Transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is a non-invasive method which induces depolarization or hyperpolarization in the brain neurons. TMS is based on the principle of electromagnetic induction. It creates weak electric currents by rapidly changing magnetic fields. This causes appearance of activity in specific or all parts of the brain with minimal discomfort to the patient. This allows to study the functioning of the brain. Clinical trials of a type of TMS (repeated TMS) were conducted for treatment of various neurological and psychiatric diseases, such as stroke, migraine, Parkinson's disease, hallucinations, tinnitus, depression, and so on.

The principle of inductive brain stimulation which uses current was applied for the first time in the 20th century. The first successful TMS studies were conducted in 1985 by Anthony Barker and his colleagues in Sheffield. This study involved carrying nerve impulses from the motor cortex to the spinal cord with further stimulation of muscle contractions. The use of magnets instead of a more traditional constant electric current reduced the discomfort of the procedure and allowed researchers to look at the cerebral cortex and its liaisons.

How it influences the brain

Currently the effects of TMS on the brain are actively being investigated. Depending on the mode of stimulation, these effects can be divided into two types:

• Single or double impulses of TMS lead to the depolarization of neurons located in the stimulation zone of the brain cortex. This activates and spreads the action potential. When this activation occurs in the primary motor zone of the cerebral cortex, it produces muscle activity, called Motor Evoked Potentials (MVP). MVP can be recorded by electromyography. When the occipital area of the cerebral cortex is activated, the patient can see "phosphenes" (flashes of light), whereas the therapy is applied in other areas of the cortex, the patient does not experience any profound sensations. Nevertheless, special equipment does really track some changes in his/her behavior, such as delayed responses to cognitive tasks or in brain activity;
• Repeated TMS leads to long term consequences, which persist even after the initial period of stimulation is finished. Depending on the intensity of stimulation, coil orientation and its frequency, TMS can increase or decrease reflexes of the corticospinal tract.

Indications for TMS

TMS of the brain and peripheral nerves enables the doctors to track condition of the motor cortex and determine the extent of damage to corticospinal motor tracts. It also checks various parts of peripheral motor axons processes(including the motor roots of the spinal cord).

Disruption of reflexes through the central structures of the spinal cord and the brain is not something atypical - similar changes occur in various forms of pathology.

These disorders include increase in the latent time of the evoked potential, decrease in the amplitude or lack of response to the stimulation of the motor cortex of the cerebral cortex. They also include dispersion of the brain; various combinations of this dispersion.

Increase of time in central conduction may be indicated for demyelination, pathology of motoneurons, hereditary degenerative diseases of the corticospinal tract, glioblastoma of the cerebral hemispheres, cerebrovascular disorders or discogenic compression of the spinal cord.

Another indication for TMS is pyramidal syndrome, regardless of its etiology. In most cases TMS is used for treatment of various types of demyelinating lesions of the central nervous system(i.e, is especially true for multiple sclerosis), degenerative and hereditary diseases, vascular diseases, as well as tumors of the brain and spinal cord..

Contraindications

TMS is forbidden for patients with a pacemaker, if there is suspicion of an aneurysm of the cerebral vessels, and also for pregnant women, Epileptic patients require extra care as TMS can cause an attack.

Risks

Although TMS has been mostly viewed by specialists as a safe procedure, it still can cause fainting and induce seizures. Such cases have been mentioned in literature approximately 16 times. Seven of these times had been reported before the publication of safety instructions in 1998 and more than 9 cases had been reported thereafter. Single impulses and TMS are thought to be the cause of these seizures. Investigative studies have revealed that some of these cases may have been caused by some additional factors. These factors could have been the effect of drugs, brain damage or genetic predisposition. A closer examination of nine cases of seizures associated with TMS that were registered after 1998 showed that:

• four attacks occurred even when all safety measures were followed;
• four attacks occurred when safety measures were violated;
• one attack occurred to an ostensibly healthy volunteers who did not have any signs of predisposing factors.

International consensus gathered in 2009 to discuss TMS. After reviewing the above mentioned cases they concluded that, based on a number of TMS studies, both theoretical and clinical, the risk of a seizure initiated by TMS is very low.

Additionally to seizures, there can be such side effects as fainting, mild headaches, local discomfort, minor cognitive changes and psychiatric symptoms (there is a low risk of mania in depressed patients). Although other side effects associated with TMS (changes in the endocrine system, neurotransmitters and the immune system) are theoretically possible, although they have never been detected yet. This should be the subject of further scientific research.

Other side effects of TMS:

• Discomfort or pain when the scalp, nerves and muscles are affected by the therapy; this side effect is more frequent for TMS than for single impulses;
• Rapid deformation of the coil produces a loud clicking sound, which increases when stimulation increases as well. This may harm the hearing a little, but this side effect is easily eliminated by using appropriate protection for ears;
• If TMS is used with incompatible EEG electrodes, they can heat which may cause burns of the skin.

Clinical usage

TMS can be used for both diagnostic and therapeutic purposes.

