Performance of timed motor sequences relies on the cerebellum and basal ganglia, which integrate proprioceptive information during the motor task and set internal timing mechanisms. Accordingly, these structures are also involved in other temporal processes, such as the discrimination of the different afferent information in the domain of time. In the present study we tested temporal processing of proprioceptive and tactile stimuli in 20 patients with neurodegenerative cerebellar ataxia and 20 age- and sex-matched healthy subjects. Tactile temporal discrimination threshold was defined as the value at which subjects recognized the two stimuli as asynchronous. Temporal discrimination movement threshold of the first dorsal interosseous and flexor carpi radialis was defined as the shortest interval between two paired electrical stimuli in which the subjects blindfolded perceived two separate index finger abductions and wrist flexions. Both tactile and movement temporal discrimination thresholds were higher in patients with cerebellar ataxia. No correlation was found with disease duration and severity. Our study demonstrates that temporal processing of tactile and proprioceptive stimuli is impaired in patients with cerebellar neurodegeneration and highlights the involvement of cerebellum in temporal processing of somatosensory stimuli of different type.
References
[1]
Del Olmo MF, Cheeran B, Koch G, Rothwell JC (2007) Role of the cerebellum in externally paced rhythmic finger movements. J Neurophysiol 98: 145–152.
[2]
Tinazzi M, Frasson E, Bertolasi L, Fiaschi A, Aglioti S (1999) Temporal discrimination of somesthetic stimuli is impaired in dystonic patients. Neuroreport 10: 1547–1550.
[3]
Tinazzi M, Stanzani C, Fiorio M, Smania N, Moretto G, et al. (2005) Temporal discrimination of two passive movements in humans: a new psychophysical approach to assessing kinaesthesia. Exp Brain Res 166: 184–189.
[4]
Pastor MA, Day BL, Macaluso E, Friston KJ, Frackowiak RS (2004) The functional neuroanatomy of temporal discrimination. J Neurosci 24: 2585–2591.
[5]
Scontrini A, Conte A, Defazio G, Fiorio M, Fabbrini G, et al. (2009) Somatosensory temporal discrimination in patients with primary focal dystonia. J Neurol Neurosurg Psychiatry 80: 1315–1319.
[6]
Fiorio M, Gambarin M, Valente EM, Liberini P, Loi M, et al. (2007) Defective temporal processing of sensory stimuli in DYT1 mutation carriers: a new endophenotype of dystonia? Brain 130: 134–142.
[7]
Bradley D, Whelan R, Walsh R, Reilly RB, Hutchinson S, et al. (2009) Temporal discrimination threshold: VBM evidence for an endophenotype in adult onset primary torsion dystonia. Brain 132: 2327–2335.
[8]
Artieda J, Pastor MA, Lacruz F, Obeso JA (1992) Temporal discrimination is abnormal in Parkinson’s disease. Brain 115 Pt 1: 199–210.
[9]
Fiorio M, Stanzani C, Rothwell JC, Bhatia KP, Moretto G, et al. (2007) Defective temporal discrimination of passive movements in Parkinson’s disease. Neurosci Lett 417: 312–315.
[10]
Tinazzi M, Fiorio M, Stanzani C, Moretto G, Smania N, et al. (2006) Temporal discrimination of two passive movements in writer’s cramp. Mov Disord 21: 1131–1135.
[11]
Tinazzi M, Fasano A, Di Matteo A, Conte A, Bove F, et al. (2013) Temporal discrimination in patients with dystonia and tremor and patients with essential tremor. Neurology 80: 76–84.
[12]
Elble R, Deuschl G (2011) Milestones in tremor research. Mov Disord 26: 1096–1105.
[13]
Butterworth S, Francis S, Kelly E, McGlone F, Bowtell R, et al. (2003) Abnormal cortical sensory activation in dystonia: an fMRI study. Mov Disord 18: 673–682.
[14]
Proske U, Gandevia SC (2009) The kinaesthetic senses. J Physiol 587: 4139–4146.
[15]
Bosco G, Poppele RE (2001) Proprioception from a spinocerebellar perspective. Physiol Rev 81: 539–568.
[16]
Klockgether T (2010) Sporadic ataxia with adult onset: classification and diagnostic criteria. Lancet Neurol 9: 94–104.
[17]
Schmitz-Hubsch T, du Montcel ST, Baliko L, Berciano J, Boesch S, et al. (2006) Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology 66: 1717–1720.
[18]
Morgante F, Tinazzi M, Squintani G, Martino D, Defazio G, et al. (2011) Abnormal tactile temporal discrimination in psychogenic dystonia. Neurology 77: 1191–1197.
[19]
Fiorio M, Tinazzi M, Bertolasi L, Aglioti SM (2003) Temporal processing of visuotactile and tactile stimuli in writer’s cramp. Ann Neurol 53: 630–635.
[20]
Gandevia SC, McCloskey DI, Burke D (1992) Kinaesthetic signals and muscle contraction. Trends Neurosci 15: 62–65.
[21]
Grill SE, Hallett M, Marcus C, McShane L (1994) Disturbances of kinaesthesia in patients with cerebellar disorders. Brain 117 (Pt 6): 1433–1447.
[22]
Maschke M, Gomez CM, Tuite PJ, Konczak J (2003) Dysfunction of the basal ganglia, but not the cerebellum, impairs kinaesthesia. Brain 126: 2312–2322.
