Difference between revisions of "Transcranial magnetic stimulation"

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{{Other uses|TMS (disambiguation)}}
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   Name        = Transcranial magnetic stimulation |
 
   Name        = Transcranial magnetic stimulation |
 
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   Image      = File:Transcranial magnetic stimulation.jpg|
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'''Transcranial magnetic stimulation''' ('''TMS''') is a noninvasive method to cause [[depolarization]] or [[Hyperpolarization (biology)|hyperpolarization]] in the [[neuron]]s of the [[brain]].  TMS uses [[electromagnetic induction]] to induce weak [[electric current]]s using a rapidly changing [[magnetic field]]; this can cause activity in specific or general parts of the brain with little discomfort, allowing for study of the brain's functioning and interconnections. A variant of TMS, '''repetitive transcranial magnetic stimulation''' ('''rTMS'''). According to the National Institute of Mental Health, it “uses a magnet instead of an electrical current to activate the brain. An electromagnetic coil is held against the forehead and short electromagnetic pulses are administered through the coil. The magnetic pulse easily passes through the skull, and causes small electrical currents that stimulate nerve cells in the targeted brain region. And because this type of pulse generally does not reach further than two inches into the brain, scientists can select which parts of the brain will be affected and which will not be. The magnetic field is about the same strength as that of a magnetic resonance imaging (MRI) scan.<ref>{{cite web |url=http://www.nimh.nih.gov/health/topics/brain-stimulation-therapies/brain-stimulation-therapies.shtml |title=Brain Stimulation Therapies |author=National Institute of Mental Health |publisher=nimh.nih.gov |year=2009 |accessdate=12 December 2013}}</ref> Repetitive transcranial magnetic stimulation has been tested as a treatment tool for various [[neurological disorder|neurological]] and [[mental disorder|psychiatric]] disorders including [[migraine]], [[stroke]], [[Parkinson's disease]], [[dystonia]], [[tinnitus]] and [[major depressive disorder|depression]].
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'''Transcranial magnetic stimulation''' ('''TMS''') is a noninvasive method used to stimulate small regions of the brain.  During a TMS procedure, a magnetic field generator, or "coil" is placed near the head of the person receiving the treatment.<ref name=NICE2014>NiCE. January 2014 [http://www.nice.org.uk/guidance/ipg477/resources/guidance-transcranial-magnetic-stimulation-for-treating-and-preventing-migraine-pdf Transcranial magnetic stimulation for treating and preventing migraine]</ref>{{rp|3}}  The coil produces small electrical currents in the region of the brain just under the coil via [[electromagnetic induction]]. The coil is connected to a pulse generator, or stimulator, that delivers electrical current to the coil.<ref name=Harvard>Michael Craig Miller for  Harvard Health Publications. July 26, 2012 [http://www.health.harvard.edu/blog/magnetic-stimulation-a-new-approach-to-treating-depression-201207265064 Magnetic stimulation: a new approach to treating depression?]</ref>
  
==Background==
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TMS is used diagnostically to measure the connection between the brain and a muscle to evaluate damage from stroke, [[multiple sclerosis]], [[amyotrophic lateral sclerosis]], [[movement disorder]]s, [[motor neuron disease]] and injuries and other disorders affecting the [[facial nerve|facial]] and other [[cranial nerve]]s and the [[spinal cord]].<ref name=diagnostic1>{{cite doi|10.1016.2Fj.clinph.2012.01.010}}</ref>
Early attempts at stimulation of the brain using a magnetic field included those, in 1910, of [[Silvanus P. Thompson]] in London.<ref>{{cite web |url=http://www.scholarpedia.org/article/Transcranial_magnetic_stimulation |title=Transcranial magnetic stimulation |author=Anthony T. Barker and Ian Freeston |publisher=scholarpedia.org |year=2007 |accessdate=28 June 2013}}</ref> The principle of inductive brain stimulation with [[eddy current]]s has been noted since the 20th century. The first successful TMS study was performed in 1985 by Anthony Barker and his colleagues at the [[Royal Hallamshire Hospital]] in [[Sheffield]], England.<ref name=Barker>{{cite doi|10.1016/S0140-6736(85)92413-4}}</ref>  Its earliest application demonstrated conduction of nerve impulses from the [[motor cortex]] to the [[spinal cord]], stimulating muscle contractions in the hand. As compared to the previous method of transcranial stimulation proposed by Merton and Morton in 1980<ref name=Merton>{{cite doi|10.1038/285227a0}}</ref> in which direct electrical current was applied to the scalp, the use of [[electromagnet]]s greatly reduced the discomfort of the procedure, and allowed mapping of the [[cerebral cortex]] and its connections.
 
  
==Theory==
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TMS was approved by the FDA for use in [[migraine]]<ref name=MigraineApprov>FDA 13 December 2013 [http://www.accessdata.fda.gov/cdrh_docs/pdf13/K130556.pdf FDA letter to eNeura re ''de novo'' classification review]</ref> and treatment-resistant [[major depressive disorder]].<ref name="Melkerson">{{cite web|url=http://www.accessdata.fda.gov/cdrh_docs/pdf8/K083538.pdf|format=pdf|date=2008-12-16|accessdate=2010-07-16 |publisher=[[Food and Drug Administration]]|last=Melkerson|first=MN|title=Special Premarket 510(k) Notification for NeuroStar® TMS Therapy System for Major Depressive Disorder}}</ref>
  
From the [[Biot-Savart Law]]  
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Clinical evidence to date shows that TMS is useful for [[neuropathic pain]] (a condition for which [[evidence-based medicine]] fails to treat a significant number of people with the condition)<ref name=Lefaucher1>{{cite journal|author=Lefaucheur, JP  et al. |title=Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS)|journal=Clinical Neurophysiology|year=2014|doi=10.1016/j.clinph.2014.05.021|pmid=25034472}}</ref> and treatment-resistant [[major depressive disorder]].<ref name=Lefaucher1/><ref name=AHRQ>{{cite doi|10.1176/appi.ajp.2010.10060864}}<br>(6) {{cite web|author=Gaynes BN, Lux L, Lloyd S, Hansen RA, Gartlehner G, Thieda P, Brode S, Swinson Evans T, Jonas D, Crotty K, Viswanathan M, Lohr KN, [[Research Triangle Park]], [[North Carolina]]|archiveurl=http://www.webcitation.org/6BLBRlpyk|archivedate=2012-10-11|url=http://www.effectivehealthcare.ahrq.gov/ehc/products/76/792/TRD_CER33_20111110.pdf|title=Nonpharmacologic Interventions for Treatment-Resistant Depression in Adults. Comparative Effectiveness Review Number 33. (Prepared by RTI International-University of North Carolina (RTI-UNC) Evidence-based Practice Center)|work=AHRQ Publication No. 11-EHC056-EF|page=36|location=[[Rockville, Maryland]]|publisher=[[Agency for Healthcare Research and Quality]]|date=September 2011|accessdate=2011-10-11}}</ref> Clinical evidence shows that TMS may be useful for [[negative symptoms]] of [[schizophrenia]] and loss of function caused by stroke.<ref name=Lefaucher1/> As of 2014, all other potential uses have only possible or no efficacy.<ref name=Lefaucher1/>
<center><math> \mathbf B = \frac{\mu_0}{4\pi} I \int_C \frac{d\mathbf l \times \mathbf{\hat r}}{r^2}</math> </center>
 
it has been shown that a current through a wire generates a magnetic field around that wire. Transcranial magnetic stimulation is achieved by quickly discharging current from a large capacitor into a coil to produce pulsed magnetic fields of 1-10 mT.<ref name=Walsh>V. Walsh and A. Pascual-Leone, "Transcranial Magnetic Stimulation: A Neurochronometrics of Mind." Cambridge, MA: MIT Press, 2003.</ref> By directing the magnetic field pulse at a targeted area of the brain, one can either depolarize or hyperpolarize neurons in the brain. The magnetic flux density pulse generated by the current pulse through the coil causes an electric field due to the [[Electromagnetic induction#Maxwell–Faraday equation|Maxwell-Faraday equation]],
 
<center><math>\nabla \times \mathbf{E} = -\frac{\partial \mathbf{B}} {\partial t}</math> .</center>  
 
This electric field causes a change in the transmembrane current of the neuron, which leads to the depolarization or hyperpolarization of the neuron and the firing of an action potential.<ref name=Walsh/>
 
  
==Effects on the brain==
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The greatest risks of TMS are the rare occurrence of [[syncope (medicine)|syncope (fainting)]] and even less commonly, induced [[epileptic seizure|seizures]].<ref name = Rossi>Rossi S et al.  Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-39. PMID 19833552 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260536/ PMC 3260536]</ref>  Other adverse effects of TMS include discomfort or pain, transient induction of [[hypomania]], transient cognitive changes, transient hearing loss, transient impairment of working memory, and induced currents in electrical circuits in implanted devices.<ref name = Rossi/>
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{{TOC limit|3}}
  
The exact details of how TMS functions are still being explored. The effects of TMS can be divided into two types depending on the mode of stimulation:
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==Medical uses==
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The use of TMS can be divided into diagnostic and therapeutic uses.
  
*Single or paired pulse TMS causes neurons in the neocortex under the site of stimulation to [[Depolarization|depolarize]] and discharge an [[action potential]]. If used in the [[primary motor cortex]], it produces muscle activity referred to as a [[Evoked potential#Motor evoked potentials|motor evoked potential]] (MEP) which can be recorded on [[electromyography]]. If used on the [[occipital cortex]], '[[phosphene]]s' (flashes of light) might be perceived by the subject. In most other areas of the cortex, the participant does not consciously experience any effect, but his or her behaviour may be slightly altered (e.g., slower reaction time on a cognitive task), or changes in brain activity may be detected using sensing equipment.<ref name="Handbook of Transcranial Magnetic Stimulation">{{cite book | author = [[Alvaro Pascual-Leone|Pascual-Leone A]]; Davey N; Rothwell J; Wassermann EM; Puri BK | year = 2002 | title = Handbook of Transcranial Magnetic Stimulation | publisher = [[Edward Arnold (publisher)|Arnold]]|location=[[London]] | isbn = 0-340-72009-3  }}</ref>
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===Diagnosis===
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TMS can be used clinically to measure activity and function of specific brain circuits in humans.<ref name=diagnostic1/> The most robust and widely accepted use is in measuring the connection between the [[primary motor cortex]] and a muscle to evaluate damage from stroke, [[multiple sclerosis]], [[amyotrophic lateral sclerosis]], [[movement disorder]]s, [[motor neuron disease]] and  injuries and other disorders affecting the [[facial nerve|facial]] and other [[cranial nerve]]s and the [[spinal cord]].<ref name=diagnostic1/><ref>{{cite doi|10.1212.2F01.wnl.0000250268.13789.b2}}</ref><ref name="Dimyan">{{cite doi|10.1177/1545968309345270}}</ref><ref name="Nowak">{{cite doi|10.3233/RNN-2010-0552}}</ref> TMS has been suggested as a means of assessing short-interval intracortical inhibition (SICI) which measures the internal pathways of the [[motor cortex]] but this use has not yet been validated.<ref name=Kujirai>{{cite pmid|8120818}}</ref>
  
*Repetitive TMS produces longer-lasting effects which persist past the initial period of stimulation. rTMS can increase or decrease the excitability of the [[corticospinal tract]] depending on the intensity of stimulation, coil orientation, and frequency. The mechanism of these effects is not clear, though it is widely believed to reflect changes in synaptic efficacy akin to [[long-term potentiation]] (LTP) and [[long-term depression]] (LTD).<ref name=Fitzgerald>{{cite doi|10.1016/j.clinph.2006.06.712}}</ref>
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===Treatment===
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For [[neuropathic pain]], a condition for which [[evidence-based medicine]] fails to treat a significant number of people with the condition, high-frequency (HF) rTMS of the brain region corresponding to the part of the body in pain, is effective.<ref name=Lefaucher1/>
  
