024-12-01T10:04:24.699Z Has data issue: false hasContentIssue false

The Role of the Cerebellum in the Pathophysiology of Parkinson's Disease

Published online by Cambridge University Press:  23 September 2014

Mechelle M. Lewis
Affiliation:
Department of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey PA, USA Department of Pharmacology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey PA, USA
Shawna Galley
Affiliation:
Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada
Samantha Johnson
Affiliation:
Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada
James Stevenson
Affiliation:
Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada
Xuemei Huang
Affiliation:
Department of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey PA, USA Department of Pharmacology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey PA, USA Department of Radiology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey PA, USA Department of Neurosurgery, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey PA, USA Department of Kinesiology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey PA, USA Department of Bioengineering, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey PA, USA
Martin J. McKeown*
Affiliation:
Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada Department of Medicine (Neurology), University of British Columbia, Vancouver, British Columbia, Canada Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada Department of Electrical and Computer Engineering, University of British Columbia, Vancouver, British Columbia, Canada
*
Neurology, Pacific Parkinson's Research Centre, Brain Research Centre, University of British Columbia, M31, Purdy Pavillion, Vancouver, British Columbia, V6T 2B5, Canada. Email: [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Parkinson's disease (PD), the most common neurodegenerative movement disorder, has traditionally been considered a “classic” basal ganglia disease, as the most obvious pathology is seen in the dopaminergic cells in the substantia nigra pars compacta. Nevertheless recent discoveries in anatomical connections linking the basal ganglia and the cerebellum have led to a re-examination of the role of the cerebellum in the pathophysiology of PD. This review summarizes the role of the cerebellum in explaining many curious features of PD: the significant variation in disease progression between individuals; why severity of dopaminergic deficit correlates with many features of PD such as bradykinesia, but not tremor; and why PD subjects with a tremor-predominant presentation tend to have a more benign prognosis. It is clear that the cerebellum participates in compensatory mechanisms associated with the disease and must be considered an essential contributor to the overall pathophysiology of PD.

Résumé:

Résumé:

La Maladie de Parkinson (MP), le trouble du mouvement de nature neurodégénérative le plus fréquent, a traditionnellement été considérée comme une maladie « classique » des noyaux gris centraux, étant donné que la pathologie la plus évidente se retrouve dans les cellules dopaminergiques de la substance noire de la pars compacta. Néanmoins, des découvertes récentes concernant les connections anatomiques liant les noyaux gris centraux et le cervelet ont mené à un nouvel examen du rôle du cervelet dans la physiopathologie de la MP. Cette revue explique de façon résumée plusieurs aspects singuliers de la MP dans lesquels le cervelet joue un rôle : la variation importante dans la progression de la maladie entre les patients ; pourquoi la sévérité du déficit dopaminergique est en corrélation avec plusieurs manifestations de la MP telle la bradykinésie, mais non avec le tremblement ; et pourquoi les patients chez qui le tremblement prédomine ont tendance à avoir un meilleur pronostic. il est certain que le cervelet participe à des mécanismes compensatoires associés à la maladie et sa contribution doit être considérée comme essentielle à la physiopathologie globale de la MP.

