Transcranial magnetic stimulation (TMS) is an indirect, non-invasive means of stimulating the human brain. In the procedure, an electromagnetic coil, placed against a subject’s head, is used to generate a strong magnetic field that passes through the scalp and into the individual's targeted brain region in order to induce action potentials.
As a technique, transcranial magnetic stimulation can be used to interfere with brain function to make causal inferences about the involvement about brain areas in cognitive processes. Alternatively, TMS can also be applied at certain frequencies or burst intervals to induce changes in plasticity, which can cause changes in the excitability of the cortex. The changes in excitability have been likened to long-term potentiation and long-term depression, which are thought to underly an increase or decrease in the likelihood of action potentials taking place, respectively.
TMS was first used by Anthony Barker and his team in 1985 to non-invasively stimulate the motor cortex (M1) while measurements from muscle tissue (caused by the application of TMS) were made using electromyography (EMG) techniques. Since these early experiments, TMS has now become one of the primary methods of exploring brain functionality in human subjects. With the advent of neuronavigation and neuroimaging, imaging techniques can be used to derive co-ordinates or targets for TMS, allowing TMS coils to be placed accurately and reliably to confirm whether the involvement of brain regions is causal or correlational.
Transcranial magnetic stimulation (and repetitive transcranial magnetic stimulation (rTMS) in particular) are commonly used today in research exploring the technique’s effects on neurological diseases and conditions such as depression, Alzheimer's disease, Parkinson’s disease, migraine and more.
TMS is often used in conjunction with electroencephalography (EEG) techniques in TMS-EEG experiments: this combination provides researchers with a clear means of examining TMS' effects on the brain through the measurement of TMS-evoked potentials and cortical oscillations.
Applications of TMS
What is TMS?
TMS, which stands for 'transcranial magnetic stimulation', is a non-invasive method of stimulating the brain through applying a strong magnetic field to an individual's head. The electric field passes through the scalp and into the targeted brain region in order to induce action potentials.
TMS is generally considered a safe and painless method of non-invasive brain stimulation, and the technique has been used extensively in research and clinical applications since the 1980s.
What kinds of TMS are there?
It is possible to deliver transcranial magnetic stimulation in a number of ways: from single-pulse TMS methods, up to complex quadripulse paradigms. Each different method of delivering TMS offers distinct advantages and drawbacks that researchers should be aware of when planning their research.
Single Pulse TMS
Single pulse TMS can be used to probe the chronometry of basic processes within the brain. In an influential study, Amassian et al. (1989) delivered single pulses of TMS to the early visual cortex at specific intervals after a visual target (displayed to the subject) appeared. These early applications of TMS revealed that the early visual cortex is critical in reporting target identity from 80ms - 120ms after a visual target appears. This is goes beyond simply associating a brain area with a certain task; it potentially reveals when a brain area is engaged in a certain process.
In addition to this, TMS pulses can be applied to probe changes in excitability as a function of pharmaceutical interventions or repetitive TMS. Here, the delivery of TMS to the motor cortex can be used as vehicle to understand whether these interventions have changed cortico-spinal excitability using the motor evoked potential (MEP). For instance, Darmani et al. (2016) administered GABA-AR antagonists and then used TMS to reveal that the drug decreased the motor threshold. This suggests that the drug increased excitability of the cortex as it was subsequently easier for TMS to evoke a certain amplitude of MEP.
Paired-Pulse TMS (ppTMS)
With paired pulse transcranial magnetic stimulation (ppTMS), TMS can be used to probe both intra-cortical connections (within the targeted brain region) and inter-cortical connections (between two separate brain regions).
For instance, by delivering a low-intensity TMS pulse prior to a higher-intensity TMS pulse (from the same coil), it is possible to reduce the resultant motor evoked potential (MEP) amplitude by altering the activating inhibitory neutrons within the motor cortex (M1). (Kujirai et al., 1991)
Conversely, using two TMS coils to study inter-cortical connections, it becomes possible to examine the interactions between the motor cortex in the left and right hemisphere (Chen et al., 2003 for hierarchical connections between the visual system, such as V5 and V1, V2 and V3 (Walsh & Pascual-Leone, 2005).
Repetitive Transcranial Magnetic Stimulation (rTMS)
In one example by Chen et al. (1997), the application of rTMS for 15 minutes at 0.9 Hz to the left motor cortex led to a noted decrease in the amplitude of motor evoked potentials (MEPs) in a prolonged effect that lasted for at least 15 minutes.
Other researchers have applied rTMS in ‘bursts’ (sometimes referred to as ‘trains’) of TMS pulses at fixed intervals— separated by an inter-burst or inter-train interval.
Repetitive TMS has been widely and extensively investigated for its potential therapeutic intervention applications and is currently a US Food and Drug Administration (FDA) approved treatment for depression, anxiety, and migraine.
Theta-Burst Stimulation (TBS)
Perhaps the most widely-known rTMS protocol amongst non-invasive brain stimulation researchers is ‘theta-burst stimulation’ (Huang et al., 2005), which requires administering three TMS pulses at 50 Hz every 200 ms (5 Hz). Theta-burst stimulation can be applied continuously (in the case of cTBS), or with eight-second intervals where no TMS is administered between the ‘trains’ (in the case of iTBS) (Huang et al., 2005).
