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Open Access Highly Accessed Research article

Synergistic effects of noradrenergic modulation with atomoxetine and 10 Hz repetitive transcranial magnetic stimulation on motor learning in healthy humans

Matthias Sczesny-Kaiser1*, Alica Bauknecht1, Oliver Höffken1, Martin Tegenthoff1, Hubert R Dinse2, Dirk Jancke2, Klaus Funke3 and Peter Schwenkreis1

Author Affiliations

1 Department of Neurology, BG-Universitaetsklinikum Bergmannsheil Bochum, Buerkle-de-la-Camp-Platz 1, 44789 Bochum, Germany

2 Institute for Neuroinformatics, Ruhr-University Bochum, 44780 Bochum, Germany

3 Department of Neurophysiology, Medical Faculty, Institute of Physiology, Ruhr-University Bochum, 44780 Bochum, Germany

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BMC Neuroscience 2014, 15:46  doi:10.1186/1471-2202-15-46

Published: 2 April 2014



Repetitive transcranial magnetic stimulation (rTMS) is able to induce changes in neuronal activity that outlast stimulation. The underlying mechanisms are not completely understood. They might be analogous to long-term potentiation or depression, as the duration of the effects seems to implicate changes in synaptic plasticity. Norepinephrine (NE) has been shown to play a crucial role in neuronal plasticity in the healthy and injured human brain. Atomoxetine (ATX) and other NE reuptake inhibitors have been shown to increase excitability in different systems and to influence learning processes. Thus, the combination of two facilitative interventions may lead to further increase in excitability and motor learning. But in some cases homeostatic metaplasticity might protect the brain from harmful hyperexcitability. In this study, the combination of 60 mg ATX and 10 Hz rTMS over the primary motor cortex was used to examine changes in cortical excitability and motor learning and to investigate their influence on synaptic plasticity mechanisms.


The results of this double-blind placebo-controlled study showed that ATX facilitated corticospinal and intracortical excitability in motor cortex. 10 Hertz rTMS applied during a motor task was able to further increase intracortical excitability only in combination with ATX. In addition, only the combination of 10 Hz rTMS and ATX was capable of enhancing the total number of correct responses and reaction time significantly, indicating an interaction effect between rTMS and ATX without signs of homeostatic metaplasticity.


These results suggest that pharmacologically enhanced NE transmission and 10 Hz rTMS exert a synergistic effect on motor cortex excitability and motor learning in healthy humans.

rTMS; Neuromodulation; Norepinephrine; Atomoxetine; Plasticity; Motor cortex