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{{Short description|Brain stimulation using magnetic fields}}

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Image	File:Transcranial magnetic stimulation.jpg| Caption = Transcranial magnetic stimulation(schematic diagram)| Speciality = Psychiatry, neurology | ICD10 = | ICD9 = | MeshID = D050781 | OtherCodes = |

Transcranial magnetic stimulation (TMS) is a noninvasive 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.NICE. January 2014 Transcranial magnetic stimulation for treating and preventing migraine{{rp|3}}Michael Craig Miller for Harvard Health Publications. July 26, 2012 Magnetic stimulation: a new approach to treating depression?TMS has shown diagnostic and therapeutic potential in the central nervous system with a wide variety of disease states in neurology and mental health, with research still evolving.JOURNAL, Groppa S, Oliviero A, Eisen A, Quartarone A, Cohen LG, Mall V, Kaelin-Lang A, Mima T, Rossi S, Thickbroom GW, Rossini PM, Ziemann U, Valls-Solé J, Siebner HR, 6, A practical guide to diagnostic transcranial magnetic stimulation: report of an IFCN committee, Clinical Neurophysiology, 123, 5, 858–882, May 2012, 22349304, 4890546, 10.1016/j.clinph.2012.01.010, JOURNAL, Lefaucheur JP, André-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipović SR, Hummel FC, Jääskeläinen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schönfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, Garcia-Larrea L, 6, Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS), Clinical Neurophysiology, 125, 11, 2150–2206, November 2014, 25034472, 10.1016/j.clinph.2014.05.021, 206798663,weblink JOURNAL, George, Mark S., Post, Robert M., Daily Left Prefrontal Repetitive Transcranial Magnetic Stimulation for Acute Treatment of Medication-Resistant Depression, American Journal of Psychiatry, April 2011, 168, 4, 356–364, 10.1176/appi.ajp.2010.10060864, 21474597, BOOK, Gaynes, Bradley N., Lux, Linda J., Lloyd, Stacey W., Hansen, Richard A., Gartlehner, Gerald, Keener, Patricia, Brode, Shannon, Evans, Tammeka Swinson, Jonas, Dan, Crotty, Karen, Viswanathan, Meera, Lohr, Kathleen N., Nonpharmacologic Interventions for Treatment-Resistant Depression in Adults, 2011, 22091472,weblink Agency for Healthcare Research and Quality, AHRQ Comparative Effectiveness Reviews, JOURNAL, Berlim, Marcelo T, Van den Eynde, Frederique, Jeff Daskalakis, Z, Clinically Meaningful Efficacy and Acceptability of Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) for Treating Primary Major Depression: A Meta-Analysis of Randomized, Double-Blind and Sham-Controlled Trials, Neuropsychopharmacology, 19 November 2012, 38, 4, 543–551, 10.1038/npp.2012.237, 23249815, 3572468, REPORT, Tarique, Perera, Mark, George, Geoffrey, Grammer, Philip, Janicak, Alvaro, Pascual-Leone, Theodore, Wirecki, April 27, 2015, TMS Therapy For Major Depressive Disorder: Evidence Review and Treatment Recommendations for Clinical Practice,weblink JOURNAL, Bersani, F.S., Minichino, A., Enticott, P.G., Mazzarini, L., Khan, N., Antonacci, G., Raccah, R.N., Salviati, M., Delle Chiaie, R., Bersani, G., Fitzgerald, P.B., Biondi, M., Deep transcranial magnetic stimulation as a treatment for psychiatric disorders: A comprehensive review, European Psychiatry, January 2013, 28, 1, 30–39, 10.1016/j.eurpsy.2012.02.006, 22559998, 29053871, JOURNAL, Dougall N, Maayan N, Soares-Weiser K, McDermott LM, McIntosh A, Transcranial magnetic stimulation (TMS) for schizophrenia, The Cochrane Database of Systematic Reviews, 2015, 8, CD006081, August 2015, 26289586, 10.1002/14651858.CD006081.pub2, 9395125,weblink 1893/22520, free, WEB, Pupil response may shed light on who responds best to transcranial magnetic stimulation for depression,weblink 2024-01-06, www.uclahealth.org, en, Adverse effects of TMS appear rare and include fainting and seizure.JOURNAL, Rossi, et al., Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines., Clinical Neurophysiology, January 2021, 132, 1, 269–306, 10.1016/j.clinph.2020.10.003, 33243615, 9094636, 225049093, Other potential issues include discomfort, pain, hypomania, cognitive change, hearing loss, and inadvertent current induction in implanted devices such as pacemakers or defibrillators.{{TOC limit|3}}

Medical uses

(File:Neuro-ms.png|thumb|285x285px|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.JOURNAL, 2015-09-01, Basic principles of transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS), Annals of Physical and Rehabilitation Medicine, en, 58, 4, 208–213, 10.1016/j.rehab.2015.05.005, 1877-0657, free, Klomjai, Wanalee, Katz, Rose, Lackmy-Vallée, Alexandra, 26319963, TMS treatments are approved by the FDA in the US and by NICE in the UK for the treatment of depression and are predominantly provided by private clinics. TMS stimulates cortical tissue without the pain sensations produced in transcranial electrical stimulation.BOOK, Lefaucher, Jean-Pascal, Handbook of Clinical Neurology, 2019, Elsevier, 9780444640321, 559–580,weblink 29 March 2024, 37,

