Effects of methylphenidate on motor system excitability in a response inhibition task

BACKGROUND: Motor system excitability is based on a complex interaction of excitatory and inhibitory processes, which in turn are modulated by internal (e.g., volitional inhibition) and external (e.g., drugs) factors. A well proven tool to investigate motor system excitability in vivo is the transcranial magnetic stimulation (TMS). In this study, we used TMS to investigate the effects of methylphenidate (MPH) on the temporal dynamics of motor system excitability during a go/nogo task. METHODS: Using a double-blind, placebo-controlled, crossover design, 14 healthy adults (8 male, 6 female; aged 20–40 yrs) performed a spatial go/nogo task (S1-S2 paradigm) either under dl-methylphenidate (MPH, 20 mg) or placebo. TMS single and double-pulses (interstimulus interval: 3 ms) were delivered either at 120, 230 or 350 ms after the S2 stimulus (control, go and nogo trials). RESULTS: At the performance level, faster reaction times and a trend towards less impulsivity errors under MPH vs. placebo were observed. In nogo trials, i.e., when a prepared response had to be inhibited, motor evoked potentials (MEPs) had a smaller amplitude at an interval of 230 ms compared to 120 and 350 ms. The short-interval intracortical inhibition (SICI) increased over time. Under MPH, SICI in nogo trials was larger compared to placebo. With the interval between S2 and the TMS-pulse increasing, MEP amplitudes increased under MPH in nogo trials but an early inhibitory effect (at 120 ms) could also be observed. CONCLUSION: Our results show a distinct pattern of excitatory and inhibitory phenomena in a go/nogo task. MPH appears to significantly alter the dynamics of motor system excitability. Our findings suggest that a single dose of 20 mg MPH provides some fine-tuning of the motor system in healthy adults.