Disruption of Saccadic Adaptation with Repetitive Transcranial Magnetic Stimulation of the Posterior Cerebellum in Humans

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.

[1]  Sara Torriero,et al.  Increased facilitation of the primary motor cortex following 1Hz repetitive transcranial magnetic stimulation of the contralateral cerebellum in normal humans , 2005, Neuroscience Letters.

[2]  Robert Chen,et al.  Exploring the connectivity between the cerebellum and motor cortex in humans , 2004, The Journal of physiology.

[3]  B. Langguth,et al.  Modulating cerebello-thalamocortical pathways by neuronavigated cerebellar repetitive transcranial stimulation (rTMS) , 2008, Neurophysiologie Clinique/Clinical Neurophysiology.

[4]  Giacomo Koch,et al.  Role of the cerebellum in externally paced rhythmic finger movements. , 2007, Journal of neurophysiology.

[5]  Peter Thier,et al.  Cerebellar Complex Spike Firing Is Suitable to Induce as Well as to Stabilize Motor Learning , 2005, Current Biology.

[6]  K. Ohtsuka,et al.  Saccadic burst neurons in the oculomotor region of the fastigial nucleus of macaque monkeys. , 1991, Journal of neurophysiology.

[7]  W. H. Z. M. Nagel Transcranial Magnetic Stimulation Over the Cerebellum Delays Predictive Head Movements in the Coordination of Gaze , 2001, Acta oto-laryngologica. Supplementum.

[8]  I. Kanazawa,et al.  Predominant activation of I1-waves from the leg motor area by transcranial magnetic stimulation , 2000, Brain Research.

[9]  A. Fuchs,et al.  Role of the caudal fastigial nucleus in saccade generation. I. Neuronal discharge pattern. , 1993, Journal of neurophysiology.

[10]  D. Marr A theory of cerebellar cortex , 1969, The Journal of physiology.

[11]  Yoshiko Kojima,et al.  Complex spike activity in the oculomotor vermis of the cerebellum: a vectorial error signal for saccade motor learning? , 2008, Journal of neurophysiology.

[12]  A. Fuchs,et al.  Cerebellar Influences on Saccade Plasticity , 2002, Annals of the New York Academy of Sciences.

[13]  L. Optican,et al.  Cerebellar-dependent adaptive control of primate saccadic system. , 1980, Journal of neurophysiology.

[14]  Peter Thier,et al.  Cerebellar-dependent motor learning is based on pruning a Purkinje cell population response , 2008, Proceedings of the National Academy of Sciences.

[15]  R. Miall,et al.  The effect of rTMS over the cerebellum in normal human volunteers on peg-board movement performance , 2004, Neuroscience Letters.

[16]  M. Hallett,et al.  Depression of motor cortex excitability by low‐frequency transcranial magnetic stimulation , 1997, Neurology.

[17]  H. Noda,et al.  Involvement of Purkinje cells in evoking saccadic eye movements by microstimulation of the posterior cerebellar vermis of monkeys. , 1987, Journal of neurophysiology.

[18]  D. Pélisson,et al.  Sensorimotor adaptation of saccadic eye movements , 2010, Neuroscience & Biobehavioral Reviews.

[19]  J. Albus A Theory of Cerebellar Function , 1971 .

[20]  O. Larsell,et al.  The comparative anatomy and histology of the cerebellum , 1967 .

[21]  D. Robinson,et al.  Eye movements evoked by cerebellar stimulation in the alert monkey. , 1973, Journal of neurophysiology.

[22]  L. Ritchie Effects of cerebellar lesions on saccadic eye movements. , 1976, Journal of neurophysiology.

[23]  Mark Hallett,et al.  A Coil Design for Transcranial Magnetic Stimulation of Deep Brain Regions , 2002, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[24]  J. Rothwell,et al.  Transcranial magnetic stimulation: new insights into representational cortical plasticity , 2002, Experimental Brain Research.