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.JOURNAL, Rossini PM, Rossi S, Transcranial magnetic stimulation: diagnostic, therapeutic, and research potential, Neurology, 68, 7, 484–488, February 2007, 17296913, 10.1212/01.wnl.0000250268.13789.b2, 19629888, JOURNAL, Dimyan MA, Cohen LG, Contribution of transcranial magnetic stimulation to the understanding of functional recovery mechanisms after stroke, Neurorehabilitation and Neural Repair, 24, 2, 125–135, February 2010, 19767591, 2945387, 10.1177/1545968309345270, JOURNAL, Nowak DA, Bösl K, Podubeckà J, Carey JR, Noninvasive brain stimulation and motor recovery after stroke, Restorative Neurology and Neuroscience, 28, 4, 531–544, 2010, 20714076, 10.3233/RNN-2010-0552, TMS has utility as a diagnostic instrument for myelopathy, amyotrophic lateral sclerosis, and multiple sclerosis.JOURNAL, Chen, Robert, Cros, Didier, Curra, Antonio, Di Lazzaro, Vincenzo, Lefaucheur, Jean-Pascal, Magistris, Michel R., Mills, Kerry, Rösler, Kai M., Triggs, William J., Ugawa, Yoshikazu, Ziemann, Ulf, The clinical diagnostic utility of transcranial magnetic stimulation: Report of an IFCN committee, Clinical Neurophysiology, March 2008, 119, 3, 504–532, 10.1016/j.clinph.2007.10.014,

Treatment

{{expand section|date=January 2024}}Repetitive high frequency TMS (rTMS) has been investigated as a possible treatment option with various degrees of success in conditions includingJOURNAL, Lefaucheur, Jean-Pascal, André-Obadia, Nathalie, Antal, Andrea, Ayache, Samar S., Baeken, Chris, Benninger, David H., Cantello, Roberto M., Cincotta, Massimo, de Carvalho, Mamede, De Ridder, Dirk, Devanne, Hervé, Di Lazzaro, Vincenzo, Filipović, Saša R., Hummel, Friedhelm C., Jääskeläinen, Satu K., November 2014, Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS),weblink Clinical Neurophysiology, 125, 11, 2150–2206, 10.1016/j.clinph.2014.05.021, 1388-2457,

• Chronic neuropathic pain
• Motor diseases (e.g., Parkinson's disease, essential tremor)
• Amyotrophic lateral sclerosis
• Multiple sclerosis
• Epilepsy
• Disorders of consciousness (e.g., vegetative state or minimally conscious state)
• Alzheimer’s disease
• Psychiatric diseases, such as depression, obsessive compulsive disorder, schizophrenia, anxiety and Tourette syndrome

Adverse effects

Although TMS is generally regarded as safe, risks are increased for therapeutic rTMS compared to single or paired diagnostic TMS.JOURNAL, van den Noort M, Lim S, Bosch P, Recognizing the risks of brain stimulation, Science, 346, 6215, 1307, December 2014, 25504707, 10.1126/science.346.6215.1307-a, Adverse effects generally increase with higher frequency stimulation.The greatest immediate risk from TMS is fainting, though this is uncommon. Seizures have been reported, but are rare.JOURNAL, Dobek CE, Blumberger DM, Downar J, Daskalakis ZJ, Vila-Rodriguez F, Risk of seizures in transcranial magnetic stimulation: a clinical review to inform consent process focused on bupropion, Neuropsychiatric Disease and Treatment, 11, 2975–2987, 2015, 26664122, 4670017, 10.2147/NDT.S91126, free, BOOK, Fitzgerald PB, Daskalakis ZJ,weblink Repetitive Transcranial Magnetic Stimulation for Depressive Disorders, 7. rTMS-Associated Adverse Events, 81–90, Berlin Heidelberg, Springer-Verlag, 2013, 10.1007/978-3-642-36467-9, 978-3-642-36466-2, Other adverse effects include short term discomfort, pain, brief episodes of hypomania, cognitive change, hearing loss, impaired working memory, and the induction of electrical currents in implanted devices such as cardiac pacemakers.

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.JOURNAL, Nauczyciel C, Hellier P, Morandi X, Blestel S, Drapier D, Ferre JC, Barillot C, Millet B, 6, Assessment of standard coil positioning in transcranial magnetic stimulation in depression, Psychiatry Research, 186, 2–3, 232–238, April 2011, 20692709, 10.1016/j.psychres.2010.06.012, 25100990, The coil is then connected to a pulse generator, or stimulator, that delivers electric current to the coil.

