Physiological Mechanisms of Modulation of Motor Cortex Excitability by 1Hz Suprathreshold rTMS

Many studies show consistently that repetitive transcranial magnetic stimulation (rTMS) with a frequency of 1Hz and an intensity of 115% of the resting motor threshold (RMT) performed for several minutes over the primary motor cortex (M1) leads to a depression of cortical excitability. Furthermore, most of the available studies concur on a facilitation of the non-stimulated contralateral M1. Little, however, is known about the physiological mechanisms underlying these effects. It is currently unclear whether the changes in the stimulated M1 are produced by increased excitability in cortical inhibitory circuits or decreased excitability in facilitatory neuronal circuits, and vice versa in the non-stimulated M1. In 11 healthy volunteers, we stimulated the left M1 for 15min with 1Hz rTMS of 115% RMT. Before, immediately after, and 30min after the rTMS train, we examined short-interval intracortical inhibition (SICI; ISI 2 and 4 ms), intracortical facilitation (ICF; ISI 10 ms), and short-interval cortical facilitation (SICF; ISI 1.5 ms) with an established paired-pulse protocol. Mean unconditioned MEP amplitudes and RMT were measured at the same time points. Two sessions were run at least one week apart, in one session the stimulated M1 was tested, in the other one the non-stimulated M1. Repetitive TMS led to the expected reduction of MEP amplitude in the stimulated M1, which was significant only immediately after the rTMS train. rTMS resulted in an increase in MEP amplitude in the non-stimulated M1, which lasted for at least 30min. RMT, SICI, ICF and SICF did not show any significant change in either M1, except of a long-lasting increase of SICF in the non-stimulated M1. In conclusion, the MEP increase in the non-stimulated M1 lasted longer than the MEP decrease in the stimulated M1. Only the long-lasting MEP increase was associated with a specific change in intracortical excitability (increase in SICF) compatible with an LTP-like mechanism. In contrast, modulation of motor cortical inhibition did not play a role in explaining the rTMS-induced changes in MEP amplitude.