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SimTMS · training guide

TMS motor hotspot and motor threshold

Why the hotspot matters, what motor threshold is and how it is measured: a summary based on clinical guidelines and the methodological literature.

01About this guide

This guide is written to be read alongside the SimTMS · simHotpoint simulator. Each section gives the reasoning and evidence behind the procedure, and the In the simulator boxes show how the same topic is handled in the simulator. Citations link to sources verified in PubMed; the full list is at the end.

The guide is for teaching. It does not replace your laboratory's own protocol, your device manual or current safety guidelines.

02How TMS excites the motor cortex

A brief, strong current pulse through the TMS coil produces a rapidly changing magnetic field. By electromagnetic induction, this field drives an electric field (E-field) in the tissue below. The field strength is proportional to the rate of change of coil current (dI/dt); under a figure-of-eight coil it peaks beneath the junction of the two wings and falls off quickly with depth.

The hand muscles are represented in the primary motor cortex (M1) at the omega-shaped "hand knob" of the precentral gyrus (Yousry et al., 1997). TMS excites corticospinal neurons mostly indirectly, through synapses. Which descending volleys (D- and I-waves) are recruited depends on the type of stimulation, the direction of current in the cortex, the waveform and the coil (Di Lazzaro et al., 2004).

Coil orientation is therefore a critical variable. Over the hand area the largest responses are obtained when the induced current flows roughly perpendicular to the central sulcus, from posterior to anterior (PA). With a figure-of-eight coil this means holding the handle pointing about 45–50° backward and laterally from the midline (Mills et al., 1992; Brasil-Neto et al., 1992). Thresholds also differ with waveform (monophasic or biphasic), current direction and device (Kammer et al., 2001).

The response recorded from the target muscle with surface EMG is the motor evoked potential (MEP), usually described by its peak-to-peak amplitude (µV or mV) and latency (about 20–25 ms for hand muscles). As intensity increases, MEP amplitude grows along a sigmoid input–output curve (Devanne et al., 1997). MEPs vary considerably from trial to trial; the variability is largely random and reflects spontaneous fluctuations in cortical excitability (Kiers et al., 1993). That is why you judge the average of several trials, never a single MEP.

In the simulator

The MEP is a sigmoid function of effective stimulation under the coil, with trial-to-trial variability in cortical excitability and amplitude. Responses shrink as the handle angle departs from the optimum. Every MEP is measured peak to peak on screen.

03The motor hotspot and why it matters

Definition

The motor hotspot (optimal site) is the coil position and orientation at which a slightly suprathreshold stimulus evokes the largest and most consistent MEPs in the target muscle. (Groppa et al., 2012; Rossini et al., 2015)

The hotspot is more than a starting point; it is the reference for every measurement that follows:

  • Motor threshold is measured at the hotspot. By definition the hotspot is where the threshold is lowest. As the coil moves away, the field at the target falls and a higher intensity is needed for the same response. A threshold measured at the wrong site comes out too high.
  • Treatment dose is set relative to threshold. rTMS intensity is prescribed as a percentage of motor threshold; the pivotal multisite depression trial used 120% of rMT at 10 Hz (O'Reardon et al., 2007). An error in threshold is an error in dose: overestimation means overdosing and a safety risk, underestimation means ineffective treatment.
  • Other targets are measured from the hotspot. The classic "5-cm rule" for the dorsolateral prefrontal cortex (DLPFC) starts at the hotspot. Neuronavigation studies showed that the rule misses the DLPFC in many people: one study hit the intended area (BA9) in only 7 of 22 subjects (Herwig et al., 2001), and in another the standard procedure missed the DLPFC by about 2 cm (Ahdab et al., 2010).
  • All MEP-based measures are recorded at the hotspot. MEP amplitude, input–output curves, the cortical silent period and paired-pulse measures are only comparable when repeated at the same site and orientation. Guidelines stress that orientation is at least as critical as position (Rossini et al., 2015).

Note that the hotspot does not always coincide with the anatomical hand knob. In a neuronavigated study the hotspot lay over the central sulcus in only 45% of healthy and 25% of patient hemispheres, and was usually more anterior in the rest (Ahdab et al., 2016). The hotspot is therefore found functionally, with MEPs, not predicted from anatomy.

04Methods for finding the hotspot

In practice the methods complement each other: head measurement gives a starting point, the functional search finds the hotspot, navigation makes it reproducible, and modelling explains it.