Physics

(File:TMS focal field.png|right|150px)(File:TMS Butterfly Coil HEAD.png|right|thumb|240px|TMS – butterfly coils)TMS uses electromagnetic induction to generate an electric current across the scalp and skull.JOURNAL, Cavaleri R, Schabrun SM, Chipchase LS, The number of stimuli required to reliably assess corticomotor excitability and primary motor cortical representations using transcranial magnetic stimulation (TMS): a systematic review and meta-analysis, Systematic Reviews, 6, 1, 48, March 2017, 28264713, 5340029, 10.1186/s13643-017-0440-8, free, WEB, Brain Stimulation Therapies,weblink NIMH, 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.BOOK, Handbook of psychophysiology, 2007, Cambridge Univ. Press, New York, 978-0-521-84471-0, 3rd, Cacioppo JT, Tassinary LG, Berntson GG, 121, 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.V. Walsh and A. Pascual-Leone, "Transcranial Magnetic Stimulation: A Neurochronometrics of Mind." Cambridge, Massachusetts: MIT Press, 2003. 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.JOURNAL, Lefaucheur, Jean-Pascal, André-Obadia, Nathalie, Antal, Andrea, Ayache, Samar S., Baeken, Chris, Benninger, David H., Cantello, Roberto M., Cincotta, Massimo, de Carvalho, Mamede, De Ridder, Dirk, Devanne, Hervé, Di Lazzaro, Vincenzo, Filipović, SaÅ¡a R., Hummel, Friedhelm C., Jääskeläinen, Satu K., November 2014, Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS),weblink Clinical Neurophysiology, en, 125, 11, 2150–2206, 10.1016/j.clinph.2014.05.021, 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.See:

1. JOURNAL, Zangen A, Roth Y, Voller B, Hallett M, Transcranial magnetic stimulation of deep brain regions: evidence for efficacy of the H-coil, Clinical Neurophysiology, 116, 4, 775–779, April 2005, 15792886, 10.1016/j.clinph.2004.11.008, 25101101,
2. JOURNAL, Huang YZ, Sommer M, Thickbroom G, Hamada M, Pascual-Leonne A, Paulus W, Classen J, Peterchev AV, Zangen A, Ugawa Y, 6, Consensus: New methodologies for brain stimulation, Brain Stimulation, 2, 1, 2–13, January 2009, 20633398, 5507351, 10.1016/j.brs.2008.09.007,

Frequency and duration

The effects of TMS can be divided based on frequency, duration and intensity (amplitude) of stimulation:JOURNAL, Rubens MT, Zanto TP, Parameterization of transcranial magnetic stimulation, Journal of Neurophysiology, 107, 5, 1257–1259, March 2012, 22072509, 3311692, 10.1152/jn.00716.2011,

• 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. 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 behaviour may be altered (e.g., slower reaction time on a cognitive task), or changes in brain activity may be detected using diagnostic equipment.BOOK, Alvaro Pascual-Leone, Pascual-Leone A, Davey N, Rothwell J, Wassermann EM, Puri BK, 2002, Handbook of Transcranial Magnetic Stimulation, Edward Arnold, London, 978-0-340-72009-7,
• Repetitive TMS produces longer-lasting effects which 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, or high frequency, is believed to provoke it.JOURNAL, Cusin C, Dougherty DD, Somatic therapies for treatment-resistant depression: ECT, TMS, VNS, DBS, Biology of Mood & Anxiety Disorders, 2, 1, 14, August 2012, 22901565, 3514332, 10.1186/2045-5380-2-14, free, 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).JOURNAL, Fitzgerald PB, Fountain S, Daskalakis ZJ, A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition, Clinical Neurophysiology, 117, 12, 2584–2596, December 2006, 16890483, 10.1016/j.clinph.2006.06.712, 31458874, Baur D, Galevska D, Hussain S, Cohen LG, Ziemann U, Zrenner C. Induction of LTD-like corticospinal plasticity by low-frequency rTMS depends on pre-stimulus phase of sensorimotor μ-rhythm. Brain Stimul. 2020 Nov-Dec;13(6):1580-1587. doi: 10.1016/j.brs.2020.09.005. Epub 2020 Sep 17. PMID 32949780; PMCID: PMC7710977.

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.BOOK, Oxford Handbook of Transcranial Stimulation, Wassermann EM, Epstein CM, Ziemann U, Walsh V, Paus T, Lisanby SH, TMS Stimulator Design, Riehl M, 2008, Oxford University Press, Oxford, 978-0-19-856892-6, 13–23, 25–32, 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.JOURNAL, Roth BJ, Maccabee PJ, Eberle LP, Amassian VE, Hallett M, Cadwell J, Anselmi GD, Tatarian GT, 6, In vitro evaluation of a 4-leaf coil design for magnetic stimulation of peripheral nerve, Electroencephalography and Clinical Neurophysiology, 93, 1, 68–74, February 1994, 7511524, 10.1016/0168-5597(94)90093-0, 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.

