Traditionally, the pathophysiology of cervical dystonia has been regarded mainly in relation to neurochemical abnormities in the basal ganglia. Recently, however, substantial evidence has emerged for cerebellar involvement. While the absence of neurological "cerebellar signs" in most dystonia patients may be considered at least provoking, there are more subtle indications of cerebellar dysfunction in complex, demanding tasks. Specifically, given the role of the cerebellum in the neural representation of time, in the millisecond range, dysfunction to this structure is considered to be of greater importance than dysfunction of the basal ganglia. In the current study, we investigated the performance of cervical dystonia patients on a computer task known to engage the cerebellum, namely, the interception of a moving target with changing parameters (speed, acceleration, and angle) with a simple response (pushing a button). The cervical dystonia patients achieved significantly worse results than a sample of healthy controls. Our results suggest that the cervical dystonia patients are impaired at integrating incoming visual information with motor responses during the prediction of upcoming actions, an impairment we interpret as evidence of cerebellar dysfunction.

Central European Institute of Technology CEITEC MU Behavioral and Social Neuroscience Research Group Masaryk University 625 00 Brno Czech Republic ; 1st Department of Neurology Faculty of Medicine Masaryk University and St Anne's Teaching Hospital 656 91 Brno Czech Republic

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Fahn S, Bressman SB, Marsden CD. Classification of dystonia. Advances in Neurology. 1998;78:1–10. PubMed

Albanese A, Bhatia K, Bressman SB, et al. Phenomenology and classification of dystonia: a consensus update. Movement Disorders. 2013;28(7):863–873. PubMed PMC

Oppenheim H. Uber eine eigenartige kramotkrankheit des kindlichen und jugendlichen alters (dysbasia lordotica progressiva, dystonia musculorum deformans) Neurologie Centralblatt. 1911;30:1090–1107.

Vitek JL. Pathophysiology of dystonia: a neuronal model. Movement Disorders. 2002;17(3):S49–S62. PubMed

DeLong MR, Wichmann T. Circuits and circuit disorders of the basal ganglia. Archives of Neurology. 2007;64(1):20–24. PubMed

Fletcher NA, Stell R, Harding AE, Marsden CD. Degenerative cerebellar ataxia and focal dystonia. Movement Disorders. 1988;3(4):336–342. PubMed

Vidailhet M, Grabli D, Roze E. Pathophysiology of dystonia. Current Opinion in Neurology. 2009;22(4):406–413. PubMed

Sadnicka A, Hoffland BS, Bhatia KP, van de Warrenburg BP, Edwards MJ. The cerebellum in dystonia—help or hindrance? Clinical Neurophysiology. 2012;123(1):65–70. PubMed

Filip P, Lungu OV, Bareš M. Dystonia and the cerebellum: a new field of interest in movement disorders? Clinical Neurophysiology. 2013;124(7):1269–1276. PubMed

Liepert J, Kucinski T, Tüscher O, Pawlas F, Bäumer T, Weiller C. Motor cortex excitability after cerebellar infarction. Stroke. 2004;35(11):2484–2488. PubMed

Obermann M, Vollrath C, de Greiff A, et al. Sensory disinhibition on passive movement in cervical dystonia. Movement Disorders. 2010;25(15):2627–2633. PubMed

Draganski B, Thun-Hohenstein C, Bogdahn U, Winkler J, May A. ‘Motor circuit’ gray matter changes in idiopathic cervical dystonia. Neurology. 2003;61(9):1228–1231. PubMed

Kadota H, Nakajima Y, Miyazaki M, et al. An fMRI study of musicians with focal dystonia during tapping tasks. Journal of Neurology. 2010;257(7):1092–1098. PubMed

Hu X-Y, Wang L, Liu H, Zhang S-Z. Functional magnetic resonance imaging study of writer’s cramp. Chinese Medical Journal. 2006;119(15):1263–1271. PubMed

Baker RS, Andersen AH, Morecraft RJ, Smith CD. A functional magnetic resonance imaging study in patients with benign essential blepharospasm. Journal of Neuro-Ophthalmology. 2003;23(1):11–15. PubMed

Niethammer M, Carbon M, Argyelan M, Eidelberg D. Hereditary dystonia as a neurodevelopmental circuit disorder: evidence from neuroimaging. Neurobiology of Disease. 2011;42(2):202–209. PubMed PMC