==Use in localisation of sensorimotor cortex==
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For treatment-resistant [[major depressive disorder]], HF-rTMS of the left [[dorsolateral prefrontal cortex]] (DLPFC) is effective and low-frequency (LF) rTMS of the right DLPFC has probably efficacy.<ref name=Lefaucher1/><ref name=AHRQ/>  The American Psychiatric Association,<ref>American Psychiatric Association (2010). (eds: Gelenberg, AJ, Freeman, MP, Markowitz, JC, Rosenbaum, JF, Thase, ME, Trivedi, MH, Van Rhoads, RS). [http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf Practice Guidelines for the Treatment of Patients with Major Depressive Disorder, 3rd Edition]</ref>{{rp|46}} the Canadian Network for Mood and Anxiety Disorders,<ref>Kennedy, SH, et al (2009) [http://www.canmat.org/resources/CANMAT%20Depression%20Guidelines%202009.pdf Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. IV. Neurostimulation therapies. J Aff Disorders 117:S44-S53.  PMID 19682750]</ref> and the Royal Australia and New Zealand College of Psychiatrists have endorsed rTMS for trMDD.<ref>The Royal Australian and New Zealand College of Psychiatrists. (2013) [https://www.ranzcp.org/Files/Resources/College_Statements/Position_Statements/PS-79-PPC-Repetitive-Transcranial-Magnetic-Stimula.aspx Position Statement 79. Repetitive Transcranial Magnetic Stimulation. Practice and Partnerships Committee]</ref>
  
MRI images, recorded during TMS of the motor cortex of the brain, have been found to match very closely with [[Positron emission tomography|PET]] produced by during voluntary movements of the hand muscles innervated by TMS, to 5–22&nbsp;mm of accuracy.<ref name=Wassermann1996>{{cite doi|10.1006/nimg.1996.0001}}</ref>
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For [[negative symptoms]] of [[schizophrenia]], HF-rTMS of the left DLPFC has probable efficacy.<ref name=Lefaucher1/>
The localisation of motor areas with TMS has also been seen to correlate closely to [[Magnetoencephalography|MEG]]<ref name=Morioka>T. Morioka, T. Yamamoto, A. Mizushima, S. Tombimatsu, H. Shigeto, K. Hasuo, S. Nishio, K. Fujii and M. Fukui. Comparison of magnetoencephalography, functional MRI, and motor evoked potentials in the localization of the sensory-motor cortex. Neurol.  Res., vol. 17, no. 5, pp. 361-367. 1995</ref> and also [[Functional magnetic resonance imaging|fMRI]].<ref name=Terao>{{cite doi|10.1007/s002210050446}}</ref>
 
  
==Risks==
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For loss of function caused by stroke LF-rTMS of the corresponding brain region has probable efficacy.<ref name=Lefaucher1/>
  
A comprehensive safety study of rTMS in the treatment of major depression looked at three separate groups totalling over 300 patients. It found that rTMS was associated with a low incidence of side effects, most of which were mild to moderate. Additionally, only 4.5% of patients discontinued their participation during acute treatment because of adverse events.<ref name = Janicak>{{cite pmid|18232722}}</ref> Although TMS is generally regarded as safe, the greatest acute risk is the rare occurrence of induced [[epileptic seizure|seizures]] and [[syncope (medicine)|syncope (fainting)]].<ref name = Rossi>{{cite doi| 10.1016/j.clinph.2009.08.016}}</ref><ref name=Fitzgerald2>{{cite book|last=Fitzgerald|first=PB|last2=Daskalakis|first2=ZJ|url=http://books.google.com/books?id=2VFEAAAAQBAJ&printsec=frontcover&f=false#v=onepage&q&f=false|title=Repetitive Transcranial Magnetic Stimulation for Depressive Disorders|chapter=7. rTMS-Associated Adverse Events|pages=81–90|location=Berlin Heidelberg|publisher=Springer-Verlag|year=2013|doi=10.1007/978-3-642-36467-9|isbn=978-3-642-36466-2}} ''At'' [[Google Books]].</ref>  There have been 16 reports of TMS-related seizures (as of 2009), with seven reported before the publication of safety guidelines in 1998,<ref name=Wassermann1998 /> and nine reported afterwards. The seizures are primarily associated with rTMS, although they have been reported following single-pulse TMS. Reports have stated that, in at least some cases, predisposing factors (medication, brain lesions or genetic susceptibility) may have contributed to the seizure.  A review of nine seizures associated with rTMS that had been reported after 1998 stated that four seizures were within the safety parameters, four were outside of those parameters, and one had occurred in a healthy volunteer with no predisposing factors. A 2009 international consensus statement on TMS that contained this review concluded that based on the number of studies, subjects, and patients involved with TMS research, the risk of seizure with rTMS is considered very low.<ref name = Rossi/>
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As of 2014, all other potential uses have only possible or no efficacy;  TMS has failed to show effectiveness for the treatment of [[brain death]], [[coma]], and other [[persistent vegetative state]]s.<ref name=Lefaucher1/><ref>Bersani FS et al. Deep transcranial magnetic stimulation as a treatment for psychiatric disorders: a comprehensive review. Eur Psychiatry. 2013 Jan;28(1):30-9. PMID 22559998</ref><ref>{{cite journal|last1=Li|first1=H|last2=Wang|first2=J|last3=Li|first3=C|last4=Xiao|first4=Z|title=Repetitive transcranial magnetic stimulation (rTMS) for panic disorder in adults.|journal=The Cochrane database of systematic reviews|date=Sep 17, 2014|volume=9|pages=CD009083|pmid=25230088|doi=10.1002/14651858.CD009083.pub2}}</ref>
  
Other adverse effects of TMS are:
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==Adverse effects==
* Discomfort or pain from the stimulation of the scalp and associated [[nerves]] and [[muscle]]s on the overlying skin;<ref name=nami>{{cite web | url=http://www.nami.org/Content/ContentGroups/Helpline1/Transcranial_Magnetic_Stimulation_(rTMS).htm | title=Transcranial Magnetic Stimulation (TMS) | publisher=[[National Alliance on Mental Illness]] | accessdate=2008-12-15}}</ref> this is more common with rTMS than single pulse TMS.<ref name=Wassermann1998>{{cite doi|10.1016/S0168-5597(97)00096-8}}</ref>
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Although TMS is generally regarded as safe, risks increase for therapeutic rTMS compared to single or paired TMS for diagnostic purposes.   In the field of therapeutic TMS, risks increase with higher frequencies.<ref name = Rossi/>
* Minor cognitive changes, and psychiatric symptoms (particularly a low risk of [[mania]] in [[Depression (mood)|depressed]] patients).<ref name = Rossi/><ref name=Fitzgerald2/>
 
* Rapid deformation of the TMS coil produces a loud clicking sound that increases with the stimulation intensity and can affect hearing with sufficient exposure, which is particularly relevant for rTMS (hearing protection may be used to prevent this).<ref name=Wassermann1998/>
 
* rTMS in the presence of EEG-incompatible electrodes can result in electrode heating and, in severe cases, skin burns.<ref name=roth>{{cite doi|10.1016/0168-5597(92)90077-O}}</ref> Non-metallic electrodes are used if concurrent EEG data is required.
 
* Other side effects may be associated with TMS, such as alterations to the [[endocrine system]], altered [[neurotransmitter]], and [[immune system]] activity, but these side effects are considered lacking substantive proof.<ref name = Rossi/>
 
  
==Clinical uses==
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The greatest risk is the rare occurrence of [[syncope (medicine)|syncope (fainting)]] and even less commonly, induced [[epileptic seizure|seizures]].<ref name = Rossi/><ref name=Fitzgerald2>{{cite book|last=Fitzgerald|first=PB|last2=Daskalakis|first2=ZJ|url=http://books.google.com/books?id=2VFEAAAAQBAJ&printsec=frontcover&f=false#v=onepage&q&f=false|title=Repetitive Transcranial Magnetic Stimulation for Depressive Disorders|chapter=7. rTMS-Associated Adverse Events|pages=81–90|location=Berlin Heidelberg|publisher=Springer-Verlag|year=2013|doi=10.1007/978-3-642-36467-9|isbn=978-3-642-36466-2}} ''At'' [[Google Books]].</ref>
The uses of TMS and rTMS can be divided into diagnostic and therapeutic uses.
 
  
===Diagnostic use===
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Other adverse effects of TMS include discomfort or pain, transient induction of [[hypomania]], transient cognitive changes, transient hearing loss, transient impairment of working memory, and induced currents in electrical circuits in implanted devices.<ref name = Rossi/>
TMS can be used clinically to measure activity and function of specific brain circuits in humans.<ref name=diagnostic1>{{cite doi|10.1016.2Fj.clinph.2012.01.010}}</ref> The most robust and widely accepted use is in measuring the connection between the [[primary motor cortex]] and a muscle to evaluate damage from [[stroke]], [[multiple sclerosis]], [[amyotrophic lateral sclerosis]], [[movement disorder]]s, [[motor neuron disease]] and injuries and other disorders affecting the [[facial nerve|facial]] and other [[cranial nerve]]s and the [[spinal cord]].<ref name=diagnostic1/><ref>{{cite doi|10.1212.2F01.wnl.0000250268.13789.b2}}</ref><ref name="Dimyan">{{cite doi|10.1177/1545968309345270}}</ref><ref name="Nowak">{{cite doi|10.3233/RNN-2010-0552}}</ref> TMS has been suggested as a means of assessing short-interval intracortical inhibition (SICI) which measures the internal pathways of the [[motor cortex]] but this use has not yet been validated.<ref name=Kujirai>{{cite pmid|8120818}}</ref>
 
  
===Therapeutic use===
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== Devices and procedure==
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During a transcranial magnetic stimulation (TMS) procedure, a magnetic field generator, or "coil" is placed near the head of the person receiving the treatment.<ref name=NICE2014/>{{rp|3}}  The coil produces small electrical currents in the region of the brain just under the coil via [[electromagnetic induction]]. The coil is positioned by finding anatomical landmarks on the skull including, but not limited to, the [[inion]] or the [[nasion]].<ref>{{cite journal|last=Nauczyciel |first=C |last2=Hellier |first2=P |last3=Morandi |first3=X |last4=Blestel |first4=S |last5=Drapier |first5=D |last6=Ferre |first6=JC |last7=Barillot |first7=C |last8=Millet |first8=B |title=Assessment of standard coil positioning in transcranial magnetic stimulation in depression | journal=Psychiatry Research| date=30 April 2011 |volume=186|issue=2-3 |pmid=    20692709 |doi=10.1016/j.psychres.2010.06.012 |pages=232–8}}</ref>  The coil is connected to a pulse generator, or stimulator, that delivers electrical current to the coil.<ref name=Harvard/>
  
Studies of the use of TMS and rTMS to treat many neurological and psychiatric conditions have generally shown only modest effects with little confirmation of results.<ref name=Slotema>{{cite pmid|20361902}}</ref><ref>{{cite pmid|22347797}}</ref> However, publications reporting the results of reviews and statistical [[meta-analysis|meta-analyses]] of earlier investigations have stated that rTMS appeared to be effective in the treatment of certain types of [[Major depressive disorder|major depression]] under certain specific conditions.<ref name=Slotema/><ref name="pmid17655558">{{cite doi|10.1111.2Fj.1600-0447.2007.01033.x}}</ref><ref>(1) {{cite journal|author=Medical Advisory Secretariat|archiveurl=http://www.webcitation.org/6CWM44LTG|archivedate=2012-11-28|url=http://www.health.gov.on.ca/english/providers/program/mas/tech/reviews/pdf/rev_rtms_060104.pdf|title=Repetitive transcranial magnetic stimulation for the treatment of major depressive disorder: an evidence-based analysis|journal=Ontario Health Technology Assessment Series|format=pdf|year=2004|volume=4|accessdate=2012-11-28|issue=7}}<br>(2) {{cite doi|10.1111.2Fj.1600-0447.2007.01033.x}}<br>(3) {{cite doi|10.1017.2FS0033291708003462}}<br>(4) {{cite pmid|18801225}}<br>(5) {{cite doi|10.2174.2F1745017901107010167}}<br>(6) {{cite doi|10.1176/appi.ajp.2010.10060864}}<br>(7) {{cite web|author=Gaynes BN, Lux L, Lloyd S, Hansen RA, Gartlehner G, Thieda P, Brode S, Swinson Evans T, Jonas D, Crotty K, Viswanathan M, Lohr KN, [[Research Triangle Park]], [[North Carolina]]|archiveurl=http://www.webcitation.org/6BLBRlpyk|archivedate=2012-10-11|url=http://www.effectivehealthcare.ahrq.gov/ehc/products/76/792/TRD_CER33_20111110.pdf|title=Nonpharmacologic Interventions for Treatment-Resistant Depression in Adults. Comparative Effectiveness Review Number 33. (Prepared by RTI International-University of North Carolina (RTI-UNC) Evidence-based Practice Center)|work=AHRQ Publication No. 11-EHC056-EF|page=36|location=[[Rockville, Maryland]]|publisher=[[Agency for Healthcare Research and Quality]]|date=September 2011|accessdate=2011-10-11}}<br>(8) {{cite pmid|22353197}}<br>(9) {{cite pmid|22559998}}<br>(10) {{cite book|last=Fitzgerald|first=PB|last2=Daskalakis|first2=ZJ|url=http://books.google.com/books?id=2VFEAAAAQBAJ&printsec=frontcover&f=false#v=onepage&q&f=false|title=Repetitive Transcranial Magnetic Stimulation for Depressive Disorders|location=Berlin Heidelberg|publisher=Springer-Verlag|year=2013|doi=10.1007/978-3-642-36467-9|isbn=978-3-642-36466-2}} ''At'' [[Google Books]].</ref> rTMS devices are marketed for the treatment of such disorders in Canada, Australia, New Zealand, the European Union, Israel and the United States.<ref name="pmid17655558" /><ref name="Melkerson">{{cite web | url = http://www.accessdata.fda.gov/cdrh_docs/pdf8/K083538.pdf|format= pdf|date=2008-12-16|accessdate=2010-07-16|publisher=[[Food and Drug Administration]]|last=Melkerson|first=MN|title=Special Premarket 510(k) Notification for NeuroStar TMS Therapy System for Major Depressive Disorder}}</ref>
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==Society and culture==
  
