Individual characterization of fast intracortical facilitation with paired biphasic-wave transcranial magnetic stimulation.

We characterized the short-interval intracortical facilitation (SICF) via modulation of transcranial magnetic stimulation (TMS) induced motor evoked potentials (MEPs) using paired-pulse stimulation, and analyzed the interactions with known SICF I-wave behavior. The objective was to optimize individual SICF to enhance TMS effects in motor mapping and therapeutic stimulations. We applied navigated TMS in nine healthy volunteers to study SICF. MEPs were measured for baseline using single-pulse TMS, and subsequently, paired-pulse TMS was applied to study SICF. The interstimulus interval (ISI) between the pulses was varied between 1.2 and 4.3 ms at 0.1 ms intervals. Ten MEPs were measured from three muscles (FDI, APB and ADM) in the dominant hand of the volunteer. We then fitted a 3-peak Gaussian model to the individual paired-pulse MEP vs. ISI curves to characterize each peak by latency, amplitude and width. Individual SICF I-wave interaction characteristics were successfully determined. The average peak latencies were 1.36 (I1-wave), 2.80 (I2-wave) and 4.29 (I3-wave) for the targeted FDI muscle. The peak amplitudes differed depending on the muscle (p = 0.001), with ADM muscle exhibiting greatest SICF effect, but no significant difference between the three peaks. In addition, the peak widths differed between all muscles (p<0.001), second peak being the widest. In conclusion, the individual SICF I-wave interaction characteristics were successfully determined revealing significant differences in peak features. This could enable application of SICF for enhancement of TMS effects in therapy, cortical mapping and basic neuroscience applications.

Efficient Mapping of the Motor Cortex with Navigated Biphasic Paired-Pulse Transcranial Magnetic Stimulation.

Navigated transcranial magnetic stimulation (nTMS) can be applied to locate cortical muscle representations. Usually, single TMS pulses are targeted to the motor cortex with the help of neuronavigation and by measuring motor evoked potential (MEP) amplitudes from the peripheral muscles. The efficacy of single-pulse TMS to induce MEPs has been shown to increase by applying facilitatory paired-pulse TMS (ppTMS). Therefore, the aim was to study whether the facilitatory ppTMS could enable more efficient motor mapping. Biphasic single-pulse TMS and ppTMS with inter-stimulus intervals (ISIs) of 1.4 and 2.8 ms were applied to measure resting motor thresholds (rMTs) as a percentage of the maximal stimulator output and to determine the cortical representation areas of the right first dorsal interosseous muscle in healthy volunteers. The areas, shapes, hotspots, and center of gravities (CoGs) of the representations were calculated. Biphasic ppTMS with ISI of 1.4 ms resulted in lower rMTs than those obtained with the other protocols (p = 0.001). With ISI of 2.8 ms, rMT was lower than with single-pulse TMS (p = 0.032). The ppTMS mapping was thus performed with lower intensity than when using single-pulse TMS. The areas, shapes, hotspots, and CoGs of the muscle representations were in agreement. Hence, biphasic ppTMS has potential in the mapping of cortical hand representations in healthy individuals as an alternative for single-pulses, but with lower stimulation intensity by utilizing cortical facilitatory mechanism. This could improve application of nTMS in subjects with low motor tract excitability.

Transcranial magnetic stimulation modulation of corticospinal excitability by targeting cortical I-waves with biphasic paired-pulses.

BACKGROUND: Transcranial magnetic stimulation (TMS) induced I-wave behavior can be demonstrated at neuronal population level using paired-pulses and by observing short-interval cortical facilitation (SICF). Advancements in stimulator technology have made it possible to apply biphasic paired-pulses to induce SICF. OBJECTIVE: Our aim was to characterize the SICF I-wave interaction by biphasic paired-pulses with the ultimate objective to enhance TMS effects via SICF in various TMS-applications. METHODS: We used biphasic paired-pulses in 15 volunteers to characterize corticospinal SICF using various 1.2-8.0ms inter-stimulus intervals, and measuring SICF input-output response. RESULTS: SICF interaction with the first I-wave (I1) was observed in the output responses (motor evoked potentials; MEPs) in all subjects. Most subjects (≥80%) also exhibited later SICF I-wave interaction. SICF at I1 was present at all applied intensities below 140% of resting motor threshold. At I2, we observed SICF only with intensities just above motor threshold. CONCLUSIONS: Biphasic paired-pulses can reliably induce SICF shown by the facilitatory I-wave interaction, and could therefore be applied with repetitive bursts to enhance responsiveness to TMS.

Facilitatory effect of paired-pulse stimulation by transcranial magnetic stimulation with biphasic wave-form.

Transcranial magnetic stimulation (TMS) is used to probe corticospinal excitability by stimulating the motor cortex. Our aim was to enhance the effects of biphasic TMS by coupling a suprathreshold test pulse and a following subthreshold priming pulse to induce short-interval intracortical facilitation (SICF), which is conventionally produced with monophasic TMS. Biphasic TMS could potentially induce the SICF effect with better energy-efficiency and with lower stimulus intensities. This would make the biphasic paired-pulses better applicable in patients with reduced cortical excitability. A prototype stimulator was built to produce biphasic paired-pulses. Resting motor thresholds (rMTs) from the right and left hand abductor pollicis brevis muscles, and the right tibialis anterior muscle of eight healthy volunteers were determined using single-pulse paradigm with neuronavigated TMS. The rMTs and MEPs were measured using single-pulses and three paired-pulse setups (interstimulus interval, ISI of 3, 7 or 15ms). The rMTs were lower and MEPs were higher with biphasic paired-pulses compared to single-pulses. The SICF effect was greatest at 3ms ISI. This suggests that the application of biphasic paired-pulses to enhance stimulation effects is possible.