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.JOURNAL, Horvath JC, Perez JM, Forrow L, Fregni F, Pascual-Leone A, Transcranial magnetic stimulation: a historical evaluation and future prognosis of therapeutically relevant ethical concerns, Journal of Medical Ethics, 37, 3, 137–143, March 2011, 21106996, 10.1136/jme.2010.039966, 23034661, 13262044, 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.JOURNAL, Noohi S, Amirsalari S, History, Studies and Specific Uses of Repetitive Transcranial Magnetic Stimulation (rTMS) in Treating Epilepsy, Iranian Journal of Child Neurology, 10, 1, 1–8, 2016, 27057180, 4815479, 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). 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.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.JOURNAL, Klomjai W, Katz R, Lackmy-Vallée A, Basic principles of transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS), Annals of Physical and Rehabilitation Medicine, 58, 4, 208–213, September 2015, 26319963, 10.1016/j.rehab.2015.05.005, free, 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. They were originally intended as diagnostic and research devices, with evaluation of their therapeutic potential being a later development. The United States' FDA first approved TMS devices in October 2008.

Research

{{expand section|date=January 2024}}TMS has shown potential therapeutic effect on neurologic conditions such as mild to moderate Alzheimer's disease, amyotrophic lateral sclerosis,JOURNAL, Fang J, Zhou M, Yang M, Zhu C, He L, Repetitive transcranial magnetic stimulation for the treatment of amyotrophic lateral sclerosis or motor neuron disease, The Cochrane Database of Systematic Reviews, 5, CD008554, May 2013, 2013, 23728676, 10.1002/14651858.CD008554.pub3, 7173713, persistent vegetative states, epilepsy,JOURNAL, Pereira LS, Müller VT, da Mota Gomes M, Rotenberg A, Fregni F, Safety of repetitive transcranial magnetic stimulation in patients with epilepsy: A systematic review, Epilepsy & Behavior, 57, Pt A, 167–176, April 2016, 26970993, 10.1016/j.yebeh.2016.01.015, 3880211, stroke related disability,JOURNAL, Martin PI, Naeser MA, Ho M, Treglia E, Kaplan E, Baker EH, Pascual-Leone A, Research with transcranial magnetic stimulation in the treatment of aphasia, Current Neurology and Neuroscience Reports, 9, 6, 451–458, November 2009, 19818232, 2887285, 10.1007/s11910-009-0067-9, JOURNAL, Corti M, Patten C, Triggs W, Repetitive transcranial magnetic stimulation of motor cortex after stroke: a focused review, American Journal of Physical Medicine & Rehabilitation, 91, 3, 254–270, March 2012, 22042336, 10.1097/PHM.0b013e318228bf0c, 16233265, tinnitus,JOURNAL, Kleinjung T, Vielsmeier V, Landgrebe M, Hajak G, Langguth B, Transcranial magnetic stimulation: a new diagnostic and therapeutic tool for tinnitus patients, The International Tinnitus Journal, 14, 2, 112–118, 2008, 19205161, multiple sclerosis, schizophrenia, and traumatic brain injury.JOURNAL, Shin SS, Dixon CE, Okonkwo DO, Richardson RM, Neurostimulation for traumatic brain injury, Journal of Neurosurgery, 121, 5, 1219–1231, November 2014, 25170668, 10.3171/2014.7.JNS131826, free, With 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.JOURNAL, Machado S, Bittencourt J, Minc D, Portella CE, Velasques B, Cunha M, Budde H, Basile LF, Chadi G, Cagy M, Piedade R, Riberio P, 6, Therapeutic applications of repetitive transcranial magnetic stimulation in clinical neurorehabilitation, Functional Neurology, 23, 3, 113–122, 2008, 19152730, JOURNAL, Liu, Xuan, Li, Lei, Liu, Ye, 2023-09-29, Comparative motor effectiveness of non-invasive brain stimulation techniques in patients with Parkinson's disease: A network meta-analysis, Medicine, 102, 39, e34960, 10.1097/MD.0000000000034960, 1536-5964, 37773851, 10545289, The most effective treatment protocols appear to involve high frequency stimulation of the motor cortex, particularly on the dominant side,JOURNAL, Chou YH, Hickey PT, Sundman M, Song AW, Chen NK, Effects of repetitive transcranial magnetic stimulation on motor symptoms in Parkinson disease: a systematic review and meta-analysis, JAMA Neurology, 72, 4, 432–440, April 2015, 25686212, 4425190, 10.1001/jamaneurol.2014.4380, but with more variable results for treatment of the dorsolateral prefrontal cortex.JOURNAL, Yang C, Guo Z, Peng H, Xing G, Chen H, McClure MA, He B, He L, Du F, Xiong L, Mu Q, 6, Repetitive transcranial magnetic stimulation therapy for motor recovery in Parkinson's disease: A Meta-analysis, Brain and Behavior, 8, 11, e01132, November 2018, 30264518, 6236247, 10.1002/brb3.1132, It is less effective than electroconvulsive therapy for motor symptoms, though both appear to have utility.JOURNAL, Fregni F, Simon DK, Wu A, Pascual-Leone