GloNeuro

Virtual laboratory / Brain regions and the whole brain

Transcranial magnetic stimulation and motor evoked potentials

A TMS session with simulated participants: screening, hotspot, motor threshold, recruitment curve and paired-pulse inhibition, recorded by EMG.

Guided experiment: Measuring motor cortex excitability with TMS.

Transcranial magnetic stimulation and motor evoked potentials

Transcranial magnetic stimulation (TMS) passes a brief, strong current through a coil held on the scalp; the changing magnetic field induces a current in the cortex beneath it. Barker and colleagues first stimulated the human motor cortex in this way, non-invasively through the intact scalp (Barker et al., 1985). The response, recorded from a hand muscle with surface electromyography (EMG) as a motor evoked potential (MEP), is used in research to measure the excitability of the motor cortex and corticospinal pathway, for example as the resting motor threshold (RMT), the lowest stimulus intensity that evokes MEPs of at least 50 µV in at least 5 of 10 trials in the relaxed muscle. Intensities are set in %MSO (percentage of maximum stimulator output) or as a percentage of RMT. Standard procedures for these measures have been set out by a committee of the International Federation of Clinical Neurophysiology (IFCN) (Rossini et al., 2015). With paired pulses, a weak conditioning stimulus a few milliseconds before a test stimulus reduces the test response, an effect called short-interval intracortical inhibition (SICI), and the evidence placed this suppression in the cortex (Kujirai et al., 1993).

Design the experiment

Questions to investigate

  1. Move the coil across the grid. How quickly does the MEP fall with distance from the hotspot, and does the hotspot lie in the same place in every participant?
  2. Determine the resting motor threshold step by step, then automatically. How many blocks of 10 pulses does the relative-frequency method need, and how much do thresholds differ between participants?
  3. Record a recruitment curve. Where does it rise most steeply, and how does a light contraction of the muscle change it?
  4. Compare interstimulus intervals of 1 to 15 ms. At which intervals is the test MEP inhibited and at which facilitated, and how does this depend on the conditioning intensity?
  5. Reduce the number of trials per condition. How does the precision of a participant’s SICI ratio change, and what does that mean for the size of a study?
  6. Switch off the rejection of pre-activated trials, or run the conditions in blocks rather than in random order. How are the results biased?

In a real laboratory

A TMS study requires approval by an ethics committee (in India, an Institutional Ethics Committee following the ICMR National Ethical Guidelines of 2017; elsewhere, the equivalent body), written informed consent and, before every session, a safety-screening questionnaire (about implants, metal in the head, seizures and medication, for example), judged against exclusion criteria set in advance; staff trained in first aid are present. The checklist in the simulation is a simplified teaching example, not medical advice or a complete list. Surface electrodes are placed over the first dorsal interosseous in a belly–tendon montage after the skin is cleaned, with a ground at the wrist, and the EMG is monitored so that the hand stays relaxed. The coil is held tangentially to the scalp with the handle pointing backwards and laterally at about 45°. The hotspot is found systematically and marked or tracked by neuronavigation, and intensities are set relative to each participant’s threshold. Because single MEPs vary widely, many trials are recorded per condition; conditions are randomised, the gaps between pulses varied, and trials with pre-stimulus muscle activity rejected by a rule fixed in advance. Participants and, where possible, analysts are unaware of the condition. Ear plugs protect hearing from the click of the coil.

How the simulation works

Each participant has a motor threshold, hotspot position, spatial spread, maximal MEP, recruitment slope, trial-to-trial variability, MEP latency in the FDI (about 20–25 ms near threshold at rest, slightly shorter at higher intensities and during contraction) and paired-pulse sensitivity, drawn at random; all are approximate. The median MEP is a Boltzmann function of the effective intensity, which falls with distance from the hotspot and with a non-standard coil orientation. Single MEPs vary log-normally about the median, responses below about 10 µV are absent, and a light contraction lowers the threshold and enlarges the MEP. Paired pulses scale the test MEP by a factor that depends on the interstimulus interval (inhibition at short intervals, facilitation at 10–15 ms) and on the conditioning intensity, with the strongest inhibition at about 0.7–0.9 times threshold. Each EMG sweep combines stimulus artefacts, the MEP, electrode noise, mains interference (larger without a ground or skin preparation), occasional pre-activation and a slow drift of excitability within each block; amplitude and latency are measured within the chosen window. The anatomy of the induced field, neuronavigation, silent periods, the effect of test-pulse intensity on inhibition and the cumulative effects of repeated stimulation are not simulated.

  1. Barker, A. T., Jalinous, R., & Freeston, I. L. (1985). Non-invasive magnetic stimulation of human motor cortex. Lancet, 1(8437), 1106–1107. https://doi.org/10.1016/S0140-6736(85)92413-4
  2. Rossini, P. M., Burke, D., Chen, R., et al. (2015). Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clinical Neurophysiology, 126(6), 1071–1107. https://doi.org/10.1016/j.clinph.2015.02.001
  3. Kujirai, T., Caramia, M. D., Rothwell, J. C., et al. (1993). Corticocortical inhibition in human motor cortex. Journal of Physiology, 471, 501–519. https://doi.org/10.1113/jphysiol.1993.sp019912

About the simulations

Each simulator is a simplified version of a published model of cells, signals, instruments or behaviour, and runs in the web browser. The simulations show how the techniques work and how design choices change the results; they do not replace training in a laboratory.

All data are simulated and generated afresh on each run, so results vary between runs, as in real experiments. Nothing is stored or sent: designs and results are lost when the page is closed, unless the protocol is copied or the data file is downloaded.

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