Transcranial magnetic stimulation

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Transcranial magnetic stimulation
Transcranial magnetic stimulation.jpg
Transcranial magnetic stimulation
(schematic diagram)
Specialty Psychiatry, neurology
MeSH D050781

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. [1] [2]

Contents

Repetitive transcranial magnetic stimulation (rTMS) is a safe, effective, and FDA-approved treatment for major depressive disorder (approved in 2008), chronic pain (2013), and obsessive-compulsive disorder (2018). [3] It has strong evidence for certain neurological and psychiatric conditions—especially depression (with a large effect size), neuropathic pain, and stroke recovery—and emerging advancements like iTBS and image-guided targeting may improve its efficacy and efficiency. [4] [5]

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. [6]

Medical uses

A magnetic coil is positioned on the patient's head. Neuro-ms.png
A magnetic coil is positioned on the patient's head.

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. [8] TMS treatments are approved by the FDA in the US and by NICE in the UK for the treatment of depression and are provided by private clinics and some VA medical centers. TMS stimulates cortical tissue without the pain sensations produced in transcranial electrical stimulation. [9]

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. [10] 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. [10] [11] [12] [13] TMS has utility as a diagnostic instrument for myelopathy, amyotrophic lateral sclerosis, and multiple sclerosis. [14]

Treatment and efficacy

Repetitive transcranial magnetic stimulation (rTMS) is a safe, effective, and FDA-approved treatment for major depressive disorder (approved in 2008), chronic pain (2013), and obsessive-compulsive disorder (2018). [15]

Repetitive transcranial magnetic stimulation (rTMS) has been shown to produce significant clinical improvements in various neurological and psychiatric disorders. A group of European experts updated the therapeutic guidelines, reviewing studies up to the end of 2018. The highest level of evidence, Level A (definite efficacy), was found for high-frequency rTMS of the primary motor cortex (primary motor cortex) for neuropathic pain, high-frequency rTMS of the left dorsolateral prefrontal cortex (DLPFC) for depression, and low-frequency rTMS of the contralesional motor cortex for hand motor recovery after stroke. Level B evidence (probable efficacy) was found in conditions such as fibromyalgia, Parkinson’s disease, multiple sclerosis, post-traumatic stress disorder (PTSD), depression, and post-stroke aphasia, depending on the rTMS protocol used. No other conditions reached Level A or B evidence. These recommendations are based on differences in therapeutic outcomes between real and sham rTMS, replicated in multiple independent studies, although clinical relevance may still vary. [4]

A 2025 consensus review published in the Journal of the Neurological Sciences evaluated current clinical practices and recent advancements in TMS for depression. The review confirms that TMS is a safe and effective treatment modality, with a growing body of evidence supporting its use in treatment-resistant depression. Repetitive transcranial magnetic stimulation (rTMS), particularly high-frequency stimulation of the left dorsolateral prefrontal cortex, has demonstrated robust and reproducible acute antidepressant effects in major depressive disorder, with growing evidence supporting its efficacy, durability, and potential superiority over medication in treatment-resistant cases. Traditional repetitive TMS (rTMS) protocols have been well-established, while newer approaches—such as intermittent theta burst stimulation (iTBS) and individualized, image-guided targeting—have shown promise in reducing treatment time and potentially enhancing clinical outcomes. [16]

The effectiveness of TMS and quality of evidence behind it for treatment of depression have been questioned. [17] [18] [19] As with antidepressants and other interventions for depression, there is a large placebo response with sham control groups in TMS trials (Hedges's g = 0.8). [20] In any case, in a 2023 meta-analysis, TMS showed a large effect size advantage over sham for depression (Hedges' g = 0.791). [21]

Adverse effects

TMS is generally advertised as a safe alternative to medications such as SSRI's. The greatest immediate risk from TMS is fainting, though this is uncommon. Seizures have been reported, but are rare. [6] [22] [23]

