Table 1. Description of transcranial magnetic stimulation (TMS) outcomes.
| TMS outcome | Stimulation characteristics | Mechanism of action | Studies |
|---|---|---|---|
| Motor thresholds | |||
| Resting motor threshold (RMT) | Lowest TMS stimulus intensity to elicit MEP with peak-to-peak amplitude of 50 μV in at least five of 10 consecutive trials, in resting target muscle (Rossini et al., 2015). Reported as % MSO. | Reflects the strength and size of the most excitable elements of the target muscle cortical representation, activity of glutamate its receptors (e.g., AMPA), and function of ion channels (e.g., VGSC) in cortical and spinal neuron populations (Rossini et al., 2015; Ziemann et al., 2015). Indicates the bias level of the cortical representation (Groppa et al., 2012; Rossini et al., 2015). May index demyelination and axonal damage (Snow et al., 2019). | Cruz-Martínez et al. (2000), Schmierer et al. (2002) |
| Corticospinal excitability | |||
| Motor evoked potential (MEP) | Deflection in EMG trace of target muscle following delivery of threshold or suprathreshold TMS pulse to target muscle cortical representation (Rossini et al., 2015; Ziemann et al., 2015). Measured in active or resting muscle. MEP amplitude increases in sigmoidal relationship with TMS stimulus intensity. This stimulus-response curve requires incrementally increasing TMS stimulus intensity to examine corresponding increases in MEP amplitudes due to faster temporo-spatial summation at cortico-motoneuronal synapses (Rossini et al., 2015). Higher stimulus intensities improve synchronization of neuronal firing (Magistris et al., 1998). The stimulus-response curve indexes the excitability of the least to most excitable neuronal populations in the motor representation (Groppa et al., 2012; Ridding & Rothwell, 1997). Corticospinal conduction properties can be examined by observing MEP latency or waveform characteristics (Groppa et al., 2012; Rossini et al., 2015; Snow et al., 2019). | Reflects summation of action potentials in corticospinal axons which synapse on spinal motor neurons. MEP amplitudes and stimulus-response curves characterize the recruitment gain, variability, and excitability of corticospinal neuron populations (Capaday, 1997; Carson et al., 2013; Devanne, Lavoie & Capaday, 1997; Ridding & Rothwell, 1997; Talelli et al., 2008). Reflects activity of glutamatergic, GABAergic, and putatively serotonergic and noradrenergic neurons (Rossini et al., 2015; Ziemann et al., 2015). May index demyelination-induced conduction deficits or axonal damage (Snow et al., 2019). |
Cruz-Martínez et al. (2000), Hess et al. (1987), Kale et al. (2009), Kale, Agaoglu & Tanik (2010), Kandler et al. (1991), Mayr et al. (1991), Pisa et al. (2020), Ravnborg et al. (1992), Schmierer et al. (2000), Tataroglu et al. (2003) |
| Corticospinal conduction | |||
| Central motor conduction time (CMCT) | Difference between motor cortex-to-muscle latency (onset latency of MEP) and spinal cord-/brainstem-to-muscle latency (Rossini et al., 2015). Spinal cord-/brainstem-to-muscle latency is estimated by stimulating spinal nerve roots (nerve root latency) or the peripheral nerve (F-wave latency) innervating the target muscle (Rossini et al., 2015). Measured in active or resting muscle. Reported as difference between motor cortex-to-muscle and spinal cord-/brainstem-to-muscle latencies. | Reflects cortical output latency, the conduction time of the corticospinal tract between the motor cortex and brainstem or spinal motor neurons (Rossini et al., 2015). Posited as one of the more clinically useful TMS methods in examinations of MS because of its ability to detect demyelination and conduction loss (Chen et al., 2008; Vucic et al., 2023) | Beer, Rösler & Hess (1995), Caramia et al. (2004), Cruz-Martínez et al. (2000), Facchetti et al. (1997), Hess et al. (1987), Jung et al. (2006), Kale et al. (2009), Kale, Agaoglu & Tanik (2010), Kandler et al. (1991), Leocani et al. (2006), Magistris et al. (1999), Mayr et al. (1991), Ravnborg et al. (1992), Schmierer et al. (2000, 2002), Tataroglu et al. (2003) |
| Triple stimulation technique (TST) | Delivery of suprathreshold TMS over the target muscle cortical representation, supramaximal electrical stimulation over the distal part of the peripheral nerve supplying the target muscle, and a second supramaximal electrical stimulation over the proximal part of the same nerve (Erb’s point) (Rossini et al., 2015). Timing of stimuli is individualized to ensure action potentials induced by TMS collide with the corticospinal volleys from peripheral nerve stimulations (Rossini et al., 2015). A TST test curve is compared to a control curve derived from triple stimulation of the peripheral neve (Rossini et al., 2015). Reported as amplitude/area ratio of test curve relative to control curve. | This method results in “re-synchronization” of corticospinal action potentials at the level of the peripheral motor neuron and overcomes trial-to-trial variability in MEPs that is caused by phase cancellation and asynchronous firing of corticospinal motor neurons (Rossini et al., 2015). The main utility of TST is to examine corticospinal conduction deficits induced by demyelination (Chen et al., 2008; Vucic et al., 2023). | Magistris et al. (1999) |
| Silent periods | |||
| Corticospinal silent period (CSP) | Also known as contralateral silent period (CSP). Quiescence in rectified EMG trace after MEP, when TMS is delivered during tonic contraction of target muscle (Rossini et al., 2015). CSP duration increases linearly with TMS stimulus intensity (stimulus-response curve) (Rossini et al., 2015). Reported as onset latency or duration of silent period. | Generated by spinal (recurrent inhibition, refractoriness of spinal motor neurons, post-synaptic inhibition) and intracortical inhibitory circuits (Rossini et al., 2015). The stimulus-response curve partly reflects gain and excitability characteristics of GABAergic inhibitory interneurons (Rossini et al., 2015; Ziemann et al., 2015). Short and long CSPs are mediated by GABAA- and GABAB-receptor activity, respectively (Rossini et al., 2015; Ziemann et al., 2015). The exact structural and functional mechanisms–including cortical versus spinal contributions–represent an area of intense scrutiny across the literature (Hupfeld et al., 2020; Škarabot et al., 2019; Yacyshyn et al., 2016). May index excitotoxicity (Snow et al., 2019). | Tataroglu et al. (2003) |
| Ipsilateral silent period (iSP) | Suppression of background rectified EMG trace following a suprathreshold TMS pulse, during tonic contraction of the homologous muscle ipsilateral to the target motor area (Rossini et al., 2015). Reported as onset latency, duration, depth, or transcallosal conduction time. | Reflects interhemispheric or transcallosal inhibition (Wassermann et al., 1991), the influence of one brain hemisphere over the other via projections across the corpus callosum or other commissural pathways (Hupfeld et al., 2020). Proxy of cortical glutamatergic and GABABergic neuron activity (Ferbert et al., 1992; Wassermann et al., 1991). May index interhemispheric conduction loss or axonal damage (Jung et al., 2006; Llufriu et al., 2012; Neva et al., 2016; Snow et al., 2019). | Jung et al. (2006), Schmierer et al. (2000), Schmierer et al. (2002) |
Note:
AMPA, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, ionotropic transmembrane glutamate receptor; EMG, electromyography; GABA, gamma-aminobutyric acid; GABAA, ionotropic GABA receptor and ligand-gated ion (chloride, bicarbonate) channel; GABAB, G-protein (via potassium channels) coupled metabotropic GABA receptor; MSO, maximum stimulator output; VGSC, voltage-gated sodium channel.