MethodHowStrengthLimitation
Head measurement (10-20) (Klem et al., 1999) Cz lies where the nasion–inion and inter-tragal lines cross; the hand area start is around C3/C4, roughly 5 cm lateral to Cz. No equipment, quick. Ignores individual anatomy; a starting point only.
Functional search (with MEPs) (Groppa et al., 2012; Rossini et al., 2015) Slightly suprathreshold stimuli at a fixed orientation in small steps around the start; several MEPs per site; largest and most consistent response. Standard practice; reflects individual physiology. Operator dependent; needs enough trials because of MEP variability.
Visual observation Watching for a muscle twitch without EMG. No EMG needed. Crude; overestimates threshold (see motor threshold).
Neuronavigation (Julkunen et al., 2009; Gugino et al., 2001) Coil position and orientation are tracked in real time on the subject's MRI and recorded. Better placement precision and session-to-session reproducibility; more stable and larger MEPs. Needs equipment and MRI; does not by itself change the threshold value or remove MEP variability.
Mapping (Wilson et al., 1993) MEPs at every point of a grid; map, centre of gravity (CoG) and area. Shows the shape and shift of the representation; reproducible over months. Many stimuli and much time; a research method.
Automated / closed-loop search (Harquel et al., 2017; Tervo et al., 2020) A Bayesian algorithm picks the next site from the MEPs so far, with robotic or multi-locus systems. Fewer stimuli, operator independent, reproducible. Requires dedicated hardware.
E-field-based mapping (Weise et al., 2020; Numssen et al., 2021; Weise et al., 2023) MEPs from varied coil poses are related to E-fields computed in an individual head model; the muscle's cortical representation and the best coil pose are computed. Localisation at the cortical level; shows where stimulation acts. Needs MRI, modelling and about 180 stimuli; the protocol takes about 2 h of TMS.
In the simulator

You find Cz with a tape measure, move to the muscle-specific start, set the handle angle, then search functionally by firing pulses at any site and intensity. Results collect on a map, and those taken at a different intensity are marked as not comparable. Locking requires at least 6 distinct sites and 15 pulses.

05Motor threshold

Definitions

Resting motor threshold (rMT): the lowest stimulus intensity that evokes an MEP of ≥ 50 µV peak to peak in at least half of consecutive trials in the fully relaxed muscle, expressed as a percentage of maximum stimulator output (%MSO) (Rossini et al., 1994; Groppa et al., 2012; Rossini et al., 2015).

Active motor threshold (aMT): the lowest intensity that evokes an MEP in half of the trials while the target muscle contracts slightly, at about 10–20% of maximal force. The criterion differs by source: the 2015 IFCN report uses > 100 µV, while the 2012 IFCN practical guide says 200 µV is usually applied (Rossini et al., 2015; Groppa et al., 2012).

Motor threshold reflects the momentary excitability of the corticospinal system and membrane (ion-channel) excitability. Antiepileptic drugs that block sodium and calcium channels (carbamazepine, lamotrigine) raised the threshold, whereas vigabatrin, baclofen and gabapentin left it unchanged while reducing intracortical excitability (Ziemann et al., 1996).

Thresholds vary widely between people and also shift between sessions. In 102 hands the upper threshold averaged 46.6 ± 9.4% and the lower threshold 38.0 ± 8.6% MSO; over 1–3 months, changes larger than 13% (upper) or 11% (lower) were considered significant (Mills & Nithi, 1997).

Scalp–cortex distance has a strong effect: each additional millimetre from the coil requires about 3% more stimulator output (Stokes et al., 2005), a relation also used to adjust dose at targets outside the motor cortex. Thresholds also depend on waveform, current direction and device, so thresholds from different stimulators are not directly comparable (Kammer et al., 2001).

06Methods for determining threshold

Relative-frequency method (IFCN)

The procedure described in the 2015 IFCN report: start at about 35% MSO and increase in 5% steps until every trial gives an MEP > 50 µV. Then decrease in 1% steps until fewer than 5 of 10 trials are positive; that intensity plus 1% is the rMT (Rossini et al., 2015). The 2012 practical guide also uses ≥ 50 µV in 5 of 10 trials (Groppa et al., 2012).

The 2015 report adds a caution: the 5/10 rule has an accuracy of only 47.6%, against 96.2% for a 10/20 rule. It concludes that 10 of 20 trials are needed for reproducible results in clinical and research use, and notes that adaptive threshold-tracking methods are more accurate and usually faster (Rossini et al., 2015).

Two-threshold method (Mills–Nithi)

Two limits are measured: the lower threshold, the highest intensity with response probability 0, and the upper threshold, the lowest intensity with response probability 1 (Mills & Nithi, 1997). The true threshold lies between them. The method makes explicit that threshold is a probabilistic transition, not a sharp boundary.

