TRANSCRANIAL MAGNETIC STIMULATION
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'Transcranial magnetic stimulation' ('TMS') is a noninvasive method to excite neurons in the brain. The excitation is caused by weak electric currents induced in the tissue by rapidly changing magnetic fields (electromagnetic induction). This way, brain activity can be triggered or modulated without the need for surgery or external electrodes. Repetitive transcranial magnetic stimulation is known as 'rTMS'. TMS is a powerful tool in research and diagnosis for mapping out how the brain functions, and has shown promise for noninvasive treatment of a host of disorders, including depression and auditory hallucinations.
The International Federation of Clinical Neurophysiology has developed the following description of TMS and rTMS:
A study from the Journal of Clinical Psychiatry stated the following:
The principle of inductive brain stimulation with eddy currents has been noted since the 19th century. The first successful TMS study was performed by Anthony Barker et al.[1] in Sheffield, England. Its earliest application was in the demonstration of conduction of nerve impulses from the motor cortex to the spinal cord. This had been done with transcranial electrical stimulation a few years earlier, but use of this technique is limited by severe discomfort. By stimulating different points of the cortex and recording responses, e.g., from muscles, one may obtain maps of functional brain areas. By measuring EEG, information may be obtained about the healthiness of the cortex (its reaction to TMS) and about area-to-area connections.
One reason TMS is important in neuroscience is that it can demonstrate causality. A noninvasive mapping technique such as fMRI allows researchers to see what regions of the brain are activated when a subject performs a certain task, but this is not proof that those regions are actually used for the task; it merely shows that a region is ''associated'' with a task. If activity in the associated region is suppressed with TMS stimulation and a subject then performs worse on a task, this is much stronger evidence that the region is ''used'' in performing the task.
For instance, subjects asked to memorize and repeat a stream of numbers would likely show, via fMRI, activation in the prefrontal cortex (PFC), which seems to be important in short-term memory. If the researcher then interfered with the PFC via TMS, the subjects' ability to remember numbers would decline, and the researcher would have evidence that the PFC is important for short-term memory, because reducing subjects' PFC capability led to reduced short-term memory.
Pioneers in the use of TMS in neuroscience research include Anthony Barker, Vahe Amassian, John Rothwell of the Institute of Neurology, Queen Square, London, Mark S. George, MD of the Medical University of South Carolina, David H. Avery, MD of the University of Washington at Seattle, Charles M. Epstein of Emory University, Drs. Mark Hallett, Leonardo G. Cohen, and Eric M. Wassermann of the National Institutes of Health, and Ãlvaro Pascual-Leone of Harvard Medical School. Currently, thousands of TMS stimulators are in use. More than [3000 scientific publications] have been published describing scientific, diagnostic, and therapeutic trials.
Allan Snyder, at the University of Sydney, has reported being able to enhance certain mental skills and increased creativity by using the TMS on the frontal lobes of volunteer students. Some of these temporarily acquired skills bear remarkable similarity to those of autistic savants.[1] [2] It is important to note that the effect, although significant, is very small and has yet to be replicated.
In May 2006, during the annual meeting of the American Psychiatric Association, researchers announced that a recently-completed large-scale clinical program demonstrated efficacy of TMS in the treatment of major depressive disorders. The clinical program was sponsored by Neuronetics, Inc. for its NeuroStar TMS TherapyTM system. This clinical trial program was conducted at 23 centers in the US, Canada, and Australia. It consisted of three phases. The first phase was a 6-week, randomized, sham (placebo)-controlled, double-blind, monotherapy study. The study population was 325 medication-free outpatients who had been resistant to at least 1, but no more than 4, previous antidepressant medications of an adequate dose and duration during the current episode. In the second phase, 136 patients who responded in the acute study were subsequently enrolled in a 6-month extension study, where they received single medication treatment, and were observed for maintenance of response. In the third phase, 158 patients who did not respond in the acute study entered into a 6-week, open-label treatment study. The results of this clinical program have been submitted for publication in peer-reviewed journals and are being evaluated by the FDA as part of an application for clearance of TMS Therapy in the treatment of major depressive disorder.
