If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Center for Information and Neural Networks (CiNet), Advanced ICT Research Institute, National Institute of Information and Communications Technology, Suita, 565-0871, JapanGraduate School of Frontier Biosciences, Osaka University, Suita, 565-0871, Japan
1 These two authors equally contributed to this work.
Masamichi J. Hayashi
Footnotes
1 These two authors equally contributed to this work.
Affiliations
Center for Information and Neural Networks (CiNet), Advanced ICT Research Institute, National Institute of Information and Communications Technology, Suita, 565-0871, JapanGraduate School of Frontier Biosciences, Osaka University, Suita, 565-0871, Japan
1 These two authors equally contributed to this work.
Affiliations
Center for Information and Neural Networks (CiNet), Advanced ICT Research Institute, National Institute of Information and Communications Technology, Suita, 565-0871, JapanGraduate School of Frontier Biosciences, Osaka University, Suita, 565-0871, JapanGraduate School of Information Science and Technology, The University of Tokyo, Tokyo, 113-8656, Japan
Quadripulse stimulation (QPS) is a patterned repetitive transcranial magnetic stimulation (rTMS) protocol that induces long term potentiation (LTP) and depression (LTD) like after-effect [
]. The after-effect of QPS, compared to another patterned rTMS protocol – theta burst stimulation, was reported to be stronger and less variable across participants [
Determinants of the induction of cortical plasticity by non-invasive brain stimulation in healthy subjects: induction of cortical plasticity by non-invasive brain stimulation.
]. Therefore, QPS emerges as a promising rTMS protocol for neuro-modulational research and treatment.
Recently, Deymed Diagnostic has developed a new stimulator specifically designed for QPS (DuoMAG MP-Quad, https://deymed.com/duomag-qps), which appears as a promising QPS-stimulator [
]. However, the after-effect induced by the DuoMAG MP-Quad has not yet been systematically investigated. The degree of after-effect may differ between QPS-stimulators considering that the waveform of stimulation pulses slightly differs between manufacturers [
]. We thus studied the QPS after-effects induced by the DuoMAG MP-Quad stimulator.
The participants were thirteen healthy adult volunteers comprising five females, 20–24 years of age (mean ± standard deviation: 21.5 ± 1.3). They were right-handed without a history of neurological or psychiatric disorders. Our study comprised two sessions with a within-subject design, applying two different types of QPS: QPS with an interpulse-interval of 5 ms (QPS5) and 50 ms (QPS50). These two protocols are expected to potentiate and depress the stimulated region most effectively [
]. The two sessions were separated by over a week, while their order was randomly assigned and counterbalanced across the participants. QPS was delivered over the left primary motor cortex (M1) using DuoMAG MP-Quad (Deymed Diagnostic s.r.o., Hronov, Czech Republic) with a butterfly-shaped 70-mm air-cooling coil (DuoMAG 70BF Air Cooled Coil; Deymed Diagnostic s.r.o., Hronov, Czech Republic). Throughout the session, motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous (FDI) muscle using a Brainsight surface-electromyogram (Rogue Research Inc., Montreal, Canada).
In each session, we first localized the hotspot, defined as the location evoking the largest MEPs, for the right FDI, and measured active motor threshold (AMT), defined as the intensity evoking MEPs larger than 100 μV in 5 out of 10 trials, with a slight contraction of the right FDI (∼10% of maximum voluntary contraction). We then measured 30 MEPs at the intensity evoking ∼500 μV of MEPs in the relaxed FDI as a baseline (pre-QPS). We further assessed alertness of the participants with a Stanford Sleepiness Scale (SSS; one participant presenting SSS >4 was excluded) [
]. After applying QPS, we measured 20 MEPs every 10 min until 90 min after QPS (post-10 to post-90) using the same intensity as for the pre-QPS. The coil position was monitored with a Brainsight (Rogue Research Inc.) to confirm stable coil position.
To evaluate the overall after-effect in QPS5 and QPS50, we first compared the MEPs between pre- and post-QPS (post-10 to post-90) for each QPS protocol. The grand mean MEP amplitudes of post-QPS normalized to pre-QPS (normalized MEP) was 1.71 ± 0.41 (from below mean ± standard deviation) in QPS5 and 0.82 ± 0.23 in QPS50 (Fig. 1A). Two-tailed paired Student's t-tests of the absolute MEP amplitude between pre- and post-QPS revealed significant enlargement after QPS5 (P < 0.001, d’ = 1.40) and significant reduction after QPS50 (P = 0.019, d’ = −0.80).