Type
Review Article
Copyright
Copyright © The Canadian Journal of Neurological 2013

References

1. Jankovic, J, McDermott, M, Carter, J, et al. Variable expression of Parkinson's disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group. Neurology. 1990;40: 1529–34.Google Scholar
2. Hoehn, MM, Yahr, MD. Parkinsonism - onset progression and mortality. Neurology. 1967;17(5):427–42.Google Scholar
3. Guillard, A, Chastang, C. Long-term prognostic factors in Parkinson's disease. Rev Neurol. 1978;134(5):341–54.Google Scholar
4. Guillard, A, Chastang, C, Fenelon, G. Long-term study of 416 cases of Parkinson disease. Prognostic factors and therapeutic implications. Rev Neurol. 1986;142(3):207–14.Google ScholarPubMed
5. Goetz, CG, Tanner, CM, Stebbins, GT, Buchman, AS. Risk factors for progression in Parkinson's disease. Neurology. 1988;38(12): 1841–4.Google Scholar
6. Jankovic, J, Kapadia, AS. Functional decline in Parkinson disease. Arch Neurol. 2001;58(10):1611–15.CrossRefGoogle ScholarPubMed
7. Marras, C, Rochon, P, Lang, AE. Predicting motor decline and disability in Parkinson disease: a systematic review. Arch Neurol. 2002;59(11):1724–8.Google Scholar
8. Koller, WC, Hubble, JP. Levodopa therapy in Parkinson's disease. Neurology. 1990;40(Suppl 3):40–7.Google Scholar
9. Marjama-Lyons, J, Koller, W. Tremor-predominant Parkinson's disease. Approaches to treatment. Drugs Aging. 2000;16(4): 273–8.CrossRefGoogle ScholarPubMed
10. Vingerhoets, FJ, Schulzer, M, Calne, DB, Snow, BJ. Which clinical sign of Parkinson's disease best reflects the nigrostriatal lesion? Ann Neurol. 1997;41(1):5864.Google Scholar
11. Afifi, AK, Bergman, RA. Functional Neuroanatomy: text and atlas. New York: McGraw-Hill; 1998.Google Scholar
12. Alexander, GE, DeLong, MR, Strick, PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci. 1986;9(1):357–81.Google Scholar
13. Middleton, FA, Strick, PL. Basal ganglia and cerebellar loops: motor and cognitive circuits. Brain Res Rev. 2000;31:236–50.Google Scholar
14. Jueptner, M, Weiller, C. A review of differences between basal ganglia and cerebellar control of movements as revealed by functional imaging studies. Brain. 1998;121(Pt 8):1437–49.CrossRefGoogle ScholarPubMed
15. Bar-Gad, I, Bergman, H. Stepping out of the box: information processing in the neural networks of the basal ganglia. Curr Opin Neurobiol. 2001;11(6):689–95.Google Scholar
16. Mushiake, H, Strick, PL. Pallidal neuron activity during sequential arm movements. J Neurophysiol. 1995;74(6):2754–8.Google Scholar
17. van Donkelaar, P, Stein, JF, Passingham, RE, Miall, RC. Neuronal activity in the primate motor thalamus during visually triggered and internally generated limb movements. J Cereb Blood Flow Metab. 1999;16:2333.Google Scholar
18. van Donkelaar, P, Stein, JF, Passingham, RE, Miall, RC. Temporary inactivation in the primate motor thalamus during visually triggered and internally generated limb movements. J Neurophysiol. 2000;83(5):2780–90.CrossRefGoogle ScholarPubMed
19. Blakemore, SJ, Frith, CD, Wolpert, DM. The cerebellum is involved in predicting the sensory consequences of action. Neuroreport. 2001;12(9):1879–84.Google Scholar
20. Miall, RC, Jenkinson, EW. Functional imaging of changes in cerebellar activity related to learning during a novel eye-hand tracking task. Exp Brain Res. 2005;166(2):170–83.Google Scholar
21. Jueptner, J, Jueptner, M, Jenkins, IH, Brooks, DJ, Frackowiak, RSJ, Passingham, RE. The sensory guidance of movement: a comparison of the cerebellum and basal ganglia. Exp Brain Res. 1996;112(3):462–74.CrossRefGoogle ScholarPubMed
22. Cerasa, A, Hagberg, GE, Peppe, A, et al. Functional changes in the activity of cerebellum and frontostriatal regions during externally and internally timed movement in Parkinson's disease. Brain Res Bull. 2006 Dec;71(1-3):259–69.CrossRefGoogle ScholarPubMed
23. Gowen, E, Miall, R. Differentiation between external and internal cuing: An fMRI study comparing tracing with drawing. Neuroimage. 2007;36(2):396410.CrossRefGoogle ScholarPubMed
