View source for Transcranial magnetic stimulation

{{Other uses|TMS (disambiguation)}}
{{Refimprove|date=February 2009}}
[[File:Repetitive transcranial magnetic stimulation (rTMS) is a technique for noninvasive stimulation of the adult brain.jpg|thumb|rTMS in a rodent. From Oscar Arias-Carrión, 2008]]

'''Transcranial magnetic stimulation''' ('''TMS''') is a noninvasive method to cause [[depolarization]] 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 minimal discomfort, allowing the functioning and interconnections of the brain to be studied.  A variant of TMS, '''repetitive transcranial magnetic stimulation''' ('''rTMS''') has been tested as a treatment tool for various [[neurological disorder|neurological]] and [[mental disorder|psychiatric]] disorders including [[migraine]]s, [[stroke]]s, [[Parkinson's disease]], [[dystonia]], [[tinnitus]], [[major depressive disorder|depression]] and auditory [[hallucinations]].

==Background==

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 TMS pioneer Anthony Barker in [[Sheffield]], [[England]].<ref name=Barker>{{cite journal | author = Barker AT, Jalinous R, Freeston IL. | year = 1985 | month = May | title = Non-invasive magnetic stimulation of human motor cortex | journal = [[The Lancet]] | volume = 1  | issue = 8437 | pages = 1106–1107 | doi =10.1016/S0140-6736(85)92413-4 | pmid = 2860322 }}</ref>  Its earliest application demonstrated conduction of nerve impulses from the [[motor cortex]] to the [[spinal cord]], stimulating muscle contractions.  The use of magnets rather than a direct electric current to the brain reduced the discomfort of the procedure and research and allowed mapping of the [[cerebral cortex]] and its connections between areas.

==Effects on the brain==
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 [[Depolarization|depolarise]] 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]], '[[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 = Hodder Arnold | isbn = 0340720093  }}</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 although 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 journal | author = Fitzgerald PB; Fountain S; Daskalakis J
 | year = 2006 | month = December | title = A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition | journal = Clinical Neurophysiology | volume = 117 | issue = 12 | pages = 2584–96 | doi = 10.1016/j.clinph.2006.06.712  | pmid = 16890483  }}</ref> 

==Risks ==
Although TMS is often regarded as safe, the greatest [[Acute (medicine)|acute]] risk of TMS is the rare occurrence of [[epileptic seizure|seizures]].  More than 16 cases of TMS-related seizure have been reported in the literature, with at least seven reported before the publication of safety guidelines in 1998,<ref name=Wassermann1998 /> and more than nine reported afterwards.  The seizures have been associated with single-pulse and rTMS. 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>{{cite journal|last=Rossi|first=S| coauthors = et al. |url = http://www.aipass.org/files/TMS_Safety,%20ethical%20considerations,%20and%20application%20guidelines.pdf | format = pdf |title=The Safety of TMS Consensus Group, Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research|journal= Clinical Neurophysiology | year = 2009 | volume = 120 | issue= 12 |pages=2008–2039 | pmid=19833552 | doi = 10.1016/j.clinph.2009.08.016}}</ref>

Besides seizures, other risks include [[syncope (medicine)|fainting]], minor pains such as headache or local discomfort, minor cognitive changes and psychiatric symptoms (particularly a low risk of [[mania]] in depressed patients).  Though other side effects are thought to be possibly associated with TMS (alterations to the [[endocrine system]], altered [[neurotransmitter]] and [[immune system]] activity) they are considered investigational and lacking substantive proof.<ref name = Rossi/>

Other adverse effects of TMS are:
* 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 journal |author=Wassermann EM |title=Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5–7, 1996 |journal=Electroencephalography and clinical Neurophysiology |volume=108 |issue= 1|pages=1–16 |year=1998 | month = | pmid = 9474057 | pmc = | format = pdf | url = http://www.icts.uci.edu/neuroimaging/Wassermann_rTMS_Safety1998.pdf |doi=10.1016/S0168-5597(97)00096-8}}</ref>
* Rapid deformation of the TMS coil produces a loud clicking sound which increases with the stimulator intensity that can affect hearing with sufficient exposure, particularly relevant for rTMS (hearing protection may be used to prevent this)<ref name=Wassermann1998/>
* rTMS in the presence of EEG electrodes can result in electrode heating and, in severe cases, skin burns<ref name=roth>{{cite journal | author = Roth BJ; Pascual-Leone A; Cohen LG; Hallett M  | year = 1992  | title =  The heating of metal electrodes during rapid-rate magnetic stimulation: A possible safety hazard | journal = Electroenceph. Clin. Neurophysiol. | volume = 85 | pages = 116–123 | doi = 10.1016/0168-5597(92)90077-O | pmid = 1373364 | issue = 2 }}</ref>

==Clinical uses==
The uses of TMS and rTMS 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. 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]]s, [[spinal cord]] injuries, [[multiple sclerosis]] and [[motor neuron disease]].  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 journal |author=Kujirai T, Caramia MD, Rothwell JC, ''et al.'' |title=Corticocortical inhibition in human motor cortex |journal=J. Physiol. (Lond.) |volume=471 |issue= |pages=501–19 |year=1993 |month=November |pmid=8120818 |pmc=1143973 |url=http://www.jphysiol.org/cgi/pmidlookup?view=long&pmid=8120818}}</ref>