Adaptive threshold hunting (PEST, maximum likelihood, Bayesian)

Each stimulus intensity is chosen from the threshold estimate computed from all responses so far, so stimuli concentrate around threshold (Awiszus, 2003). The maximum-likelihood strategy (MLS-PEST) gave the same EMG rMT as the IFCN method with fewer pulses (Mishory et al., 2004). Computer simulations compared PEST variants, and freely available software (MTAT) came from that work (Borckardt et al., 2006). In a head-to-head comparison there was no difference in rMT between the relative-frequency method and PEST (52.6% vs 53.7% MSO), and PEST needed fewer stimuli (Silbert et al., 2013). A Bayesian method using prior knowledge reached similar accuracy in about 7 pulses (Qi et al., 2011). It has also been pointed out that these tools can misestimate threshold when misconfigured (Koponen & Peterchev, 2022).

Visual method

Setting threshold by a visible twitch instead of EMG is practical but unreliable. An early six-subject study reported agreement within 10% (Pridmore et al., 1998). In a larger study, however, the visual threshold was on average 11.3% higher than the EMG threshold (range 0–27.8%). The difference exceeded 10% in 8 of 20 subjects and 25% in 2, and rTMS doses based on it would have exceeded safety limits in more than half of the subjects (Westin et al., 2014).

MethodCriterionPulsesNote
Relative frequency 5/10≥ 50 µV, 5/10dozensWidely used; low accuracy per the 2015 report
Relative frequency 10/20≥ 50 µV, 10/20moreRecommended by the 2015 IFCN report
Mills–Nithilower and upper thresholdmoderateShows the probabilistic nature of threshold
Adaptive (PEST/MLS)50% point of the probability curvefewEquivalent to relative frequency, faster
Bayesian (with prior)50% point of the probability curve~7Sensitive to the choice of prior
Visualvisible twitchvariableOverestimates threshold; not advised for dosing
In the simulator

In the rMT step you fire blocks of 10 pulses and count responses ≥ 50 µV, with a 50 µV band drawn on screen. The current version uses the 5/10 rule. Because the 10/20 rule recommended in the 2015 report and adaptive methods are described here, agree with your team which one you use clinically.

07Step-by-step procedure

The sequence below follows the seven steps of simHotpoint.

  1. Preparation

    Complete the safety screening questionnaire (Rossi et al., 2011). The subject sits comfortably with the target muscle fully relaxed. Surface EMG electrodes go in a belly–tendon montage, and the baseline is checked to be quiet. Give hearing protection to subject and operator.

  2. Find Cz

    Measure nasion–inion and tragus-to-tragus distances; Cz is where the midpoints cross. Distances from the mark to both ends should be equal on each line. (Klem et al., 1999)

  3. Starting point

    For right-hand muscles, start around C3 over the left hemisphere (about 5 cm lateral to Cz). For leg muscles, start near the midline around Cz.

  4. Coil orientation

    Keep the coil tangential to and touching the scalp. For the hand area the handle points about 45° backward and lateral to the midline, giving PA current in the cortex. (Mills et al., 1992; Brasil-Neto et al., 1992)

  5. Hotspot search

    Choose a fixed, slightly suprathreshold intensity. Move in small steps around the start and give several stimuli per site. For single-site MEP measurement, 5 stimuli gave within-session and 10 gave between-session reliability (Cavaleri et al., 2017). At the site with the largest, most consistent responses fine-tune the orientation, then mark the position or save it in the navigation system.

  6. Motor threshold

    At the hotspot, with the muscle relaxed, determine rMT with your chosen method (relative frequency or adaptive). Record the method and criterion.

  7. Record and review

    Record hotspot position (relative to Cz or as navigation coordinates), handle angle, rMT (%MSO), method, device, coil, waveform and muscle. If MEP amplitude will be compared, average 20–30 trials. (Goldsworthy et al., 2016)

08Common errors

  • The muscle is not fully relaxed. Slight contraction lowers threshold and steepens the input–output slope several-fold (Devanne et al., 1997), so you measure something closer to aMT than rMT. Watch the EMG baseline.
  • Trusting a single MEP. MEP variability is large (Kiers et al., 1993); give several stimuli per site.
  • Comparing MEPs taken at different intensities. Run the hotspot search at one fixed intensity.
  • Neglecting orientation. A reversed (AP) or badly angled handle raises the threshold (Kammer et al., 2001).
  • Tilting the coil. A coil that is not tangential or not touching increases coil–cortex distance, and each millimetre costs about 3% MSO (Stokes et al., 2005).
  • Setting threshold by eye. Use EMG whenever a dose will be derived from it (Westin et al., 2014).
  • Not marking the site. The coil drifts during and between sessions; without a mark or navigation record the same site cannot be found again (Julkunen et al., 2009).
  • Relying on few trials with the 5/10 rule. If a precise value is needed, use 10/20 or an adaptive method (Rossini et al., 2015).