A, Non-invasive brain stimulation for Parkinson's disease: a systematic review and meta-analysis of the literature, Journal of Neurology, Neurosurgery, and Psychiatry, 76, 12, 1614–1623, December 2005, 16291882, 1739437, 10.1136/jnnp.2005.069849, JOURNAL, Lefaucheur JP, Treatment of Parkinson's disease by cortical stimulation, Expert Review of Neurotherapeutics, 9, 12, 1755–1771, December 2009, 19951135, 10.1586/ern.09.132, 6404434, JOURNAL, Arias-Carrión O, Basic mechanisms of rTMS: Implications in Parkinson's disease, International Archives of Medicine, 1, 1, 2, April 2008, 18471317, 2375865, 10.1186/1755-7682-1-2, free, Cerebellar stimulation has also shown potential for the treatment of levodopa associated dyskinesia.JOURNAL, França C, de Andrade DC, Teixeira MJ, Galhardoni R, Silva V, Barbosa ER, Cury RG, Effects of cerebellar neuromodulation in movement disorders: A systematic review, Brain Stimulation, 11, 2, 249–260, 29191439, 10.1016/j.brs.2017.11.015, 2018, 46810543, In psychiatry, it has shown potential with anxiety disorders, including panic disorderJOURNAL, Li H, Wang J, Li C, Xiao Z, Repetitive transcranial magnetic stimulation (rTMS) for panic disorder in adults, The Cochrane Database of Systematic Reviews, 9, 9, CD009083, September 2014, 25230088, 10.1002/14651858.CD009083.pub2, 6885044, and obsessive–compulsive disorder (OCD). The most promising areas to target for OCD appear to be the orbitofrontal cortex and the supplementary motor area.JOURNAL, Berlim MT, Neufeld NH, Van den Eynde F, Repetitive transcranial magnetic stimulation (rTMS) for obsessive-compulsive disorder (OCD): an exploratory meta-analysis of randomized and sham-controlled trials, Journal of Psychiatric Research, 47, 8, 999–1006, August 2013, 23615189, 10.1016/j.jpsychires.2013.03.022, Older protocols that targeted the prefrontal dorsal cortex were less successful.JOURNAL, Saba G, Moukheiber A, Pelissolo A, Transcranial cortical stimulation in the treatment of obsessive-compulsive disorders: efficacy studies, Current Psychiatry Reports, 17, 5, 36, May 2015, 25825002, 10.1007/s11920-015-0571-3, 22071333, It has also been studied with autism,JOURNAL, Oberman LM, Enticott PG, Casanova MF, Rotenberg A, Pascual-Leone A, McCracken JT, Transcranial magnetic stimulation in autism spectrum disorder: Challenges, promise, and roadmap for future research, Autism Research, 9, 2, 184–203, February 2016, 26536383, 4956084, 10.1002/aur.1567, substance abuse, addiction,JOURNAL, Nizard J, Lefaucheur JP, Helbert M, de Chauvigny E, Nguyen JP, Non-invasive stimulation therapies for the treatment of refractory pain, Discovery Medicine, 14, 74, 21–31, July 2012, 22846200,weblinkweblink" title="web.archive.org/web/20140226110824weblink">weblink dead, 2014-02-26, JOURNAL, Ponciano-Rodríguez, Guadalupe, Chávez-Castillo, Carlos A., Ríos-Ponce, Alma E., Villafuerte, Gabriel, 2021, High Frequency and Low Intensity Transcranial Magnetic Stimulation for Smoking Cessation, Journal of Addiction, 2021, 9988618, 10.1155/2021/9988618, 2090-7834, 8476253, 34589245, free, and post-traumatic stress disorder (PTSD). For treatment-resistant major depressive disorder, high-frequency (HF) rTMS of the left dorsolateral prefrontal cortex (DLPFC) appears effective and low-frequency (LF) rTMS of the right DLPFC has probable efficacy. Research on the efficacy of rTMS in non-treatment-resistant depression is limited.JOURNAL, Kiebs, Maximilian, Hurlemann, René, Mutz, Julian, August 2019, Repetitive transcranial magnetic stimulation in non-treatment-resistant depression, British Journal of Psychiatry, en, 215, 2, 445–446, 10.1192/bjp.2019.75, 31014413, 0007-1250, free, TMS can also be used to map functional connectivity between the cerebellum and other areas of the brain.JOURNAL, van Dun K, Bodranghien F, Manto M, Mariën P, Targeting the Cerebellum by Noninvasive Neurostimulation: a Review, Cerebellum, 16, 3, 695–741, June 2017, 28032321, 10.1007/s12311-016-0840-7, 3999098, A study on alternative Alzheimer's treatments at the Wahrendorff Clinic in Germany in 2021WEB, 11 April 2023, Alternative Alzheimer's Treatments Offering Hope - 84% of the subjects surveyed rated their psychological well-being after the TPS treatment as medium to good,weblink Hitoshin, reported that 84% of participants in the study have experienced positive effects after using the treatment.Under the supervision of Professor Marc Ziegenbein, a psychiatry and psychotherapy specialist, the study of 77 subjects with mild to moderate Alzheimer's disease received frequent transcranial magnetic stimulation applications and observed over a period of time.Improvements were mainly found in the areas of orientation in the environment, concentration, general well-being and satisfaction.

