Dose response curve of Associative Plasticity in human motor 1 cortex and interactions with motor practice

24 Associative plasticity is hypothesized to be an important neurophysiological correlate of 25 memory formation and learning with potentials for applications in neurorehabilitation and for 26 the development as new electrophysiological measures to study disorders of cortical plasticity. 27 We hypothesized that magnitude of paired associative stimulation (PAS) induced long term 28 potentiation like effect (LTP-like) depends on the number of pairs in PAS protocol. We also 29 hypothesized that homeostatic interaction of PAS with subsequent motor learning was related 30 to the magnitude of PAS induced LTP-like effect. We studied 10 healthy subjects. In 31 Experiment 1a, subjects received 90 (PAS90), 180 (PAS180), or 270 (PAS270) pairs of 32 stimuli, followed by a dynamic motor practice (DMP) 1 hour after the end of the PAS 33 protocols. In Experiment 1b, the DMP preceded the PAS protocol. In Experiment 2, the time 34 course of PAS270 was studied. We found that PAS270 resulted in greater increase in MEP 35 amplitudes compared to protocols with fewer pairs of stimuli. Moreover, the interaction 36 between PAS protocols with motor learning differed depending on the number of stimulus 37 pairs used to induce PAS. While DMP alone increased MEP amplitudes, DMP during the 38 LTP-like effects induced by PAS270 led to a LTD-like effect (homeostatic interaction). This 39 homeostatic interaction did not occur after PAS90 and PAS180. In conclusion, we found a 40 dose dependent effect of the number of stimulus pairs used in the PAS protocol on cortical 41 plasticity. Homeostatic interaction between PAS and DMP was observed only after PAS270. 42