The Role of the Posterior Cerebellum in Saccadic Adaptation: A Transcranial Direct Current Stimulation Study

The posterior vermis of the cerebellum is considered to be critically involved in saccadic adaptation. However, recent evidence suggests that the adaptive decrease (backward adaptation) and the adaptive increase (forward adaptation) of saccade amplitude rely on partially separate neural substrates. We investigated whether the posterior cerebellum could be differentially involved in backward and forward adaptation by using transcranial direct current stimulation (TDCS). To do so, participants' saccades were adapted backward or forward while they received anodal, cathodal, or sham TDCS. In two extra groups, subjects underwent a nonadaptation session while receiving anodal or cathodal TDCS to control for the direct effects of TDCS on saccadic execution. Surprisingly, cathodal stimulation tended to increase the extent of both forward and backward adaptations, while anodal TDCS strongly impaired forward adaptation and, to a smaller extent, backward adaptation. Forward adaptation was accompanied by a greater increase in velocity with cathodal stimulation, and reduced duration of change for anodal stimulation. In contrast, the expected velocity decrease in backward adaptation was noticeably weaker with anodal stimulation. Stimulation applied during nonadaptation sessions did not affect saccadic gain, velocity, or duration, demonstrating that the reported effects are not due to direct effects of the stimulation on the generation of eye movements. Our results demonstrate that cerebellar excitability is critical for saccadic adaptation. Based on our results and the growing evidence from studies of vestibulo-ocular reflex and saccadic adaptation, we conclude that the plasticity at the level of the oculomotor vermis is more fundamentally important for forward adaptation than for backward adaptation.

[1]  Reza Shadmehr,et al.  Contributions of the cerebellum and the motor cortex to acquisition and retention of motor memories , 2014, NeuroImage.

[2]  W. Waespe,et al.  Enduring dysmetria and impaired gain adaptivity of saccadic eye movements in Wallenberg's lateral medullary syndrome. , 1992, Brain : a journal of neurology.

[3]  D. Timmann,et al.  Visuomotor adaptive improvement and aftereffects are impaired differentially following cerebellar lesions in SCA and PICA territory , 2009, Experimental Brain Research.

[4]  Rhea R. Kimpo,et al.  Cerebellar Purkinje cell activity drives motor learning , 2013, Nature Neuroscience.

[5]  M. Nitsche,et al.  Physiological Basis of Transcranial Direct Current Stimulation , 2011, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[6]  M. Nitsche,et al.  Partially non‐linear stimulation intensity‐dependent effects of direct current stimulation on motor cortex excitability in humans , 2013, The Journal of physiology.

[7]  Edward S Boyden,et al.  Active Reversal of Motor Memories Reveals Rules Governing Memory Encoding , 2003, Neuron.

[8]  Ned Jenkinson,et al.  Disruption of Saccadic Adaptation with Repetitive Transcranial Magnetic Stimulation of the Posterior Cerebellum in Humans , 2010, The Cerebellum.

[9]  M Ito,et al.  Questions in modeling the cerebellum. , 1982, Journal of theoretical biology.

[10]  E. Boyden,et al.  Selective Engagement of Plasticity Mechanisms for Motor Memory Storage , 2006, Neuron.

[11]  R. Shadmehr,et al.  Cerebellar Contributions to Adaptive Control of Saccades in Humans , 2009, The Journal of Neuroscience.

[12]  J. Krakauer,et al.  Sensory prediction errors drive cerebellum-dependent adaptation of reaching. , 2007, Journal of neurophysiology.

[13]  R. Shadmehr,et al.  Intact ability to learn internal models of arm dynamics in Huntington's disease but not cerebellar degeneration. , 2005, Journal of neurophysiology.

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

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

[16]  K. Arnell,et al.  That's my name, don't wear it out: Attentional blink and the cocktail party effect , 2010 .

[17]  Kaoru Yoshida,et al.  Memory of Learning Facilitates Saccadic Adaptation in the Monkey , 2004, The Journal of Neuroscience.

[18]  M. Lappe,et al.  Motor signals in visual localization. , 2010, Journal of vision.

[19]  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.

[20]  S G Lisberger,et al.  Cerebellar LTD: A Molecular Mechanism of Behavioral Learning? , 1998, Cell.

[21]  Rhea R. Kimpo,et al.  Gating of neural error signals during motor learning , 2014, eLife.

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

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

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

[25]  Christopher T. Noto,et al.  Characteristics of simian adaptation fields produced by behavioral changes in saccade size and direction. , 1999, Journal of neurophysiology.

[26]  C. Scudder Role of the Fastigial Nucleus in Controlling Horizontal Saccades during Adaptation , 2002, Annals of the New York Academy of Sciences.

[27]  T. Ebner,et al.  Hereditary cerebellar ataxia progressively impairs force adaptation during goal-directed arm movements. , 2004, Journal of neurophysiology.

[28]  W. T. Thach,et al.  Throwing while looking through prisms. II. Specificity and storage of multiple gaze-throw calibrations. , 1996, Brain : a journal of neurology.

[29]  A. Antal,et al.  Electrode-distance dependent after-effects of transcranial direct and random noise stimulation with extracephalic reference electrodes , 2010, Clinical Neurophysiology.

[30]  Á. Kristjánsson,et al.  Violating the main sequence: asymmetries in saccadic peak velocities for saccades into the temporal versus nasal hemifields , 2013, Experimental Brain Research.