[25]  H. Deubel,et al.  Cerebellar lesions impair rapid saccade amplitude adaptation , 2001, Neurology.

[26]  J. Yelnik,et al.  Involvement of the cerebellar thalamus in human saccade adaptation , 2001, The European journal of neuroscience.

[27]  J. Rothwell,et al.  Stimulus intensity and coil characteristics influence the efficacy of rTMS to suppress cortical excitability , 2006, Clinical Neurophysiology.

[28]  R. Hanajima,et al.  Magnetic stimulation over the cerebellum in humans , 1995, Annals of neurology.

[29]  M Glickstein,et al.  Proceedings: Role of cerebellum in prism adaptation. , 1974, The Journal of physiology.

[30]  K Ohtsuka,et al.  Transcranial magnetic stimulation over the posterior cerebellum during visually guided saccades in man. , 1995, Brain : a journal of neurology.

[31]  Robijanto Soetedjo,et al.  Complex Spike Activity of Purkinje Cells in the Oculomotor Vermis during Behavioral Adaptation of Monkey Saccades , 2006, The Journal of Neuroscience.

[32]  Jörn Diedrichsen,et al.  A spatially unbiased atlas template of the human cerebellum , 2006, NeuroImage.

[33]  S. C. Mclaughlin Parametric adjustment in saccadic eye movements , 1967 .

[34]  P. Thier,et al.  Reduced saccadic resilience and impaired saccadic adaptation due to cerebellar disease , 2007, The European journal of neuroscience.

[35]  R. F. Thompson,et al.  Cerebellum: essential involvement in the classically conditioned eyelid response. , 1984, Science.

[36]  Scott T. Grafton,et al.  Functional adaptation of reactive saccades in humans: a PET study , 2000, Experimental Brain Research.

[37]  L. Christensen,et al.  University of Birmingham Disruption of state estimation in the human lateral cerebellum , 2007 .

[38]  Adam Possner,et al.  Cerebellum , 2012, Neurology.

[39]  K. Ohtsuka,et al.  Transcranial magnetic stimulation over the posterior cerebellum during smooth pursuit eye movements in man. , 1998, Brain : a journal of neurology.

[40]  T Fujikado,et al.  Saccadic eye movements evoked by microstimulation of lobule VII of the cerebellar vermis of macaque monkeys. , 1987, The Journal of physiology.

[41]  Scott T. Grafton,et al.  Genetic dissection of Alzheimer's disease and related dementias: amyloid and its relationship to tau , 1998, Nature Neuroscience.

[42]  D. Zee,et al.  Effects of lesions of the oculomotor vermis on eye movements in primate: saccades. , 1998, Journal of neurophysiology.

[43]  J. Baizer,et al.  Cerebellar lesions and prism adaptation in macaque monkeys. , 1999, Journal of neurophysiology.

[44]  J C Rothwell,et al.  Effect of transcranial magnetic stimulation over the cerebellum on the excitability of human motor cortex. , 1996, Electroencephalography and clinical neurophysiology.

[45]  Ji Soo Kim,et al.  Saccadic adaptation in lateral medullary and cerebellar infarction , 2008, Experimental Brain Research.

[46]  D. Robinson Adaptive gain control of vestibuloocular reflex by the cerebellum. , 1976, Journal of neurophysiology.

[47]  P. Thier,et al.  Saccadic Dysmetria and Adaptation after Lesions of the Cerebellar Cortex , 1999, The Journal of Neuroscience.

[48]  R. Carpenter,et al.  Cerebellectomy and the transfer function of the vestibulo-ocular reflex in the decerebrate cat , 1972, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[49]  D. Robinson Eye movements evoked by collicular stimulation in the alert monkey. , 1972, Vision research.

[50]  M. Glickstein,et al.  Discrete lesions of the cerebellar cortex abolish the classically conditioned nictitating membrane response of the rabbit , 1984, Behavioural Brain Research.