A meta-analysis of 34 studies comparing rTMS to sham treatment for the acute treatment of depression found that rTMS was effective with an [[effect size]] of 0.55 (p<.001).<ref name=Slotema/> This is comparable to commonly reported effect sizes of pharmacotherapeutic strategies for treatment of depression in the range of 0.17-0.46.<ref name=Slotema/> However, this meta-analysis found that rTMS was significantly worse than [[electroconvulsive therapy]] (ECT) (effect size = -0.47), although there were significantly fewer adverse effects with rTMS. An analysis of one of the studies included in the meta-analysis found that one extra remission from depression occured for every 3 patients given electroconvulsive therapy rather than rTMS (number needed to treat 2.36).<ref>{{cite doi|10.1176.2Fappi.ajp.164.1.73}}</ref>  rTMS has been found to temporarily reduce chronic pain and change pain-related brain and nerve activity, and to predict the success of surgically implanted electrical brain stimulation for the treatment of pain.<ref>{{cite doi|10.1016/j.brs.2011.02.002}}</ref>
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===Regulatory approvals===
  
Other areas of research include the rehabilitation of [[aphasia]] and motor disability after stroke,<ref name=Rossi /><ref name="Dimyan" /><ref name="Nowak" /><ref>(1) {{cite pmid|19818232}}<br>(2) {{cite doi|10.1097.2FPHM.0b013e318228bf0c}}</ref> [[tinnitus]],<ref>{{cite pmid |19205161}}</ref> [[Parkinson's disease]],<ref>{{cite doi|10.1586.2Fern.09.132}}<br>(2) {{cite doi|10.1186.2F1755-7682-1-2}}</ref> [[tic]] disorders,<ref>{{cite pmid|22398000}}</ref> and [[posttraumatic stress disorder]] (PTSD).<ref>(1) {{cite doi|10.1016/j.janxdis.2008.03.015}}<br>(2) {{cite doi|10.1016/j.brs.2011.02.002}}</ref> TMS has failed to show effectiveness for the treatment of [[brain death]], [[coma]], and other [[persistent vegetative state]]s.<ref>{{cite pmid | 20157993 }}</ref>
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====Navigated TMS====
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Nexstim obtained [[Federal Food, Drug, and Cosmetic Act#Section 510(k) and the device approval process|510(k)]] FDA clearance of Navigated Brain Stimulation for the assessment of the primary motor cortex for pre-procedural planning in December 2009.<ref name="NBS">{{cite web|url=http://www.nexstim.com/news-and-events/press-releases/press-releases-archive/fda-clears-nexstim-s-navigated-brain-stimulation-for-non-invasive-cortical-mapping-prior-to-neurosurgery/}}</ref>
  
It is difficult to establish a convincing form of "sham" TMS to test for [[placebo]] effects during [[Scientific control|controlled]] [[Clinical trial|trials]] in [[conscious]] individuals, due to the neck pain, headache and twitching in the scalp or upper face associated with the intervention.<ref name = Rossi/> "Sham" TMS manipulations can affect [[cerebrum|cerebral]] [[Glycolysis|glucose metabolism]] and MEPs, which may confound results.<ref name="pmid17655558" /> This problem is exacerbated when using [[Subjectivity|subjective]] measures of improvement.<ref name = Rossi/>  Placebo responses in trials of rTMS in major depression are [[Negative relationship|negatively associated]] with refractoriness to treatment, vary among studies and can influence results.<ref>{{pmid|19293925}}</ref>  Depending on the research question asked and the [[design of experiments|experimental design]], matching the discomfort of rTMS to distinguish true effects from placebo can be an important and challenging issue.<ref name = Rossi/>
+
Nexstim obtained FDA 510K clearance for NexSpeech navigated brain stimulation device for neurosurgical planning in June 2011.<ref name="Nexspeech">{{cite web|url=http://www.businesswire.com/news/home/20120611005730/en/Nexstim-Announces-FDA-Clearance-NexSpeech%C2%AE-%E2%80%93-Enabling#.VGm4MGNjmnw/}}</ref>
  
One [[multicenter trial]] of rTMS in depression used an active  "sham" placebo treatment that appeared to mimic the sound and scalp stimulation associated with active TMS treatment.  The investigators reported that the patients and clinical raters were unable to guess the treatment better than chance, suggesting that the sham placebo adequately [[Blind experiment|blinded]] these people to treatment.<ref name=sham/> The investigators concluded: "Although the treatment effect was statistically significant on a clinically meaningful variable (remission), the overall number of remitters and responders was less than one would like with a treatment that requires daily intervention for 3 weeks or more, even with a benign adverse effect profile".<ref name=sham>{{cite doi|10.1001.2Farchgenpsychiatry.2010.46}}</ref> However, a review of the trial's report has questioned the adequacy of the placebo, noting that treaters were able to guess whether patients were receiving treatment with active or sham TMS, better than chance.<ref>{{cite journal|last=Mattes|first=Jeffrey A|archiveurl=http://web.archive.org/web/20110116075558/http://archpsyc.ama-assn.org/cgi/eletters/67/5/507|archivedate=2011-01-16|url=http://archpsyc.ama-assn.org/cgi/eletters/67/5/507#13743|title=TMS: Does it Really Work|journal=[[Archives of General Psychiatry]]|publisher=[[American Medical Association]]|date=2010-06-29|accessdate=2012-08-01}}</ref> In this regard, the trial's report stated that the confidence ratings for the treaters' guesses were low.<ref name=sham/>
+
====Depression====
 +
[[Neuronetics]] obtained FDA 510K clearance to market its NeuroStar System for use in adults with treatment-resistant [[major depressive disorder]] (December 2008).<ref name="Melkerson"/>
  
In 2013 in the United Kingdom, the [[National Institute for Health and Care Excellence]] recommended the use of transcranial magnetic stimulators in the treatment of migraine. In clinical trials, 39 per cent of patients treated with the device were found to be pain free after two hours and 30 per cent were still without pain after 24 hours. In a separate study, three-quarters of patients with migraine who were treated repeatedly with the device had a reduction in headache frequency.<ref>{{cite web |url=http://www.telegraph.co.uk/health/healthnews/10588318/Magentic-pulse-can-stop-migraine.html |title=Magentic pulse can stop migraine |author=Sarah Knapton| publisher=telegraph.co.uk |date=22 January 2014 |accessdate= 22 January 2014}}</ref>
+
====Migraine====
 +
eNeura Therapeutics obtained classification of Cenera System for use to treat migraine headache as a Class II medical device under the "''de novo'' pathway"<ref>Michael Drues, for Med Device Online. 5 February 2014 [http://www.meddeviceonline.com/doc/secrets-of-the-de-novo-pathway-part-why-aren-t-more-device-makers-using-it-0001 Secrets Of The De Novo Pathway, Part 1: Why Aren't More Device Makers Using It?]</ref> in December 2013.<ref name=MigraineApprov/>
  
==FDA actions==
+
===Health insurance considerations===
  
In January 2007, an advisory panel of the United States [[Food and Drug Administration]] (FDA) did not recommend clearance for marketing of an rTMS device, stating that the device appeared to be reasonably safe but had failed to demonstrate [[efficacy]] in a study of people with major depression who had not benefitted from prior adequate treatment with oral antidepressants during their current major depressive episode.<ref name="Scudiero">{{cite web | publisher = [[Food and Drug Administration|FDA]] | last = Scudiero | first = JL | url = http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/NeurologicalDevicesPanel/ucm124779.htm | title = Brief Summary From the Neurological Devices Panel Meeting - January 26, 2007| accessdate = 2010-07-14 | date = 2007-01-26 | quote=The Panel’s consensus was that the efficacy was not established; some stated that the device’s effectiveness was “small,” “borderline,” “marginal” and “of questionable clinical significance.” }}</ref> The panel agreed that "unblinding was greater in the active group, and considering the magnitude of the effect size, it may have influenced the study results."<ref name="Scudiero" />  However, the FDA determined in December 2008 that the rTMS device was sufficiently similar to existing devices that did not require a [[premarket approval]] application and allowed the device to be marketed in accordance with [[Federal Food, Drug, and Cosmetic Act#Section 510(k) and the device approval process|Section 510(k)]] of the [[Federal Food, Drug, and Cosmetic Act]] for "the treatment of Major Depressive Disorder in adult patients who have failed to achieve satisfactory improvement from one prior [[antidepressant]] medication at or above the minimal effective dose and duration in the current episode".<ref name="Melkerson"/>  The user manual for the device warns that effectiveness has not been established in patients with major depressive disorder who have failed to achieve satisfactory improvement from zero and from two or more antidepressant medications in the current episode and that the device has not been studied in patients who have had no prior antidepressant medication.<ref>{{cite book|url=http://www.neuronetics.com/pdf/Prescribing%20Information.pdf|title=NeuroStar TMS Therapy System User Manual|volume=1|pages=1–5|publisher=[[Neuronetics|Neuronetics, Inc.]]|accessdate=2010-09-13}}</ref>
+
====United States====
  
