Characterization of the effect of associative cortical and peripheral nerve stimulation on the somatosensory evoked potentials and tactile discrimination performance in human subjects

Abstract

Repetitive median nerve stimulation combined with transcranial magnetic stimulation (TMS) over the contralateral postcentral region (paired associative stimulation, PAS) may induce changes in the amplitude of the P25 component of median nerve somatosensory evoked potentials (MN-SSEP). Here we used 64-channel electroencephalography (EEG) to reveal the early cortical MN-SSEP source(s) that is modified by PAS. In addition, spatial two-point discrimination was tested one day before (day1), immediately after (day2) and one day after (day3) PAS-intervention to assess possible changes of tactile sensitivity corresponding to somatosensory representations inside or outside of the cortical PAS-target, respectively. Eleven healthy volunteers participated in five experiments. MN-SSEPs (1800 trials, ˜3 Hz, 300% perceptual threshold) were recorded before and after PAS intervention. During the intervention the magnetic pulse (180 repetitions at 0.1 Hz, 150% resting motor threshold) was delivered over S1 at one of the following times relative to the subject’s N20 peak: −20, −2.5, 0 and 100 ms (PASN20 − 20, PASN20 − 2.5, PASN20 + 0, PASN20 + 100 ms, respectively). As a control, the TMS pulse was delivered at half time between two median nerve stimulations (PAS+5 s). Following PASN20 − 2.5 and PASN20 + 100 ms, a nonparametric permutation test across all subjects revealed an EEG amplitude increase between 21 and 31 ms. Source analysis showed that the effect of PASN20 − 2.5 ms could be accounted for by an amplitude increase of a tangential source localized at S1. The effect of PASN20 + 100 ms differed in its scalp topography from that of PASN20 − 2.5 ms and may be attributed to a different source at S1. In addition, PAS induced differential effects on tactile performance. Following PASN20 − 20 ms, performance in D2, but not in D5, improved significantly. In contrast, following PASN20 − 2.5 ms, there was a tendency for deterioration in tactile performance of the index finger which was correlated with MN-SSEP changes between 28 and 32 ms (R2 = 0.8). These results lend support to the notion that PASN20 − 2.5 modifies synapses located in superficial cortical layers in Brodmann area 3b and thereby may induce spatially specific differential behavioral changes in tactile performance.