In June 2006, researchers at the American Headache Society announced that TMS is an effective and medically non-invasive method for treating migraines.[3] It appears to disrupt the aura phase of migraines before patients can develop a full migraine headache.
In May 2007, researchers at the University of Wisconsin-Madison announced that they were able to induce slow oscillations that looked similar to stage 4 sleep (as determined by EEG) using TMS pulses in the 0.8-1 HZ range. They were able to achieve this only in subjects that were concurrently experiencing non-REM sleep, not in subjects that were awake.[4]
Also in May 2007, new data was presented at the American Psychiatric Association's annual meeting that demonstrated that Neuronetics' NeuroStar TMS Therapy system improved quality of life in patients with major depression. The data were presented by lead author H. Brent Solvason, MD, PhD, Assistant Professor of Psychiatry at Stanford University. At baseline, the study population (N = 301) had significant symptomatic and functional impairment related to depression. After four weeks of treatment, patients receiving NeuroStar TMS Therapy (N = 155) experienced statistically significant improvements in the General Health (P = 0.049) and Mental Health (P = 0.006) subscales, as well as Mental Component Score (P = 0.019) of the SF-36, a widely used health outcomes measure. After six weeks, significant improvements were also seen in the SF-36 Role-Emotional (P = 0.044) subscale and the Quality of Life Enjoyment and Satisfaction Questionnaire--Q-LES-Q (P = 0.035), a common measurement tool used to assess quality of life in patients suffering from depression. The effect sizes observed in functional status improvement were similar in magnitude to the effect sizes observed in symptomatic benefit.
NeuroStar(R) TMS Therapy Improved Quality Of Life In Patients With Major Depression In Clinical Trials, , , , ,
The clinical program was sponsored by Neuronetics, Inc. for its NeuroStar TMS TherapyTM system. The results of this clinical program have been submitted for publication in peer-reviewed journals and are being evaluated by the FDA as part of an application for clearance of TMS Therapy in the treatment of major depressive disorder (see below).
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.' The pulse(s) causes a population of neurons in the neocortex to depolarise and discharge an action potential. If used in the primary motor cortex, it produces a motor-evoked potential (MEP) which can be recorded on electromyography (EMG). If used on the occipital cortex, phosphenes (flashes of light) might be detected 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 Positron Emission Tomography or fMRI. These effects do not outlast the period of stimulation. A review of TMS can be found in the Handbook of Transcranial Magnetic Stimulation.[2]
'Repetitive TMS (rTMS)' produces effects which last longer than the period of stimulation. rTMS can increase or decrease the excitability of corticospinal or corticocortical pathways depending on the intensity of stimulation, coil orientation and frequency of stimulation. The mechanism of these effects are not clear although it is widely believed to reflect changes in synaptic efficacy akin to long-term potentiation (LTP) and long-term depression (LTD). A recent review of rTMS can be found in Fitzgerald et al, 2006 .[3]
In simple terms, the idea behind the clinical use of TMS is that, in people with various mental disorders, different areas of the brain are sluggish or overactive. In people with depression, for example, the left prefrontal cortex is less active than in people without depression. In people with anxiety disorders, the right prefrontal cortex is more active than in people without anxiety disorders; and in people with obsessive-compulsive disorder, the cingulate gyrus is hyperactive. When aimed and operated correctly, a TMS machine can "jump start" or calm down the appropriate areas of the brain.
TMS is simply the application of the principle of induction to get electrical current across the insulating tissues of the scalp and skull without discomfort. A coil of wire, encased in plastic, is held to the head. When the coil is energized by the rapid discharge of a large capacitor, a rapidly changing current flows in its windings. This produces a magnetic field oriented 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 flows tangentially with respect to skull. The current induced in the structure of the brain activates nearby nerve cells in much the same way as currents applied directly to the cortical surface. The path of this current is complex to model because the brain is a non-uniform conductor with an irregular shape. With stereotactic, MRI-based control the precision of targeting TMS can be approximated to a few millimeters (Hannula et al., Human Brain Mapping 2005).