In July 2011, the FDA published a final rule in the [[Federal Register]] that classified the rTMS system into [[Medical device#Class II: General controls with special controls|Class II (special controls)]] "in order to provide a reasonable assurance of safety and effectiveness of these devices".  The rule identified the rTMS system as "an external device that delivers transcranial pulsed magnetic fields of sufficient magnitude to induce neural action potentials in the prefrontal cortex to treat the symptoms of major depressive disorder without inducing seizure in patients who have failed at least one antidepressant medication and are currently not on any antidepressant therapy".<ref>{{cite journal|last=Stade|first=NK, Deputy Director for Policy, Center for Devices and Radiological Health, Food and Drug Administration, [[United States Department of Health and Human Services]]|url=http://www.gpo.gov/fdsys/pkg/FR-2011-07-26/pdf/2011-18806.pdf|title=Medical Devices; Neurological Devices; Classification of Repetitive Transcranial Magnetic Stimulation System: Final rule|journal=[[Federal Register]]|volume=76|pages=44489–44491|publisher=[[United States Government Printing Office]]|date=2011-07-26|accessdate=2011-08-11|issue=143}}</ref> An FDA guidance document issued in conjunction with the final rule describes the special controls that support the classification of the rTMS system into Class II.<ref>{{cite web|author=U.S. Department of Health and Human Services: Food and Drug Administration: Center for Devices and Radiological Health: Office of Device Evaluation: Division of Ophthalmic, Neurological and Ear, Nose and Throat Devices: Neurodiagnostic and Neurotherapeutic Devices Branch|url=http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm265269.htm|title=Guidance for Industry and FDA Staff - Class II Special Controls Guidance Document: Repetitive Transcranial Magnetic Stimulation (rTMS) Systems|publisher=U.S. Food and Drug Administration|date=2011-07-26|accessdate=2011-08-10}}</ref>
+
=====Commercial health insurance=====
 +
In 2013, several commercial health insurance plans in the United States, including [[Anthem (insurance)|Anthem]], [[Health Net]], and [[Blue Cross Blue Shield Association|Blue Cross Blue Shield]] of [[Nebraska]] and of [[Rhode Island]], covered TMS for the treatment of depression for the first time.<ref>(1) {{cite web|author=Anthem|archiveurl=http://www.webcitation.org/6LnDHQcJA|archivedate=2013-12-11|url=http://www.anthem.com/ca/medicalpolicies/policies/mp_pw_a047769.htm|title=Medical Policy: Transcranial Magnetic Stimulation for Depression and Other Neuropsychiatric Disorders|work=Policy No. BEH.00002|publisher=Anthem |date=2013-04-16|accessdate=2013-12-11}}<br>(2) {{cite web|author=Health Net|archiveurl=http://www.webcitation.org/6BLNdUZpk|archivedate=2012-10-11|url=https://www.healthnet.com/static/general/unprotected/pdfs/national/policies/Transcranial_Magnetic_Stimulation_Mar_12.pdf|title=National Medical Policy: Transcranial Magnetic Stimulation|work=Policy Number NMP 508|publisher=Health Net|date=March 2012|accessdate=2012-09-05}}<br> (3) {{cite web|author=Blue Cross Blue Shield of Nebraska|archiveurl=http://www.webcitation.org/6BLN4D8mx|archivedate=2012-10-11|work=Section IV.67|title=Medical Policy Manual|date=2011-05-2011|publisher= Blue Cross Blue Shield of Nebraska |year=2012|url=https://www.nebraskablue.com/~/media/pdf/Provider/Policy%20Procedure%20Manuals/MedicalPolicies.pdf}}<br>(4) {{cite web|author=Blue Cross Blue Shield of Rhode Island|archiveurl=http://www.webcitation.org/6BLNAY6l7|archivedate=2012-10-11|url=https://www.bcbsri.com/sites/default/files/polices/TranscranialMagneticStimulationasaTreatmentofDepressionandOtherPsychiatricNeurologicDisorders_0.pdf|title=Medical Coverage Policy: Transcranial Magnetic Stimulation for Treatment of Depression and Other Psychiatric/Neurologic Disorders|publisher= Blue Cross Blue Shield of Rhode Island |date=2012-05-15|accessdate=2012-09-05}}</ref>  In contrast, [[UnitedHealth Group|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.<ref>{{cite web|author=[[UnitedHealthcare]]|archiveurl=http://www.webcitation.org/6Ln87XaDU|archivedate=2013-12-11|url=https://www.unitedhealthcareonline.com/ccmcontent/ProviderII/UHC/en-US/Assets/ProviderStaticFiles/ProviderStaticFilesPdf/Tools%20and%20Resources/Policies%20and%20Protocols/Medical%20Policies/Medical%20Policies/Transcranial_Magnetic_Stimulation.pdf|title=Transcranial Magnetic Stimulation|date=2013-12-01|publisher=UnitedHealthCare|page=2|accessdate=2013-12-11}}</ref> 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 [[The Regence Group|Regence]].<ref>(1) {{cite web|author=[[Aetna]]|archiveurl=http://www.webcitation.org/6Ln95sNWy|archivedate=2013-12-11|url=http://www.aetna.com/cpb/medical/data/400_499/0469.html|title=Clinical Policy Bulletin: Transcranial Magnetic Stimulation and Cranial Electrical Stimulation|date=2013-10-11|work=Number 0469|publisher=Aetna|accessdate=2013-12-11}}<br>(2) {{cite web|author=[[Cigna]]|archiveurl=http://www.webcitation.org/6LnADO1zQ|archivedate=2013-12-11|url=http://www.cigna.com/assets/docs/health-care-professionals/coverage_positions/mm_0383_coveragepositioncriteria_transcranial_magnetic_stimulation.pdf|title=Cigna Medical Coverage Policy: Transcranial Magnetic Stimulation|date=2013-01-15|work=Coverage Policy Number 0383|publisher=Cigna|accessdate=2013-12-11}}<br>(3) {{cite web|archiveurl=http://www.webcitation.org/6LnArSxDn|archivedate=2013-12-11|author=[[The Regence Group|Regence]]|url=http://blue.regence.com/trgmedpol/medicine/med148.pdf|title=Medical Policy: Transcranial Magnetic Stimulation as a Treatment of Depression and Other Disorders|work=Policy No. 17|date=2013-06-01|publisher=Regence|accessdate=2013-12-11}}</ref>
  
===Response to FDA decision===
+
=====Medicare=====
Soon after the FDA cleared the device, several members of [[Public Citizen]] stated in a [[letter to the editor]] of the medical journal ''[[Neuropsychopharmacology (journal)|Neuropsychopharmacology]]'' that the FDA seemed to have based its decision on a [[post-hoc analysis|''post-hoc'' analysis]] that did not establish the effectiveness of rTMS for the treatment of depressionThe writers of the letter expressed their concern that patients would be diverted from therapies such as antidepressant medications that have an established history of effectiveness.<ref>{{cite journal|last=Hines |first=JZ |last2=Lurie |first2=P |last3=Wolfe SM|first3=Sidney M|url=http://www.nature.com/npp/journal/v34/n8/pdf/npp200922a.pdf|title=Reply to Lisanby et al.: ''Post hoc'' analysis does not establish effectiveness of rTMS for depression|journal=[[Neuropsychopharmacology (journal)|Neuropsychopharmacology]]| year = 2009| volume=34 |issue=8 |pages=2053–2054 |pmid=19528946 |doi=10.1038/npp.2009.22 | format = pdf |authorlink3= Sidney M. Wolfe }}</ref>
+
There is no national  policy for [[Medicare (United States)|Medicare]] coverage of TMS in the United States.  Policies vary according to local coverage determinations (LCDs) that Medicare administrative contractors (MACs) for the [[Centers for Medicare and Medicaid Services]] (CMS) make for geographical areas over which they have jurisdictionCMS presently has ten to fifteen MAC jurisdictions that each cover several [[U.S. state]]s.<ref>(1)  {{cite web|url=https://www.cms.gov/Medicare/Medicare-Contracting/Medicare-Administrative-Contractors/MedicareAdministrativeContractors.html|archiveurl=http://www.webcitation.org/6NSYlBOml|archivedate=2014-02-17|title=Medicare Administrative Contractors
 +
|publisher=[[Centers for Medicare and Medicaid Services]]|date=2013-07-10|accessdate=2014-02-14}}<br>(2) {{cite web|url=http://www.cms.gov/Medicare/Medicare-Contracting/Medicare-Administrative-Contractors/MACJurisdictions.html|archiveurl=http://www.webcitation.org/6NSdw41eX|archivedate=2014-02-17|title=MAC Jurisdictions|work=[https://www.cms.gov/Medicare/Medicare-Contracting/Medicare-Administrative-Contractors/MedicareAdministrativeContractors.html Medicare Administrative Contractors]|publisher=[[Centers for Medicare and Medicaid Services]]|date=2014-02-14|accessdate=2014-02-17}}</ref>
  
==Health insurance considerations==
+
LCDs for individual MAC jurisdictions can change over time.  For example:
 +
*In early 2012, the efforts of TMS treatment advocates resulted in the establishment by a MAC with jurisdiction over [[New England]] of the first Medicare coverage policy for TMS in the United States.<ref>(1)  {{cite web|author=NHIC, Corp.|url=http://coverage.cms.fu.com/mcd_archive/viewlcd.asp?lcd_id=32228&lcd_version=5&basket=lcd%3A32228%3A5%3ARepetitive+Transcranial+Magnetic+Stimulation+%28rTMS%29%3AMAC+%2D+Part+B%3ANHIC%7C%7C+Corp%2E+%2814202%29%3A|title=Local Coverage Determination (LCD) for Repetitive Transcranial Magnetic Stimulation (rTMS) (L32228)|publisher=[[Centers for Medicare and Medicaid Services]]|date=2013-10-24|accessdate=2014-02-17}}<br>(2) {{cite web|archiveurl=http://www.webcitation.org/6BLOZQP6W|archivedate=2012-10-11|accessdate=2012-10-11|url=http://www.pbn.com/Important-Treatment-Option-for-Depression-Receives-Medicare-Coverage,66462|title=Important Treatment Option for Depression Receives Medicare Coverage|work=Press Release|date=2012-03-30|publisher=[http://www.pbn.com/ PBN.com: Providence Business News]}}<br>(3) {{cite web|author=The Institute for Clinical and Economic Review|date=June 2012|archiveurl=http://www.webcitation.org/6LnIhPFhU|archivedate=2013-12-11|url=http://cepac.icer-review.org/wp-content/uploads/2012/07/rTMS-Coverage-Policy-Analysis.pdf|title=Coverage Policy Analysis: Repetitive Transcranial Magnetic Stimulation (rTMS)|publisher=[http://cepac.icer-review.org/?page_id=18 The New England Comparative Effectiveness Public Advisory Council (CEPAC)]|accessdate=2013-12-11}}<br>(4) {{cite web|archiveurl=http://www.webcitation.org/6BN4UpUXK|archivedate=2012-10-12|url=http://www.cvmc.org/news/2012-theresa-fama-cepac|title=Transcranial Magnetic Stimulation Cites Influence of New England Comparative Effectiveness Public Advisory Council (CEPAC)|date=2012-02-06|location=[[Berlin, Vermont]]|publisher=[[Central Vermont Medical Center]]|accessdate=2012-10-12}}</ref>  However, a new MAC for the same jurisdiction subsequently determined that Medicare would not cover services for TMS performed in New England on or after October 25, 2013.<ref>{{cite web|author=[http://www.cms.gov/medicare-coverage-database/staticpages/contractor-details.aspx?ContrId=178&ver=1 National Government Services, Inc.]|url=http://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=32038&ContrId=178&&bc=IAAAABAAAAAAAA%3d%3d&|date=2013-10-25|title=Local Coverage Determination (LCD):  Transcranial Magnetic Stimulation (L32038)|publisher= [[Centers for Medicare and Medicaid Services]]|accessdate=2014-02-17}}</ref>
  
===United States===
+
*In August 2012, the MAC whose jurisdiction covered [[Arkansas]], [[Louisiana]], [[Mississippi]], [[Colorado]], [[Texas]], [[Oklahoma]] and [[New Mexico]] determined that, based on limitations in the published literature there was insufficient evidence to cover the treatment,<ref>{{cite web|url=http://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=32752&ContrId=259&ver=15&ContrVer=1&DocID=L32752&SearchType=Advanced&bc=IAAAAAgAAAAAAA%3d%3d&l|title=LCD L32752 - Transcranial Magnetic Stimulation for Depression|author=Novitas Solutions, Inc.|work=Contractor's Determination Number L32752|date=2013-12-04|publisher=[[Centers for Medicare and Medicaid Services]]|accessdate=2014-02-17}}</ref> but the same MAC subsequently determined that Medicare would cover TMS for the treatment of depression for services performed within the MAC's jurisdiction on or after December 5, 2013,<ref>{{cite web|url=http://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=33660&ContrId=259&bc=IAAAAAgAAAAAAA%3d%3d&|title=LCD L33660 - Transcranial Magnetic Stimulation (TMS) for the Treatment of Depression|author=Novitas Solutions, Inc.|work=Contractor's Determination Number L33660|publisher= [[Centers for Medicare and Medicaid Services]]|date=2013-12-05|accessdate=2014-02-17}}</ref>
  
====Commercial health insurance====
+
*In December 2012, Medicare began covering TMS for the treatment of depression in [[Tennessee]], [[Alabama]] and [[Georgia (U.S. state)|Georgia]].<ref>(1) {{cite web|author=Cahaba Government Benefit Administrators®, LLC|url=http://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=32834&ContrId=215&bc=IAAAABAAAAAAAA%3d%3d&|title=Local Coverage Determination (LCD):  Medicine: Repetitive Transcranial Magnetic Stimulation (rTMS) for Resistant Depression (L32834)|date=2012-12-01|accessdate=2014-02-17}}<br>(2){{cite web|first=Phillip|last=Nannie|url=http://nashvillepost.com/blogs/postbusiness/2012/10/31/medicare_agrees_to_cover_tms_treatment_for_depression_in_tn_ga_al|archiveurl=http://www.webcitation.org/6LnGKnmZw|archivedate=2013-12-11|title=Medicare agrees to cover TMS treatment for depression in TN, GA, AL|work=[[NashvillePost.com]]|publisher=[http://www.southcomm.com/ SouthComm Communications, Inc.]|location=Nashville, Tennessee|date=2012-10-31|accessdate=2013-11-13}}</ref>
In July 2011, the Technology Evaluation Center (TEC) of the [[Blue Cross Blue Shield Association]], in cooperation with the [[Kaiser Permanente|Kaiser Foundation Health Plan and the Southern California Permanente Medical Group]], determined that TMS for the treatment of depression did not meet the TEC's criteria, which assess whether a technology improves health outcomes such as length of life, quality of life and functional ability.<ref>{{cite web|url=http://www.bcbs.com/blueresources/tec/|title=Technology Evaluation Center Criteria|work=Technology Evaluation Center (TEC)]|publisher=[[Blue Cross Blue Shield Association]]|accessdate=2013-12-11}}</ref><ref name=TEC1>{{cite journal|archiveurl=http://www.webcitation.org/6BMxPPs8X|archivedate=2012-10-12|url=http://www.elsevierbi.com/~/media/Images/Publications/Archive/The%20Gray%20Sheet/37/35/01110829008/082911_bcbs_tms_august11.pdf|title=Transcranial Magnetic Stimulation for Depression|journal=[http://www.bcbs.com/blueresources/tec/ TEC Assessment Program]|volume=26|date=July 2011|publisher=[[Blue Cross Blue Shield Association]]|accessdate=2012-10-12|issue=3}}</ref> The TEC's report stated that "the meta-analyses and recent clinical trials of TMS generally show statistically significant effects on depression outcomes at the end of the TMS treatment period. However, there is a lack of rigorous evaluation beyond the treatment period", which was, with a few exceptions, one to four weeks.<ref name=TEC1 /> The Blue Cross Blue Shield Association's medical advisory panel concluded that "the available evidence does not permit conclusions regarding the effect of TMS on health outcomes or compared with alternatives.”<ref name=TEC1 />
 