24. Purzner, J, Paradiso, GO, Cunic, D, et al. Involvement of the basal ganglia and cerebellar motor pathways in the preparation of self-initiated and externally triggered movements in humans. J Neurosci. 2007;27(22):6029.Google Scholar
25. MacMillan, ML, Dostrovsky, JO, Lozano, AM, Hutchison, WD. Involvement of human thalamic neurons in internally and externally generated movements. Am Physiol Soc; 2004. p. 1085-90.CrossRefGoogle Scholar
26. Vaillancourt, DE, Thulborn, KR, Corcos, DM. Neural basis for the processes that underlie visually guided and internally guided force control in humans. J Neurophsyiol. 2003;90(5):3330–40.CrossRefGoogle ScholarPubMed
27. Borghammer, P, Østergaard, K, Cumming, P, et al. A deformation-based morphometry study of patients with early-stage Parkinson's disease. Eur J Neurol. 2010;17(2):314–20.Google Scholar
28. Linder, J, Birgander, R, Olsson, I, et al. Degenerative changes were common in brain magnetic resonance imaging in patients with newly diagnosed Parkinson's disease in a population-based cohort. J Neurol. 2009;256(10):1671–80.Google Scholar
29. Messina, D, Cerasa, A, Condino, F, et al. Patterns of brain atrophy in Parkinson's disease, progressive supranuclear palsy and multiple system atrophy. Parkinsonism Relat Disord. 2011;17(3):172–6.Google Scholar
30. Molnar, GF, Pilliar, A, Lozano, AM, Dostrovsky, JO. Differences in neuronal firing rates in pallidal and cerebellar receiving areas of thalamus in patients with Parkinson's disease, essential tremor, and pain. J Neurophysiol. 2005;93(6):3094–101.Google Scholar
31. Narabayashi, H, Maeda, T, Yokochi, F. Long-term follow-up study of nucleus ventralis intermedius and ventrolateralis thalamotomy using a microelectrode technique in parkinsonism. App Neurophysiol. 1987;50(1-6):330–7.Google Scholar
32. Jellinger, KA. Pathology of Parkinson's disease. Mol Chem Neuropathol. 1991;14(3):153–97.Google Scholar
33. Devi, L, Raghavendran, V, Prabhu, BM, Avadhani, NG, Anawdatheerthavarada, HK. Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain. J Biol Chem. 2008 Apr 4;283(14):9089–100.Google Scholar
34. Engelender, S, Kaminsky, Z, Guo, X, et al. Synphilin-1 associates with alpha-synuclein and promotes the formation of cytosolic inclusions. Nat Genet. 1999;22(1):110–14.Google Scholar
35. Nuber, S, Franck, T, Wolburg, H, et al. Transgenic overexpression of the alpha-synuclein interacting protein synphilin-1 leads to behavioral and neuropathological alterations in mice. Neurogenetics. 2010;11(1):107–20.CrossRefGoogle ScholarPubMed
36. Louis, ED, Yi, H, Erickson-Davis, C, Vonsattel, JPG, Faust, PL. Structural study of Purkinje cell axonal torpedoes in essential tremor. Neurosci Lett. 2009;450(3):287–91.CrossRefGoogle ScholarPubMed
37. Bostan, AC, Dum, RP, Strick, PL. The basal ganglia communicate with the cerebellum. P Natl Acad Sci USA. 2010;107(18): 8452–6.Google Scholar
38. Hoshi, E, Tremblay, L, Feger, J, Carras, PL, Strick, PL. The cerebellum communicates with the basal ganglia. Nat Neurosci. 2005;8:1491–3.Google Scholar
39. Lewis, MM, Du, G, Sen, S, et al. Differential involvement of striato-and cerebello-thalamo-cortical pathways in tremor-and akinetic/rigid-predominant Parkinson's disease. Neurosci. 2011 Mar 17;177:230–9.Google Scholar
40. Bostan, AC, Strick, PL. The cerebellum and basal ganglia are interconnected. Neuropsychol Rev. 2010;20(3):261–70.Google Scholar
41. Hurley, MJ, Mash, DC, Jenner, P. Markers for dopaminergic neurotransmission in the cerebellum in normal individuals and patients with Parkinson's disease examined by RT-PCR. Eur J Neurosci.18(9):2668–72.Google Scholar
42. Courtemanche, R, Pellerin, J-P, Lamarre, Y. Local field potential oscillations in primate cerebellar cortex: modulation during active and passive expectancy. J Neurophysiol. 2002;88(2): 771–82.Google Scholar
