Abstract
BackgroundRepetitive 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.ResultsThe 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.ConclusionThese 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.
Highlights
Repetitive transcranial magnetic stimulation is able to induce changes in neuronal activity that outlast stimulation
These results suggest that pharmacologically enhanced NE transmission and 10 Hz Repetitive transcranial magnetic stimulation (rTMS) exert a synergistic effect on motor cortex excitability and motor learning in healthy humans
Excitability measurements Considering the slopes of the stimulus response curve” (SRC), repeated measurement analysis of variance showed a significant effect of the within-subject factor “time” (F(1,2) = 19.26, p < 0.000)
Summary
Repetitive transcranial magnetic stimulation (rTMS) is able to induce changes in neuronal activity that outlast stimulation. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive tool for brain stimulation and is able to modulate brain activity beyond stimulation [1,2] The mechanisms underlying these long-term rTMS-effects could be analogous to long-term potentiation (LTP) or depression (LTD). These rTMS-induced changes in cortical excitability and brain activity can be measured by. For the measurement of rTMS-induced changes of cortical excitability, a single-pulse TMS (spTMS) protocol called “stimulus response curve” (SRC) is used. It tests stimulus intensity-dependent recruitment of corticospinal projections by means of spTMS [4]. The normalized ICF and SICI ratios give information about the activity of excitatory and inhibitory intracortical interneuronal circuits [7]
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