title: Short-term and long-term plasticity interaction in human primary motor cortex.
abstract: 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.
authors.affiliation: Neuromed Institute, Sapienza University of Rome, Viale dell'Università, 30 00185 Rome, Italy.
authors.forename: Ennio
authors.initials: E
authors.lastname: Iezzi
authors.forename: Antonio
authors.initials: A
authors.lastname: Suppa
authors.forename: Antonella
authors.initials: A
authors.lastname: Conte
authors.forename: Pietro
authors.initials: P
authors.lastname: Li Voti
authors.forename: Matteo
authors.initials: M
authors.lastname: Bologna
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berardelli
mesh_terms: D000328:Adult; D000818:Animals; D019054:Evoked Potentials, Motor / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D011897:Random Allocation; D050781:Transcranial Magnetic Stimulation / Q000379:methods