The timing of transcranial magnetic stimulation, and intensity and scalp site stimulated as variables influencing motor sequence performance in healthy subjects

Objective: The increasing therapeutic use of transcranial magnetic stimulation (TMS) in disorders of cortical excitability raises the need for reliable stimulus variables. Stimulation of cortical motor areas influences motor programming and execution. We investigated the effects of TMS delivered over various cortical motor areas during the reaction time (RT) on the execution of sequential rapid arm movements in healthy subjects. Methods: Subjects performed a five-submovement (S1–S5) motor sequence mainly involving upper limb proximal muscles. RT and movement time (MT) were measured. We delivered late (close to movement onset) and early (close to the go signal) TMS over the primary motor area (M1-FDI hot-spot for the first dorsal interosseus, M1-D hot-spot for the deltoid muscle), the premotor (PM) area, and the supplementary motor area (SMA), using subthreshold and suprathreshold intensity, single and triple pulses. Results: The motor sequence showed a characteristic pattern of submovement duration, S2–S3–S4 being faster than S1 and S5. Late TMS prolonged RT only when high-intensity pulses were delivered over M1-FDI. Single- and triple-pulse TMS over M1-D or M1-FDI significantly prolonged MT with a dose-related effect. Suprathreshold triplepulse TMS over the PM—but not over the SMA—also lengthened the MT but did not change RT. Early triplepulse TMS reduced the RT independently from the stimulus intensity and scalp site. SMA and PM—but not M1-D—stimulation also reduced the MT. Single-pulse TMS over the SMA, despite being delivered through a double-cone coil, did not change RT or MT. Conclusions: TMS-induced changes in the kinematics of a sequential arm movement depend closely on the timing of TMS interference, the scalp site stimulated, and the intensity (and number) of stimuli delivered. Late TMS interference inhibits, whereas early interference facilitates, motor performance. The cortical motor region most sensitive to TMS-induced inhibition is that below the scalp site for M1-FDI. In contrast, TMS-induced facilitation has no strict topographic organization. Particularly for MT (although inhibitory and facilitatory effects both depend on stimulation at high intensities) intensity is less crucial than timing of interference and scalp site.