[31]  Dorine Vergilino-Perez,et al.  Are there any left-right asymmetries in saccade parameters? Examination of latency, gain, and peak velocity. , 2012, Investigative ophthalmology & visual science.

[32]  A. Fuchs,et al.  Characteristics of saccadic gain adaptation in rhesus macaques. , 1997, Journal of neurophysiology.

[33]  Denis Pélisson,et al.  Transcranial magnetic stimulation and motor plasticity in human lateral cerebellum: Dual effect on saccadic adaptation , 2012, Human brain mapping.

[34]  W. T. Thach,et al.  Throwing while looking through prisms. I. Focal olivocerebellar lesions impair adaptation. , 1996, Brain : a journal of neurology.

[35]  Walter Paulus,et al.  Induction of Late LTP-Like Plasticity in the Human Motor Cortex by Repeated Non-Invasive Brain Stimulation , 2013, Brain Stimulation.

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

[37]  C. D. De Zeeuw,et al.  Cerebellar LTD facilitates but is not essential for long‐term adaptation of the vestibulo‐ocular reflex , 2002, The European journal of neuroscience.

[38]  Hannah J. Block,et al.  Stimulating the Cerebellum Affects Visuomotor Adaptation but not Intermanual Transfer of Learning , 2013, The Cerebellum.

[39]  L. Cohen,et al.  Transcranial direct current stimulation: State of the art 2008 , 2008, Brain Stimulation.

[40]  D. Pelisson,et al.  Separate Neural Substrates in the Human Cerebellum for Sensory-motor Adaptation of Reactive and of Scanning Voluntary Saccades , 2008, The Cerebellum.

[41]  Chris I. De Zeeuw,et al.  αCaMKII Is Essential for Cerebellar LTD and Motor Learning , 2006, Neuron.

[42]  Reza Shadmehr,et al.  Changes in Control of Saccades during Gain Adaptation , 2008, The Journal of Neuroscience.

[43]  D. Timmann,et al.  Acquisition of Conditioned Eyeblink Responses is Modulated by Cerebellar tDCS , 2014, Brain Stimulation.

[44]  Otmar Bock,et al.  The effect of cerebellar cortical degeneration on adaptive plasticity and movement control , 2009, Experimental Brain Research.

[45]  Markus Lappe,et al.  Differences in intersaccadic adaptation transfer between inward and outward adaptation. , 2011, Journal of neurophysiology.

[46]  Yuki Kaku,et al.  Learning Signals from the Superior Colliculus for Adaptation of Saccadic Eye Movements in the Monkey , 2009, The Journal of Neuroscience.

[47]  S. M. Morton,et al.  Cerebellar Contributions to Locomotor Adaptations during Splitbelt Treadmill Walking , 2006, The Journal of Neuroscience.

[48]  P. Celnik,et al.  Modulation of Cerebellar Excitability by Polarity-Specific Noninvasive Direct Current Stimulation , 2009, The Journal of Neuroscience.

[49]  A. Bastian Understanding sensorimotor adaptation and learning for rehabilitation , 2008, Current opinion in neurology.

[50]  M. Nitsche,et al.  Shaping the effects of transcranial direct current stimulation of the human motor cortex. , 2007, Journal of neurophysiology.

[51]  Chris I. De Zeeuw,et al.  Expression of a Protein Kinase C Inhibitor in Purkinje Cells Blocks Cerebellar LTD and Adaptation of the Vestibulo-Ocular Reflex , 1998, Neuron.

[52]  Kaoru Yoshida,et al.  Microstimulation of the Midbrain Tegmentum Creates Learning Signals for Saccade Adaptation , 2007, The Journal of Neuroscience.

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

[54]  P. Celnik,et al.  Dissociating the roles of the cerebellum and motor cortex during adaptive learning: the motor cortex retains what the cerebellum learns. , 2011, Cerebral cortex.

[55]  Denis Pélisson,et al.  Behavioral evidence of separate adaptation mechanisms controlling saccade amplitude lengthening and shortening. , 2009, Journal of neurophysiology.

[56]  D. Pélisson,et al.  Effects of structural and functional cerebellar lesions on sensorimotor adaptation of saccades , 2013, Experimental Brain Research.

[57]  D. Linden,et al.  Mechanisms underlying cerebellar motor deficits due to mGluR1‐autoantibodies , 2003, Annals of neurology.

[58]  Kaoru Yoshida,et al.  Changes in cerebellar fastigial burst activity related to saccadic gain adaptation in the monkey , 2003, Neuroscience Research.

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

[60]  Markus Lappe,et al.  Mislocalization of stationary and flashed bars after saccadic inward and outward adaptation of reactive saccades. , 2012, Journal of neurophysiology.

[61]  M. Banks,et al.  How does saccade adaptation affect visual perception? , 2008, Journal of vision.

[62]  Erin V. L. Vasudevan,et al.  Modulating locomotor adaptation with cerebellar stimulation. , 2012, Journal of neurophysiology.

[63]  C. Scudder,et al.  Adaptive modification of saccade size produces correlated changes in the discharges of fastigial nucleus neurons. , 2003, Journal of neurophysiology.

[64]  P. Thier,et al.  The Role of the Oculomotor Vermis in the Control of Saccadic Eye Movements , 2002, Annals of the New York Academy of Sciences.

[65]  Yoshiko Kojima,et al.  Subthreshold Activation of the Superior Colliculus Drives Saccade Motor Learning , 2009, The Journal of Neuroscience.