Measuring motor cortex excitability with TMS

Transcranial magnetic stimulation (TMS) is used on people only by trained staff, under a protocol approved by an ethics committee and after a safety screening of every volunteer. It is generally well tolerated, but it is not free of risk: very rarely a pulse can provoke a seizure, and the strong magnetic field can act on metal and electronic implants near the coil. This page explains how the method works and how a session is run; it is not a guide to stimulating anyone, and its safety questionnaire is a simplified example, not medical advice.

In TMS a brief, strong current is passed through a coil held against the scalp. The rapidly changing magnetic field passes through the skull without pain and induces a small electric current in the cortex beneath the coil. Barker and colleagues showed in 1985 that a pulse over the motor cortex can make a hand muscle twitch in this way, through the intact scalp (Barker et al., 1985). The twitch is recorded with surface electrodes on the skin over the muscle (electromyography, EMG) as a motor evoked potential (MEP), a short biphasic wave about 20 to 25 ms after the pulse in a hand muscle.

Because MEPs are easy to record, they are used to measure how excitable the motor cortex and its pathway to the muscle are. The basic measures are the resting motor threshold (the weakest pulse that reliably gives a small MEP), the recruitment curve (how the MEP grows with intensity) and paired-pulse measures. In short-interval intracortical inhibition (SICI) a weak conditioning pulse a few milliseconds before a test pulse makes the test MEP smaller; Kujirai et al. (1993) found this suppression at intervals of 1 to 6 ms, and facilitation at 10 and 15 ms, and argued that it arises in the cortex. Standard procedures for these measures have been set out by a committee of the International Federation of Clinical Neurophysiology (Rossini et al., 2015).

Every step is run with one simulated volunteer, and a group is then tested with the chosen protocol. The simulator records each person's true threshold and hotspot, so the consequence of each decision is shown.

Learning objectives

• Explain why each safety-screening question is asked, and why exclusion criteria set in an approved protocol cannot be waived by the experimenter or the volunteer
• Place surface EMG electrodes over the first dorsal interosseous in a belly–tendon montage with a ground, and judge whether the baseline is quiet enough
• Explain how a figure-of-eight coil is held and oriented, and find the motor hotspot by a systematic search at a fixed intensity
• Determine the resting motor threshold by the relative-frequency method, counting MEPs of at least 50 µV yourself
• Record a recruitment curve and a paired-pulse SICI protocol with intensities set relative to each person's threshold
• Analyse a group study with the participant as the unit of analysis, a correction for multiple comparisons and an honest interpretation

Ethics and safety

A TMS study needs approval from an ethics committee (in India, an Institutional Ethics Committee following the ICMR National Ethical Guidelines of 2017; elsewhere, a research ethics committee or, in the United States, an institutional review board) before anyone is recruited, in line with the Declaration of Helsinki, written informed consent from every participant, and a safety screening before every session with the questionnaire approved for the study; the exclusion criteria are fixed in the protocol in advance and are not waived on the day. Stimulation is given only by staff trained in TMS, with a member of staff trained in first aid present and the local emergency procedures in place, within the limits on intensity and number of pulses that the protocol sets. Participants are offered ear plugs because the coil clicks loudly with each pulse, may stop at any moment without giving a reason, and are told about the usual mild side effects such as a passing headache. Data are stored under a participant code and handled under data protection law (in India, the Digital Personal Data Protection Act 2023; in the European Union, the General Data Protection Regulation).

Key terms

• TMS: Transcranial magnetic stimulation: a brief magnetic pulse from a coil on the scalp induces a current in the cortex beneath it.
• %MSO: Percentage of maximum stimulator output, the unit of TMS intensity. It depends on the machine and coil, so it is not comparable between laboratories.
• Figure-of-eight coil: A coil with two round wings side by side. The induced current is strongest under the junction of the wings, which makes stimulation focal.
• EMG: Electromyography: recording a muscle's electrical activity, here with electrodes on the skin.
• FDI: First dorsal interosseous: the small hand muscle between thumb and index finger that moves the index finger towards the thumb.
• Belly–tendon montage: Active electrode over the muscle belly and reference over a nearby bony point (here the index-finger knuckle), so that the recorded difference comes mainly from the muscle.
• MEP: Motor evoked potential: the EMG response to a TMS pulse, measured as its peak-to-peak amplitude in µV or mV.
• Hotspot: The coil position over the motor cortex that gives the largest and most consistent MEPs in the target muscle.
• RMT: Resting motor threshold: the lowest intensity giving MEPs of at least 50 µV in at least 5 of 10 trials in the relaxed muscle (the relative-frequency method).
• Recruitment curve: Also called the input–output curve: MEP amplitude plotted against intensity. It is sigmoidal and is often summarised by a Boltzmann fit with a plateau (MEPmax) and a midpoint (S50).
• SICI: Short-interval intracortical inhibition: a subthreshold conditioning pulse a few milliseconds before the test pulse (1 to 6 ms in Kujirai’s study; 2 or 3 ms is common) reduces the test MEP.
• ICF: Intracortical facilitation: with a conditioning–test interval of about 10 to 15 ms the test MEP becomes larger.
• ISI: Interstimulus interval: the time between the conditioning and the test pulse, in milliseconds.
• Holm correction: A correction for multiple comparisons: the p values of several tests are ranked and adjusted step by step, so that the chance of any false positive stays at or below 5%.