Multi-pulse transcranial magnetic stimulation of human motor cortex produces short-latency corticomotor facilitation via two distinct mechanisms

Kesselheim, J.; Siebner, H. R.; Takemi, M.; Christiansen, L.; Karabanov, A. N.

doi:10.1101/2022.02.19.481138

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bioRxiv · 10.1101/2022.02.19.481138

Multi-pulse transcranial magnetic stimulation of human motor cortex produces short-latency corticomotor facilitation via two distinct mechanisms

Kesselheim, J.·Siebner, H. R.·Takemi, M.·Christiansen, L.·Karabanov, A. N.

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Abstract

BackgroundSingle-pulse transcranial magnetic stimulation of the precentral hand representation (M1HAND) can elicit indirect waves in the corticospinal tract at a periodicity of ~660 Hz, called indirect or I-waves. These synchronized descending volleys are produced by transsynaptic excitation of fastconducting monosynaptic corticospinal axons in M1-HAND. Paired-pulse TMS can induce short-interval intracortical facilitation (SICF) of motor evoked potentials (MEPs) at inter-pulse intervals that match I-wave periodicity. ObjectiveTo examine whether short-latency corticospinal facilitation engages additional mechanisms independently of I-wave periodicity. MethodsIn 19 volunteers, one to four biphasic TMS pulses were applied to left M1-HAND with interpulse interval was adjusted to the first peak or first trough of the individual SICF curve. TMS was applied at different intensities to probe the intensity-response relationship. ResultsPairs, triplets, or quadruplets at individual peak-latency facilitated MEP amplitudes across a wide range of TMS intensities compared to single pulses. Multi-pulse TMSHAND at individual troughlatency also produced a consistent facilitation of MEP amplitude. Short-latency facilitation at trough-latency was less pronounced than short-latency facilitation at peak-latency, but the relative difference in facilitation decreased with increasing stimulus intensity. Increasing the number of pulses from two to four pulses had only a modest effect on MEP facilitation. ConclusionTwo mechanisms underly short-latency corticomotor facilitation caused by biphasic multi-pulse TMS. An intracortical mechanism is related to I-wave periodicity and engages fast-conducting direct projections to spinal motoneurons. A second corticospinal mechanism does not rely on I-wave rhythmicity and may be mediated by slower conducting indirect pyramidal tract projections from M1-HAND to spinal interneurons. The latter mechanism deserves more attention in TMS studies of the corticomotor system.

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Kesselheim, J., Siebner, H. R., Takemi, M., Christiansen, L., Karabanov, A. N.. 2022-02-22. Multi-pulse transcranial magnetic stimulation of human motor cortex produces short-latency corticomotor facilitation via two distinct mechanisms. https://doi.org/10.1101/2022.02.19.481138

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