The effect of pulse shape in theta-burst stimulation: monophasic vs biphasic TMS

Background Intermittent theta-burst stimulation (i)(TBS) is a transcranial magnetic stimulation (TMS) plasticity protocol. Conventionally, TBS is applied using biphasic pulses due to hardware limitations. However, monophasic pulses are hypothesised to recruit cortical neurons more selectively than biphasic pulses, thus yielding stronger plasticity effects. Monophasic and biphasic TBS can be generated using a custom-made pulse-width modulation-based TMS device (pTMS). Objective Using pTMS, we tested the hypothesis that monophasic iTBS would induce greater plasticity effects than biphasic, measured as induced changes in motor corticospinal excitability. Methods In a repeated-measures design, thirty healthy volunteers participated in three separate sessions, where monophasic and biphasic iTBS was applied to the primary motor cortex (M1 condition) or the vertex (control condition). Plasticity was quantified as changes in motor corticospinal excitability after versus before iTBS, by comparing peak-to-peak amplitudes of motor evoked potentials (MEP) measured at baseline and over 60 minutes after iTBS. Results Both monophasic and biphasic M1 iTBS led to significant increases in MEP amplitude. As predicted, monophasic iTBS induced a significantly larger effect than biphasic iTBS (linear mixed effect model analysis: (χ 2 (1) = 7.48, p = 0.006), which persisted even after subtracting each individual’s control (vertex) condition data from the M1 conditions (χ 2 (1) = 5.48, p = 0.019). Conclusions In this study, monophasic iTBS induced a stronger motor corticospinal excitability increase than biphasic within participants. This greater physiological effect suggests that monophasic iTBS may also have potential for greater functional impact, of interest for future fundamental and clinical applications of TBS.