  
In 2013, several commercial health insurance plans in the United States, including [[Anthem (insurance)|Anthem]], [[Health Net]], and [[Blue Cross Blue Shield Association|Blue Cross Blue Shield]] of [[Nebraska]] and of [[Rhode Island]], covered TMS for the treatment of depression.<ref>(1) {{cite web|author=Anthem|archiveurl=http://www.webcitation.org/6LnDHQcJA|archivedate=2013-12-11|url=http://www.anthem.com/ca/medicalpolicies/policies/mp_pw_a047769.htm|title=Medical Policy: Transcranial Magnetic Stimulation for Depression and Other Neuropsychiatric Disorders|work=Policy No. BEH.00002|publisher=Anthem |date=2013-04-16|accessdate=2013-12-11}}<br>(2) {{cite web|author=Health Net|archiveurl=http://www.webcitation.org/6BLNdUZpk|archivedate=2012-10-11|url=https://www.healthnet.com/static/general/unprotected/pdfs/national/policies/Transcranial_Magnetic_Stimulation_Mar_12.pdf|title=National Medical Policy: Transcranial Magnetic Stimulation|work=Policy Number NMP 508|publisher=Health Net|date=March 2012|accessdate=2012-09-05}}<br> (3) {{cite web|author=Blue Cross Blue Shield of Nebraska|archiveurl=http://www.webcitation.org/6BLN4D8mx|archivedate=2012-10-11|work=Section IV.67|title=Medical Policy Manual|date=2011-05-2011|publisher= Blue Cross Blue Shield of Nebraska |year=2012|url=https://www.nebraskablue.com/~/media/pdf/Provider/Policy%20Procedure%20Manuals/MedicalPolicies.pdf}}<br>(4) {{cite web|author=Blue Cross Blue Shield of Rhode Island|archiveurl=http://www.webcitation.org/6BLNAY6l7|archivedate=2012-10-11|url=https://www.bcbsri.com/sites/default/files/polices/TranscranialMagneticStimulationasaTreatmentofDepressionandOtherPsychiatricNeurologicDisorders_0.pdf|title=Medical Coverage Policy: Transcranial Magnetic Stimulation for Treatment of Depression and Other Psychiatric/Neurologic Disorders|publisher= Blue Cross Blue Shield of Rhode Island |date=2012-05-15|accessdate=2012-09-05}}</ref>  In contrast, [[UnitedHealth Group|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.<ref>{{cite web|author=[[UnitedHealthcare]]|archiveurl=http://www.webcitation.org/6Ln87XaDU|archivedate=2013-12-11|url=https://www.unitedhealthcareonline.com/ccmcontent/ProviderII/UHC/en-US/Assets/ProviderStaticFiles/ProviderStaticFilesPdf/Tools%20and%20Resources/Policies%20and%20Protocols/Medical%20Policies/Medical%20Policies/Transcranial_Magnetic_Stimulation.pdf|title=Transcranial Magnetic Stimulation|date=2013-12-01|publisher=UnitedHealthCare|page=2|accessdate=2013-12-11}}</ref> 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 [[The Regence Group|Regence]].<ref>(1) {{cite web|author=[[Aetna]]|archiveurl=http://www.webcitation.org/6Ln95sNWy|archivedate=2013-12-11|url=http://www.aetna.com/cpb/medical/data/400_499/0469.html|title=Clinical Policy Bulletin: Transcranial Magnetic Stimulation and Cranial Electrical Stimulation|date=2013-10-11|work=Number 0469|publisher=Aetna|accessdate=2013-12-11}}<br>(2) {{cite web|author=[[Cigna]]|archiveurl=http://www.webcitation.org/6LnADO1zQ|archivedate=2013-12-11|url=http://www.cigna.com/assets/docs/health-care-professionals/coverage_positions/mm_0383_coveragepositioncriteria_transcranial_magnetic_stimulation.pdf|title=Cigna Medical Coverage Policy: Transcranial Magnetic Stimulation|date=2013-01-15|work=Coverage Policy Number 0383|publisher=Cigna|accessdate=2013-12-11}}<br>(3) {{cite web|archiveurl=http://www.webcitation.org/6LnArSxDn|archivedate=2013-12-11|author=[[The Regence Group|Regence]]|url=http://blue.regence.com/trgmedpol/medicine/med148.pdf|title=Medical Policy: Transcranial Magnetic Stimulation as a Treatment of Depression and Other Disorders|work=Policy No. 17|date=2013-06-01|publisher=Regence|accessdate=2013-12-11}}</ref>
+
CMS maintains a searchable database that enables users to find current Medicare LCDs for TMS for individual U.S. states.<ref>{{cite web|url=http://www.cms.gov/medicare-coverage-database/search/advanced-search.aspx?SearchType=Advanced&CoverageSelection=Local&PolicyType=Final&s=All&KeyWord=transcranial+magnetic+stimulation&KeyWordLookUp=Title&KeyWordSearchType=Exact&kq=true&bc=IAAAAAAAAAAAAA%3d%3d&|title=Advanced Search: Transcranial Magnetic Stimulation|publisher=[[Centers for Medicare and Medicaid Services]]|accessdate=2014-02-17}}</ref>
  
====Medicare====
+
====United Kingdom's National Health Service====
In early 2012, the efforts of TMS treatment advocates resulted in the approval for the [[New England]] region of the first [[Medicare (United States)|Medicare]] coverage policy for TMS in the United States.<ref>(1) {{cite web|author=[[Centers for Medicare and Medicaid Services]] |url=http://www.cms.gov/medicare-coverage-database/indexes/lcd-list.aspx?Cntrctr=207#ResultsAnchor|title= Repetitive Transcranial Magnetic Stimulation (rTMS) |publisher= [[United States Department of Health and Human Services]]|year=2012|accessdate=2012-09-05}}<br>(2) {{cite web|url=http://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=32228&ContrId=208&ver=3&ContrVer=1&CntrctrSelected=208*1&Cntrctr=208&name=NHIC%2c+Corp.+(14202%2c+MAC+-+Part+B)&DocStatus=Future&s=24&bc=AggAAAIAQAAA&|title=Local Coverage Determination (LCD) for Repetitive Transcranial Magnetic Stimulation (rTMS) (L32228)|author=[[Centers for Medicare and Medicaid Services]]|publisher=[[United States Department of Health and Human Services]]|date=2012-01-27|accessdate=2012-10-12}}<br>(3) {{cite web|archiveurl=http://www.webcitation.org/6BLOZQP6W|archivedate=2012-10-11|accessdate=2012-10-11|url=http://www.pbn.com/Important-Treatment-Option-for-Depression-Receives-Medicare-Coverage,66462|title=Important Treatment Option for Depression Receives Medicare Coverage|work=Press Release|date=2012-03-30|publisher=[http://www.pbn.com/ PBN.com: Providence Business News]}}<br>(4) {{cite web|author=The Institute for Clinical and Economic Review|date=June 2012|archiveurl=http://www.webcitation.org/6LnIhPFhU|archivedate=2013-12-11|url=http://cepac.icer-review.org/wp-content/uploads/2012/07/rTMS-Coverage-Policy-Analysis.pdf|title=Coverage Policy Analysis: Repetitive Transcranial Magnetic Stimulation (rTMS)|publisher=[http://cepac.icer-review.org/?page_id=18 The New England Comparative Effectiveness Public Advisory Council (CEPAC)]|accessdate=2013-12-11}}<br>(5) {{cite web|archiveurl=http://www.webcitation.org/6BN4UpUXK|archivedate=2012-10-12|url=http://www.cvmc.org/news/2012-theresa-fama-cepac|title=Transcranial Magnetic Stimulation Cites Influence of New England Comparative Effectiveness Public Advisory Council (CEPAC)|date=2012-02-06|location=[[Berlin, Vermont]]|publisher=[[Central Vermont Medical Center]]|accessdate=2012-10-12}}</ref> In December 2012, Medicare began covering TMS for the treatment of depression in [[Tennessee]], [[Alabama]] and [[Georgia (U.S. state)|Georgia]].<ref>{{cite web|first=Phillip|last=Nannie|url=http://nashvillepost.com/blogs/postbusiness/2012/10/31/medicare_agrees_to_cover_tms_treatment_for_depression_in_tn_ga_al|archiveurl=http://www.webcitation.org/6LnGKnmZw|archivedate=2013-12-11|title=Medicare agrees to cover TMS treatment for depression in TN, GA, AL|work=[[NashvillePost.com]]|publisher=[http://www.southcomm.com/ SouthComm Communications, Inc.]|location=Nashville, Tennessee|date=2012-10-31|accessdate=2013-11-13}}</ref> In contrast, in August 2012, the Medicare administrative contractor for the [[Centers for Medicare and Medicaid Services]] jurisdiction covering [[Arkansas]], [[Louisiana]], [[Mississippi]], [[Colorado]], [[Texas]], [[Oklahoma]] and [[New Mexico]] determined that, based on limitations in the published literature, <blockquote>... the evidence is insufficient to determine rTMS improves health outcomes in the Medicare or general population. ... The contractor considers repetitive transcranial magnetic stimulation (rTMS) not medically necessary when used for its FDA-approved indication and for all [[off-label use]]s.<ref>{{cite web|url=https://www.novitas-solutions.com/policy/jh/l32752-r1.html|title=LCD L32752 - Transcranial Magnetic Stimulation for Depression|author=Novitas Solutions, Inc.|work=Contractor's Determination Number L32752|publisher=[https://www.novitas-solutions.com/ Novitas Solutions]|date=2012-08-20|accessdate=2012-10-12}}</ref></blockquote>
+
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. NICE guidance does not cover whether or not the NHS should fund a procedure. Local NHS bodies ([[NHS primary care trust|primary care trusts]] and [[NHS hospital trust|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.<ref>NICE [https://www.nice.org.uk/about/what-we-do About NICE: What we do]</ref>
  
===United Kingdom===
+
NICE evaluated TMS for severe depression (IPG 242) in 2007, and subsequently considered TMS for reassessment in January 2011 but did not change its evaluation.<ref name=TMSdepress>{{cite web|url=https://www.nice.org.uk/guidance/ipg242|title=Transcranial magnetic stimulation for severe depression (IPG242)|location=London, England|publisher=National Institute for Health and Clinical Excellence|date=2011-03-04}}</ref> The Institute found that TMS is safe, but there is insufficient evidence for its efficacy.<ref name=TMSdepress/>
  
====National Health Service====
+
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.<ref>{{cite web|url=https://www.nice.org.uk/guidance/ipg477|title=Transcranial magnetic stimulation for treating and preventing migraine|date=January 2014|location=London, England|publisher=National Institute for Health and Clinical Excellence}}</ref>
The [[United Kingdom]]'s [[National Institute for Health and Clinical Excellence]] 2007 guidance to the [[National Health Service]] in [[England]], [[Wales]], [[Scotland]] and [[Northern Ireland]] on transcranial magnetic stimulation for severe depression (IPG242), considered for reassessment in January 2011, states:
 
