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Repetitive transcranial magnetic stimulation (rTMS) over primary motor cortex (M1) elicits changes in motor evoked potential (MEP) size thought to reflect short- and long-term forms of synaptic plasticity, resembling short-term potentiation (STP) and long-term potentiation/depression (LTP/LTD) observed in animal experiments. We designed this study in healthy humans to investigate whether STP as elicited by 5-Hz rTMS interferes with LTP/LTD-like plasticity induced by intermittent and continuous theta-burst stimulation (iTBS and cTBS). The effects induced by 5-Hz rTMS and iTBS/cTBS were indexed as changes in MEP size. We separately evaluated changes induced by 5-Hz rTMS, iTBS and cTBS applied alone and those induced by iTBS and cTBS delivered after priming 5-Hz rTMS. Interactions between 5-Hz rTMS and iTBS/cTBS were investigated under several experimental conditions by delivering 5-Hz rTMS at suprathreshold and subthreshold intensity, allowing 1 and 5 min intervals to elapse between 5-Hz rTMS and TBS, and delivering one and ten 5-Hz rTMS trains. We also investigated whether 5-Hz rTMS induces changes in intracortical excitability tested with paired-pulse transcranial magnetic stimulation. When given alone, 5-Hz rTMS induced short-lasting and iTBS/cTBS induced long-lasting changes in MEP amplitudes. When M1 was primed with 10 suprathreshold 5-Hz rTMS trains at 1 min before iTBS or cTBS, the iTBS/cTBS-induced after-effects disappeared. The 5-Hz rTMS left intracortical excitability unchanged. We suggest that STP elicited by suprathreshold 5-Hz rTMS abolishes iTBS/cTBS-induced LTP/LTD-like plasticity through non-homeostatic metaplasticity mechanisms. Our study provides new information on interactions between short-term and long-term rTMS-induced plasticity in human M1.

Theta-burst stimulation (TBS) is currently used for inducing long-lasting changes in primary motor cortex (M1) excitability. More information is needed on how M1 is involved in early motor learning (practice-related improvement in motor performance, motor retention and motor consolidation). We investigated whether inhibitory continuous TBS (cTBS) is an effective experimental approach for modulating early motor learning of a simple finger movement in healthy humans. In a short task, 11 subjects practised 160 movements, and in a longer task also testing motor consolidation ten subjects practised 600 movements. During both experiments subjects randomly received real or sham cTBS over the left M1. Motor evoked potentials were tested at baseline and 7 min after cTBS. In the 160-movement experiment to test motor retention, 20 movements were repeated 30 min after motor practice ended. In the 600-movement experiment motor retention was assessed 15 and 30 min after motor practice ended, motor consolidation was tested by performing 20 movements 24 h after motor practice ended. Kinematic variables - movement amplitude, peak velocity and peak acceleration - were measured. cTBS significantly reduced the practice-related improvement in motor performance of finger movements in the experiment involving 160 movements and in the first part of the experiment involving 600 movements. After cTBS, peak velocity and peak acceleration of the 20 movements testing motor retention decreased whereas those testing motor consolidation remained unchanged. cTBS over M1 degrades practice-related improvement in motor performance and motor retention, but not motor consolidation of a voluntary finger movement.