Fig. 1(A–C) Motor evoked potentials (MEPs) measured after QPS. (A) shows the grand-mean MEP amplitudes pooled across all post periods (post-10 to post-90), while (B) and (C) show the individual time courses of MEP amplitudes after QPS5 and QPS50, respectively. The vertical axis indicates the MEP amplitudes normalized by the baseline MEP amplitude in log scale, while the horizontal axes indicate QPS condition (A) or the time-block after QPS (B, C). (D) Comparison of baseline neurophysiological features between the QPS5 and QPS50 protocols. The active motor threshold (AMT), stimulus intensity (SI) for recording MEPs, SI for applying QPS, and mean baseline MEP amplitude are shown. The vertical axis of the left three panels shows the percentage of maximum stimulator output (% MSO), while the vertical axis of the rightmost panel shows the mean baseline MEP amplitude (micro volt). The mean (black cross) and standard error (error bar) are also provided.
To evaluate the time-course of MEPs, we separated the time-course into three time-blocks (post-10–30, post-40–60, and post-70–90), then averaged MEPs among each time-block [
]. The mean of normalized MEP in post-10–30, post-40–60, and post-70–90 was 1.51 ± 0.36, 1.79 ± 0.48, 1.79 ± 0.48, respectively, for QPS5 (Figs. 1B), and 0.84 ± 0.32, 0.80 ± 0.26, and 0.83 ± 0.17, respectively, for QPS50 (Fig. 1C) (see Supplementary Fig. 1 for the individual time courses of MEPs). Repeated-measures one-way ANOVA revealed significant effect of time-block in QPS5 (P < 0.001, η2 = 0.60) and moderate effect of time-block in QPS50 (P = 0.051, η2 = 0.24). Post-hoc paired t-tests of the absolute MEP amplitude with correction for multiple comparisons using the Holm's method also showed significant enlargement in all time-blocks by QPS5 (post-10–30, P = 0.002, d’ = 1.14; post-40–60, P = 0.001, d’ = 1.35; post-70–90, P = 0.001, d’ = 1.42), together with a moderate reduction in post-10–30 and significant reduction in post-40–60 and post-70–90 by QPS50 (post-10–30, P = 0.093, d’ = −0.53; post-40–60, P = 0.030, d’ = −0.90; post-70–90, P = 0.047, d’ = −0.76). In terms of baseline physiological parameters, no significant differences were found in AMT (P = 0.73), stimulus intensity (SI) for recording MEPs (P = 0.49), SI for applying QPS (P = 0.68) or mean baseline MEP amplitude (P = 0.29) (Fig. 1D) between the QPS5 and QPS50 sessions. These findings confirm steady experimental conditions across the sessions.
As expected from previous studies using the Magstim stimulator (The Magstim Co. Ltd., Whitland, UK) [
], MEPs were bidirectionally modulated for over 60 min by QPS with the newly developed stimulator. In previous studies, the grand mean normalized MEP was ∼2.0 [
] in QPS50. The grand means of normalized MEP measured in the present study (1.71 ± 0.41 in QPS5 and 0.82 ± 0.23 in QPS50) were comparable to those induced by the Magstim stimulator. These effects induced by the newly developed stimulator are supported by previous observations showing that short-interval intracortical inhibition is not sensitive to slight differences in TMS pulse waveform [
]. In the present study, the effect sizes of MEP-changes after QPS50 were found to be smaller than those measured after QPS5. A similar trend was reported in previous studies [
]. A promising approach to boost the after-effect of QPS50 would be to combine QPS with afferent electric stimulation of the peripheral nerves using paired-associative QPS [
Enhancement of LTD-like aftereffects by combining quadripulse stimulation for LTD with paired-associative peripheral nerve stimulation (paired-associative QPS).
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Appendix A. Supplementary data
The following is the Supplementary data to this article:
Determinants of the induction of cortical plasticity by non-invasive brain stimulation in healthy subjects: induction of cortical plasticity by non-invasive brain stimulation.
Enhancement of LTD-like aftereffects by combining quadripulse stimulation for LTD with paired-associative peripheral nerve stimulation (paired-associative QPS).
00057-2&id=gr1.jpg){kind=link}