Disruption of saccadic adaptation with repetitive transcranial magnetic stimulation of the posterior cerebellum in humans

Ned Jenkinson, R Chris Miall, Ned Jenkinson, R Chris Miall

Abstract

Saccadic eye movements are driven by motor commands that are continuously modified so that errors created by eye muscle fatigue, injury, or-in humans-wearing spectacles can be corrected. It is possible to rapidly adapt saccades in the laboratory by introducing a discrepancy between the intended and actual saccadic target. Neurophysiological and lesion studies in the non-human primate as well as neuroimaging and patient studies in humans have demonstrated that the oculomotor vermis (lobules VI and VII of the posterior cerebellum) is critical for saccadic adaptation. We studied the effect of transiently disrupting the function of posterior cerebellum with repetitive transcranial magnetic stimulation (rTMS) on the ability of healthy human subjects to adapt saccadic eye movements. rTMS significantly impaired the adaptation of the amplitude of saccades, without modulating saccadic amplitude or variability in baseline conditions. Moreover, increasing the intensity of rTMS produced a larger impairment in the ability to adapt saccadic size. These results provide direct evidence for the role of the posterior cerebellum in man and further evidence that TMS can modulate cerebellar function.

Figures

Fig. 1.
Fig. 1.
Site of rTMS stimulation. MRIs of two of the subjects in the study showing the site stimulated; the white crosshairs represent the intended target of stimulation. Note the position of the visual cortex in relation to the inion. There is a 5-cm white scale bar to the left side of each image
Fig. 2
Fig. 2
Individual and mean results of the three groups performing the saccadic adaptation task. The line plots on the right-hand side of each panel show the mean saccadic amplitude of the 10 pre-adaptation baseline saccades made to a 16° target and the mean saccadic amplitude of the last 10 saccades of the adaptation experiment; error bars represent the standard error of the means. The scatter plots on the left of each panel represent the trial-by-trial amplitude of the primary reactive saccade for each individual in the group, after exclusion of outliers. Different symbols are used for each participant in each group. The left-most data are for baseline trial symbol in which participants moved towards static targets; the central data points are the primary saccades made by each individual during the time course of 100 adaptive trials. Horizontal dotted lines indicate the amplitude of the ideal initial and final saccades

