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Cerebral Cortex Advance Access originally published online on October 12, 2005
Cerebral Cortex 2006 16(8):1106-1115; doi:10.1093/cercor/bhj052
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Modification of Practice-dependent Plasticity in Human Motor Cortex by Neuromodulators

Frank Meintzschel and Ulf Ziemann

Motor Cortex Laboratory, Department of Neurology, J.W. Goethe-University Frankfurt, Schleusenweg 2–16, D-60528 Frankfurt am Main, Germany

Address correspondence to Prof. Ulf Ziemann. Department of Neurology, Johann Wolfgang Goethe-University Frankfurt, Schleusenweg 2–16, D-60528 Frankfurt am Main, Germany. Email: u.ziemann{at}em.uni-frankfurt.de.

Practice-dependent plasticity underlies motor learning in everyday life and motor relearning after lesions of the nervous system. Previous studies showed that practice-dependent plasticity is modifiable by neuromodulating transmitters such as norepinephrine (NE), dopamine (DA) or acetylcholine (ACh). Here we explored, for the first time comprehensively and systematically, the modifying effects of an agonist versus antagonist in each of these neuromodulating transmitter systems on practice-dependent plasticity in healthy subjects in a placebo-controlled, randomized, double-blind crossover design. We found that the agonists in all three neuromodulating transmitter systems (NE: methylphenidate; DA: cabergoline; ACh: tacrine) enhanced practice-dependent plasticity, whereas the antagonists decreased it (NE: prazosin; DA: haloperidol; ACh: biperiden). Enhancement of plasticity under methylphenidate and tacrine was associated with an increase in corticomotoneuronal excitability of the prime mover of the practice, as measured by the motor evoked potential amplitude, but with a decrease under cabergoline. Our findings demonstrate that agonists and antagonists in various neuromodulating transmitter systems produce significant and oppositely directed modifications of practice-dependent plasticity in human motor cortex. Enhancement of plasticity occurred through different strategies that either favoured extrinsic (NE, ACh) or intrinsic (DA) modulating influence on the motor cortical output network.

Key Words: acetylcholine • human motor cortex • monoamines • practice-dependent plasticity • transcranial magnetic stimulation


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