Short-term and long-term plasticity interaction in human primary motor cortex

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.