Alvarez-Fischer D, Grundmann M, Lu L, et al. Prolonged generalized dystonia after chronic cerebellar application of kainic acid. Brain Research. 2012;1464:82–88. PubMed

LeDoux MS, Brand KA. Secondary cervical dystonia associated with structural lesions of the central nervous system. Movement Disorders. 2003;18(1):60–69. PubMed

Perlov E, Tebarzt van Elst L, Buechert M, et al. H1-MR-spectroscopy of cerebellum in adult attention deficit/hyperactivity disorder. Journal of Psychiatric Research. 2010;44(14):938–943. PubMed

Bledsoe JC, Semrud-Clikeman M, Pliszka SR. Neuroanatomical and neuropsychological correlates of the cerebellum in children with attention-deficit/hyperactivity disorder-combined type. Journal of the American Academy of Child and Adolescent Psychiatry. 2011;50(6):593–601. PubMed PMC

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. PubMed

Bauer DJ, Kerr AL, Swain RA. Cerebellar dentate nuclei lesions reduce motivation in appetitive operant conditioning and open field exploration. Neurobiology of Learning and Memory. 2011;95(2):166–175. PubMed

Bares M, Lungu O, Liu T, Waechter T, Gomez CM, Ashe J. Impaired predictive motor timing in patients with cerebellar disorders. Experimental Brain Research. 2007;180(2):355–365. PubMed

Bares M, Lungu OV, Liu T, Waechter T, Gomez CM, Ashe J. The neural substrate of predictive motor timing in spinocerebellar ataxia. The Cerebellum. 2011;10(2):233–244. PubMed

Bareš M, Lungu OV, Husárová I, Gescheidt T. Predictive motor timing performance dissociates between early diseases of the cerebellum and parkinson’s disease. Cerebellum. 2010;9(1):124–135. PubMed

Husárová I, Lungu OV, Mareček R, et al. Functional imaging of the cerebellum and basal ganglia during predictive motor timing in early parkinson's disease. Journal of Neuroimaging. 2011 PubMed

Harrington DL, Lee RR, Boyd LA, Rapcsak SZ, Knight RT. Does the representation of time depend on the cerebellum? Effect of cerebellar stroke. Brain. 2004;127(3):561–574. PubMed

Coull JT, Cheng R-K, Meck WH. Neuroanatomical and neurochemical substrates of timing. Neuropsychopharmacology. 2011;36(1):3–25. PubMed PMC

Harrington DL, Zimbelman JL, Hinton SC, Rao SM. Neural modulation of temporal encoding, maintenance, and decision processes. Cerebral Cortex. 2010;20(6):1274–1285. PubMed PMC

Koch G, Oliveri M, Torriero S, Salerno S, Gerfo EL, Caltagirone C. Repetitive TMS of cerebellum interferes with millisecond time processing. Experimental Brain Research. 2007;179(2):291–299. PubMed

D’Angelo E, de Zeeuw CI. Timing and plasticity in the cerebellum: focus on the granular layer. Trends in Neurosciences. 2009;32(1):30–40. PubMed

Lewis PA, Miall RC. Distinct systems for automatic and cognitively controlled time measurement: evidence from neuroimaging. Current Opinion in Neurobiology. 2003;13(2):250–255. PubMed

Almeida QJ, Frank JS, Roy EA, Patla AE, Jog MS. Dopaminergic modulation of timing control and variability in the gait of Parkinson’s disease. Movement Disorders. 2007;22(12):1735–1742. PubMed

Jahanshahi M, Jones CRG, Zijlmans J, et al. Dopaminergic modulation of striato-frontal connectivity during motor timing in Parkinson’s disease. Brain. 2010;133(3):727–745. PubMed

Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. The British Journal of Psychiatry. 1979;134(4):382–389. PubMed

Consky ES, Lang AE. Clinical assessments of patients with cervical dystonia. Neurological Disease and Therapy. 1994;25:p. 211.

Grant MP, Leigh RJ, Seidman SH, Riley DE, Hanna JP. Comparison of predictable smooth ocular and combined eye-head tracking behaviour in patients with lesions affecting the brainstem and cerebellum. Brain. 1992;115(5):1323–1342. PubMed

Avanzino L, Abbruzzese G. How does the cerebellum contribute to the pathophysiology of dystonia? Basal Ganglia. 2012;2(4):231–235.

