Abstract
Theta-burst stimulation (TBS) is a patterned form of repetitive transcranial magnetic stimulation (rTMS) that has been used to induce long-term modulation (plasticity) of corticospinal excitability in a drastically shorter duration protocol than conventional rTMS protocols. In this study we tested the reliability of the effects of two well defined TBS protocols, continuous TBS (cTBS) and intermittent TBS (iTBS), especially in relation to sham TBS, within and across the same 24 participants. All TBS protocols were repeated after approximately 1 month to assess the magnitude and reliability of the modulatory effects of each TBS protocol. Baseline and post-TBS changes in motor evoked potentials (MEP—measure of corticospinal excitability) amplitudes were compared across the cTBS, iTBS and sham TBS protocols and between the initial and retest visits. Overall, across participants, at the initial visit, iTBS facilitated MEPs as compared to baseline excitability, with sham eliciting the same effect. cTBS did not show a significant suppression of excitability compared to baseline MEPs at either visit, and even facilitated MEPs above baseline excitability at a single time point during the repeat visit. Otherwise, effects of TBS were generally diminished in the repeat visit, with iTBS and sham TBS replicating facilitation of MEPs above baseline excitability at similar time points. However, no protocol demonstrated consistent intra-individual modulation of corticospinal excitability upon retest. As the first study to test both iTBS and cTBS against sham TBS across repeat visits, our findings challenge the efficacy and reliability of TBS protocols and emphasize the importance of accounting for sham effects of TBS. Furthermore, given that therapeutic effects of TBS are hypothetically derived from consistent and repeated modulation of brain activity, the non-replicability of plasticity and sham effects call into question these basic mechanisms.
Highlights
Theta-burst stimulation (TBS) is a patterned form of repetitive transcranial magnetic stimulation that has been used to induce long-term modulation of corticospinal excitability in a drastically shorter duration protocol than conventional rTMS protocols
In an effort to disentangle the impact of real and sham TMS effects, we corrected for the non-specific effects of cortical excitability by subtracting the modulation obtained by sham TBS at each time point from the active TBS data, better approximating the net effects of continuous TBS (cTBS) and intermittent TBS (iTBS) on corticospinal excitability
Bonferroni corrected paired t-tests confirmed that motor evoked potentials (MEPs) following iTBS were significantly larger than cTBS at T20 (p = 0.015) (Fig. 2a, Left Panel) and MEPs following sham were significantly larger than cTBS at T20 (p = 0.028), and T60 (p = 0.014)
Summary
Theta-burst stimulation (TBS) is a patterned form of repetitive transcranial magnetic stimulation (rTMS) that has been used to induce long-term modulation (plasticity) of corticospinal excitability in a drastically shorter duration protocol than conventional rTMS protocols. Effects of TBS were generally diminished in the repeat visit, with iTBS and sham TBS replicating facilitation of MEPs above baseline excitability at similar time points. We hypothesized that iTBS and cTBS would increase and decrease corticospinal excitability, respectively, whereas sham TBS would not modulate corticospinal excitability We expected these effects to hold at the group level across repeated visits and that individual responses to the protocols would be reliable. In an effort to disentangle the impact of real and sham (including mechanical and electrical activation of peripherical nervous system) TMS effects, we corrected for the non-specific effects of cortical excitability by subtracting the modulation obtained by sham TBS at each time point from the active TBS data, better approximating the net effects of cTBS and iTBS on corticospinal excitability
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