===Therapy===
Studies of the use of TMS and rTMS to treat neurological and psychiatric conditions have shown only modest effects with little confirmation of results.<ref>{{cite journal|last=Slotema|first=CW|last2=Blom|first2=JD|last3=Hoek|first3=HW|last4=Sommer|first4=IE|title=Should we expand the toolbox of psychiatric treatment methods to include Repetitive Transcranial Magnetic Stimulation (rTMS)? a meta-analysis of the efficacy of rTMS in psychiatric disorders|journal=Journal of Clinical Psychiatry|publisher=Physicians Postgraduate Press, Inc.|year=2010|month=July|volume=71|issue=7|pages=873–884|pmid=20361902}}</ref>  However, investigators and regulatory agencies have found rTMS to be effective in the treatment of certain types of [[Major depressive disorder|major depression]] under certain specific conditions.<ref name="pmid17655558">{{cite pmid | 17655558 }}</ref><ref>{{cite journal|last=Lam|first=RW|last2=Chan|first2=P|last3=Wilkins-Ho|first3=M|last4=Yatham|first4=LV|title=Repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and metaanalysis|journal=Canadian Journal of Psychiatry|year=2008|month=September|volume=53|issue=9|pages=621–631|pmid=18801225}}</ref>  rTMS devices are marketed for the treatment of such disorders in Europe, Canada, Australia, and the United States.<ref name="pmid18447962">{{cite pmid | 18447962 }}</ref><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|FDA]] | last = Melkerson | first = MN | title = Special Premarket 510(k) Notification for NeuroStar TMS Therapy System for Major Depressive Disorder}}</ref>  Other promising areas of research include treating [[tinnitus]],<ref>{{cite pmid |19205161}}</ref> short term relief of [[Parkinson's disease]]<ref>{{cite pmid | 19951135 }}</ref><ref>{{cite pmid | 18471317 }}</ref> and the negative symptoms of [[schizophrenia]].<ref>{{cite pmid|20361909 }}</ref>  TMS has failed to show effectiveness for the treatment of [[brain death]], [[coma]] patients and other [[persistent vegetative state]]s.<ref>{{cite pmid | 20157993 }}</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.  This problem is exacerbated when using [[Subjectivity|subjective]] measures of improvement.  Depending on the research question asked and the [[design of experiments|experimental design]], matching this discomfort to distinguish true effects from placebo can be an important and challenging issue.<ref name = Rossi/>

==FDA actions==
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 had a good safety record but had failed to demonstrate that it was effective for the treatment of depression. The panel agreed that "[[Blind experiment|unblind]]ing was greater in the active group, and considering the magnitude of the [[effect size]], it may have influenced the study results."<ref>{{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 }}</ref>  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|page=1-5|publisher=Neuronetics, Inc.|accessdate=2010-09-13}}</ref> 

Soon after the FDA cleared the device, several members of [[Public Citizen]] stated in a [[letter to the editor]] of a medical journal 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 depression.  The 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=[[Sidney M. Wolfe|Wolfe SM]] |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 | year = 2009| volume=34 |issue=8 |pages=2053–2054 |pmid=19528946 |doi=10.1038/npp.2009.22 | format = pdf }}</ref>

==Technical information==
[[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 [[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|orthogonally]] 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. 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 penetrates only to a maximum depth of three centimeters into the brain, in the area directly adjacent to the coil.<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>  

=== 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 (ie, 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.<ref>{{cite book |title=Oxford Handbook of Transcranial Stimulation |editor=Wassermann EM, Epstein CM, Ziemann U, Walsh V, Paus T, Lisanby SH |chapter=TMS Stimulator Design |author=Riehl M |year=2008 |publisher=Oxford University Press |location=Oxford |isbn=0198568924 |pages=[http://books.google.com/books?id=YeKleGrKwC4C&pg=PA13#v=onepage&q&f=false 13–23], [http://books.google.com/books?id=YeKleGrKwC4C&pg=PA25#v=onepage&q&f=false 25–32] }}</ref>

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<ref name=roth2>{{cite journal | author = Roth BJ, Maccabee PJ, Eberle L, Amassian VE, Hallett M, Cadwell J, Anselmi GD,  Tatarian GT | year = 1994 | title =   In-vitro evaluation of a four-leaf coil design for magnetic stimulation of peripheral nerve. | journal = Electroenceph. Clin. Neurophysiol. | volume = 93 | pages = 68–74 | doi = 10.1016/0168-5597(94)90093-0 | pmid = 7511524 | issue = 1 }}</ref>

Design variations in the shape of the TMS coils allow much deeper penetration of the brain than the standard depth of 1.5&nbsp;cm.  Circular, H-shaped, 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 focussed, localized response and are relatively non-focal.<ref name = Rossi/>

==See also==
* [[Cranial electrotherapy stimulation]]
* [[Transcranial direct current stimulation]]
* [[Electroconvulsive therapy]]
* [[God helmet]]

==References==
{{reflist}}

==Further reading==
* {{cite book |author=Ziemann, Ulf; Eric Wassermann; Epstein, Charles J. |title=Oxford Handbook of Transcranial Stimulation (Oxford Handbooks) |publisher=[[Oxford University Press]], USA |location= |year=2008 |pages= |isbn=0-19-856892-4 |oclc= |doi= |accessdate= | url = http://books.google.com/?id=YeKleGrKwC4C&printsec=frontcover#v=onepage&q}}

==External links==
*[http://www.overstream.net/view.php?oid=n7aomgtia5ul Stuttering Triggered by Transcranial Magnetic Stimulation (video)]

[[Category:Neurophysiology]]
[[Category:Neuropsychology]]
[[Category:Neurotechnology]]
[[Category:Magnetic devices]]
[[Category:Electrotherapy]]
[[Category:Psychiatric treatments]]
[[Category:Treatment of bipolar disorder]]

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[[de:Transkranielle Magnetstimulation]]
[[es:Estimulación Magnética Transcraneana]]
[[fr:Stimulation magnétique transcranienne]]
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[[nl:Transcraniële magnetische stimulatie]]
[[ja:経頭蓋磁気刺激法]]
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[[ru:Транскраниальная магнитная стимуляция]]
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