Diagnostic purpose

TMS can be used to assess the activity and function of connections in the brain. The most reliable and traditional usage of TMS is the study of connections between primary motor cortex of the brain and muscles. This is done to assess the extent of damage caused by stroke, spinal cord injury, multiple sclerosis and motor neuron diseases. TMS can also be used for assessing short-interval intracortical inhibition (SICI). This helps to measure internal pathways of the motor cortex of the cerebral cortex. However, the real possibility of this TMS usage has not been proven yet.

Therapeutic purpose

Studies about using TMS and pTMS for therapeutic purposes of neurological and psychiatric diseases have shown positive results. Publication of the results and the statistical meta-analysis of earlier studies showed pTMS is an effective method for treating certain types of depression. A recent meta-analysis of 34 studies which compared the positive results of pTMS treatment showed an effect of approximately 0.55 (p <0.001). This is comparable to the pharmacotherapeutic effect in depression treatment in the range of 0.17-0.46.

There is evidence that mMTS can reduce chronic pain by changing nervous activity in the brain. TMS is also used to determine if surgically implanted brain stimulators can treat chronic pain. TMS is also used in the rehabilitation of people with disabilities and patients with motor aphasia after a stroke, tinnitus, Parkinson's disease and negative symptoms of schizophrenia. The benefits of using TMS for the treatment of coma brain and other autonomic disorders have not yet been proven.

It is difficult to check a placebo effect of this procedure. During trials patients often complained about the neck pain, headaches and cramps associated with the intervention. The metabolism of glucose in these patients also changed. All this can mislead the doctors. Another problem is that any improvement on the patient’s condition is often perceived subjectively by the patient. Depending on the research conditions and the questions asked by the researchers, it is almost impossible to distinguish the true results of the actual procedure from the placebo effect. This important and complex issue remains open.

Recent study, conducted jointly by several large research centers, recorded sounds appearing during active treatment of TMS to study the placebo effect. The researches also stimulated the patient's scalp to fully reproduce sensations of the treatment. The scientists concluded that although the obtained data was statistically reliable, the adequacy of the study should be doubted. The number of remissions, the cost of TMS, the need for daily intervention for at least 3 weeks, side effects, even the benign ones, are the reason for that. Nevertheless, experts assure that the results could not be accidental, since patients could not have known in advance whether they received a placebo or real TMS.

TMS after a stroke.

Technical information

TMS uses electromagnetic induction to generate the electric current through the scalp and skull bones without physical contact. Plastic wire coil passes next to the skull. When it is activated, it produces a magnetic field located orthogonally to the plane of the coil. The magnetic field passes without obstructions through the scalp and skull bones. This causes oppositely directed fluxes of charged particles to activate nerve cells the same way the cells of the cortical surface are activated.

The trajectory of this current is difficult to model because of the geometrically irregular shape of the brain. Hence both electric currents and magnetic fields are not uniformly distributed throughout the tissues. The magnetic field has similar strength to MRI. It does not penetrate deeper than 5 cm into the brain tissue.

The Type of Coil

The coils used for either diagnostics or treatment are different. This must be taken into account when determining the results of any studies. The type of coil should also be mentioned when processing the data obtained for publication.

The most important factors are:

• type of material used to build the core of the coil;
• configuration of the coil geometry;
• biophysical characteristics of the impulse produced by the coil.

Composition of the coil: the base material can be either a magnetically inert substrate (the so-called air-nuclear design) or it could be a solid ferromagnet (the so-called solid-nuclear design). The solid core of the coil causes a more efficient conversion of electrical energy into a magnetic field with a significant reduction in the amount of energy dissipated as heat. Therefore this type of coil can operate in a more strenuous mode, when frequent operating cycles are required. It can also work without interruptions for heat accumulation. This coil also uses special detail that cools it during operation.

Different geometric shapes of the coil can also lead to changes in the focality, shape and depth of magnetic penetration into the cerebral cortex. Different composition and amplitude of the coil can also lead to changes in the biophysical characteristics of the resulting magnetic impulse (for example, the width or duration of the magnetic impulse).

All these must be taken into account when results obtained from various studies are compared in terms of safety and effectiveness.

There are several types of coils, each of them produces different models of the magnetic field. For example:

• round coils - original type of TMS coil;
• coil-eight (coil in the form of butterfly);
• double cone - the shape of coil corresponds to the shape of the head. It is useful for deeper stimulation;
• four-tier coils - used for stimulation of coordination of peripheral nerves.

TMC coils of some other forms achieve a much deeper penetration into the brain tissues from what standard coils - 1.5 cm - achieve. Circular, H-shaped coils, double-cone coils and other types can promote the activation or inhibition of neurons in the brain tissues, including activation of the neurons in the cerebellum. Although deeper penetration is possible, the increase in the penetration can make TSN lose its purposefulness, localization and the possibility of coordination.

Also see other methods:

• Audiovisual stimulation
• Darsonvalization
• Physiotherapy

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