Transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is the use of powerful rapidly changing magnetic fields to induce electric fields in the brain by electromagnetic induction without the need for surgery or external electrodes. Repetitive transcranial magnetic stimulation is known as rTMS.

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."

TMS in research
The principle of inductive brain stimulation with eddy currents has been known since the 19th century. The first successful TMS study was performed by Anthony Barker et al. (Lancet, 1985) in Sheffield, England. Its earliest application was to demonstrate conduction of nerve impulses from the motor cortex to the spinal cord noninvasively. 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, one may obtain information 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 the 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 Barker et al., Vahe Amassian and Alvaro 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. Massimini et al. (Science, 2005) used EEG to show that during sleep, brain areas do not pass signals to other brain areas as effectively as during wakefulness.

How TMS works
The exact details of how TMS functions are still being explored, but the MIT Technology Review listed some potential mechanisms:

"A doctor typically holds a powerful magnet 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)"

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 bone of the head, 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 to 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 as good as a few millimeters (Hannula et al., Human Brain Mapping 2005).

TMS as therapy
TMS is currently under study as a treatment for severe depression, auditory hallucinations, 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.

Although research in this area is in its infancy, there is now strong evidence that TMS is an effective treatment for both depression and auditory hallucinations, with more symptoms and disorders being researched.

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. 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.