Quadripulse Stimulation (QPS)
Quadripulse Stimulation (QPS) is a relatively new rTMS protocol that involves delivering a burst of four TMS pulses with either 5ms or 50ms between each pulse. Each of these bursts is then punctuated with a five-second interval, irrespective of whether a 5ms or 50ms delay was used (Hamada et al., 2008).
While the response to rTMS in general can be very variable (Hamada et al., 2013), research with quadripulse stimulation does seem to indicate that it may be less variable than other rTMS protocols. Research from Hamada et al. (2013) suggests that this could be a result of the monophasic pulse shape employed by quadripulse stimulation, which may be superior to the commonly-employed biphasic pulse shape in other types of rTMS.
A comprehensive list of TMS example studies and publications can be found in the 'references' section below.
Combination with Electroencephalography (TMS-EEG)
TMS can be combined with encephalography in order to provide a unique means of both manipulating the ongoing processes of the brain with TMS, as well as observing the consequences of these techniques on electrophysiology or participant behaviour. Read a full overview of TMS-EEG techniques, the ongoing research carried out with TMS-EEG, and how to set up your own TMS-EEG experiment on this page.
How is TMS applied to the correct brain region?
When using transcranial magnetic stimulation techniques, a researcher or clinician will generally need to target a very specific region of the brain. While it is possible to target a brain region manually by using a direct reference on the subject's scalp, the effort of holding a - often fairly heavy - TMS coil for an extended period of time can cause the operator to gradually drift away from the intended site of stimulation.
To alleviate this, some researchers make use of digital neuronavigation systems - such as Brainsight TMS Neuronavigation - which allow the TMS coil's position relative to the patient's head to be tracked in real time. Visual feedback delivered by the software can indicate immediately to the operator if they have moved away from their intended site of stimulation, and provides an easily-interpreted frame of reference to help them correct the positioning of the coil.
Additionally, advances in robotic technology have opened up new avenues for ensuring the accuracy of delivering transcranial magnetic stimulation. Robotic navigation systems work in tandem with neuronavigation software to help the TMS operator automatically navigate to the desired state of stimulation and to actively monitor and adjust the position of the TMS coil throughout the experiment to ensure that stimulation is always delivered to the correct site. These systems also offer built-in safety measures, such as pressure detectors, to ensure the maximum comfort and safety of the participant during all studies.
TMS Side Effects
While TMS is generally considered to be a safe and painless method of non-invasive brain stimulation, some individuals may experience some common mild side effects, including:
- Mild scalp discomfort at the stimulation site
- Twitching or tingling of facial muscles
- A feeling of lightheadedness
In rare occasions, more serious side effects may occur, including:
- Hearing loss, where recommended protection has not been worn.
A full review of TMS safety can be found in this journal reference.
Contraindications for TMS
Although TMS is well tolerated by the vast majority of subjects, there are a number of important contraindications that should be considered. Transcranial magnetic stimulation should not be used in populations with:
- Increased risk of, or susceptibility to, seizures
- Implanted/internal metal hardware (surgical plates, screws, etc.)
- Implanted medical electrical devices (cardiac pacemakers, medication pumps etc.)
- Other unstable medical conditions/disorders.
- The Brain Electrophysiological recording & STimulation (BEST) toolbox. Umair Hassan, Stephen Pillen, Christoph Zrenner, Til Ole Bergmann.. Brain Stimulation. November 2021
- The Role of Interneuron Networks in Driving Human Motor Cortical Plasticity. Masashi Hamada, Nagako Murase, Alkomiet Hasan, Michelle Balaratnam, John C. Rothwell. Cerebral Cortex. July 2013
- Bidirectional long-term motor cortical plasticity and metaplasticity induced by quadripulse transcranial magnetic stimulation. Masashi Hamada, Yasuo Terao, Ritsuko Hanajima, Yuichiro Shirota, Setsu Nakatani-Enomoto, Toshiaki Furubayashi, Hideyuki Matsumoto, Yoshikazu Ugawa. The Journal of Physiology. August 2008
- Theta burst stimulation of the human motor cortex. Ying-Zu Huang, Mark J Edwards, Elisabeth Rounis, Kailash P Bhatia, John C Rothwell. Neuron. January 2005
- Plasticity of the human motor system following muscle reconstruction: a magnetic stimulation and functional magnetic resonance imaging study. Robert Chen, Dimitri J Anastakis, Catherine T Haywood, David J Mikulis, Ralph T Manktelow. Clinical Neurophysiology. December 2003
- Fast backprojections from the motion to the primary visual area necessary for visual awareness. A Pascual-Leone, V Walsh. Science. April 2001
- Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. R. Chen, J. Classen, C. Gerloff, P. Celnik, E. M. Wassermann, M. Hallett, L. G. Cohen. Neurology. May 1997
- Corticocortical inhibition in human motor cortex. T Kujirai, M D Caramia, J C Rothwell, B L Day, P D Thompson, A Ferbert, S Wroe, P Asselman, C D Marsden. The Journal of Physiology. November 1993
- Suppression of visual perception by magnetic coil stimulation of human occipital cortex. Vahe E. Amassian, Roger Q. Cracco, Paul J.Maccabee, Joan B. Cracco, Alan Rudell, Larry Eberle. Electroencephalography and Clinical Neurophysiology. November 1989
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