References

    1. Ron S, Robinson D. Eye movements evoked by cerebellar stimulation in the alert monkey. J Neurophysiol. 1973;36(6):1004–22.
    1. Noda H, Fujikado T. Involvement of Purkinje cells in evoking saccadic eye movements by microstimulation of the posterior cerebellar vermis of monkeys. J Neurophysiol. 1987;57(5):1247–61.
    1. Fujikado T, Noda H. Saccadic eye movements evoked by microstimulation of lobule VII of the cerebellar vermis of macaque monkeys. J Physiol. 1987;394:573–94.
    1. Ohtsuka K, Noda H. Saccadic burst neurons in the oculomotor region of the fastigial nucleus of macaque monkeys. J Neurophysiol. 1991;65(6):1422–34.
    1. Fuchs A, Robinson F, Straube A. Role of the caudal fastigial nucleus in saccade generation. I. Neuronal discharge pattern. J Neurophysiol. 1993;70(5):1723–40.
    1. Ritchie L. Effects of cerebellar lesions on saccadic eye movements. J Neurophysiol. 1976;39(6):1246–56.
    1. Optican L, Robinson D. Cerebellar-dependent adaptive control of primate saccadic system. J Neurophysiol. 1980;44(6):1058–76.
    1. Goldberg M, Musil S, Fitzgibbon E, Smith M, Olson C. The role of the cerebellum in the control of saccadic eye-movements. Role Cerebellum Basal Ganglia Voluntary Movement. 1993;1024:203–11.
    1. Robinson F, Fuchs A, Noto C. Cerebellar influences on saccade plasticity. Ann NY Acad Sci. 2002;956:155–63. doi: 10.1111/j.1749-6632.2002.tb02816.x.
    1. Barash S, Melikyan A, Sivakov A, Zhang M, Glickstein M, Thier P. Saccadic dysmetria and adaptation after lesions of the cerebellar cortex. J Neurosci. 1999;19(24):10931–9.
    1. Takagi M, Zee D, Tamargo R. Effects of lesions of the oculomotor vermis on eye movements in primate: saccades. J Neurophysiol. 1998;80(4):1911–31.
    1. Carpenter R. Cerebellectomy and the transfer function of the vestibulo-ocular reflex in the decerebrate cat. Proc R Soc Lond B Biol Sci. 1972;181(1065):353–74. doi: 10.1098/rspb.1972.0055.
    1. Robinson D. Adaptive gain control of vestibulo-ocular reflex by the cerebellum. J Neurophysiol. 1976;39(5):954–69.
    1. McCormick D, Thompson R. Cerebellum: essential involvement in the classically conditioned eyelid response. Science. 1984;223(4633):296–9. doi: 10.1126/science.6701513.
    1. Yeo CH, Hardiman MJ, Glickstein M. Discrete lesions of the cerebellar cortex abolish the classically conditioned nictitating membrane response of the rabbit. Behav Brain Res. 1984;13(3):261–6. doi: 10.1016/0166-4328(84)90168-2.
    1. Baizer J, Kralj-Hans I, Glickstein M. Cerebellar lesions and prism adaptation in macaque monkeys. J Neurophysiol. 1999;81(4):1960–5.
    1. Baizer J, Glickstein M. Proceedings: role of cerebellum in prism adaptation. J Physiol (Lond) 1974;236(1):34P–5.
    1. Marr D. A theory of cerebellar cortex. J Physiol (Lond) 1969;202(2):437–70.
    1. Albus J. A theory of cerebellar function. Math Biosci. 1971;10(1–2):61–25.
    1. Soetedjo R, Fuchs A. Complex spike activity of Purkinje cells in the oculomotor vermis during behavioral adaptation of monkey saccades. J Neurosci. 2006;26(29):7741–55. doi: 10.1523/JNEUROSCI.4658-05.2006.
    1. Catz N, Dicke P, Thier P. Cerebellar complex spike firing is suitable to induce as well as to stabilize motor learning. Curr Biol. 2005;15(24):2179–89. doi: 10.1016/j.cub.2005.11.037.
    1. Pélisson D, Alahyane N, Panouillères M, Tilikete C. Sensorimotor adaptation of saccadic eye movements. Neurosci Biobehav Rev. 2010;34(8):1103–20. doi: 10.1016/j.neubiorev.2009.12.010.
    1. McLaughlin S. Parametric adjustment in saccadic eye movements. Percept Psychophys. 1967;2:359–62.
    1. Siebner H, Rothwell J. Transcranial magnetic stimulation: new insights into representational cortical plasticity. Exp Brain Res. 2003;148(1):1–16. doi: 10.1007/s00221-002-1234-2.
    1. Ugawa Y, Uesaka Y, Terao Y, Hanajima R, Kanazawa I. Magnetic stimulation over the cerebellum in humans. Ann Neurol. 1995;37(6):703–13. doi: 10.1002/ana.410370603.
    1. Chen RM, Gerloff C, Celnik P, Wassermann EM, Hallett M, et al. Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. Neurology. 1997;48(5):1398–403.
    1. Golla H, Tziridis K, Haarmeier T, Catz N, Barash S, Thier P. Reduced saccadic resilience and impaired saccadic adaptation due to cerebellar disease. Eur J Neurosci. 2008;27(1):132–44. doi: 10.1111/j.1460-9568.2007.05996.x.
    1. Straube A, Deubel H, Ditterich J, Eggert T. Cerebellar lesions impair rapid saccade amplitude adaptation. Neurology. 2001;57(11):2105–8.
    1. Choi K, Kim H, Cho B, Kim J. Saccadic adaptation in lateral medullary and cerebellar infarction. Exp Brain Res. 2008;188(3):475–82. doi: 10.1007/s00221-008-1375-z.
    1. Catz N, Dicke P, Thier P. Cerebellar-dependent motor learning is based on pruning a Purkinje cell population response. Proc Natl Acad Sci U S A. 2008;105(20):7309–14. doi: 10.1073/pnas.0706032105.
    1. Soetedjo R, Kojima Y, Fuchs AF. Complex spike activity in the oculomotor vermis of the cerebellum: a vectorial error signal for saccade motor learning? J Neurophysiol. 2008;100(4):1949–66. doi: 10.1152/jn.90526.2008.
    1. Hashimoto M, Ohtsuka K. Transcranial magnetic stimulation over the posterior cerebellum during visually guided saccades in man. Brain. 1995;118(5):1185–93. doi: 10.1093/brain/118.5.1185.
    1. Ohtsuka K, Enoki T. Transcranial magnetic stimulation over the posterior cerebellum during smooth pursuit eye movements in man. Brain. 1998;121(3):429–35. doi: 10.1093/brain/121.3.429.
    1. Zangemeister WH, Nagel M. Transcranial magnetic stimulation over the cerebellum delays predictive head movements in the coordination of gaze. Acta Otolaryngol Suppl. 2001;545:140–4. doi: 10.1080/000164801750388324.
    1. Miall R, Christensen L, Cain O, Stanley J. Disruption of state estimation in the human lateral cerebellum. PLoS Biol. 2007;5(11):e316. doi: 10.1371/journal.pbio.0050316.
    1. Werhahn KJ, Taylor J, Ridding M, Meyer BU, Rothwell JC. Effect of transcranial magnetic stimulation over the cerebellum on the excitability of human motor cortex. Electroencephalogr Clin Neurophysiol. 1996;101(1):58–66. doi: 10.1016/0013-4694(95)00213-8.
    1. Oliveri M, Koch G, Torriero S, Caltagirone C. Increased facilitation of the primary motor cortex following 1 Hz repetitive transcranial magnetic stimulation of the contralateral cerebellum in normal humans. Neurosci Lett. 2005;376(3):188–93. doi: 10.1016/j.neulet.2004.11.053.
    1. Miall R, Christensen L. The effect of rTMS over the cerebellum in normal human volunteers on peg-board movement performance. Neurosci Lett. 2004;371(2–3):185–9. doi: 10.1016/j.neulet.2004.08.067.
    1. Del Olmo M, Cheeran B, Koch G, Rothwell J. Role of the cerebellum in externally paced rhythmic finger movements. J Neurophysiol. 2007;98(1):145–52. doi: 10.1152/jn.01088.2006.
    1. Langguth B, Eichhammer P, Zowe M, Landgrebe M, Binder H, Sand P, et al. Modulating cerebello-thalamocortical pathways by neuronavigated cerebellar repetitive transcranial stimulation (rTMS) Clin Neurophysiol. 2008;38(5):289–95. doi: 10.1016/j.neucli.2008.08.003.
    1. Daskalakis ZJ, Paradiso GO, Christensen BK, Fitzgerald PB, Gunraj C, Chen R. Exploring the connectivity between the cerebellum and motor cortex in humans. J Physiol. 2004;557(2):689–700. doi: 10.1113/jphysiol.2003.059808.
    1. Larsell O. The comparative anatomy and histology of the cerebellum. Minneapolis: University of Minnesota Press; 1967.
    1. Diedrichsen J. A spatially unbiased atlas template of the human cerebellum. Neuroimage. 2006;33(1):127–38. doi: 10.1016/j.neuroimage.2006.05.056.
    1. Roth Y, Zangen A, Hallett M. A coil design for transcranial magnetic stimulation of deep brain regions. J Clin Neurophysiol. 2002;19(4):361–70. doi: 10.1097/00004691-200208000-00008.
    1. Terao Y, Ugawa Y, Hanajima R, Machii K, Furubayashi T, Mochizuki H, et al. Predominant activation of I1-waves from the leg motor area by transcranial magnetic stimulation. Brain Res. 2000;859(1):137–46. doi: 10.1016/S0006-8993(00)01975-2.
    1. Desmurget M, Pelisson D, Urquizar C, Prablanc C, Alexander G, Grafton S. Functional anatomy of saccadic adaptation in humans. Nat Neurosci. 1998;1(6):524–8. doi: 10.1038/2241.
    1. Desmurget M, Pelisson D, Grethe J, Alexander G, Urquizar C, Prablanc C, et al. Functional adaptation of reactive saccades in humans: a PET study. Exp Brain Res. 2000;132(2):243–59. doi: 10.1007/s002210000342.
    1. Lang N, Harms J, Weyh T, Lemon R, Paulus W, Rothwell J, et al. Stimulus intensity and coil characteristics influence the efficacy of rTMS to suppress cortical excitability. Clin Neurophysiol. 2006;117(10):2292–301. doi: 10.1016/j.clinph.2006.05.030.
    1. Gaymard B, Rivaud-Péchoux S, Yelnik J, Pidoux B, Ploner C. Involvement of the cerebellar thalamus in human saccade adaptation. Eur J Neurosci. 2001;14(3):554–60. doi: 10.1046/j.0953-816x.2001.01669.x.

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