[23]
Hagura N, Oouchida Y, Aramaki Y, Okada T, Matsumura M, et al. (2009) Visuokinesthetic perception of hand movement is mediated by cerebro-cerebellar interaction between the left cerebellum and right parietal cortex. Cereb Cortex 19: 176–186.
[24]
Francis S, Lin X, Aboushoushah S, White TP, Phillips M, et al. (2009) fMRI analysis of active, passive and electrically stimulated ankle dorsiflexion. Neuroimage 44: 469–479.
[25]
Ivry RB (1996) The representation of temporal information in perception and motor control. Curr Opin Neurobiol 6: 851–857.
[26]
Aglioti SM, Fiorio M, Forster B, Tinazzi M (2003) Temporal discrimination of cross-modal and unimodal stimuli in generalized dystonia. Neurology 60: 782–785.
[27]
Lacruz F, Artieda J, Pastor MA, Obeso JA (1991) The anatomical basis of somaesthetic temporal discrimination in humans. J Neurol Neurosurg Psychiatry 54: 1077–1081.
[28]
Harrington DL, Haaland KY, Knight RT (1998) Cortical networks underlying mechanisms of time perception. J Neurosci 18: 1085–1095.
[29]
Manganelli F, Dubbioso R, Pisciotta C, Antenora A, Nolano M et al. (2013) Somatosensory Temporal Discrimination Threshold Is Increased in Patients with Cerebellar Atrophy. Cerebellum.
[30]
Conte A, Rocchi L, Nardella A, Dispenza S, Scontrini A, et al. (2012) Theta-burst stimulation-induced plasticity over primary somatosensory cortex changes somatosensory temporal discrimination in healthy humans. PLoS One 7: e32979.
[31]
Louis ED (2010) Essential tremor: evolving clinicopathological concepts in an era of intensive post-mortem enquiry. Lancet Neurol 9: 613–622.
[32]
Redgrave P, Rodriguez M, Smith Y, Rodriguez-Oroz MC, Lehericy S, et al. (2010) Goal-directed and habitual control in the basal ganglia: implications for Parkinson’s disease. Nat Rev Neurosci 11: 760–772.
[33]
Marsden CD (1982) The mysterious motor function of the basal ganglia: the Robert Wartenberg Lecture. Neurology 32: 514–539.
[34]
Allen G, Buxton RB, Wong EC, Courchesne E (1997) Attentional activation of the cerebellum independent of motor involvement. Science 275: 1940–1943.
[35]
Hagura N, Oouchida Y, Aramaki Y, Okada T, Matsumura M, et al. (2009) Visuokinesthetic perception of hand movement is mediated by cerebro-cerebellar interaction between the left cerebellum and right parietal cortex. Cereb Cortex 19: 176–186.
[36]
Jueptner M, Ottinger S, Fellows SJ, Adamschewski J, Flerich L, et al. (1997) The relevance of sensory input for the cerebellar control of movements. Neuroimage 5: 41–48.
[37]
Gao JH, Parsons LM, Bower JM, Xiong J, Li J, et al. (1996) Cerebellum implicated in sensory acquisition and discrimination rather than motor control. Science 272: 545–547.
Keele SW, Ivry R (1990) Does the cerebellum provide a common computation for diverse tasks? A timing hypothesis. Ann N Y Acad Sci 608: 179–207.
[40]
Manto M, Bower JM, Conforto AB, Delgado-Garcia JM, da Guarda SN, et al. (2012) Consensus paper: roles of the cerebellum in motor control–the diversity of ideas on cerebellar involvement in movement. Cerebellum 11: 457–487.
[41]
Molinari M, Leggio MG, Thaut MH (2007) The cerebellum and neural networks for rhythmic sensorimotor synchronization in the human brain. Cerebellum 6: 18–23.
[42]
Tesche CD, Karhu JJ (2000) Anticipatory cerebellar responses during somatosensory omission in man. Hum Brain Mapp 9: 119–142.
[43]
Restuccia D, Valeriani M, Barba C, Le Pera D, Capecci M, et al. (2001) Functional changes of the primary somatosensory cortex in patients with unilateral cerebellar lesions. Brain 124: 757–768.
[44]
Wu T, Liu J, Hallett M, Zheng Z, Chan P (2013) Cerebellum and integration of neural networks in dual-task processing. Neuroimage 65: 466–475.
[45]
Ravizza SM, Goudreau J, Delgado MR, Ruiz S (2012) Executive function in Parkinson’s disease: contributions of the dorsal frontostriatal pathways to action and motivation. Cogn Affect Behav Neurosci 12: 193–206.
[46]
Klinke I, Minnerop M, Schmitz-Hubsch T, Hendriks M, Klockgether T, et al. (2010) Neuropsychological features of patients with spinocerebellar ataxia (SCA) types 1, 2, 3, and 6. Cerebellum 9: 433–442.
[47]
Orsi L, D’Agata F, Caroppo P, Franco A, Caglio MM, et al. (2011) Neuropsychological picture of 33 spinocerebellar ataxia cases. J Clin Exp Neuropsychol 33: 315–325.
[48]
Conte A, Modugno N, Lena F, Dispenza S, Gandolfi B, et al. (2010) Subthalamic nucleus stimulation and somatosensory temporal discrimination in Parkinson’s disease. Brain 133: 2656–2663.
[49]
Neychev VK, Gross RE, Lehericy S, Hess EJ, Jinnah HA (2011) The functional neuroanatomy of dystonia. Neurobiol Dis 42: 185–201.