43. Courtemanche, R, Lamarre, Y. Local field potential oscillations in primate cerebellar cortex: synchronization with cerebral cortex during active and passive expectancy. J Neurophysiol. 2005;93 (4):2039–52.Google Scholar
44. Courtemanche, R, Fujii, N, Graybiel, AM. Synchronous, focally modulated beta-band oscillations characterize local field potential activity in the striatum of awake behaving monkeys. J Neurosci. 2003 Dec 17;23(37):1174152.CrossRefGoogle ScholarPubMed
45. Brown, P, Oliviero, A, Mazzone, P, Insola, A, Tonali, P, Di Lazzaro, V. Dopamine dependency of oscillations between subthalamic nucleus and pallidum in Parkinson's disease. J Neurosci. 2001; 21(3):1033.Google Scholar
46. Raz, A, Frechter-Mazar, V, Feingold, A, Abeles, M, Vaadia, E, Bergman, H. Activity of pallidal and striatal tonically active neurons is correlated in MPTP-treated monkeys but not in normal monkeys. J Neurosci. 2001;21(3):RC128.Google Scholar
47. Williams, D, Tijssen, M, Van Bruggen, G, et al. Dopamine-dependent changes in the functional connectivity between basal ganglia and cerebral cortex in humans. Brain. 2002 Jul;125(Pt 7):1558–69.Google Scholar
48. Schnitzler, A, Gross, J. Normal and pathological oscillatory communication in the brain. Nat Rev Neurosci. 2005;6:113.CrossRefGoogle ScholarPubMed
49. Poirier, LJ, Pechadre, JC, Larochelle, L, Dankova, J, Boucher, R. Stereotaxic lesions and movement disorders in monkeys. Adv Neurol. 1975;10:522.Google ScholarPubMed
50. Burns, RS, Chiueh, CC, Markey, SP, Ebert, MH, Jacobowitz, DM, Kopin, IJ. A primate model of Parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine. P Natl Acad Sci USA. 1983;80(14):4546–50.Google Scholar
51. Ni, Z, Pinto, AD, Lang, AE, Chen, R. Involvement of the cerebellothalamocortical pathway in Parkinson disease. Ann Neurol. 2010;68(6):816–24.Google Scholar
52. Cohen, O, Pullman, S, Jurewicz, E, Watner, D, Louis, ED. Rest tremor in patients with essential tremor: prevalence, clinical correlates, and electrophysiologic characteristics. Arch Neurol. 2003;60 (3):405.Google Scholar
53. Minen, MT, Louis, ED. Emergence of Parkinson's disease in essential tremor: a study of the clinical correlates in 53 patients. Mov Dis. 2008;23(11):1602–5.Google Scholar
54. Pechadre, JC, Larochelle, L, Poirier, LJ. Parkinsonian akinesia, rigidity and tremor in the monkey. Histopathological and neuropharmacological study. J Neurol Sci. 1976;28(2):147–57.CrossRefGoogle ScholarPubMed
55. Marsden, CD, Obeso, JA. The functions of the basal ganglia and the paradox of stereotaxic surgery in Parkinson's disease. Brain. 1994;117:877–97.Google Scholar
56. Hua, S, Reich, SG, Zirh, AT, Perry, V, Dougherty, PM, Lenz, FA. The role of the thalamus and basal ganglia in parkinsonian tremor. Mov Dis. 1998;13 Suppl 3:40–2.CrossRefGoogle ScholarPubMed
57. Lenz, FA, Kwan, HC, Martin, RL, Tasker, RR, Dostrovsky, JO, Lenz, YE. Single unit analysis of the human ventral thalamic nuclear group. Tremor-related activity in functionally identified cells. Brain. 1994;117(Pt 3):531–43.CrossRefGoogle ScholarPubMed
58. Inase, M, Tanji, J. Thalamic distribution of projection neurons to the primary motor cortex relative to afferent terminal fields from the globus pallidus in the macaque monkey. J Comp Neurol. 1995; 353(3):415–26.Google Scholar
59. Benabid, AL, Pollak, P, Gervason, C, et al. Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet. 1991;337(8738):403–6.Google Scholar
60. Caparros-Lefebvre, D, Blond, S, Vermersch, P, Pecheux, N, Guieu, JD, Petit, H. Chronic thalamic stimulation improves tremor and levodopa induced dyskinesias in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1993;56(3):268–73.CrossRefGoogle ScholarPubMed
61. Koller, W, Pahwa, R, Busenbark, K, et al. High-frequency unilateral thalamic stimulation in the treatment of essential and parkinsonian tremor. Ann Neurol. 1997;42(3):292–9.Google Scholar