Typical data: [4]
★ magnetic field ('B'): often about 2 tesla on the coil surface and 0.5 T in the cortex
★ current rise time: zero to peak, often around 70-100 microseconds
★ repetition rate for rTMS: below 1 Hz (slow TMS), above 1 Hz (rapid-rate TMS)
TMS is currently under study as a treatment for severe depression, mania, auditory hallucinations (e.g., associated with schizophrenia), post traumatic stress disorder, obsessive-compulsive disorder, generalized anxiety disorder, migraine headaches and tinnitus. It is particularly interesting as it may provide a viable treatment to certain aspects of drug resistant mental illness, particularly as an alternative to electroconvulsive therapy. TMS is also under investigation for the treatment of drug-resistant epilepsy and tinnitus. rTMS therapy for drug-resistant depression has been approved by Health Canada for clinical delivery since 2002.
Although research in this area is in its infancy, there is now some evidence that TMS is an effective treatment for depression, obsessive-compulsive disorder, generalized anxiety disorder, tinnitus, and auditory hallucinations, with more symptoms and disorders being researched. Additionally, in June 2006, US medical researchers published evidence indicating that TMS is more successful at treating migraines in patients than current medications. A larger research study involving more patients and better controls is planned to confirm the validity of these results. [5][6]
1.
'Non-invasive magnetic stimulation of human motor cortex.', Barker AT, Jalinous R, Freeston IL., , , Lancet, 1985
2.
'Handbook of Transcranial Magnetic Stimulation', Pascual-Leone A, Davey N, Rothwell JC, Wassermann EM, Puri BK, , , , 2002,
3.
'A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition', Fitzgerald PB, Fountain S, Daskalakis ZJ, , , Clinical Neurophysiology, 2006
4. "TMS terminology", ''BioMag Laboratory at Helsinki University Central Hospital''
★ Cranial Electrotherapy Stimulation (CES)
★ Transcranial direct current stimulation (tDCS)
★ Electroconvulsive therapy (ECT)
★ CIMIT - Center For Integration Of Medicine And Innovative Technology
★ Recording of EEG response due to TMS
★ Transcranial magnetic stimulation in psychiatry
★ BioMag Laboratory, Helsinki
★ OpenStim: The Open Noninvasive Brain Stimulator
★ MagVenture: Magnetic Stimulation - Principles
★ Magnets may make the brain grow stronger
★ Elata Foundation non-profit for TMS development and education
| Contents |
| Introduction |
| Background |
| TMS in research |
| How TMS affects the brain |
| Technical information on TMS |
| TMS as therapy |
| References |
| See also |
| External links |
Introduction
The International Federation of Clinical Neurophysiology has developed the following description of TMS and rTMS:
Technical developments in the devices used for TMS made it possible in the late 1980’s to apply TMS in trains of multiple stimuli per second. This form of TMS is called repetitive TMS or rTMS. In rTMS, stimuli are applied to the same brain area several times per second during several consecutive seconds. The number of stimuli per second, the strength of the stimuli, the duration of the train of stimulation, the interval between trains, the total number of trains and the total number of stimuli in a given session or to a given brain position can all be varied. All these aspects of rTMS are referred to as stimulation parameters....
Repetitive TMS can be used to study how the brain organizes different functions such as language, memory, vision, or attention. In addition, rTMS seems capable of changing the activity in a brain area even beyond the duration of the rTMS application itself. In other words, it seems possible to make a given brain area work more or less for a period of minutes, hours, days or even weeks when rTMS is applied repeatedly several days in a row. This has opened up the possibility of using rTMS for therapy of some illnesses in neurology and psychiatry. However, this therapeutic potential of rTMS is still being studied and should not be considered proven.
A study from the Journal of Clinical Psychiatry stated the following:
While it is still investigational, over 30 studies have been completed evaluating the efficacy of TMS in the treatment of depression. Eight meta-analyses evaluating TMS in depression have been published. A recent meta-analysis has reviewed 33 studies of TMS in depression and have concluded that TMS is effective in the treatment of depression
Factors Modifying the Efficacy of Transcranial Magnetic Stimulation in the Treatment of Depression: A Review, Ebmeier and Hermann, , , Journal of CLinical Psychiatry, 2006
.
