Running title: Auditory modulation of motor cortical excitability 11 Word count: 4827 (Abstract -Figure legends) 12 Abstract 22 23 Loud sounds have been demonstrated to increase motor cortex excitability when transcranial 24 magnetic stimulation (TMS) is synchronized with auditory evoked N100 potential measured from 25 electroencephalography (EEG). The N100 potential is generated by an afferent response to sound 26 onset and feature analysis, and upon novel sound it is also related to the

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... l reaction. Arousal 27 reaction is known to originate from the ascending reticular activating system of the brainstem and to 28 modulate neuronal activity throughout the central nervous system. In this study we investigated the 29 difference of motor evoked potentials (MEPs) when deviant and novelty stimuli were randomly 30 interspersed in a train of standard tones. Twelve healthy subjects participated in this study. Three 31 types of sound stimuli were used: 1) standard stimuli (800Hz), 2) deviant stimuli (560Hz) and 32 novelty stimuli (12 different sounds). In each stimulus sequence 600 stimuli were given. Of these, 33 90 were deviant stimuli randomly placed between the standard stimuli. Each of 12 novel sounds 34 was presented once in pseudo-randomized order. TMS was randomly mixed with the sound stimuli 35 so that it was either synchronized with the individual N100 or trailed the sound onset by 200 ms. 36 All sounds elicited an increase in motor cortex excitability. The type of the sound had no significant 37 effect. We also demonstrated that TMS timed at 200 ms interval caused a significant increment of 38 MEPs. This contradicted our hypothesis that MEP amplitudes to TMS synchronized with N100 39 would be greater than to TMS at 200 ms after a sound, and remains unexplained. 40 41