<blockquote>Current evidence suggests that there are no major safety concerns associated with transcranial magnetic stimulation (TMS) for severe depression. There is uncertainty about the procedure's clinical efficacy, which may depend on higher intensity, greater frequency, bilateral application and/or longer treatment durations than have appeared in the evidence to date. TMS should therefore be performed only in research studies designed to investigate these factors.<ref>(1) {{cite web|archiveurl=http://www.webcitation.org/6CUsaPbmy|archivedate=2012-11-27|url=http://publications.nice.org.uk/transcranial-magnetic-stimulation-for-severe-depression-ipg242|title=Guidance: Transcranial magnetic stimulation for severe depression (IPG242)|work=NICE interventional procedure guidance, issued November 2007|publisher=[[National Institute for Health and Clinical Excellence]]|accessdate=2012-11-27}}<br>(2) {{cite web|archiveurl=http://www.webcitation.org/6CUrsKLDq|archivedate=2012-11-27|url=http://www.nice.org.uk/guidance/IPG242|title=Transcranial magnetic stimulation for severe depression (IPG242)|publisher=[[National Institute for Health and Clinical Excellence]]|date=2011-03-04|accessdate=2012-11-27}}</ref></blockquote>
 
  
==American Medical Association category codes==
+
==Technical information==
In 2011, the [[American Medical Association]] established three Category I CPT® Codes to be used for the reporting and billing of therapeutic repetitive transcranial magnetic stimulation treatment services.<ref>{{cite web|author=American Medical Association|url=https://ocm.ama-assn.org/OCM/CPTRelativeValueSearch.do|title=Current Procedural Terminology|publisher=American Medical Association|year=2012|accessdate=2012-02-02}}</ref> The three codes effective January 1, 2012 are:
+
[[Image:TMS focal field.png|right|150px]]
 +
[[Image:TMS Butterfly Coil HEAD.png|right|thumb|240px|TMS - Butterfly Coils]]
 +
TMS uses [[electromagnetic induction]] to generate an electric current across the [[scalp]] and [[Human skull|skull]] without physical contact.  A plastic-enclosed coil of wire is held next to the skull and when activated, produces a [[magnetic field]] oriented [[Orthogonality|orthogonal]] to the plane of the coil. The magnetic field passes unimpeded through the skin and skull, inducing an oppositely directed current in the brain that activates nearby nerve cells in much the same way as currents applied directly to the cortical surface.<ref>{{cite book |title=Handbook of psychophysiology |year=2007 |publisher=Cambridge Univ. Press |location=New York |isbn=0-521-84471-1 |edition=3rd |editor=Cacioppo, JT; Tassinary, LG; Berntson, GG.|page=121}}</ref>
  
* 90867 – Therapeutic repetitive transcranial magnetic stimulation (TMS) treatment; initial, including cortical mapping, motor threshold determination, delivery and management
+
The path of this current is difficult to model because the brain is irregularly shaped and electricity and magnetism are not [[Electrical conduction|conducted]] uniformly throughout its tissues.  The magnetic field is about the same strength as an [[Magnetic resonance imaging|MRI]], and the pulse generally reaches no more than 5 centimeters into the brain unless using the [[deep transcranial magnetic stimulation]] variant of TMS.<ref>{{cite web | url = http://www.nimh.nih.gov/health/topics/brain-stimulation-therapies/brain-stimulation-therapies.shtml | title = Brain Stimulation Therapies | accessdate = 2010-07-14 | date = 2009-11-17 | publisher = [[National Institute of Mental Health]] }}</ref> Deep TMS can reach up to 6&nbsp;cm into the brain to stimulate deeper layers of the [[motor cortex]], such as that which controls leg motion.<ref>(1) {{cite doi|10.1016/j.clinph.2004.11.008}}<br>(2) {{cite pmid|20633398}}</ref>
* 90868 – Therapeutic repetitive transcranial magnetic stimulation (TMS) treatment; subsequent delivery and management, per session
+
 
* 90869 – Therapeutic repetitive transcranial magnetic stimulation (TMS) treatment; subsequent motor threshold re-determination with delivery and management
+
===Mechanism of action===
 +
From the [[Biot–Savart law]]
 +
<center><math> \mathbf B = \frac{\mu_0}{4\pi} I \int_C \frac{d\mathbf l \times \mathbf{\hat r}}{r^2}</math> </center>
 +
it has been shown that a current through a wire generates a magnetic field around that wire. Transcranial magnetic stimulation is achieved by quickly discharging current from a large [[capacitor]] into a coil to produce pulsed [[magnetic fields]] of 1-10 mT.<ref name=Walsh>V. Walsh and A. Pascual-Leone, "Transcranial Magnetic Stimulation: A Neurochronometrics of Mind." Cambridge, Massachusetts: MIT Press, 2003.</ref> By directing the magnetic field pulse at a targeted area of the [[brain]], one can either [[depolarization|depolarize]] or [[hyperpolarization (biology)|hyperpolarize]] neurons in the brain. The magnetic flux density pulse generated by the current pulse through the coil causes an electric field as explained by the [[Electromagnetic induction#Maxwell–Faraday equation|Maxwell-Faraday equation]],
 +
<center><math>\nabla \times \mathbf{E} = -\frac{\partial \mathbf{B}} {\partial t}</math> .</center>
 +
This electric field causes a change in the transmembrane current of the neuron, which leads to the depolarization or hyperpolarization of the neuron and the firing of an [[action potential]].<ref name=Walsh/>
  
==Technical information==
+
The exact details of how TMS functions are still being explored. The effects of TMS can be divided into two types depending on the mode of stimulation:
[[Image:TMS focal field .png|right|150px]]
+
 
[[Image:TMS Butterfly Coil HEAD .png|right|thumb|240px|TMS - Butterfly Coils]]
+
*Single or paired pulse TMS causes neurons in the neocortex under the site of stimulation to [[Depolarization|depolarize]] and discharge an [[action potential]]. If used in the [[primary motor cortex]], it produces muscle activity referred to as a [[Evoked potential#Motor evoked potentials|motor evoked potential]] (MEP) which can be recorded on [[electromyography]]. If used on the [[occipital cortex]], '[[phosphene]]s' (flashes of light) might be perceived by the subject. In most other areas of the cortex, the participant does not consciously experience any effect, but his or her behaviour may be slightly altered (e.g., slower reaction time on a cognitive task), or changes in brain activity may be detected using sensing equipment.<ref name="Handbook of Transcranial Magnetic Stimulation">{{cite book | author = [[Alvaro Pascual-Leone|Pascual-Leone A]]; Davey N; Rothwell J; Wassermann EM; Puri BK | year = 2002 | title = Handbook of Transcranial Magnetic Stimulation | publisher = Edward Arnold|location=London | isbn = 0-340-72009-3  }}</ref>
TMS uses [[electromagnetic induction]] to generate an electric current across the [[scalp]] and [[Human skull|skull]] without physical contact. A plastic-enclosed coil of wire is held next to the skull and when activated, produces a [[magnetic field]] oriented [[Orthogonality|orthogonal]] to the plane of the coil. The magnetic field passes unimpeded through the skin and skull, inducing an oppositely directed current in the brain that activates nearby nerve cells in much the same way as currents applied directly to the cortical surface.<ref>{{cite book |title=Handbook of psychophysiology |year=2007 |publisher=Cambridge Univ. Press |location=New York, NY |isbn=0-521-84471-1 |edition=3rd |editor=Cacioppo, JT; Tassinary, LG; Berntson, GG.|page=121}}</ref>
+
 
 +
*Repetitive TMS produces longer-lasting effects which persist past the initial period of stimulation. rTMS can increase or decrease the excitability of the [[corticospinal tract]] depending on the intensity of stimulation, coil orientation, and frequency. The mechanism of these effects is not clear, though it is widely believed to reflect changes in synaptic efficacy akin to [[long-term potentiation]] (LTP) and [[long-term depression]] (LTD).<ref name=Fitzgerald>{{cite doi|10.1016/j.clinph.2006.06.712}}</ref>
  
The path of this current is difficult to model because the brain is irregularly shaped and electricity and magnetism are not [[Electrical conduction|conducted]] uniformly throughout its tissues.  The magnetic field is about the same strength as an [[Magnetic resonance imaging|MRI]], and the pulse generally reaches no more than 5 centimeters into the brain unless using the [[deep transcranial magnetic stimulation]] variant of TMS.<ref>{{cite web | url = http://www.nimh.nih.gov/health/topics/brain-stimulation-therapies/brain-stimulation-therapies.shtml | title = Brain Stimulation Therapies | accessdate = 2010-07-14 | date = 2009-11-17 | publisher = [[National Institute of Mental Health]] }}</ref> Deep TMS can reach up to 6&nbsp;cm into the brain to stimulate deeper layers of the [[motor cortex]], such as that which controls leg motion.<ref>(1) {{cite doi|10.1016/j.clinph.2004.11.008}}<br>(2) {{cite pmid|20633398}}</ref>
+
MRI images, recorded during TMS of the motor cortex of the brain, have been found to match very closely with [[Positron emission tomography|PET]] produced by voluntary movements of the hand muscles innervated by TMS, to 5–22&nbsp;mm of accuracy.<ref name=Wassermann1996>{{cite doi|10.1006/nimg.1996.0001}}</ref>
 +
The localisation of motor areas with TMS has also been seen to correlate closely to [[Magnetoencephalography|MEG]]<ref name=Morioka>T. Morioka, T. Yamamoto, A. Mizushima, S. Tombimatsu, H. Shigeto, K. Hasuo, S. Nishio, K. Fujii and M. Fukui. Comparison of magnetoencephalography, functional MRI, and motor evoked potentials in the localization of the sensory-motor cortex. Neurol.  Res., vol. 17, no. 5, pp. 361-367. 1995</ref> and also [[Functional magnetic resonance imaging|fMRI]].<ref name=Terao>{{cite doi|10.1007/s002210050446}}</ref>
  
 
=== Coil types ===
 
=== Coil types ===
Line 125: Line 130:
 
* H-coil: for deep transcranial magnetic stimulation
 
* H-coil: for deep transcranial magnetic stimulation
  
Design variations in the shape of the TMS coils allow much deeper penetration of the brain than the standard depth of 1.5-2.5&nbsp;cm.  Circular crown coils, Hesed (or H-core) coils, double cone coils, and other experimental variations can induce excitation or inhibition of neurons deeper in the brain including activation of motor neurons for the [[cerebellum]], legs and [[pelvic floor]].  Though able to penetrate deeper in the brain, they are less able to produced a focused, localized response and are relatively non-focal.<ref name = Rossi/>
+
Design variations in the shape of the TMS coils allow much deeper penetration of the brain than the standard depth of 1.5-2.5&nbsp;cm.  Circular crown coils, Hesed (or H-core) coils, double cone coils, and other experimental variations can induce excitation or inhibition of neurons deeper in the brain including activation of motor neurons for the [[cerebellum]], legs and [[pelvic floor]].  Though able to penetrate deeper in the brain, they are less able to produce a focused, localized response and are relatively non-focal.<ref name = Rossi/>
 +
 
 +
==History==
 +
Early attempts at stimulation of the brain using a magnetic field included those, in 1910, of [[Silvanus P. Thompson]] in London.<ref>http://www.scholarpedia.org/article/Transcranial_magnetic_stimulation</ref> The principle of inductive brain stimulation with [[eddy current]]s has been noted since the 20th century{{Citation needed|date=November 2014}}.  The first successful TMS study was performed in 1985 by Anthony Barker and his colleagues at the [[Royal Hallamshire Hospital]] in [[Sheffield]], England.<ref name=Barker>{{cite doi|10.1016/S0140-6736(85)92413-4}}</ref>  Its earliest application demonstrated conduction of nerve impulses from the [[motor cortex]] to the [[spinal cord]], stimulating muscle contractions in the hand.  As compared to the previous method of transcranial stimulation proposed by Merton and Morton in 1980<ref name=Merton>{{cite doi|10.1038/285227a0}}</ref> in which direct electrical current was applied to the scalp, the use of [[electromagnet]]s greatly reduced the discomfort of the procedure, and allowed mapping of the [[cerebral cortex]] and its connections.
 +
 