Risks are higher for therapeutic repetitive TMS (rTMS) than for single or paired diagnostic TMS. [24] Adverse effects generally increase with higher frequency stimulation. [6]

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. [7] The coil is then connected to a pulse generator, or stimulator, that delivers electric current to the coil. [2]

Physics

TMS focal field.png
TMS - butterfly coils TMS Butterfly Coil HEAD.png
TMS – butterfly coils

TMS uses electromagnetic induction to generate an electric current across the scalp and skull. [25] [26] 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. [27]

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. [26]

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. [28] 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. [28]

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. [29] 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. [30]

Frequency and duration

The effects of TMS can be divided based on frequency, duration and intensity (amplitude) of stimulation: [31]

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. [36] 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. [37]

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. [38] 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. [6]

Research directions

TMS is oftentimes combined with electroencephalography (EEG) to assess functional connectivity. [39]

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. [40] [41]

The cerebellar cortex as a possible target of TMS has been investigated in combination with electromyography (EMG), and a reduction in the average amplitude of motor-evoked-potentials in small hand muscles has been observed when comparing paired-pulse TMS with a 6-8 ms interstimulus interval between cerebellar TMS and TMS to the primary motor cortex with single-pulse TMS to the primary motor cortex - a phenomenon termed cerebellum brain inhibition (CBI). [42] [43] Recent investigations have built upon this phenomenon to investigate the feasibility of combining EEG with cerebellar TMS to find signatures of the cerebellum-to-cerebrum functional connectivity in high temporal resultion. [44] By applying control conditions accounting for multisensory input and concomitant occipital cortex stimulation, and confirming effective cerebellar TMS by assessing CBI beforehand and modelling the induced electric field, EEG signatures of cerebellar TMS were proposed - as they may be utilized as therapeutic biomarkers to test pharmacotherapy efficacy in spinocerebellar ataxia in the future. [45] [46] [47] [48] However, these EEG signatures are still openly debated in the field of Brain Stimulation due to their inconsistency - likely, differing stimulation targets due to the lack of neuronavigation in these studies explain these discrepancies in results. [49] [50]

History

Luigi Galvani (1737–1798) undertook research on the effects of electricity on the body in the late-eighteenth century and laid the foundations for the field of electrophysiology. [51] In the 1830s, Michael Faraday (1791–1867) discovered that an electrical current had a corresponding magnetic field, and that changing one could induce its counterpart. [52]

Work to directly stimulate the human brain with electricity started in the late 1800s, and by the 1930s the Italian physicians Cerletti and Bini had developed electroconvulsive therapy (ECT). [51] ECT became widely used to treat mental illness, and ultimately overused, as it began to be seen as a panacea. This led to a backlash in the 1970s. [51]

In 1980, Merton and Morton successfully used transcranial electrical stimulation (TES) to stimulate the motor cortex. However, this process was very uncomfortable, and subsequently Anthony T. Barker began to search for an alternative to TES. [53] He began exploring the use of magnetic fields to alter electrical signaling within the brain, and the first stable TMS devices were developed in 1985. [51] [52] They were originally intended as diagnostic and research devices, with evaluation of their therapeutic potential being a later development. [51] [52] The United States' FDA first approved TMS devices in October 2008. [51]

Regulatory status

Speech mapping prior to neurosurgery

Nexstim obtained United States Federal Food, Drug, and Cosmetic Act§Section 510(k) clearance for the assessment of the primary motor cortex for pre-procedural planning in December 2009 [54] and for neurosurgical planning in June 2011. [55]

Depression

TMS is approved as a Class II medical device under the "de novo pathway". [56] [57]

Obsessive–compulsive disorder (OCD)

In August 2018, the US Food and Drug Administration (US FDA) authorized the use of TMS developed by the Israeli company Brainsway in the treatment of obsessive–compulsive disorder (OCD). [58]

In 2020, US FDA authorized the use of TMS developed by the U.S. company MagVenture Inc. in the treatment of OCD. [59]

In 2023, US FDA authorized the use of TMS developed by the U.S. company Neuronetics Inc. in the treatment of OCD. [60]

Other neurological areas

In the European Economic Area, various versions of deep TMS H-coils have CE marking for Alzheimer's disease, [61] autism, [61] bipolar disorder, [62] epilepsy, [63] chronic pain, [62] major depressive disorder, [62] Parkinson's disease, [64] [65] post-traumatic stress disorder (PTSD), [62] [66] schizophrenia (negative symptoms) [62] and to aid smoking cessation. [61] One review found tentative benefit for cognitive enhancement in healthy people. [67]

Coverage by health services and insurers

United Kingdom

The United Kingdom's National Institute for Health and Care Excellence (NICE) issues guidance to the National Health Service (NHS) in England, Wales, Scotland and Northern Ireland (UK). NICE guidance does not cover whether or not the NHS should fund a procedure. Local NHS bodies (primary care trusts and hospital trusts) make decisions about funding after considering the clinical effectiveness of the procedure and whether the procedure represents value for money for the NHS. [68]

NICE evaluated TMS for severe depression in 2007, finding that TMS was safe, but with insufficient evidence for its efficacy. [69] Guidance was updated and replaced in 2015, concluding that evidence for short‑term efficacy of repetitive transcranial magnetic stimulation (rTMS) for depression was adequate, although the clinical response is variable, and ruling that rTMS for depression may be used with arrangements for clinical governance and audit. [70]

In January 2014, NICE reported the results of an evaluation of TMS for treating and preventing migraine (IPG 477). NICE found that short-term TMS is safe but there is insufficient evidence to evaluate safety for long-term and frequent uses. It found that evidence on the efficacy of TMS for the treatment of migraine is limited in quantity, that evidence for the prevention of migraine is limited in both quality and quantity. [71]

As of 2025, use of rTMS in the UK was reported to have remained limited due to the cost of equipment and establishing treatment centres. Camilla Nord, head of the Mental Health Neuroscience Lab at the University of Cambridge said, "The NHS has unfortunately been far behind the US and Canada on rTMS, which is at least as effective as antidepressants, if not more". [72]

United States

Commercial health insurance

In 2013, several commercial health insurance plans in the United States, including Anthem, Health Net, Kaiser Permanente, and Blue Cross Blue Shield of Nebraska and of Rhode Island, covered TMS for the treatment of depression for the first time. [73] [74] [75] [76] In contrast, UnitedHealthcare issued a medical policy for TMS in 2013 that stated there is insufficient evidence that the procedure is beneficial for health outcomes in patients with depression. UnitedHealthcare noted that methodological concerns raised about the scientific evidence studying TMS for depression include small sample size, lack of a validated sham comparison in randomized controlled studies, and variable uses of outcome measures. [77] Other commercial insurance plans whose 2013 medical coverage policies stated that the role of TMS in the treatment of depression and other disorders had not been clearly established or remained investigational included Aetna, Cigna and Regence. [78] [79] [80]

Medicare

Policies for Medicare coverage vary among local jurisdictions within the Medicare system, [81] and Medicare coverage for TMS has varied among jurisdictions and with time. For example:

  • In early 2012 in New England, Medicare covered TMS for the first time in the United States. [82] [83] [84] [85] However, that jurisdiction later decided to end coverage after October, 2013. [86]
  • In August 2012, the jurisdiction covering Arkansas, Louisiana, Mississippi, Colorado, Texas, Oklahoma, and New Mexico determined that there was insufficient evidence to cover the treatment, [87] but the same jurisdiction subsequently determined that Medicare would cover TMS for the treatment of depression after December 2013. [88]

Limitations

There are serious concerns about stimulating brain tissue using non-invasive magnetic field methods such as uncertainty in the dose and localisation of the stimulation effect. [89] [90] [91] [92]

See also

References

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