Paired-pulse stimulation, the application of two stimuli in close succession, is a useful tool to investigate cortical excitability. Suppression of the second response after short interstimulus intervals characterizes paired-pulse behavior. Although paired-pulse suppression is often studied as a marker of cortical excitability in humans, little is known about the influence of stimulation intensity on paired-pulse suppression. To systematically explore the effect of stimulus intensity on paired-pulse suppression of median nerve somatosensory evoked potentials (MNSEPs), we recorded single-pulse or paired-pulse MNSEPs in healthy volunteers using stimulation intensities ranging from the sensory threshold to 1.2 times the motor threshold using interstimulus intervals of 10, 30, and 100 ms. Of the various somatosensory evoked potential components, only the N20-P25 component showed an effect of intensity, where higher intensities resulted in stronger paired-pulse suppression. However, when only intermediate intensities were considered, paired-pulse suppression was not or only weakly influenced. Our data suggest that stimulation intensity in contrast to single pulse-evoked MNSEPs has only a weak influence on the paired-pulse suppression of early MNSEPs. Paired-pulse suppression is believed to arise from inhibition generated by intracortical networks. The lack of intensity dependence within the range tested can be considered as a step toward creating invariance against fluctuations of stimulus intensity. Thus, intracortical computations as apparent in paired-pulse behavior might be characterized by different properties compared with feed-forward processing.
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