Study blinding

Mimicking the physical discomfort of TMS with placebo to discern its true effect is a challenging issue in research.JOURNAL, Duecker F, Sack AT, Rethinking the role of sham TMS, Frontiers in Psychology, 6, 210, 2015, 25767458, 4341423, 10.3389/fpsyg.2015.00210, free, JOURNAL, Davis NJ, Gold E, Pascual-Leone A, Bracewell RM, Challenges of proper placebo control for non-invasive brain stimulation in clinical and experimental applications, The European Journal of Neuroscience, 38, 7, 2973–2977, October 2013, 23869660, 10.1111/ejn.12307, 2152097,weblink It is difficult to establish a convincing placebo for TMS during controlled trials in conscious individuals due to the neck pain, headache and twitching in the scalp or upper face associated with the intervention. In addition, placebo manipulations can affect brain sugar metabolism and MEPs, which may confound results.JOURNAL, Marangell LB, Martinez M, Jurdi RA, Zboyan H, Neurostimulation therapies in depression: a review of new modalities, Acta Psychiatrica Scandinavica, 116, 3, 174–181, September 2007, 17655558, 10.1111/j.1600-0447.2007.01033.x, 38081703, This problem is exacerbated when using subjective measures of improvement. Placebo responses in trials of rTMS in major depression are negatively associated with refractoriness to treatment.JOURNAL, Brunoni AR, Lopes M, Kaptchuk TJ, Fregni F, Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis, PLOS ONE, 4, 3, e4824, 2009, 19293925, 2653635, 10.1371/journal.pone.0004824, 2009PLoSO...4.4824B, free, A 2011 review found that most studies did not report unblinding. In the minority that did, participants in real and sham rTMS groups were not significantly different in their ability to correctly guess their therapy, though there was a trend for participants in the real group to more often guess correctly.JOURNAL, Broadbent HJ, van den Eynde F, Guillaume S, Hanif EL, Stahl D, David AS, Campbell IC, Schmidt U, 6, Blinding success of rTMS applied to the dorsolateral prefrontal cortex in randomised sham-controlled trials: a systematic review, The World Journal of Biological Psychiatry, 12, 4, 240–248, June 2011, 21426265, 10.3109/15622975.2010.541281, 21439740,

Animal model limitations

TMS research in animal studies is limited due to its early US Food and Drug Administration approval for treatment-resistant depression, limiting development of animal specific magnetic coils.JOURNAL, Wassermann EM, Zimmermann T, Transcranial magnetic brain stimulation: therapeutic promises and scientific gaps, Pharmacology & Therapeutics, 133, 1, 98–107, January 2012, 21924290, 3241868, 10.1016/j.pharmthera.2011.09.003,

Treatments for the general public

Regulatory approvals

Neurosurgery planning

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 2009WEB,weblink FDA clears Nexstim´s Navigated Brain Stimulation for non-invasive cortical mapping prior to neurosurgery – Archive – Press Releases, nexstim.com, and for neurosurgical planning in June 2011.WEB,weblink Nexstim Announces FDA Clearance for NexSpeech® – Enabling Noninvasive Speech Mapping Prior to Neurosurgery, 11 June 2012, businesswire.com,

Depression

The National Institutes of Health estimates depression medications work for 60 percent to 70 percent of people who take them.BOOK,weblink Information about Mental Illness and the Brain, 2007, National Institutes of Health (US), In addition, the World Health Organization reports that the number of people living with depression has increased nearly 20 percent since 2005. TMS is approved as a Class II medical device under the "de novo pathway".Michael Drues, for Med Device Online. 5 February 2014 Secrets Of The De Novo Pathway, Part 1: Why Aren't More Device Makers Using It?JOURNAL, Schwedt TJ, Vargas B, Neurostimulation for Treatment of Migraine and Cluster Headache, Pain Medicine, 16, 9, 1827–1834, September 2015, 26177612, 4572909, 10.1111/pme.12792, In addition, the World Health Organization reports that the number of people living with depression has increased nearly 20 percent since 2005.WEB, "Depression: let's talk" says WHO, as depression tops list of causes of ill health,weblink 2022-08-10, www.who.int, en, In a 2012 study, TMS was found to improve depression significantly in 58 percent of patients and provide complete remission of symptoms in 37 percent of patients.JOURNAL, Carpenter LL, Janicak PG, Aaronson ST, Boyadjis T, Brock DG, Cook IA, Dunner DL, Lanocha K, Solvason HB, Demitrack MA, Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of acute treatment outcomes in clinical practice, Depress Anxiety, 29, 7, 587–96, July 2012, 22689344, 10.1002/da.21969, 22968810, In 2002, Cochrane Library reviewed randomized controlled trials using TMS to treat depression. The review did not find a difference between rTMS and sham TMS, except for a period 2 weeks after treatment.JOURNAL, Rodriguez-Martin, José Luis, Barbanoj, José Manuel, Schlaepfer, Te, Clos, Susana SC, Pérez, V, Kulisevsky, J, Gironell, A, Transcranial magnetic stimulation for treating depression, Cochrane Database of Systematic Reviews, 22 April 2002, 2018, 11, CD003493, 10.1002/14651858.CD003493, 12076483,weblink 11 December 2023, en, 6516872, In 2018, Cochrane Library stated a plan to contact authors about updating the review of rTMS for depression.JOURNAL, Hendon, Jessica, Transcranial magnetic stimulation for treating depression, Cochrane Database of Systematic Reviews, en, 10.1002/14651858.CD003493, 2002, 2018, 11, CD003493, 12076483, 6516872,