Background
The principle of inductive brain stimulation with eddy currents has been noted since the 19th century. The first successful TMS study was performed by Anthony Barker et al.[1] in Sheffield, England. Its earliest application was in the demonstration of conduction of nerve impulses from the motor cortex to the spinal cord. This had been done with transcranial electrical stimulation a few years earlier, but use of this technique is limited by severe discomfort. By stimulating different points of the cortex and recording responses, e.g., from muscles, one may obtain maps of functional brain areas. By measuring EEG, information may be obtained about the healthiness of the cortex (its reaction to TMS) and about area-to-area connections.
TMS in research
One reason TMS is important in neuroscience is that it can demonstrate causality. A noninvasive mapping technique such as fMRI allows researchers to see what regions of the brain are activated when a subject performs a certain task, but this is not proof that those regions are actually used for the task; it merely shows that a region is ''associated'' with a task. If activity in the associated region is suppressed with TMS stimulation and a subject then performs worse on a task, this is much stronger evidence that the region is ''used'' in performing the task.
For instance, subjects asked to memorize and repeat a stream of numbers would likely show, via fMRI, activation in the prefrontal cortex (PFC), which seems to be important in short-term memory. If the researcher then interfered with the PFC via TMS, the subjects' ability to remember numbers would decline, and the researcher would have evidence that the PFC is important for short-term memory, because reducing subjects' PFC capability led to reduced short-term memory.
Pioneers in the use of TMS in neuroscience research include Anthony Barker, Vahe Amassian, John Rothwell of the Institute of Neurology, Queen Square, London, Mark S. George, MD of the Medical University of South Carolina, David H. Avery, MD of the University of Washington at Seattle, Charles M. Epstein of Emory University, Drs. Mark Hallett, Leonardo G. Cohen, and Eric M. Wassermann of the National Institutes of Health, and Ãlvaro Pascual-Leone of Harvard Medical School. Currently, thousands of TMS stimulators are in use. More than [3000 scientific publications] have been published describing scientific, diagnostic, and therapeutic trials.
Allan Snyder, at the University of Sydney, has reported being able to enhance certain mental skills and increased creativity by using the TMS on the frontal lobes of volunteer students. Some of these temporarily acquired skills bear remarkable similarity to those of autistic savants.[1] [2] It is important to note that the effect, although significant, is very small and has yet to be replicated.
In May 2006, during the annual meeting of the American Psychiatric Association, researchers announced that a recently-completed large-scale clinical program demonstrated efficacy of TMS in the treatment of major depressive disorders. The clinical program was sponsored by Neuronetics, Inc. for its NeuroStar TMS TherapyTM system. This clinical trial program was conducted at 23 centers in the US, Canada, and Australia. It consisted of three phases. The first phase was a 6-week, randomized, sham (placebo)-controlled, double-blind, monotherapy study. The study population was 325 medication-free outpatients who had been resistant to at least 1, but no more than 4, previous antidepressant medications of an adequate dose and duration during the current episode. In the second phase, 136 patients who responded in the acute study were subsequently enrolled in a 6-month extension study, where they received single medication treatment, and were observed for maintenance of response. In the third phase, 158 patients who did not respond in the acute study entered into a 6-week, open-label treatment study. The results of this clinical program have been submitted for publication in peer-reviewed journals and are being evaluated by the FDA as part of an application for clearance of TMS Therapy in the treatment of major depressive disorder.
In June 2006, researchers at the American Headache Society announced that TMS is an effective and medically non-invasive method for treating migraines.[3] It appears to disrupt the aura phase of migraines before patients can develop a full migraine headache.