09Electric-field modelling and SimNIBS

Electric-field modelling computes which brain region a coil in a given pose stimulates, and how strongly. SimNIBS is open-source software that builds a head model from MRI and computes TMS and tDCS fields with the finite-element method (Thielscher et al., 2015; Saturnino et al., 2019). The CHARM segmentation in version 4 separates the head into 15 tissues (Puonti et al., 2020), and coils are described by a database of 25 validated coil models (Drakaki et al., 2022).

Modelled fields have been shown to agree with physiology: on a 5×5 grid with 1 cm spacing around the hotspot, individual E-field strength correlated strongly with MEP amplitude (mean r ≈ 0.81) (Opitz et al., 2013). The approach has since been extended to computational optimisation of coil placement (Gomez et al., 2021) and to high-resolution mapping of a muscle's cortical representation by relating MEPs to the E-field (Weise et al., 2020; Numssen et al., 2021; Weise et al., 2023).

Modelling does not replace the functional search. In the coil-model comparison, estimated motor thresholds were not strongly related to field focality or depth and had to be determined separately (Drakaki et al., 2022). The model helps you understand where and why stimulation acts; the threshold is still measured.

In the simulator

In the evaluation step your locked coil pose is matched to the nearest simulation computed in SimNIBS 4.6 for the "ernie" example head with a MagVenture MC-B70 coil and shown on axial, coronal and sagittal MRI slices. The simulator's spatial fall-off is calibrated from this model's sensitivity analysis: a 10 mm shift lowers the field at the target by about 13%.

10Safety

Determining hotspot and threshold with single-pulse TMS is low-risk, but a screening questionnaire should precede every session (Rossi et al., 2011). Safety, ethical and application principles are collected in the 2009 consensus guidelines (Rossi et al., 2009); the 2021 update addresses only new issues and keeps the 2009 recommendations valid (Rossi et al., 2021). The first parameter limits for repetitive TMS were proposed in 1998 (Wassermann, 1998). Evidence levels for therapeutic indications are summarised in a separate guideline (Lefaucheur et al., 2020).

Practical points: the coil pulse makes a loud click, so use hearing protection. Screening asks about intracranial metal, implanted devices and seizure history. When the threshold is wrong, every dose derived from it is wrong too, so measuring it correctly is itself a safety issue.

11Reporting

An international consensus checklist exists for studies that use TMS to study the motor system: 27 items for single-pulse and 30 for paired-pulse studies, covering participant, methodological and analysis factors (Chipchase et al., 2012). For hotspot and threshold, report at least:

  • Stimulator, coil type and waveform; current direction in the cortex
  • Target muscle, EMG montage and muscle state (relaxed or active, contraction level)
  • How the hotspot was found, its position and handle angle; whether navigation was used
  • Threshold method and criterion (e.g. ≥ 50 µV, 10/20 or PEST) and its value in %MSO
  • Inter-stimulus interval and number of trials per site

The limits on what MEP size can tell us about behaviour and physiology have been discussed separately. (Bestmann & Krakauer, 2015)

12Glossary

MEP
Motor evoked potential; the response recorded from the target muscle after TMS, measured peak to peak.
rMT
Resting motor threshold; lowest intensity giving ≥ 50 µV MEPs in half of the trials in relaxed muscle.
aMT
Active motor threshold; threshold measured during slight contraction.
%MSO
Percentage of maximum stimulator output; the unit of intensity.
dI/dt
Rate of change of coil current (A/µs); the induced field is proportional to it.
PA / AP
Posterior-to-anterior / anterior-to-posterior current direction in the cortex.
Hotspot
Coil position and orientation giving the largest, most consistent MEPs in the target muscle.
Cz, C3, C4
Vertex and left/right central positions of the 10-20 system.
PEST
Parameter estimation by sequential testing; an adaptive threshold-estimation method.
CoG
Centre of gravity; the amplitude-weighted centre of an MEP map.
E-field
The electric field TMS induces in tissue (V/m).
SimNIBS
Open-source software for individualised electric-field modelling of brain stimulation.

13References

Guidelines and methodological standards

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Safety and treatment dosing

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Physiology and MEP measurement

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Hotspot localisation and coil positioning

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Motor threshold methods

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  3. Koponen LM, Peterchev AV. Preventing misestimation of transcranial magnetic stimulation motor threshold with MTAT 2.0. Brain Stimul. 2022;15(5):1073-6. PMID 35940558 · doi:10.1016/j.brs.2022.07.057
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Electric-field modelling and SimNIBS

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