Facilitation of Motor Evoked Potentials in Response to a Modified 30 Hz Intermittent Theta-Burst Stimulation Protocol in Healthy Adults

Abstract

Theta-burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation (rTMS) developed to induce neuroplasticity. TBS usually consists of 50 Hz bursts at 5 Hz intervals. It can facilitate motor evoked potentials (MEPs) when applied intermittently, although this effect can vary between individuals. Here, we sought to determine whether a modified version of intermittent TBS (iTBS) consisting of 30 Hz bursts repeated at 6 Hz intervals would lead to lasting MEP facilitation. We also investigated whether recruitment of early and late indirect waves (I-waves) would predict individual responses to 30 Hz iTBS. Participants (n = 19) underwent single-pulse TMS to assess MEP amplitude at baseline and variations in MEP latency in response to anterior-posterior, posterior-anterior, and latero-medial stimulation. Then, 30 Hz iTBS was administered, and MEP amplitude was reassessed at 5-, 20- and 45-min. Post iTBS, most participants (13/19) exhibited MEP facilitation, with significant effects detected at 20- and 45-min. Contrary to previous evidence, recruitment of early I-waves predicted facilitation to 30 Hz iTBS. These observations suggest that 30 Hz/6 Hz iTBS is effective in inducing lasting facilitation in corticospinal excitability and may offer an alternative to the standard 50 Hz/5 Hz protocol.

Keywords: motor evoked potentials; neuroplasticity; theta-burst stimulation; transcranial magnetic stimulation.

Figure 1

Schematic representation of the experimental protocol. Participants first underwent monophasic single-pulse TMS to assess corticospinal excitability at baseline. Then, single-pulse TMS was applied to assess latency differences for MEPS elicited with the coil placed in different orientations: Anterior-Posterior (AP), Posterior-Anterior (PA), and Latero-Medial (LM). Afterward, participants received the modified 30 Hz/6 Hz intermittent theta-burst protocol (iTBS, 600 pulses, intensity 80% of the active motor threshold (aMT). Changes in corticospinal excitability after iTBS were measured at specific post-intervention times: 5-, 20- and 45-min. The intensity used to test corticospinal excitability at baseline and post-iTBS was set at 130% of the resting motor threshold (rMT).

Figure 2

(a) Distribution of MEP latencies observed at the different coil orientations. Note that latencies measured using the AP orientation were significantly longer than those measured with either the LM or PA orientation (*** p < 0.001, **** p < 0.0001). (b) Violin plot illustrating the frequency distribution of latency differences (AP-LM\PA) computed in all participants (b). The dashed line in the plot corresponds to the median (3.5 ms), while the upper and lower dotted lines correspond to the quartile.

Figure 3

Distribution of individual MEP log-amplitude measured across the different time points relative to iTBS application. MEP-log amplitude measured at 20- and 45-min post-iTBS were significantly different (** p < 0.01) from those measured at baseline (i.e., Time 0).

Figure 4

(a) Individual changes in MEP amplitude, when normalized relative to baseline, across the different time points post-iTBS. (b) Examples of MEP modulation recorded in response to 30 Hz iTBS. Facilitation (MEP > 110%) was observed in most (13/19) participants, while a minority exhibited either suppression (MEP < 90%, n = 3) or no modulation (90 < MEP < 110, n = 3).

Figure 5

(a) Relationship between latency differences measured in participants and corresponding normalized MEP amplitude in response to iTBS. (b) Comparison of MEP amplitude modulation post-iTBS in participants exhibiting ‘Early’ (n = 9) versus ‘Late’ I-waves recruitment. The two groups were split based on the median latency difference (i.e., Early group, differences < 3.5 ms; Late group, differences > 3.5 ms).