Metaplasticity refers to the activity-dependent modification of the ability of synapses to undergo subsequent potentiation or depression, and is thought to maintain homeostasis of cortical excitability. Continuous magnetic theta-burst stimulation (cTBS; 50 Hz-bursts of 3 subthreshold magnetic stimuli repeated at 5 Hz) is a novel repetitive magnetic stimulation protocol used to model changes of synaptic efficacy in human motor cortex. Here we examined the influence of prior activity on the effects induced by cTBS. Without prior voluntary motor activation, application of cTBS for a duration of 20 s (cTBS300) facilitated subsequently evoked motor potentials (MEP) recorded from APB muscle. In contrast, MEP-size was depressed, when cTBS300 was preceded by voluntary activity of sufficient duration. Remarkably, even without prior voluntary activation, depression of MEP-size was induced when cTBS was extended over 40 s. These findings provide in vivo evidence for extremely rapid metaplasticity reversing potentiation of corticospinal excitability to depression. Polarity-reversing metaplasticity adds considerable complexity to the brain's response toward new experiences. Conditional dependence of cTBS-induced depression of corticospinal excitability on prior neuronal activation suggests that the TBS-model of synaptic plasticity may be closer to synaptic mechanisms than previously thought.

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