Raike RS, Jinnah HA, Hess EJ. Animal models of generalized dystonia. NeuroRx. 2005;2(3):504–512. PubMed PMC

Jinnah HA, Hess EJ, LeDoux MS, Sharma N, Baxter MG, DeLong MR. Rodent models for dystonia research: characteristics, evaluation, and utility. Movement Disorders. 2005;20(3):283–292. PubMed

Carbon M, Ghilardi MF, Argyelan M, Dhawan V, Bressman SB, Eidelberg D. Increased cerebellar activation during sequence learning in DYT1 carriers: an equiperformance study. Brain. 2008;131(1):146–154. PubMed PMC

Opavský R, Hluštík P, Otruba P, Kaňovský P. Sensorimotor network in cervical dystonia and the effect ofbotulinum toxin treatment: a functional MRI study. Journal of the Neurological Sciences. 2008;306(1):71–75. PubMed

Extremera VC, Álvarez-Coca J, Rodríguez GA, Pérez JM, de Villanueva JLR, Díaz CP. Torticollis is a usual symptom in posterior fossa tumors. European Journal of Pediatrics. 2008;167(2):249–250. PubMed

Spencer RMC, Verstynen T, Brett M, Ivry R. Cerebellar activation during discrete and not continuous timed movements: an fMRI study. NeuroImage. 2007;36(2):378–387. PubMed PMC

Lorås H, Sigmundsson H, Talcott JB, Öhberg F, Stensdotter AK. Timing continuous or discontinuous movements across effectors specified by different pacing modalities and intervals. Experimental Brain Research. 2012;220(3-4):335–347. PubMed

de Gruijl JR, Bazzigaluppi P, de Jeu MTG, de Zeeuw CI. Climbing fiber burst size and olivary sub-threshold oscillations in a network setting. PLoS Computational Biology. 2012;8(12)e1002814 PubMed PMC

Manto M-U. On the cerebello-cerebral interactions. Cerebellum. 2006;5(4):286–288. PubMed

Molinari M, Leggio MG, Thaut MH. The cerebellum and neural networks for rhythmic sensorimotor synchronization in the human brain. Cerebellum. 2007;6(1):18–23. PubMed

Eidelberg D, Moeller JR, Antonini A, et al. Functional brain networks in DYT1 dystonia. Annals of Neurology. 1998;44(3):303–312. PubMed

Kaňovský P, Bareš M, Streitová H, Klajblová H, Daniel P, Rektor I. Abnormalities of cortical excitability and cortical inhibition in cervical dystonia: evidence from somatosensory evoked potentials and paired transcranial magnetic stimulation recordings. Journal of Neurology. 2003;250(1):42–50. PubMed

Dreher J-C, Grafman J. The roles of the cerebellum and basal ganglia in timing and error prediction. European Journal of Neuroscience. 2002;16(8):1609–1619. PubMed

Hallett M. Pathophysiology of dystonia. Journal of Neural Transmission, Supplement. 2006;(70):485–488. PubMed

Murase N, Rothwell JC, Kaji R, et al. Subthreshold low-frequency repetitive transcranial magnetic stimulation over the premotor cortex modulates writer’s cramp. Brain. 2005;128(1):104–115. PubMed

Neychev VK, Fan X, Mitev VI, Hess EJ, Jinnah HA. The basal ganglia and cerebellum interact in the expression of dystonic movement. Brain. 2008;131(9):2499–2509. PubMed PMC

Neychev VK, Gross RE, Lehéricy S, Hess EJ, Jinnah HA. The functional neuroanatomy of dystonia. Neurobiology of Disease. 2011;42(2):185–201. PubMed PMC

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Neural Scaffolding as the Foundation for Stable Performance of Aging Cerebellum

Changes in sensorimotor network activation after botulinum toxin type A injections in patients with cervical dystonia: a functional MRI study

The mystery of the cerebellum: clues from experimental and clinical observations

The clinical phenomenology and associations of trick maneuvers in cervical dystonia

Neural Network of Predictive Motor Timing in the Context of Gender Differences