Modulation of motor cortical excitability by paired associative stimulation (PAS) of the primary somatosensory cortex

Introduction: The primary somatosensory cortex (S1) plays a crucial role in learning and adapting of motor skills. Due to the high interconnectedness to primary motor cortex (M1), manipulation of S1 excitability offers an opportunity to alter M1 excitability function. We applied paired associative stimulation (PAS) to S1 in order to induce long-term potentiation (LTP)-like or long-term depression (LTD)-like effects in S1 and evaluated the consequences of S1-PAS on excitability in the adjacent M1. Methods: 12 young healthy right-handed subjects participated in 5 experimental sessions in a randomized crossover design. S1-PAS consisted of 225 pairs of electrical stimulation of the median nerve of the right hand followed by focal TMS to the left S1 given over 15min at a rate of 0.25Hz. The interstimulus interval was adjusted according to the individual N20 latency of the median nerve SEP, and was N20-2.5ms, N20-15ms, or N20+20ms in separate sessions in order to induce an increase, decrease or no change in S1 excitability [Wolters et al. 2005, J Physiol 565:1039]. Another two control sessions applied PAS to M1at intervals of N20-2.5ms or N20-15ms and adjusted TMS intensity. Finally, in three additional control sessions, TMS alone over S1, or median nerve stimulation alone, or 15min waiting were tested. S1 excitability was tested by median nerve cortical SEP components (N20-P25 amplitude), M1 excitability was tested by slopes of Boltzmann curve fitted MEP intensity curves centered on MEP 1mV (stimulus intensity range, 0.6-1.4 MEP 1mV) and by short-interval intracortical inhibition (SICI, interstimulus interval 2ms). Excitability measurements were obtained before and at two time points (0 and 30min) after intervention. Results: None of the interventions resulted in significant change in S1 excitability. In contrast, S1-PAS (N20-N2.5ms) but none of the other conditions resulted in a significant increase in slope of the MEP intensity curve. SICI remained unaffected in all conditions. Conclusions: Paired associative stimulation of S1 can result in M1 excitability enhancement. This effect is timing specific as it was observed only in the PAS-S1 (N20-2.5ms) condition, and topographically specific as it was not detected with M1-PAS (N20-2.5ms). Findings suggest that specific enhancement of M1 excitability is possible by modulation of S1-to-M1 input. This effect may be of therapeutic potential, for instance in stroke rehabilitation.