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).WEB, 2020-02-20, FDA permits marketing of transcranial magnetic stimulation for treatment of obsessive compulsive disorder,weblink Food and Drug Administration, In 2020, US FDA authorized the use of TMS developed by the U.S. company MagVenture Inc. in the treatment of OCD.WEB, MagVenture receives FDA clearance for OCD {{!, Clinical TMS Society |url=https://www.clinicaltmssociety.org/news/2020-08/magventure-receives-fda-clearance-ocd-0 |access-date=2023-10-11 |website=www.clinicaltmssociety.org}}In 2023, US FDA authorized the use of TMS developed by the U.S. company Neuronetics Inc. in the treatment of OCD.WEB, FDA clears OCD motor threshold cap for transcranial magnetic stimulation system,weblink 2023-10-11, www.healio.com, en,

Other neurological areas

In the European Economic Area, various versions of Deep TMS H-coils have CE marking forAlzheimer's disease,autism,bipolar disorder,epilepsy,JOURNAL, Gersner R, Oberman L, Sanchez MJ, Chiriboga N, Kaye HL, Pascual-Leone A, Libenson M, Roth Y, Zangen A, Rotenberg A, 6, H-coil repetitive transcranial magnetic stimulation for treatment of temporal lobe epilepsy: A case report, Epilepsy & Behavior Case Reports, 5, Supplement C, 52–56, 2016-01-01, 27114902, 4832041, 10.1016/j.ebcr.2016.03.001, chronic pain,major depressive disorder,Parkinson's disease,JOURNAL, Torres F, Villalon E, Poblete P, Moraga-Amaro R, Linsambarth S, Riquelme R, Zangen A, Stehberg J, 6, Retrospective Evaluation of Deep Transcranial Magnetic Stimulation as Add-On Treatment for Parkinson's Disease, Frontiers in Neurology, 6, 210, 2015-10-26, 26579065, 4620693, 10.3389/fneur.2015.00210, free, post-traumatic stress disorder (PTSD),JOURNAL, Transcranial magnetic stimulation for post-traumatic stress disorder, 34733479, 10.1177/20451253211049921, free, Nicholas J., Petrosino, Camila, Cosmo, Yosef A., Berlow, Amin, Zandvakili, Mascha, van ’t Wout-Frank, Noah S., Philip, Therapeutic Advances in Psychopharmacology, 2021, 11, 8558793, schizophrenia (negative symptoms)WEB,weblink Brainsway's Deep TMS EU Cleared for Neuropathic Chronic Pain, July 3, 2012, medGadget, December 16, 2013, and to aid smoking cessation.NEWS,weblink Brainsway reports positive Deep TMS system trial data for OCD, Medical Device Network, September 6, 2013, Medicaldevice-network, December 16, 2013, One review found tentative benefit for cognitive enhancement in healthy people.JOURNAL, Luber B, Lisanby SH, Enhancement of human cognitive performance using transcranial magnetic stimulation (TMS), NeuroImage, 85 Pt 3, 3, 961–970, January 2014, 23770409, 4083569, 10.1016/j.neuroimage.2013.06.007,

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.NICE About NICE: What we doNICE evaluated TMS for severe depression (IPG 242) in 2007, and subsequently considered TMS for reassessment in January 2011 but did not change its evaluation.WEB,weblink Transcranial magnetic stimulation for severe depression (IPG242), London, National Institute for Health and Clinical Excellence, 2011-03-04, The Institute found that TMS is safe, but there is insufficient evidence for its efficacy.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.WEB,weblink Transcranial magnetic stimulation for treating and preventing migraine, January 2014, London, National Institute for Health and Clinical Excellence, Subsequently, in 2015, NICE approved the use of TMS for the treatment of depression in the UK and IPG542 replaced IPG242.WEB, Repetitive transcranial magnetic stimulation for depression, 16 December 2015,weblink National Institute for Health and Care Excellence, 6 December 2019, NICE said "The evidence on repetitive transcranial magnetic stimulation for depression shows no major safety concerns. The evidence on its efficacy in the short-term is adequate, although the clinical response is variable. Repetitive transcranial magnetic stimulation for depression may be used with normal arrangements for clinical governance and audit."

