Transcranial magnetic stimulation (TMS) is a noninvasive neurostimulation technique in which a changing magnetic field is used to induce an electric current in a targeted area of the brain through electromagnetic induction. A device called a stimulator generates electric pulses that are delivered to a magnetic coil placed against the scalp. The resulting magnetic field penetrates the skull and induces a secondary electric current in the underlying brain tissue, modulating neural activity.
Medical devices delivering repetitive transcranial magnetic stimulation (rTMS) appear to provide reasonably safe and effective treatments for major depressive disorder (MDD), chronic pain, and obsessive–compulsive disorder (OCD).Multiple sources:
However, evidence quality is variable, effect sizes are modest, and placebo responses are large; the extent of its efficacy and optimal treatment protocols are not certain.
Adverse effects of TMS appear rare and include fainting and seizure, which occur in roughly 0.1% of patients and are usually attributable to administration error.
Medical uses
TMS does not require surgery or electrode implantation. Its use can be diagnostic and/or therapeutic. Effects vary based on frequency and intensity of the magnetic pulses as well as the length of treatment, which dictates the total number of pulses given.
The Food and Drug Administration (FDA) has cleared rTMS devices for use in the treatment of depression in the United States (US). The National Institute for Health and Care Excellence (NICE) has issued guidance in the United Kingdom (UK) for that use. Private clinics and some Veterans Affairs medical centers provide treatments for that use. TMS stimulates cortical tissue without the pain sensations produced in transcranial electrical stimulation.
Diagnosis TMS can be used clinically to measure activity and function of specific brain circuits in humans, most commonly with single or paired magnetic pulses. The most widely accepted use is in measuring the connection between the primary motor cortex of the central nervous system and the peripheral nervous system to evaluate damage related to past or progressive neurologic insult.Multiple sources:
TMS has utility as a diagnostic instrument for myelopathy, amyotrophic lateral sclerosis, and multiple sclerosis.
Treatment and efficacy The FDA has found that devices producing rTMS are reasonably safe and effective for the treatment of MDD, chronic pain, and OCD; only minor adverse effects have usually accompanied these improvements. Guidelines issued through 2018 have claimed that TMS has shown strong evidence of effectiveness for depression, neuropathic pain, and post-stroke motor recovery, probable benefit for several other conditions, and insufficient evidence for the rest. Newer modalities of TMS, such as intermittent theta burst stimulation (iTBS), appear to match standard rTMS in efficacy while offering shorter treatment times and promising avenues for further optimization.Multiple sources:
rTMS had a large effect size advantage over sham for depression (Hedges's g = 0.791) in a 2023 meta-analysis.
Existing evidence suggests that rTMS, particularly targeting the dorsolateral prefrontal cortex (DLPFC) and the supplementary motor area, reduces OCD symptoms. Results for the medial prefrontal cortex and anterior cingulate cortex using deep transcranial magnetic stimulation are more variable; the overall heterogeneity of studies highlights the need for further research.
However, the effectiveness of rTMS and the quality of evidence behind it for treatment of depression have long been questioned.Multiple sources:
A 2023 re-analysis of 15 meta-analyses on TMS for major depression found that treatment effects vary widely, many reviews have a high risk of bias, and the apparent safety and efficacy of TMS may be overstated. As with antidepressants and other interventions for depression, there is a large placebo response with sham control groups in rTMS trials (Hedges's g = 0.8).
A 2011 review found that only 13.5% of 96 randomized control studies of rTMS to the DLPFC had reported blinding success and that, in those studies, people in real rTMS groups were significantly more likely to think that they had received real rTMS, compared with those in sham rTMS groups. Depending on the research question asked and the experimental design, matching the discomforts of rTMS (such as muscle twitching and pain) to distinguish the true effects of treatments from those of placebos can be an important and challenging issue.
Two pivotal clinical trials led to the first FDA marketing authorizations for rTMS devices indicated for use in treatment-resistant MDD in 2011 and 2013.Multiple sources:
Multiple sources:
While the results of both trials reportedly had statistical significance at 6weeks post-treatment, interventions outperformed sham by means of only 2 to 3points on the 60-point Montgomery–Åsberg Depression Rating Scale (MADRS).Multiple sources:
In the primary outcome measure for the second such trial, there were only 18 remitters (9.5% of the intention-to-treat population): 14.1% in the active treatment arm and 5.1% in the sham treatment arm. The odds ratio for the remitters was 4.2; 95% confidence interval, 1.32–13.24; p = 0.02. The number needed to treat (the average number of patients who need to be treated to prevent one additional bad outcome) was 12.
Adverse effects TMS is generally advertised as a safe alternative to medications such as SSRIs. The greatest immediate risk from TMS is fainting, though this is uncommon. Seizures have been reported, but are rare.Multiple sources:
Risks are higher for therapeutic rTMS than for single or paired diagnostic TMS. Adverse effects generally increase with higher frequency stimulation.