62. Limousin-Dowsey, P, Pollak, P, Van Blercom, N, Krack, P, Benazzouz, A, Benabid, A. Thalamic, subthalamic nucleus and internal pallidum stimulation in Parkinson's disease. J Neurol. 1999;246 Suppl 2:II425.Google Scholar
63. Lenz, FA, Normand, SL, Kwan, HC, et al. Statistical prediction of the optimal site for thalamotomy in parkinsonian tremor. Mov Dis. 1995;10(3):318–28.Google Scholar
64. Jankovic, J, Cardoso, F, Grossman, RG, Hamilton, WJ. Outcome after stereotactic thalamotomy for parkinsonian, essential, and other types of tremor. Neurosurgery. 1995;37(4):680–7.Google Scholar
65. Mure, H, Hirano, S, Tang, CC, et al. Parkinson's disease tremorrelated metabolic network: characterization, progression, and treatment effects. Neuroimage. 2011;54(2):1244–53.Google Scholar
66. Duffau, H, Tzourio, N, Caparros-Lefebvre, D, Parker, F, Mazoyer, B. Tremor and voluntary repetitive movement in Parkinson's disease: comparison before and after L-dopa with positron emission tomography. Exp Brain Res. 1996;107(3):453–62.Google Scholar
67. Antonini, A, Moeller, JR, Nakamura, T, Spetsieris, P, Dhawan, V, Eidelberg, D. The metabolic anatomy of tremor in Parkinson's disease. Neurology. 1998;51(3):803–10.CrossRefGoogle ScholarPubMed
68. Deiber, MP, Pollak, P, Passingham, R, et al. Thalamic stimulation and suppression of parkinsonian tremor. Evidence of a cerebellar deactivation using positron emission tomography. Brain. 1993; 116(Pt 1):267–79.CrossRefGoogle ScholarPubMed
69. Fukuda, M, Barnes, A, Simon, ES, et al. Thalamic stimulation for parkinsonian tremor: correlation between regional cerebral blood flow and physiological tremor characteristics. Neuroimage. 2004 Feb;21(2):608–15.Google Scholar
70. Benninger, DH, Thees, S, Kollias, SS, Bassetti, CL, Waldvogel, D. Morphological differences in Parkinson's disease with and without rest tremor. J Neurol. 2009;256(2):256–63.Google Scholar
71. Timmermann, L, Gross, J, Dirks, M, Volkmann, J, Freund, HJ, Schnitzler, A. The cerebral oscillatory network of parkinsonian resting tremor. Brain. 2003;126(Pt 1):199212.Google Scholar
72. Caraceni, T, Scigliano, G, Musicco, M. The occurrence of motor fluctuations in parkinsonian patients treated long term with levodopa. Role of early treatment and disease progression. Neurology. 1991 Mar;41(3):380–4.Google Scholar
73. Mayeux, R, Stern, Y, Rosen, J, Frank Benson D. Is “subcortical dementia” a recognizable clinical entity? Ann Neurol. 1983;14 (3):278–83.Google Scholar
74. Fearnley, JM, Lees, AJ. Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain. 1991;114(Pt 5):2283–301.CrossRefGoogle ScholarPubMed
75. Lee, CS, Samii, A, Sossi, V, et al. In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson's disease. Ann Neurol. 2000;47:493503.Google Scholar
76. Morrish, PK, Sawle, GV, Brooks, DJ. An [18F]dopa-PET and clinical study of the rate of progression in Parkinson's disease. Brain. 1996;119(Pt 2):585–91.CrossRefGoogle ScholarPubMed
77. Zigmond, MJ, Abercrombie, ED, Berger, TW, Grace, AA, Stricker, EM. Compensations after lesions of central dopaminergic neurons: some clinical and basic implications. Trends Neurosci. 1990;13(7):290–6.CrossRefGoogle ScholarPubMed
78. Bezard, E, Crossman, AR, Gross, CE, Brotchie, JM. Structures outside the basal ganglia may compensate for dopamine loss in the presymptomatic stages of Parkinson's disease. FASEB J. 2001;15(6):1092–4.Google Scholar
79. Chuma, T, Faruque Reza, M, Ikoma, K, Mano, Y. Motor learning of hands with auditory cue in patients with Parkinson's disease. J Neural Transm. 2006;113(2):175–85.Google Scholar
80. Jahanshahi, M, Jenkins, I, Brown, R, Marsden, C, Passingham, R, Brooks, D. Self-initiated versus externally triggered movements: I. An investigation using measurement of regional cerebral blood flow with PET and movement-related potentials in normal and Parkinson's disease subjects. Brain. 1995;118(4):913.Google Scholar
81. Georgiou, N, Iansek, R, Bradshaw, JL, Phillips, JG, Mattingley, JB, Bradshaw, JA. An evaluation of the role of internal cues in the pathogenesis of parkinsonian hypokinesia. Brain. 1993;116(Pt 6):1575–87.Google Scholar
82. Lewis, GN, Byblow, WD, Walt, SE. Stride length regulation in Parkinson's disease: the use of extrinsic, visual cues. Brain. 2000;123(Pt 10):2077–90.Google Scholar
83. Oliveira, RM, Gurd, JM, Nixon, P, Marshall, JC, Passingham, RE. Micrographia in Parkinson's disease: the effect of providing external cues. J Neurol Neurosurg Psychiatry. 1997 oct;63(4): 429–33.Google Scholar
84. Glickstein, M, Stein, J. Paradoxical movement in Parkinson's disease. Trends Neurosci. 1991;14(11):480–2.Google Scholar
85. Suzuki, DA, Keller, EL. Visual signals in the dorsolateral pontine nucleus of the alert monkey: their relationship to smooth-pursuit eye movements. Exp Brain Res. 1984;53(2):473–8.Google Scholar
86. Ballanger, B, Baraduc, P, Broussolle, E, Le Bars, D, Desmurget, M, Thobois, S. Motor urgency is mediated by the contralateral cerebellum in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2008 oct;79(10):1110–16.Google Scholar
87. Lewis, M, Slagle, C, Smith, A, et al. Task specific influences of Parkinson's disease on the striato-thalamo-cortical and cerebello-thalamo-cortical motor circuitries. Neurosci. 2007;147 (1):224–35.Google Scholar
88. Sen, S, Kawaguchi, A, Truong, Y, Lewis, MM, Huang, X. Dynamic changes in cerebello-thalamo-cortical motor circuitry during progression of Parkinson's disease. Neurosci. 2010;166(2): 712–19.Google Scholar
89. Yu, H, Sternad, D, Corcos, DM, Vaillancourt, DE. Role of hyperactive cerebellum and motor cortex in Parkinson's disease. Neuroimage. 2007 Mar;35(1):222–33.Google Scholar
90. Palmer, S, Ng, B, Abugharbieh, R, Eigenraam, L, McKeown, MJ. Motor reserve and novel area recruitment: amplitude and spatial characteristics of compensation in Parkinson's disease. Eur J Neurosci. 2009;29:2187–96.Google Scholar
91. Stern, Y. Cognitive reserve. Neuropsychologia. 2009 Aug;47(10): 2015–28.Google Scholar
92. Friston, KJ. Commentary and opinion: II. Statistical parametric mapping: ontology and current issues. J Cereb Blood Flow Metab. 1995;15(3):361–70.Google Scholar
93. Palmer, SJ. Compensatory Mechanisms in Parkinson's Disease. PhD thesis: Vancouver: University of British Columbia; 2010.Google Scholar
94. Kwak, Y, Peltier, S, Bohnen, NI, Muller, ML, Dayalu, P, Seidler, RD. Altered resting state cortico-striatal connectivity in mild to moderate stage Parkinson's disease. Front Syst Neurosci. 2010 Sep 15;4:143.Google Scholar
95. Palmer, SJ, Li, J, Wang, ZJ, McKeown, MJ. Joint amplitude and connectivity compensatory mechanisms in Parkinson's disease. Neurosci. 2010;166(4):1110–18.Google Scholar
96. Stevenson, J, Oishi, MMK, Farajian, S, Cretu, E, Ty, E, McKeown, MJ. Response to sensory uncertainty in Parkinson's disease: a marker of cerebellar dysfunction? Eur J Neurosci. 2010;33(2):298305.Google Scholar
97. Baddeley, RJ, Ingram, HA, Miall, RC. System identification applied to a visuomotor task: near-optimal human performance in a noisy changing task. J Neurosci. 2003;23(7):3066.Google Scholar
98. Kording, KP, Wolpert, DM. Bayesian integration in sensorimotor learning. Nature. 2004;427(6971):244–7.CrossRefGoogle ScholarPubMed
99. Vaziri, S, Diedrichsen, J, Shadmehr, R. Why does the brain predict sensory consequences of oculomotor commands? Optimal integration of the predicted and the actual sensory feedback. J Neurosci. 2006;26(16):4188–97.Google Scholar
100. Wei, K, Stevenson, IH, Kording, KP. The uncertainty associated with visual flow fields and their influence on postural sway: Weber's law suffices to explain the nonlinearity of vection. J Vis. 2010;10 (14):4.Google Scholar
101. Wolpert, DM, Ghahramani, Z. Computational principles of movement neuroscience. Nat Neurosci. 2000 Nov;3 Suppl: 1212–17.Google Scholar
102. van Beers, RJ, Baraduc, P, Wolpert, DM. Role of uncertainty in sensorimotor control. Philos T Roy Soc B. 2002;357(1424): 1137–45.Google Scholar