In May 2007, researchers at the University of Wisconsin-Madison announced that they were able to induce slow oscillations that looked similar to stage 4 sleep (as determined by EEG) using TMS pulses in the 0.8-1 HZ range. They were able to achieve this only in subjects that were concurrently experiencing non-REM sleep, not in subjects that were awake.[4]
Also in May 2007, new data was presented at the American Psychiatric Association's annual meeting that demonstrated that Neuronetics' NeuroStar TMS Therapy system improved quality of life in patients with major depression. The data were presented by lead author H. Brent Solvason, MD, PhD, Assistant Professor of Psychiatry at Stanford University. At baseline, the study population (N = 301) had significant symptomatic and functional impairment related to depression. After four weeks of treatment, patients receiving NeuroStar TMS Therapy (N = 155) experienced statistically significant improvements in the General Health (P = 0.049) and Mental Health (P = 0.006) subscales, as well as Mental Component Score (P = 0.019) of the SF-36, a widely used health outcomes measure. After six weeks, significant improvements were also seen in the SF-36 Role-Emotional (P = 0.044) subscale and the Quality of Life Enjoyment and Satisfaction Questionnaire--Q-LES-Q (P = 0.035), a common measurement tool used to assess quality of life in patients suffering from depression. The effect sizes observed in functional status improvement were similar in magnitude to the effect sizes observed in symptomatic benefit.
NeuroStar(R) TMS Therapy Improved Quality Of Life In Patients With Major Depression In Clinical Trials, , , , ,
The clinical program was sponsored by Neuronetics, Inc. for its NeuroStar TMS TherapyTM system. The results of this clinical program have been submitted for publication in peer-reviewed journals and are being evaluated by the FDA as part of an application for clearance of TMS Therapy in the treatment of major depressive disorder (see below).
How TMS affects 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:
A lay summary in the MIT Technology Review listed some potential mechanisms:
A powerful magnet is held over the frontal regions of the patient’s skull and delivers magnetic pulses for a few minutes a day, over the course of a few weeks. The treatment alters the biochemistry and firing patterns of neurons in the cortex, the part of the brain nearest the surface. Preliminary research indicates that the treatment affects gene activity, levels of neurotransmitters like serotonin and dopamine, and the formation of proteins important for cellular signaling—any of which could play a role in alleviating depression. What’s more, magnetic stimulation seems to affect several interconnected brain regions, starting in the cortex and moving to the deep brain, where new cell growth may be important in regulating moods. (Technology Review, March 2004 PDF)
In simple terms, the idea behind the clinical use of TMS is that, in people with various mental disorders, different areas of the brain are sluggish or overactive. In people with depression, for example, the left prefrontal cortex is less active than in people without depression. In people with anxiety disorders, the right prefrontal cortex is more active than in people without anxiety disorders; and in people with obsessive-compulsive disorder, the cingulate gyrus is hyperactive. When aimed and operated correctly, a TMS machine can "jump start" or calm down the appropriate areas of the brain.
Technical information on TMS
TMS is simply the application of the principle of induction to get electrical current across the insulating tissues of the scalp and skull without discomfort. A coil of wire, encased in plastic, is held to the head. When the coil is energized by the rapid discharge of a large capacitor, a rapidly changing current flows in its windings. This produces a magnetic field oriented 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 flows tangentially with respect to skull. The current induced in the structure of the brain activates nearby nerve cells in much the same way as currents applied directly to the cortical surface. The path of this current is complex to model because the brain is a non-uniform conductor with an irregular shape. With stereotactic, MRI-based control the precision of targeting TMS can be approximated to a few millimeters (Hannula et al., Human Brain Mapping 2005).
Typical data: [4]
★ magnetic field ('B'): often about 2 tesla on the coil surface and 0.5 T in the cortex
★ current rise time: zero to peak, often around 70-100 microseconds
★ repetition rate for rTMS: below 1 Hz (slow TMS), above 1 Hz (rapid-rate TMS)
TMS as therapy
TMS is currently under study as a treatment for severe depression, mania, auditory hallucinations (e.g., associated with schizophrenia), post traumatic stress disorder, obsessive-compulsive disorder, generalized anxiety disorder, migraine headaches and tinnitus. It is particularly interesting as it may provide a viable treatment to certain aspects of drug resistant mental illness, particularly as an alternative to electroconvulsive therapy. TMS is also under investigation for the treatment of drug-resistant epilepsy and tinnitus. rTMS therapy for drug-resistant depression has been approved by Health Canada for clinical delivery since 2002.