 +
==Research==
 +
Areas of research include the rehabilitation of [[aphasia]] and motor disability after stroke,<ref name="Dimyan" /><ref name="Nowak" /><ref name=Lefaucher1/><ref name=Rossi /><ref>(1) {{cite pmid|19818232}}<br>(2) {{cite doi|10.1097.2FPHM.0b013e318228bf0c}}</ref> tinnitus,<ref name=Lefaucher1/><ref>{{cite pmid |19205161}}</ref> [[anxiety disorders]],<ref name=Lefaucher1/> [[obsessive-compulsive disorder]],<ref name=Lefaucher1/> [[amyotrophic lateral sclerosis]],<ref name=Lefaucher1/> [[multiple sclerosis]],<ref name=Lefaucher1/> [[epilepsy]],<ref name=Lefaucher1/> [[Alzheimer's disease]],<ref name=Lefaucher1/> [[Parkinson's disease]],<ref>{{cite doi|10.1586.2Fern.09.132}}<br>(2) {{cite doi|10.1186.2F1755-7682-1-2}}</ref>[[schizophrenia]],<ref name=Lefaucher1/> [[substance abuse]],<ref name=Lefaucher1/> [[addiction]],<ref name=Lefaucher1/><ref>{{cite journal|author=Nizard J; Lefaucher J-P; Helbert M; de Chauvigny E; Nguyen J-P|archiveurl=http://www.webcitation.org/6NZCOko3C|archivedate=2014-02-21|url=http://www.discoverymedicine.com/Julien-Nizard/2012/07/24/non-invasive-stimulation-therapies-for-the-treatment-of-refractory-pain/|title=Non-invasive stimulation therapies for the treatment of chronic pain|journal=Discovery Medicine|volume=14|number=74|pages=21–31|year=2012|issn=1539-6509|pmid=22846200}}</ref> and [[posttraumatic stress disorder]] (PTSD).<ref name=Lefaucher1/><ref>(1) {{cite doi|10.1016/j.janxdis.2008.03.015}}<br>(2) {{cite doi|10.1016/j.brs.2011.02.002}}</ref>
  
=== Devices used in transcranial magnetic stimulation ===
+
It is difficult to establish a convincing form of "sham" TMS to test for [[placebo]] effects during [[Scientific control|controlled]] [[Clinical trial|trials]] in [[conscious]] individuals, due to the neck pain, headache and twitching in the scalp or upper face associated with the intervention.<ref name=Lefaucher1/><ref name = Rossi/> "Sham" TMS manipulations can affect [[cerebrum|cerebral]] [[Glycolysis|glucose metabolism]] and MEPs, which may confound results.<ref name="pmid17655558">{{cite doi|10.1111.2Fj.1600-0447.2007.01033.x}}</ref> This problem is exacerbated when using [[Subjectivity|subjective]] measures of improvement.<ref name = Rossi/>  Placebo responses in trials of rTMS in major depression are [[Negative relationship|negatively associated]] with refractoriness to treatment, vary among studies and can influence results.<ref>{{cite pmid|19293925}}</ref> Depending on the research question asked and the [[design of experiments|experimental design]], matching the discomfort of rTMS to distinguish true effects from placebo can be an important and challenging issue.<ref name=Lefaucher1/><ref name = Rossi/>
Devices available for transcranial magnetic stimulation include:
 
* Coils: This is the main component of a TMS system and the part applied directly to the head. A coil can be of different types.
 
* Stimulators: The stimulator is the machine delivering high intensity pulses of electrical current in the coil to produce [[electromagnetic induction]] in the brain. It allows to set all important stimulation parameters and to define complex patterns of pulses to be delivered to the brain. In case of rTMS, the stimulator often contains a cooling system to evacuate the heat produced by repetitive pulses of current.
 
* Neuronavigation systems: [[Neuronavigation]] is a technique originally used in [[neurosurgery]]. It makes uses of a software system able to load [[Magnetic resonance imaging|MRI]] and possibly [[fMRI]] data to localize stimulation spots directly in a [[3D reconstruction]] of the brain. Combined with [[optical motion tracking]] systems focusing on the head, neuro-navigation provides computer-assisted TMS allowing for personalized stimulations. In traditional TMS indeed, the coil is positioned based on anatomical landmarks on the skull (including, but not limited to, the [[inion]] or the [[nasion]]), thereby deriving the location of stimulation spots from the anatomical position of the brain in the head.<ref>{{cite journal|last=Fitzgerald |first=PB | last2=Hoy |first2=K |last3=McQueen |first3=S |last4=Maller |first4=JJ |last5=Herring |first5=S |last6=Segrave |first6=R |last7=Bailey first7=M |last8=Been |first8=G |last9=Kulkarni |first9=J |last10=Daskalakis |first10=ZJ |title=A randomized trial of rTMS targeted with MRI based neuro-navigation in treatment-resistant depression|journal=Neuropsychopharmacology|date=April 2009 |volume=34|issue=5 |pmid=19145228 |doi=10.1038/npp.2008.233 }}</ref><ref>{{cite journal|last=Nauczyciel |first=C |last2=Hellier |first2=P |last3=Morandi |first3=X |last4=Blestel |first4=S |last5=Drapier |first5=D |last6=Ferre |first6=JC |last7=Barillot |first7=C |last8=Millet |first8=B |title=Assessment of standard coil positioning in transcranial magnetic stimulation in depression | journal=Psychiatry Research| date=30 April 2011 |volume=186|issue=2-3 |pmid=    20692709 |doi=10.1016/j.psychres.2010.06.012 }}</ref>
 
* Coil positioning systems: positioning systems help to keep the coil in place for the whole duration of a TMS session. Such systems can be simple static coil holders or computer-controlled [[robotic arm]]s. Static holders need to be manually adjusted at the stimulation site. [[Robotic arm]]s are controlled by neuronavigation to adjust the coil position automatically.<ref>{{cite journal|last=Zorn |first=L |last2=Renaud |first2=P |last3=Bayle |first3=B |last4=Goffin |first4=L |title=Design and Evaluation of a Robotic System for Transcranial Magnetic Stimulation|journal=IEEE Transactions on Biomedical Engineering|date=March 2012 |volume=59 |issue=3 |pages=805–815  |pmid=22186930  |doi=10.1109/TBME.2011.2179938 | format = pdf }}</ref><ref name="Robotized Transcranial Magnetic Stimulation">{{cite book | author = Richter Lars | year = 2013| title = Robotized Transcranial Magnetic Stimulation | publisher = Springer | location=[[New York]] | isbn = 978-1-4614-7359-6  }}</ref>
 
  
 
==See also==
 
==See also==
Line 142: Line 148:
  
 
==References==
 
==References==
{{reflist|2}}
+
{{reflist|30em}}
  
 
==Further reading==
 
==Further reading==
Line 151: Line 157:
 
{{Commons category}}
 
{{Commons category}}
 
* [http://www.overstream.net/view.php?oid=n7aomgtia5ul Stuttering Triggered by Transcranial Magnetic Stimulation (video)]
 
* [http://www.overstream.net/view.php?oid=n7aomgtia5ul Stuttering Triggered by Transcranial Magnetic Stimulation (video)]
* [http://www.magneticstimulation.gr/index.php/information-for-the-neurophysiology-tests/ More on the diagnostic utility of Transcranial Magnetic Stimulation]
 
* coil manufacturers: [http://www.brainsway.com/ Brainsway], [http://neuronetics.com/ Neuronetics], [http://www.magstim.com/ Magstim], [http://www.magventure.com/ MagVenture], [http://www.magandmore.com/ Mag&More].
 
* stimulators: most coil manufacturers also produce stimulators.
 
* neuronavigation systems: [http://www.rogue-research.com/ Rogue Research], [http://www.nexstim.com/ Nexstim], [http://www.ant-neuro.com ANT Neuro], [http://www.localite.de LOCALITE], [http://www.brainvoyager.com/ BrainInnovation], [http://www.syneika.com/uk/home Syneika].
 
* coil holders: most coil manufacturers also provide static coil holders. Manufacturers of robotic holders include [http://www.ant-neuro.com ANT Neuro], [http://www.axilumrobotics.com/ Axilum Robotics].
 
  
 
{{DEFAULTSORT:Transcranial Magnetic Stimulation}}
 
{{DEFAULTSORT:Transcranial Magnetic Stimulation}}

Latest revision as of 17:12, 11 January 2015

Template:Lead rewrite Template:Infobox interventions Transcranial magnetic stimulation (TMS) is a noninvasive method used to stimulate small regions of the brain. During a TMS procedure, a magnetic field generator, or "coil" is placed near the head of the person receiving the treatment.[1]:3 The coil produces small electrical currents in the region of the brain just under the coil via electromagnetic induction. The coil is connected to a pulse generator, or stimulator, that delivers electrical current to the coil.[2]

TMS is used diagnostically to measure the connection between the brain and a muscle to evaluate damage from stroke, multiple sclerosis, amyotrophic lateral sclerosis, movement disorders, motor neuron disease and injuries and other disorders affecting the facial and other cranial nerves and the spinal cord.[3]

TMS was approved by the FDA for use in migraine[4] and treatment-resistant major depressive disorder.[5]

Clinical evidence to date shows that TMS is useful for neuropathic pain (a condition for which evidence-based medicine fails to treat a significant number of people with the condition)[6] and treatment-resistant major depressive disorder.[6][7] Clinical evidence shows that TMS may be useful for negative symptoms of schizophrenia and loss of function caused by stroke.[6] As of 2014, all other potential uses have only possible or no efficacy.[6]

The greatest risks of TMS are the rare occurrence of syncope (fainting) and even less commonly, induced seizures.[8] Other adverse effects of TMS include discomfort or pain, transient induction of hypomania, transient cognitive changes, transient hearing loss, transient impairment of working memory, and induced currents in electrical circuits in implanted devices.[8]

Medical uses

The use of TMS can be divided into diagnostic and therapeutic uses.

Diagnosis

TMS can be used clinically to measure activity and function of specific brain circuits in humans.[3] The most robust and widely accepted use is in measuring the connection between the primary motor cortex and a muscle to evaluate damage from stroke, multiple sclerosis, amyotrophic lateral sclerosis, movement disorders, motor neuron disease and injuries and other disorders affecting the facial and other cranial nerves and the spinal cord.[3][9][10][11] TMS has been suggested as a means of assessing short-interval intracortical inhibition (SICI) which measures the internal pathways of the motor cortex but this use has not yet been validated.[12]

Treatment

For neuropathic pain, a condition for which evidence-based medicine fails to treat a significant number of people with the condition, high-frequency (HF) rTMS of the brain region corresponding to the part of the body in pain, is effective.[6]

For treatment-resistant major depressive disorder, HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) is effective and low-frequency (LF) rTMS of the right DLPFC has probably efficacy.[6][7] The American Psychiatric Association,[13]:46 the Canadian Network for Mood and Anxiety Disorders,[14] and the Royal Australia and New Zealand College of Psychiatrists have endorsed rTMS for trMDD.[15]

For negative symptoms of schizophrenia, HF-rTMS of the left DLPFC has probable efficacy.[6]

For loss of function caused by stroke LF-rTMS of the corresponding brain region has probable efficacy.[6]

As of 2014, all other potential uses have only possible or no efficacy; TMS has failed to show effectiveness for the treatment of brain death, coma, and other persistent vegetative states.[6][16][17]

Adverse effects

Although TMS is generally regarded as safe, risks increase for therapeutic rTMS compared to single or paired TMS for diagnostic purposes. In the field of therapeutic TMS, risks increase with higher frequencies.[8]

The greatest risk is the rare occurrence of syncope (fainting) and even less commonly, induced seizures.[8][18]

Other adverse effects of TMS include discomfort or pain, transient induction of hypomania, transient cognitive changes, transient hearing loss, transient impairment of working memory, and induced currents in electrical circuits in implanted devices.[8]

Devices and procedure

During a transcranial magnetic stimulation (TMS) procedure, a magnetic field generator, or "coil" is placed near the head of the person receiving the treatment.[1]:3 The coil produces small electrical currents in the region of the brain just under the coil via electromagnetic induction. The coil is positioned by finding anatomical landmarks on the skull including, but not limited to, the inion or the nasion.[19] The coil is connected to a pulse generator, or stimulator, that delivers electrical current to the coil.[2]

Society and culture

Regulatory approvals

Navigated TMS

Nexstim obtained 510(k) FDA clearance of Navigated Brain Stimulation for the assessment of the primary motor cortex for pre-procedural planning in December 2009.[20]

Nexstim obtained FDA 510K clearance for NexSpeech navigated brain stimulation device for neurosurgical planning in June 2011.[21]

Depression

Neuronetics obtained FDA 510K clearance to market its NeuroStar System for use in adults with treatment-resistant major depressive disorder (December 2008).[5]

Migraine

eNeura Therapeutics obtained classification of Cenera System for use to treat migraine headache as a Class II medical device under the "de novo pathway"[22] in December 2013.[4]