Procedure During the procedure, a magnetic coil is positioned at the head of the person receiving the treatment using anatomical landmarks on the skull, in particular the inion and nasion. The coil is then connected to a pulse generator, or stimulator, that delivers electric current to the coil.
Physics
TMS uses electromagnetic induction to generate an electric current across the scalp and skull.Multiple sources:
A plastic-enclosed coil of wire is held next to the skull and when activated, produces a varying magnetic field oriented orthogonally to the plane of the coil. The changing magnetic field then induces an electric current in the brain that activates nearby nerve cells in a manner similar to a current applied superficially at the cortical surface.
The magnetic field is about the same strength as magnetic resonance imaging (MRI), and the pulse generally reaches no more than 5 centimeters into the brain unless using a modified coil and technique for deeper stimulation.
Transcranial magnetic stimulation is achieved by quickly discharging current from a large capacitor into a coil to produce pulsed magnetic fields between 2 and 3 teslas in strength. Directing the magnetic field pulse at a targeted area in the brain causes a localized electrical current which can then either depolarize or hyperpolarize neurons at that site. The induced electric field inside the brain tissue causes a change in transmembrane potentials resulting in depolarization or hyperpolarization of neurons, causing them to be more or less excitable, respectively.
TMS usually stimulates to a depth from 2 to 4 cm below the surface, depending on the coil and intensity used. Consequently, only superficial brain areas can be affected. Deep TMS can reach up to 6 cm into the brain to stimulate deeper layers of the motor cortex, such as that which controls leg motion. The path of this current can be difficult to model because the brain is irregularly shaped with variable internal density and water content, leading to a nonuniform magnetic field strength and conduction throughout its tissues.Multiple sources:
Frequency and duration The effects of TMS can be divided based on frequency, duration and intensity (amplitude) of stimulation: Single or paired pulse TMS causes neurons in the neocortex under the site of stimulation to depolarize and discharge an action potential. If used in the primary motor cortex, it produces muscle activity referred to as a motor evoked potential (MEP) which can be recorded on electromyography (EMG). If used on the occipital cortex, 'phosphenes' (flashes of light) might be perceived by the subject. In most other areas of the cortex, there is no conscious effect, but behavior may be altered (e.g., slower reaction time on a cognitive task), or changes in brain activity may be detected using diagnostic equipment. rTMS produces longer-lasting effects that persist past the period of stimulation. rTMS can increase or decrease the excitability of the corticospinal tract depending on the intensity of stimulation, coil orientation, and frequency. Low frequency rTMS with a stimulus frequency less than 1 Hz is believed to inhibit cortical firing, while a stimulus frequency greater than 1 Hz, referred to as high frequency, is believed to provoke it. Though its mechanism is not clear, it has been suggested as being due to a change in synaptic efficacy related to long-term potentiation (LTP) and long-term depression like plasticity (LTD-like plasticity).
Coil types Most devices use a coil shaped like a figure-eight to deliver a shallow magnetic field that affects more superficial neurons in the brain. Differences in magnetic coil design are considered when comparing results, with important elements including the type of material, geometry and specific characteristics of the associated magnetic pulse.
The core material may be either a magnetically inert substrate ('air core'), or a solid, ferromagnetically active material ('solid core'). Solid cores result in more efficient transfer of electrical energy to a magnetic field and reduce energy loss to heat, and so can be operated with the higher volume of therapy protocols without interruption due to overheating. Varying the geometric shape of the coil itself can cause variations in focality, shape, and depth of penetration. Differences in coil material and its power supply also affect magnetic pulse width and duration.
A number of different types of coils exist, each of which produce different magnetic fields. The round coil is the original used in TMS. Later, the figure-eight (butterfly) coil was developed to provide a more focal pattern of activation in the brain, and the four-leaf coil for focal stimulation of peripheral nerves. The double-cone coil conforms more to the shape of the head. The Hesed (H-core), circular crown and double cone coils allow more widespread activation and a deeper magnetic penetration. They are supposed to impact deeper areas in the motor cortex and cerebellum controlling the legs and pelvic floor, for example, though the increased depth comes at the cost of a less focused magnetic pulse.
Research directions TMS is oftentimes combined with electroencephalography (EEG) to assess functional connectivity. Low-profile electrodes have been developed for concurrent TMS–EEG in order to reduce mechanical coupling and maintain stable contact during stimulation; one example is the ultra-flat TMS–EEG electrode g.Ladybird, developed by g.tec medical engineering GmbH, an Austria-based neurotechnology company.
For Parkinson's disease, early results suggest that low frequency stimulation may have an effect on medication associated dyskinesia, and that high frequency stimulation improves motor function.Multiple sources: