Transcranial magnetic stimulation | |
---|---|
Specialty | Psychiatry, neurology |
MeSH | D050781 |
Transcranial magnetic stimulation (TMS) is a noninvasive neurotherapy, a form of brain stimulation in which a changing magnetic field is used to induce an electric current at a specific area of the brain through electromagnetic induction. An electric pulse generator, or stimulator, is connected to a magnetic coil connected to the scalp. The stimulator generates a changing electric current within the coil which creates a varying magnetic field, inducing a current within a region in the brain itself. [1] : 3 [2]
TMS has shown diagnostic and therapeutic potential in the central nervous system with a wide variety of disease states in neurology and mental health, but has not demonstrated clinical worth for treatment of any other condition. [3]
Adverse effects of TMS appear rare and include fainting and seizure. [4]
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. [6] 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. [7]
TMS can be used clinically to measure activity and function of specific brain circuits in humans, most commonly with single or paired magnetic pulses. [8] 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. [8] [9] [10] [11] TMS has utility as a diagnostic instrument for myelopathy, amyotrophic lateral sclerosis, and multiple sclerosis. [12]
There is some evidence that TMS may have applications for a number of conditions including depression, fibromyalgia and neuropathic pain, and TMS treatment is covered by most private insurance plans as well as by traditional Medicare, but for no condition does the evidence rise to the level of showing clinical relevance. [3]
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. [4] [13] [14]
Risks are higher for therapeutic repetitive TMS (rTMS) than for single or paired diagnostic TMS. [15] Adverse effects generally increase with higher frequency stimulation. [4]
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. [5] The coil is then connected to a pulse generator, or stimulator, that delivers electric current to the coil. [2]
TMS uses electromagnetic induction to generate an electric current across the scalp and skull. [16] [17] 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. [18]
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. [17]
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. [19] 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. [19]
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. [20] 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. [21]
The effects of TMS can be divided based on frequency, duration and intensity (amplitude) of stimulation: [22]
Most devices use a coil shaped like a figure-eight to deliver a shallow magnetic field that affects more superficial neurons in the brain. [27] 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. [28]
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. [29] 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. [4]
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. [30] [31]
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. [32] 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. [33]
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). [32] 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. [32]
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. [34] 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. [32] [33] They were originally intended as diagnostic and research devices, with evaluation of their therapeutic potential being a later development. [32] [33] The United States' FDA first approved TMS devices in October 2008. [32]
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 [35] and for neurosurgical planning in June 2011. [36]
TMS is approved as a Class II medical device under the "de novo pathway". [37] [38]
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). [39]
In 2020, US FDA authorized the use of TMS developed by the U.S. company MagVenture Inc. in the treatment of OCD. [40]
In 2023, US FDA authorized the use of TMS developed by the U.S. company Neuronetics Inc. in the treatment of OCD. [41]
In the European Economic Area, various versions of deep TMS H-coils have CE marking for Alzheimer's disease, [42] autism, [42] bipolar disorder, [43] epilepsy, [44] chronic pain, [43] major depressive disorder, [43] Parkinson's disease, [45] [46] post-traumatic stress disorder (PTSD), [43] [47] schizophrenia (negative symptoms) [43] and to aid smoking cessation. [42] One review found tentative benefit for cognitive enhancement in healthy people. [48]
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. [49]
NICE evaluated TMS for severe depression in 2007, finding that TMS was safe, but with insufficient evidence for its efficacy. [50] 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. [51]
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. [52]
As of 2025 [update] 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". [53]
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. [54] [55] [56] [57] 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. [58] 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. [59] [60] [61]
Policies for Medicare coverage vary among local jurisdictions within the Medicare system, [62] and Medicare coverage for TMS has varied among jurisdictions and with time. For example:
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. [70] [71] [72] [73]
A phosphene is the phenomenon of seeing light without light entering the eye. The word phosphene comes from the Greek words phos (light) and phainein. Phosphenes that are induced by movement or sound may be associated with optic neuritis.
Neurotechnology encompasses any method or electronic device which interfaces with the nervous system to monitor or modulate neural activity.
Neurohacking is a subclass of biohacking, focused specifically on the brain. Neurohackers seek to better themselves or others by “hacking the brain” to improve reflexes, learn faster, or treat psychological disorders. The modern neurohacking movement has been around since the 1980s. However, herbal supplements have been used to increase brain function for hundreds of years. After a brief period marked by a lack of research in the area, neurohacking started regaining interest in the early 2000s. Currently, most neurohacking is performed via do-it-yourself (DIY) methods by in-home users.
Bioelectromagnetics, also known as bioelectromagnetism, is the study of the interaction between electromagnetic fields and biological entities. Areas of study include electromagnetic fields produced by living cells, tissues or organisms, the effects of man-made sources of electromagnetic fields like mobile phones, and the application of electromagnetic radiation toward therapies for the treatment of various conditions.
Treatment-resistant depression (TRD) is major depressive disorder in which an affected person does not respond adequately to at least two different antidepressant medications at an adequate dose and for an adequate duration. Inadequate response has most commonly been defined as less than 25% reduction in depressive symptoms following treatment with an antidepressant. Many clinicians and researchers question the construct validity and clinical utility of treatment-resistant depression as currently conceptualized.
Transcranial direct current stimulation (tDCS) is a form of neuromodulation that uses constant, low direct current delivered via electrodes on the head. This type of neurotherapy was originally developed to help patients with brain injuries or neuropsychiatric conditions such as major depressive disorder. It can be contrasted with cranial electrotherapy stimulation, which generally uses alternating current the same way, as well as transcranial magnetic stimulation.
Neuronetics is a Malvern, PA based, publicly traded company incorporated in Delaware in April 2003, that develops non-invasive treatments for psychiatric disorders that have shown resistance or lack of improvement using traditional medicine. The treatments are based upon neuromodulation technology.
Management of depression is the treatment of depression that may involve a number of different therapies: medications, behavior therapy, psychotherapy, and medical devices.
Magnetic seizure therapy (MST) is a proposed form of electrotherapy and electrical brain stimulation. It is currently being investigated for the treatment of major depressive disorder, treatment-resistant depression (TRD), bipolar depression, schizophrenia and obsessive-compulsive disorder. MST is stated to work by inducing seizures via magnetic fields, in contrast to ECT which does so using alternating electric currents. Additionally, MST works in a more concentrated fashion than ECT, thus able to create a seizure with less of a total electric charge. In contrast to (r)TMS, the stimulation rates are higher resulting in more energy transfer. Currently it is thought that MST works in patients with major depressive disorder by activating the connection between the subgenual anterior cingulate cortex and the parietal cortex.
Neurostimulation is the purposeful modulation of the nervous system's activity using invasive or non-invasive means. Neurostimulation usually refers to the electromagnetic approaches to neuromodulation.
Cortical stimulation mapping (CSM) is a type of electrocorticography that involves a physically invasive procedure and aims to localize the function of specific brain regions through direct electrical stimulation of the cerebral cortex. It remains one of the earliest methods of analyzing the brain and has allowed researchers to study the relationship between cortical structure and systemic function. Cortical stimulation mapping is used for a number of clinical and therapeutic applications, and remains the preferred method for the pre-surgical mapping of the motor cortex and language areas to prevent unnecessary functional damage. There are also some clinical applications for cortical stimulation mapping, such as the treatment of epilepsy.
BrainsWay Ltd. is an international company that is engaged in the development of a medical device that uses H-coil for deep transcranial magnetic stimulation as a non-invasive treatment for depression, OCD, and smoking addiction. The company was founded in 2003 and has offices in the US and Jerusalem.
Neuromodulation is "the alteration of nerve activity through targeted delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body". It is carried out to normalize – or modulate – nervous tissue function. Neuromodulation is an evolving therapy that can involve a range of electromagnetic stimuli such as a magnetic field (rTMS), an electric current, or a drug instilled directly in the subdural space. Emerging applications involve targeted introduction of genes or gene regulators and light (optogenetics), and by 2014, these had been at minimum demonstrated in mammalian models, or first-in-human data had been acquired. The most clinical experience has been with electrical stimulation.
Transcranial random noise stimulation (tRNS) is a non-invasive brain stimulation technique and a form of transcranial electrical stimulation (tES). Terney et al from Göttingen University was the first group to apply tRNS in humans in 2008. They showed that by using an alternate current along with random amplitude and frequency in healthy subjects, the motor cortex excitability increased for up to 60 minutes after 10 minutes of stimulation. The study included all the frequencies up to half of the sampling rate i.e. 640 Hz, however the positive effect was limited only to higher frequencies. Although tRNS has shown positive effects in various studies the optimal parameters, as well as the potential clinical effects of this technique, remain unclear.
Gait variability seen in Parkinson's Disorders arise due to cortical changes induced by pathophysiology of the disease process. Gait rehabilitation is focused to harness the adapted connections involved actively to control these variations during the disease progression. Gait variabilities seen are attributed to the defective inputs from the Basal Ganglia. However, there is altered activation of other cortical areas that support the deficient control to bring about a movement and maintain some functional mobility.
Abraham Zangen is an Israeli professor of neuroscience, head of the brain stimulation and behavior lab and chair of the psychobiology brain program at Ben-Gurion University of the Negev (BGU).
Non-invasive cerebellar stimulation is the application of non-invasive neurostimulation techniques on the cerebellum to modify its electrical activity. Techniques such as transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) can be used. The cerebellum is a high potential target for neuromodulation of neurological and psychiatric disorders due to the high density of neurons in its superficial layer, its electrical properties, and its participation in numerous closed-loop circuits involved in motor, cognitive, and emotional functions.
Todd M. Hutton is an American psychiatrist specializing in transcranial magnetic stimulation (TMS). He is Associate Clinical Professor of Psychiatry at the Keck School of Medicine of the University of Southern California. Hutton is also currently President of the Clinical TMS Society, as well as the founder and medical director of the Southern California TMS Center.
Friedhelm Christoph Hummel is a German neuroscientist and neurologist. A full professor at École Polytechnique Fédérale de Lausanne, he is the Defitech Chair of Clinical Neuroengineering, and the head of the Hummel Laboratory at EPFL's School of Life Sciences. He also is an associate professor of clinical neuroscience at the University of Geneva.
Raffaele Nardone is an Italian medical doctor, neurologist, and neuroscientist, known for his contributions in the field of clinical neurophysiology. He is the chair of the Department of Neurology at the Franz Tappeiner Hospital in Merano, Italy.
The present work only provides arguments to be confident that some rTMS protocols do something that is different from a placebo in some indications, but not that the results obtained are clinically relevant