Although research in this area is in its infancy, there is now some evidence that TMS is an effective treatment for depression, obsessive-compulsive disorder, generalized anxiety disorder, tinnitus, and auditory hallucinations, with more symptoms and disorders being researched. Additionally, in June 2006, US medical researchers published evidence indicating that TMS is more successful at treating migraines in patients than current medications. A larger research study involving more patients and better controls is planned to confirm the validity of these results. [5][6]
Research is ongoing to determine whether TMS can effectively promote stroke rehabilitation. A stroke’s severity depends on the ability of the brain to relearn various functions with limited resources. Seeking to promote this process of compensation, researchers are attempting to use TMS to help stroke victims recover lost motor abilities.
Using functional magnetic resonance imaging (fMRI), researchers can localize areas of the brain involved in the execution of a given task. In stroke patients, one hemisphere of the brain is damaged, and tasks governed by this side of the brain can be impaired. When a stroke patient attempts to perform a task governed the damaged portion of the brain, fMRI usually shows activity in both hemispheres of the brain. The activity in the healthy hemisphere does not control the motor circuitry involved in the task; in fact, the activity in the healthy hemisphere seems to prevent the damaged hemisphere from functioning effectively. Doctors are currently working on a variety of techniques to reduce this “excessive interhemispheric interference.â€
TMS provides one means of controlling interhemispheric interference. TMS involves the positioning of an electromagnet on the surface of a patient’s scalp. Depending on the frequency of the current applied to the magnet, activity in the nearby region of the brain can be increased or decreased. By using TMS to decrease activity in areas of the stroke patient’s healthy hemisphere, doctors have been able to enhance the ability of stroke patients to perform simple tasks such as picking up a telephone. Improvements associated with TMS therapy have been shown to last for at least eight months after the therapy has concluded.
Several TMS/rTMS devices are approved by the US Food and Drug Administration (FDA) for stimulation of peripheral nerve and, therefore, can be used "off label" by individual physicians to treat brain disorders, essentially in any way they believe appropriate, analogous to the off label use of medications. However, most legitimate use of TMS in the US and elsewhere is currently being done under research protocols approved by hospital ethics boards and, in the US, often under Investigational Device Exemption from the FDA. The requirement for FDA approval for research use of TMS is determined by the degree of risk as assessed by the investigators, the FDA, and the local ethics authority. An application for clearance of TMS Therapy as a treatment for depression was submitted to the FDA in 2006. The FDA convened its Neurological Devices Panel on January 26, 2007 to review the TMS Therapy application. The results of this panel meeting were mixed with no concerns regarding the safety of this treatment, however, there was clear questioning of the efficacy of this treatment.
Panel questions magnet therapy results, Bridges, Andrew, , , , 2007
A final decision from the FDA in regard to approving TMS as a treatment for depression is expected in the first half of 2007. As regulated medical devices, TMS devices are not sold to the general public. They are also expensive (25,000-100,000 USD; together with state-of-the-art targeting and recording instruments, up to about 500,000 USD). In Europe, TMS devices that have been manufactured according to the Medical Device Directive have been granted the CE mark and can thus be freely marketed within the EU.
References
1.
'Non-invasive magnetic stimulation of human motor cortex.', Barker AT, Jalinous R, Freeston IL., , , Lancet, 1985
2.
'Handbook of Transcranial Magnetic Stimulation', Pascual-Leone A, Davey N, Rothwell JC, Wassermann EM, Puri BK, , , , 2002,
3.
'A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition', Fitzgerald PB, Fountain S, Daskalakis ZJ, , , Clinical Neurophysiology, 2006
4. "TMS terminology", ''BioMag Laboratory at Helsinki University Central Hospital''
See also
★ Cranial Electrotherapy Stimulation (CES)
★ Transcranial direct current stimulation (tDCS)
★ Electroconvulsive therapy (ECT)
External links
★ CIMIT - Center For Integration Of Medicine And Innovative Technology
★ Recording of EEG response due to TMS
★ Transcranial magnetic stimulation in psychiatry
★ BioMag Laboratory, Helsinki
★ OpenStim: The Open Noninvasive Brain Stimulator
★ MagVenture: Magnetic Stimulation - Principles
★ Magnets may make the brain grow stronger
★ Elata Foundation non-profit for TMS development and education
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