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Original Research ARTICLE

Front. Hum. Neurosci., 19 September 2012 | http://dx.doi.org/10.3389/fnhum.2012.00260

Cerebellum to motor cortex paired associative stimulation induces bidirectional STDP-like plasticity in human motor cortex

Ming-Kuei Lu1,2,3, Chon-Haw Tsai2,3 and Ulf Ziemann1,4*
  • 1Department of Neurology, Goethe-University, Frankfurt/Main, Germany
  • 2Neuroscience Laboratory, Department of Neurology, China Medical University Hospital, Taichung, Taiwan
  • 3Institute of Medical Science and School of Medicine, China Medical University, Taichung, Taiwan
  • 4Department of Neurology, Hertie-Institute for Clinical Brain Research, University Hospital Tübingen, Tübingen, Germany

The cerebellum is crucially important for motor control and adaptation. Recent non-invasive brain stimulation studies have indicated the possibility to alter the excitability of the cerebellum and its projections to the contralateral motor cortex, with behavioral consequences on motor control and adaptation. Here we sought to induce bidirectional spike-timing dependent plasticity (STDP)-like modifications of motor cortex (M1) excitability by application of paired associative stimulation (PAS) in healthy subjects. Conditioning stimulation over the right lateral cerebellum (CB) preceded focal transcranial magnetic stimulation (TMS) of the left M1 hand area at an interstimulus interval of 2 ms (CB→M1 PAS2 ms), 6 ms (CB→M1 PAS6 ms) or 10 ms (CB→M1 PAS10 ms) or randomly alternating intervals of 2 and 10 ms (CB→M1 PASControl). Effects of PAS on M1 excitability were assessed by the motor-evoked potential (MEP) amplitude, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cerebellar-motor cortex inhibition (CBI) in the first dorsal interosseous muscle of the right hand. CB→M1 PAS2 ms resulted in MEP potentiation, CB→M1 PAS6 ms and CB→M1 PAS10 ms in MEP depression, and CB→M1 PASControl in no change. The MEP changes lasted for 30–60 min after PAS. SICI and CBI decreased non-specifically after all PAS protocols, while ICF remained unaltered. The physiological mechanisms underlying these MEP changes are carefully discussed. Findings support the notion of bidirectional STDP-like plasticity in M1 mediated by associative stimulation of the cerebello-dentato-thalamo-cortical pathway and M1. Future studies may investigate the behavioral significance of this plasticity.

Keywords: cerebello-dentato-thalamo-cortical pathway, spike-timing dependent-like plasticity, cerebellum, motor cortex, transcranial magnetic stimulation, paired associative stimulation, human

Citation: Lu M-K, Tsai C-H and Ziemann U (2012) Cerebellum to motor cortex paired associative stimulation induces bidirectional STDP-like plasticity in human motor cortex. Front. Hum. Neurosci. 6:260. doi: 10.3389/fnhum.2012.00260

Received: 15 April 2012; Accepted: 31 August 2012;
Published online: 19 September 2012.

Edited by:

Sven Bestmann, University College London, UK

Reviewed by:

Joseph M. Galea, University College London, UK
Giacomo Koch, Santa Lucia IRCCS, Italy

Copyright © 2012 Lu, Tsai and Ziemann. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

*Correspondence: Ulf Ziemann, Department of Neurology and Stroke, Hertie Institute for Clinical Brain Research, Eberhard-Karls-University Tübingen, Hoppe-Seyler-Str. 3, D-72076 Tübingen, Germany. e-mail: ulf.ziemann@med.uni-tuebingen.de