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. 2025 Jan;61(1):e16671.
doi: 10.1111/ejn.16671.

Transcranial Magnetic Stimulation Inter-Pulse Interval Does Not Influence Corticospinal Excitability to the Biceps Brachii During Submaximal Isometric Elbow Flexion

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Transcranial Magnetic Stimulation Inter-Pulse Interval Does Not Influence Corticospinal Excitability to the Biceps Brachii During Submaximal Isometric Elbow Flexion

David H Imeson et al. Eur J Neurosci. 2025 Jan.

Abstract

Previous research on resting muscles has shown that inter-pulse interval (IPI) duration influences transcranial magnetic stimulation (TMS) responses, which can introduce serious confounding variables into investigations if not accounted for. However, it is far less clear how IPI influences TMS responses in active muscles. Thus, the purpose of this study was to examine the relationship between IPI and corticospinal excitability during submaximal isometric elbow flexion. Corticospinal excitability to the biceps and triceps brachii was measured using motor evoked potentials (MEPs) elicited via TMS. Stimulation intensity was set to 120% of the biceps brachii's active motor threshold while participants produced 10% of their biceps' maximal muscle activity. TMS was delivered as separate trains of five stimulations, with experimental conditions differing between IPIs of 4, 6, 8, 10, 12 or 14 s. Results demonstrated that IPI had no influence on MEP amplitudes for either the biceps or triceps. However, when MEP amplitudes were expressed as a unitless ratio to pre-stimulus muscle activity, a main effect of time was found for the biceps; MEP amplitudes progressively decreased with successive stimulations (MEP 1:32.8 ± 5.9; MEP 5:27.7 ± 4.3, p < 0.05). These results suggest that IPI is unlikely to represent a confounding variable in TMS studies utilizing active contractions. However, studies looking to compare the amplitudes of single MEPs over time should be aware of the possibility that amplitudes may decrease with continuous stimulation. Future research should seek to examine even longer IPIs and explore the influence of higher stimulation intensities.

Keywords: active motor threshold; cortical excitability; human neurophysiology; motor control; motor evoked potential.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
A) Example of the experimental setup showing participant posture and wrist cuff placement. B) Example of the real‐time RMS biceps muscle activity display. The top and bottom dashed lines represent ±1.5% of the target 10% of maximum biceps brachii muscle activity. Participants were instructed to remain between these two lines by producing sufficient biceps brachii muscle activity. Vertical lines denote when participants were instructed to start/stop their contraction. Note: this image is artificially zoomed in for demonstration's sake; in reality, participants saw the entirety of the frame, with “start” and “relax” lines shown for all five stimulations in each train. C) Raw EMG data showing a single train for the four IPI experimental condition. Trains were repeated five times per condition with 1 min of rest provided in between, and, depending on the condition, MEPs were spaced out in either 4, 6, 8, 10, 12, or 14 s IPIs.
FIGURE 2
FIGURE 2
Group (mean ± SD, n = 12) and individual pre‐stimulus muscle activity (displayed as % of MVIC) for A) the biceps brachii and B) the triceps brachii. Bars are shaded based on the MEP number within the train of five stimulations; the darkest black bars are the first MEP elicited within a train, while the lightest white bars are the fifth and final MEP elicited within a train.
FIGURE 3
FIGURE 3
Group (mean ± SD, n = 12) and individual peak‐to‐peak MEP amplitudes (displayed as % of Baseline) for A) the biceps brachii and B) the triceps brachii. Bars are shaded based on the MEP number within the train of five stimulations; the darkest black bars are the first MEP elicited within a train, while the lightest white bars are the fifth and final MEP elicited within a train.
FIGURE 4
FIGURE 4
Group (mean ± SD, n = 12) and individual peak‐to‐peak biceps brachii MEP amplitudes displayed relative to pre‐stimulus biceps brachii muscle activity. Values are displayed for each MEP number elicited within a train collapsed across all IPI conditions. *Denotes a significant difference (p < 0.05) from MEP 1. Denotes near significant difference (p = 0.051) from MEP 1.

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