Transcranial magnetic stimulation
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
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. This is used to study the circuitry and connectivity of the brain.
Repetitive transcranial magnetic stimulation is known as rTMS and can produce longer lasting changes. Numerous small-scale pilot studies have shown it could be a treatment tool for various neurological conditions (e.g. migraine, stroke, Parkinsons Disease, dystonia, tinnitus) and [psychiatric conditions (e.g. depression, auditory hallucinations), but as yet no large scale trial has been done, the therapeutic potential of rTMS should not be considered proven.
Background and history
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 elecrical stimulation a few years earlier, but use of this technique is limited by severe discomfort. By stimulating different points of the cerebral cortex and recording responses, e.g., from muscles, one may obtain maps of functional brain areas. By measuring functional imaging (e.g. MRI) or EEG, information may be obtained about the cortex (its reaction to TMS) and about area-to-area connections.
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 Wassermann of the National Institutes of Health, and Álvaro 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.
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:
As such, it is important to distinguish TMS from repetitive TMS (rTMS) as they are used in different ways for different purposes.
TMS and rTMS techniques 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 (i.e. 'knocked out') 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 example: subjects asked to memorize and repeat a stream of numbers would likely show activation in the prefrontal cortex (PFC) via fMRI, indicating the role of this brain region 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.
This ‘knock-out’ technique (also known as virtual lesioning) can be done in two ways:
Risks of TMS and rTMS
As it induces an electrical current in the human brain, TMS and rTMS can produce a seizure. The risk is very low with TMS except in patients with epilepsy and patients on medications. The risk is significantly higher in rTMS especially when given at rates >5Hz at high intensity.
The only other effects of TMS which are reported in most subjects are:
Clinical uses of TMS and rTMS
The uses of TMS and rTMS can be divided into:
TMS for diagnostic purposes
TMS is used currently 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 (i.e. MEP amplitude, MEP latency, central motor conduction time). This is most useful in stroke, spinal cord injury, multiple sclerosis and motor neuron disease. There are numerous other measures which have been shown to be abnormal in various diseases but few are validated or reproduced and more importantly, no one knows the significance of these measures. The most famous is short-interval intracortical inhibition (SICI) which measures the internal circuitry (intracortical circuits) of the motor cortex (Kujirai et al., 1993) [4]
Plasticity of the human brain can also be measured now with repetitive TMS (and variants of the technique, e.g. theta-burst stimulation, paired associative stimulation) and it has been suggested that this abnormality of plasticity is the primary abnormality in a number of conditions.
TMS for therapeutic purposes
It is important to stress that there is no strong evidence for the use of TMS for therapy of any condition. A large number of studies with TMS and repetitive TMS has been conducted for a variety of neurological and psychiatric conditions but few have been confirmed and most show very modest effects if any. Some conditions which have been reported (but not proven) to be responsive to TMS-based therapy are:
TMS is particularly attractive as a potential treatment for drug resistant mental illness, particularly as an alternative to electroconvulsive therapy as such, rTMS therapy for drug-resistant depression has been approved by Health Canada for clinical delivery since 2002.
It is important to stress that in a vast majority of these studies, no adequate control of placebo effect was possible and thus it is tempting to wonder if this effect is placebo.
TMS equipment
The major manufacturers for general purpose TMS and repetitive TMS equipment are:
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 USA 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.[5] 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 (US$25,000-100,000 for basic equipment; US$500,000 for state-of-the-art targeting and recording instruments). 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.
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: [6]
- magnetic field: 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
- wave form: monophasic or biphasic
- repetition rate for rTMS: below 1 Hz (slow TMS), above 1 Hz (rapid-rate TMS)
References
- ↑ Barker AT, Jalinous R, Freeston IL. (1985). "Non-invasive magnetic stimulation of human motor cortex.". Lancet. 1: 1106–1107.
- ↑ Pascual-Leone A, Davey N, Rothwell JC, Wassermann EM, Puri BK (2002). Handbook of Transcranial Magnetic Stimulation.
- ↑ Fitzgerald PB, Fountain S, Daskalakis ZJ (2006). "A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition". Clinical Neurophysiology.
- ↑ Kujirai, T (1993). "Corticocortical inhibition of the motor cortex". Journal of Physiology. 471: 501–509..
- ↑
Bridges, Andrew (2007). "Panel questions magnet therapy results". Unknown parameter
|month=ignored (help) - ↑ "TMS terminology", BioMag Laboratory at Helsinki University Central Hospital
See also
- [MCC - MindCare Centres]
- Cranial Electrotherapy Stimulation (CES)
- Transcranial direct current stimulation (tDCS)
- Electroconvulsive therapy (ECT)
de:Transkranielle Magnetstimulation nl:Transcraniële Magnetische Stimulatie