United States: commercial health insurance

In 2013, several commercial health insurance plans in the United States, including Anthem, Health Net, and Blue Cross Blue Shield of Nebraska and of Rhode Island, covered TMS for the treatment of depression for the first time.WEB, Anthem, Inc.,weblink" title="web.archive.org/web/20130729015624weblink">weblink 2013-07-29,weblink Medical Policy: Transcranial Magnetic Stimulation for Depression and Other Neuropsychiatric Disorders, Policy No. BEH.00002, 2013-04-16, 2013-12-11, dead, WEB, Health Net,weblink 2012-10-11,weblink National Medical Policy: Transcranial Magnetic Stimulation, Policy Number NMP 508, Health Net, March 2012, 2012-09-05, dead, WEB,weblink 2012-10-28, Section IV.67, Medical Policy Manual, 2011-05-18, Blue Cross Blue Shield of Nebraska,weblink dead, WEB,weblink 2013-05-26,weblink Medical Coverage Policy: Transcranial Magnetic Stimulation for Treatment of Depression and Other Psychiatric/Neurologic Disorders, Blue Cross Blue Shield of Rhode Island, 2012-05-15, 2012-09-05, dead, 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.WEB, UnitedHealthcare,weblink 2013-05-20,weblink Transcranial Magnetic Stimulation, 2013-12-01, UnitedHealthCare, 2, 2013-12-11, dead, UnitedHealthcare, 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.WEB, Aetna,weblink" title="web.archive.org/web/20131022055505weblink">weblink 2013-10-22,weblink Clinical Policy Bulletin: Transcranial Magnetic Stimulation and Cranial Electrical Stimulation, 2013-10-11, Number 0469, Aetna, 2013-12-11, dead, Aetna, WEB, Cigna,weblink 2017-02-04,weblink Cigna Medical Coverage Policy: Transcranial Magnetic Stimulation, 2013-01-15, Coverage Policy Number 0383, Cigna, 2013-12-11, dead, Cigna, WEB,weblink" title="web.archive.org/web/20141209145816weblink">weblink 2014-12-09, Regence,weblink Medical Policy: Transcranial Magnetic Stimulation as a Treatment of Depression and Other Disorders, Policy No. 17, 2013-06-01, Regence, 2013-12-11, dead, The Regence Group,

United States: Medicare

Policies for Medicare coverage vary among local jurisdictions within the Medicare system,WEB,weblinkweblink" title="web.archive.org/web/20140214094931weblink">weblink 2014-02-14, Medicare Administrative Contractors, Centers for Medicare and Medicaid Services, 2013-07-10, 2014-02-14, dead, 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.WEB, NHIC, Corp.,weblinkweblink" title="archive.today/20140217152734weblink">weblink dead, 2014-02-17, Local Coverage Determination (LCD) for Repetitive Transcranial Magnetic Stimulation (rTMS) (L32228), Centers for Medicare and Medicaid Services, 2013-10-24, 2014-02-17, WEB,weblink" title="web.archive.org/web/20130405070836weblink">weblink 2013-04-05, 2012-10-11,weblink Important Treatment Option for Depression Receives Medicare Coverage, Press Release, 2012-03-30, PBN.com: Providence Business News, dead, WEB, The Institute for Clinical and Economic Review, June 2012,weblink" title="web.archive.org/web/20131213211022weblink">weblink 2013-12-13,weblink Coverage Policy Analysis: Repetitive Transcranial Magnetic Stimulation (rTMS), The New England Comparative Effectiveness Public Advisory Council (CEPAC), 2013-12-11, dead, WEB,weblink" title="web.archive.org/web/20120325091400weblink">weblink 2012-03-25,weblink Transcranial Magnetic Stimulation Cites Influence of New England Comparative Effectiveness Public Advisory Council (CEPAC), 2012-02-06, Berlin, Vermont, Central Vermont Medical Center, 2012-10-12, dead, However, that jurisdiction later decided to end coverage after October, 2013.WEB, National Government Services, Inc.,weblink 2013-10-25, Local Coverage Determination (LCD): Transcranial Magnetic Stimulation (L32038), Centers for Medicare and Medicaid Services, 2014-02-17,
• 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,WEB, Novitas Solutions, Inc., 2013-12-04, LCD L32752 – Transcranial Magnetic Stimulation for Depression,weblink 2014-02-17, Contractor's Determination Number L32752, Centers for Medicare and Medicaid Services, but the same jurisdiction subsequently determined that Medicare would cover TMS for the treatment of depression after December 2013.WEB,weblink LCD L33660 – Transcranial Magnetic Stimulation (TMS) for the Treatment of Depression, Novitas Solutions, Inc., Contractor's Determination Number L33660, Centers for Medicare and Medicaid Services, 2013-12-05, 2014-02-17,
• Subsequently,{{when|date=April 2021}} some other Medicare jurisdictions added Medicare coverage for depression.{{citation needed|date=April 2021}}

See also

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• Cortical stimulation mapping
• Cranial electrotherapy stimulation
• Electrical brain stimulation
• Electroconvulsive therapy
• Low field magnetic stimulation
• My Beautiful Broken Brain
• Non-invasive cerebellar stimulation
• Transcranial alternating current stimulation
• Transcranial direct-current stimulation
• Transcranial random noise stimulation
• Vagus nerve stimulation

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References

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