title: Augmenting LTP-Like Plasticity in Human Motor Cortex by Spaced Paired Associative Stimulation.
abstract: Paired associative stimulation (PASLTP) of the human primary motor cortex (M1) can induce LTP-like plasticity by increasing corticospinal excitability beyond the stimulation period. Previous studies showed that two consecutive PASLTP protocols interact by homeostatic metaplasticity, but animal experiments provided evidence that LTP can be augmented by repeated stimulation protocols spaced by ~30 min. Here we tested in twelve healthy selected PASLTP responders the possibility that LTP-like plasticity can be augmented in the human M1 by systematically varying the interval between two consecutive PASLTP protocols. The first PASLTP protocol (PAS1) induced strong LTP-like plasticity lasting for 30-60 min. The effect of a second identical PASLTP protocol (PAS2) critically depended on the time between PAS1 and PAS2. At 10 min, PAS2 prolonged the PAS1-induced LTP-like plasticity. At 30 min, PAS2 augmented the LTP-like plasticity induced by PAS1, by increasing both magnitude and duration. At 60 min and 180 min, PAS2 had no effect on corticospinal excitability. The cumulative LTP-like plasticity after PAS1 and PAS2 at 30 min exceeded significantly the effect of PAS1 alone, and the cumulative PAS1 and PAS2 effects at 60 min and 180 min. In summary, consecutive PASLTP protocols interact in human M1 in a time-dependent manner. If spaced by 30 min, two consecutive PASLTP sessions can augment LTP-like plasticity in human M1. Findings may inspire further research on optimized therapeutic applications of non-invasive brain stimulation in neurological and psychiatric diseases.
authors.affiliation: Department of Neurology, Goethe-University Frankfurt, Germany; Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research, Eberhard-Karls-University Tübingen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Müller-Dahlhaus
authors.affiliation: Department of Neurology, Goethe-University Frankfurt, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lücke
authors.affiliation: Department of Neurology, Goethe-University Frankfurt, Germany; Department of Neurology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Ming-Kuei
authors.initials: MK
authors.lastname: Lu
authors.affiliation: Department of Neurology, Goethe-University Frankfurt, Germany.
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Arai
authors.affiliation: Department of Neurology, Goethe-University Frankfurt, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Fuhl
authors.affiliation: Institute of Biostatistics and Mathematical Modelling, Goethe-University Frankfurt, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.affiliation: Department of Neurology, Goethe-University Frankfurt, Germany; Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research, Eberhard-Karls-University Tübingen, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Ziemann
mesh_terms: D000328:Adult; D003198:Computer Simulation; D018592:Cross-Over Studies; D019054:Evoked Potentials, Motor / Q000502:physiology*; D005260:Female; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008475:Median Nerve / Q000502:physiology; D009044:Motor Cortex / Q000502:physiology*; D009473:Neuronal Plasticity; D050781:Transcranial Magnetic Stimulation / Q000523:psychology; D055815:Young Adult