Health insurance considerations

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.[23] 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.[24] 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.[25]

Medicare

There is no national policy for Medicare coverage of TMS in the United States. Policies vary according to local coverage determinations (LCDs) that Medicare administrative contractors (MACs) for the Centers for Medicare and Medicaid Services (CMS) make for geographical areas over which they have jurisdiction. CMS presently has ten to fifteen MAC jurisdictions that each cover several U.S. states.[26]

LCDs for individual MAC jurisdictions can change over time. For example:

  • In early 2012, the efforts of TMS treatment advocates resulted in the establishment by a MAC with jurisdiction over New England of the first Medicare coverage policy for TMS in the United States.[27] However, a new MAC for the same jurisdiction subsequently determined that Medicare would not cover services for TMS performed in New England on or after October 25, 2013.[28]
  • In August 2012, the MAC whose jurisdiction covered Arkansas, Louisiana, Mississippi, Colorado, Texas, Oklahoma and New Mexico determined that, based on limitations in the published literature there was insufficient evidence to cover the treatment,[29] but the same MAC subsequently determined that Medicare would cover TMS for the treatment of depression for services performed within the MAC's jurisdiction on or after December 5, 2013,[30]

CMS maintains a searchable database that enables users to find current Medicare LCDs for TMS for individual U.S. states.[32]

United Kingdom's National Health Service

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. 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.[33]

NICE evaluated TMS for severe depression (IPG 242) in 2007, and subsequently considered TMS for reassessment in January 2011 but did not change its evaluation.[34] The Institute found that TMS is safe, but there is insufficient evidence for its efficacy.[34]

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.[35]

Technical information

TMS focal field.png
TMS - Butterfly Coils

TMS uses electromagnetic induction to generate an electric current across the scalp and skull without physical contact. A plastic-enclosed coil of wire is held next to the skull and when activated, produces a magnetic field oriented orthogonal to the plane of the coil. The magnetic field passes unimpeded through the skin and skull, inducing an oppositely directed current in the brain that activates nearby nerve cells in much the same way as currents applied directly to the cortical surface.[36]

The path of this current is difficult to model because the brain is irregularly shaped and electricity and magnetism are not conducted uniformly throughout its tissues. The magnetic field is about the same strength as an MRI, and the pulse generally reaches no more than 5 centimeters into the brain unless using the deep transcranial magnetic stimulation variant of TMS.[37] 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.[38]

Mechanism of action

From the Biot–Savart law

it has been shown that a current through a wire generates a magnetic field around that wire. Transcranial magnetic stimulation is achieved by quickly discharging current from a large capacitor into a coil to produce pulsed magnetic fields of 1-10 mT.[39] By directing the magnetic field pulse at a targeted area of the brain, one can either depolarize or hyperpolarize neurons in the brain. The magnetic flux density pulse generated by the current pulse through the coil causes an electric field as explained by the Maxwell-Faraday equation,

.

This electric field causes a change in the transmembrane current of the neuron, which leads to the depolarization or hyperpolarization of the neuron and the firing of an action potential.[39]

The exact details of how TMS functions are still being explored. The effects of TMS can be divided into two types depending on the mode 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. If used on the occipital cortex, 'phosphenes' (flashes of light) might be perceived by the subject. In most other areas of the cortex, the participant does not consciously experience any effect, but his or her behaviour may be slightly altered (e.g., slower reaction time on a cognitive task), or changes in brain activity may be detected using sensing equipment.[40]
  • Repetitive TMS produces longer-lasting effects which persist past the initial period of stimulation. rTMS can increase or decrease the excitability of the corticospinal tract depending on the intensity of stimulation, coil orientation, and frequency. The mechanism of these effects is not clear, though it is widely believed to reflect changes in synaptic efficacy akin to long-term potentiation (LTP) and long-term depression (LTD).[41]

MRI images, recorded during TMS of the motor cortex of the brain, have been found to match very closely with PET produced by voluntary movements of the hand muscles innervated by TMS, to 5–22 mm of accuracy.[42] The localisation of motor areas with TMS has also been seen to correlate closely to MEG[43] and also fMRI.[44]

Coil types

The design of transcranial magnetic stimulation coils used in either treatment or diagnostic/experimental studies may differ in a variety of ways. These differences should be considered in the interpretation of any study result, and the type of coil used should be specified in the study methods for any published reports.

The most important considerations include:

  • the type of material used to construct the core of the coil
  • the geometry of the coil configuration
  • the biophysical characteristics of the pulse produced by the coil.

With regard to coil composition, the core material may be either a magnetically inert substrate (i.e., the so-called ‘air-core’ coil design), or possess a solid, ferromagnetically active material (i.e., the so-called ‘solid-core’ design). Solid core coil design result in a more efficient transfer of electrical energy into a magnetic field, with a substantially reduced amount of energy dissipated as heat, and so can be operated under more aggressive duty cycles often mandated in therapeutic protocols, without treatment interruption due to heat accumulation, or the use of an accessory method of cooling the coil during operation. Varying the geometric shape of the coil itself may also result in variations in the focality, shape, and depth of cortical penetration of the magnetic field. Differences in the coil substance as well as the electronic operation of the power supply to the coil may also result in variations in the biophysical characteristics of the resulting magnetic pulse (e.g., width or duration of the magnetic field pulse). All of these features should be considered when comparing results obtained from different studies, with respect to both safety and efficacy.[45]

A number of different types of coils exist, each of which produce different magnetic field patterns. Some examples:

  • round coil: the original type of TMS coil
  • figure-eight coil (i.e., butterfly coil): results in a more focal pattern of activation
  • double-cone coil: conforms to shape of head, useful for deeper stimulation
  • four-leaf coil: for focal stimulation of peripheral nerves[46]
  • H-coil: for deep transcranial magnetic stimulation

Design variations in the shape of the TMS coils allow much deeper penetration of the brain than the standard depth of 1.5-2.5 cm. Circular crown coils, Hesed (or H-core) coils, double cone coils, and other experimental variations can induce excitation or inhibition of neurons deeper in the brain including activation of motor neurons for the cerebellum, legs and pelvic floor. Though able to penetrate deeper in the brain, they are less able to produce a focused, localized response and are relatively non-focal.[8]

History

Early attempts at stimulation of the brain using a magnetic field included those, in 1910, of Silvanus P. Thompson in London.[47] The principle of inductive brain stimulation with eddy currents has been noted since the 20th century{{ safesubst:#invoke:Unsubst||date=__DATE__ |$B= {{#invoke:Category handler|main}}{{#invoke:Category handler|main}}[citation needed] }}. The first successful TMS study was performed in 1985 by Anthony Barker and his colleagues at the Royal Hallamshire Hospital in Sheffield, England.[48] Its earliest application demonstrated conduction of nerve impulses from the motor cortex to the spinal cord, stimulating muscle contractions in the hand. As compared to the previous method of transcranial stimulation proposed by Merton and Morton in 1980[49] in which direct electrical current was applied to the scalp, the use of electromagnets greatly reduced the discomfort of the procedure, and allowed mapping of the cerebral cortex and its connections.

Research

Areas of research include the rehabilitation of aphasia and motor disability after stroke,[10][11][6][8][50] tinnitus,[6][51] anxiety disorders,[6] obsessive-compulsive disorder,[6] amyotrophic lateral sclerosis,[6] multiple sclerosis,[6] epilepsy,[6] Alzheimer's disease,[6] Parkinson's disease,[52]schizophrenia,[6] substance abuse,[6] addiction,[6][53] and posttraumatic stress disorder (PTSD).[6][54]

It is difficult to establish a convincing form of "sham" TMS to test for placebo effects during controlled trials in conscious individuals, due to the neck pain, headache and twitching in the scalp or upper face associated with the intervention.[6][8] "Sham" TMS manipulations can affect cerebral glucose metabolism and MEPs, which may confound results.[55] This problem is exacerbated when using subjective measures of improvement.[8] Placebo responses in trials of rTMS in major depression are negatively associated with refractoriness to treatment, vary among studies and can influence results.[56] Depending on the research question asked and the experimental design, matching the discomfort of rTMS to distinguish true effects from placebo can be an important and challenging issue.[6][8]

See also

References

  1. 1.0 1.1 NiCE. January 2014 Transcranial magnetic stimulation for treating and preventing migraine
  2. 2.0 2.1 Michael Craig Miller for Harvard Health Publications. July 26, 2012 Magnetic stimulation: a new approach to treating depression?
  3. 3.0 3.1 3.2 Template:Cite doi
  4. 4.0 4.1 FDA 13 December 2013 FDA letter to eNeura re de novo classification review
  5. 5.0 5.1 Template:Cite web
  6. 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 6.14 6.15 6.16 6.17 6.18 6.19 6.20 6.21 6.22 {{#invoke:Citation/CS1|citation |CitationClass=journal }}
  7. 7.0 7.1 Template:Cite doi
    (6) Template:Cite web
  8. 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 8.8 8.9 Rossi S et al. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-39. PMID 19833552 PMC 3260536
  9. Template:Cite doi
  10. 10.0 10.1 Template:Cite doi
  11. 11.0 11.1 Template:Cite doi
  12. Template:Cite pmid
  13. American Psychiatric Association (2010). (eds: Gelenberg, AJ, Freeman, MP, Markowitz, JC, Rosenbaum, JF, Thase, ME, Trivedi, MH, Van Rhoads, RS). Practice Guidelines for the Treatment of Patients with Major Depressive Disorder, 3rd Edition
  14. Kennedy, SH, et al (2009) Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. IV. Neurostimulation therapies. J Aff Disorders 117:S44-S53. PMID 19682750
  15. The Royal Australian and New Zealand College of Psychiatrists. (2013) Position Statement 79. Repetitive Transcranial Magnetic Stimulation. Practice and Partnerships Committee
  16. Bersani FS et al. Deep transcranial magnetic stimulation as a treatment for psychiatric disorders: a comprehensive review. Eur Psychiatry. 2013 Jan;28(1):30-9. PMID 22559998
  17. {{#invoke:Citation/CS1|citation |CitationClass=journal }}
  18. {{#invoke:citation/CS1|citation |CitationClass=book }} At Google Books.
  19. {{#invoke:Citation/CS1|citation |CitationClass=journal }}
  20. Template:Cite web
  21. Template:Cite web
  22. 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?
  23. (1) Template:Cite web
    (2) Template:Cite web
    (3) Template:Cite web
    (4) Template:Cite web
  24. Template:Cite web
  25. (1) Template:Cite web
    (2) Template:Cite web
    (3) Template:Cite web
  26. (1) Template:Cite web
    (2) Template:Cite web
  27. (1) Template:Cite web
    (2) Template:Cite web
    (3) Template:Cite web
    (4) Template:Cite web
  28. Template:Cite web
  29. Template:Cite web
  30. Template:Cite web
  31. (1) Template:Cite web
    (2)Template:Cite web
  32. Template:Cite web
  33. NICE About NICE: What we do
  34. 34.0 34.1 Template:Cite web
  35. Template:Cite web
  36. {{#invoke:citation/CS1|citation |CitationClass=book }}
  37. Template:Cite web
  38. (1) Template:Cite doi
    (2) Template:Cite pmid
  39. 39.0 39.1 V. Walsh and A. Pascual-Leone, "Transcranial Magnetic Stimulation: A Neurochronometrics of Mind." Cambridge, Massachusetts: MIT Press, 2003.
  40. {{#invoke:citation/CS1|citation |CitationClass=book }}
  41. Template:Cite doi
  42. Template:Cite doi
  43. T. Morioka, T. Yamamoto, A. Mizushima, S. Tombimatsu, H. Shigeto, K. Hasuo, S. Nishio, K. Fujii and M. Fukui. Comparison of magnetoencephalography, functional MRI, and motor evoked potentials in the localization of the sensory-motor cortex. Neurol. Res., vol. 17, no. 5, pp. 361-367. 1995
  44. Template:Cite doi
  45. {{#invoke:citation/CS1|citation |CitationClass=book }}
  46. Template:Cite doi
  47. http://www.scholarpedia.org/article/Transcranial_magnetic_stimulation
  48. Template:Cite doi
  49. Template:Cite doi
  50. (1) Template:Cite pmid
    (2) Template:Cite doi
  51. Template:Cite pmid
  52. Template:Cite doi
    (2) Template:Cite doi
  53. {{#invoke:Citation/CS1|citation |CitationClass=journal }}
  54. (1) Template:Cite doi
    (2) Template:Cite doi
  55. Template:Cite doi
  56. Template:Cite pmid

Further reading

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External links

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