Theta-burst repetitive transcranial magnetic stimulation suppresses specific excitatory circuits in the human motor cortex

Abstract

In four conscious patients who had electrodes implanted in the cervical epidural space for the control of pain, we recorded corticospinal volleys evoked by single-pulse transcranial magnetic stimulation (TMS) over the motor cortex before and after a 20 s period of continuous theta-burst stimulation (cTBS). It has previously been reported that this form of repetitive TMS reduces the amplitude of motor-evoked potentials (MEPs), with the maximum effect occurring at 5-10 min after the end of stimulation. The present results show that cTBS preferentially decreases the amplitude of the corticospinal I1 wave, with approximately the same time course. This is consistent with a cortical origin of the effect on the MEP. However, other protocols that lead to MEP suppression, such as short-interval intracortical inhibition, are characterized by reduced excitability of late I waves (particularly I3), suggesting that cTBS suppresses MEPs through different mechanisms, such as long-term depression in excitatory synaptic connections.

Figures

Figure 1. Epidural volleys evoked by magnetic stimulation in baseline and at different intervals after the end of repetitive magnetic stimulation in four subjects

Epidural volleys evoked by latero–medial (LM) magnetic stimulation (upper traces) and by posterior–anterior (PA) magnetic stimulation (lower traces) in baseline, and at different intervals after the end of repetitive transcranial magnetic stimulation (rTMS). LM magnetic stimulation evokes the earliest wave, i.e. the D wave that is indicated by the vertical dotted line. PA magnetic stimulation evokes a series of descending waves (I waves) and, in subject 1 only, a large D wave. The earlier I wave, the I1, is indicated by the second vertical dotted line. The amplitude of the I1 wave is reduced after rTMS. The most pronounced inhibition is observed 301–500 s after the end of repetitive stimulation. The D wave evoked by PA magnetic stimulation in subject 1, and the D wave evoked by LM magnetic stimulation in subject 4, are not substantially modified by repetitive stimulation.

Figure 2. Effects of repetitive megnetic stimulation on the amplitude of waves

A, effects of rTMS on the mean amplitude of the I1 wave in individual subjects (dashed lines), the continuous line represents the mean from the same subjects. Error bars indicate standard deviations. rTMS has a pronounced effect on the amplitude of the I1 wave (F3,9 = 9, P < 0.005). B, effects of rTMS on the mean amplitude of later I waves.

Figure 3. Effects of repetitive magnetic stimulation on the amplitude of motor evoked potentials

Effects of rTMS on the mean amplitude of motor-evoked potentials (MEPs) in individual subjects (dashed lines); the continuous line represents the mean from the same subjects. Error bars indicate standard deviations. rTMS has a pronounced effect on the amplitude of MEPs (F3,9 = 11.7, P ≤ 0.005).