How to rewire your brain

Crack, crack, crack... The sound of cracks echoes in 52 year-old David’s ears. It’s similar to an MRI, so, to make him more comfortable, he was given earplugs. Some days he even takes his headphones to listen to music. In the skull, there’s a feeling of painless pulsating pressure with each magnetic impulse. He is awake and alert, because this therapy does not require sedation or any prior preparation.

Before you start, all jewelry, mobile phones and credit cards have to be left outside the room, as they are metallic items. A transcranial magnetic stimulation (TMS) is repetitive, the magnet is turned on and off quickly, creating an effect that is similar to a gentle bump on the head. He is sitting in the TMS room of the López Ibor Clinic in Madrid, with a device that has electromagnetic coil over his skull. After having spent three years stumbling from one specialist to another and having tried almost all the drugs available for his illness without success, David was still on leave because of a depression that he could not seem to overcome. After a detailed study, the doctors at the López Ibor Clinic proposed to try out TMS. 

"When he started, he suffered from a marked depressive symptomatology, tiredness and great sadness," stated psychiatrist María Inés López-Ibor, a professor at the Complutense University of Madrid and president of the Juan José López-Ibor Foundation. “After fifteen sessions of TMS and being supplemented on low dosages of the only antidepressant that the patient could tolerate, he has been able to return to work. It has improved a lot,” she continues. Although he still has a few memory sessions left, after completing the six months, the therapy will come to an end. As explained in the clinic, TMS acts on nerve tissue without surgery. It is a mobile therapy, in addition, “it is a good alternative to drugs,” says López-Ibor.

Other uses of TMS 

Besides depression, it is used, for example, for migraines, addictions, or some symptoms of schizophrenia, such as cases of auditory hallucinations. Several versions have been marketed in Europe to treat Alzheimer’s, autism, bipolar disorder, epilepsy, chronic pain, Parkinson's and post-traumatic stress syndrome. It also serves as a diagnostic method and tool for research on brain function.

Where is the secret of its success? The key is that “the brain is, above all, an electrical organ and a large conductive unit,” as described by Álvaro Pascual-Leone, a neurologist at Harvard University and an expert in the use of TMS to better understand neuronal functioning. Magnetic stimulation, which penetrates the skin and bone, induces a current in the brain that activates or inhibits certain neurons to regulate the nerve signals responsible for mood, pain, cognitive faculties, physical endurance, motor problems... “The aim is to stimulate very specific points, by means of coils of suitable geometry, in order to generate highly focal electric fields,” observes the expert.

“Each electrical impulse generates a magnetic field, according to Faraday’s laws of electromagnetic induction. This magnetic field acts as a bridge between the current that is applied to the coil outside the skull and the current that is induced in the brain and that reaches the deepest areas of the skull, where the drugs do not reach,” explains Pascual-Leone.

Neurons communicate by electrical impulses, and TMS uses the same language. “It is about regulating the function of neurotransmitters. It boosts its release or powers the receptors of neurons, with a long-term effect,” points out López-Ibor, adding, “although there are also cases in which it is a question of blocking and not stimulating certain areas, such as obsessive-compulsive disorder (OCD), for example. When applied in one hemisphere, it activates and inhibits the other. On the other hand, when the magnetic wave frequency is more intense, it activates, and when it is below the threshold, it inhibits this.” That is, when there is a mental disorder, certain circuits or areas in the brain appear altered. TMS is intended to restore their functionality. In the case of depression, one of the most addressed with these techniques, “there are flaws in the circuits related to emotions, with the ability to control and plan…”says López-Ibor.

For the time being, this technique is already used as a treatment in psychiatry and neurology, especially in countries such as the United States. In Spain, public centers such as the Gregorio Marañón General University Hospital in Madrid stand out, where Julio Prieto is head of the Neurophysiology Service. According to this expert, in any case, there are many advantages in proving whether it works in a particular case. To begin with, it is a non-invasive therapy, does not require the patient’s admission and no prior preparation is necessary. In addition, Prieto points out that “if the person responds to magnetic stimulation, we know that in a year or two the treatment will be equally effective. It does not diminish its effect over time, as it does with drugs, which do stop acting with the same force in subsequent intakes.”

Few side effects

Experts argue that it is a safe form of therapy, involving very little danger. Nothing to do with electroconvulsive therapy, also approved for resistant depression, but which can produce personality changes or memory loss. At his side, the side effects of TMS seem like a joke: “They are limited to a small headaches that gives way very quickly and are solved with a simple analgesic,” explains Prieto.

Although there is also the possibility of having a seizure, “the risk is very low,” adds the expert, and preventable by doing a clinical study prior to the patient. For the moment, the López-Ibor Clinic has been working with TMS for ten years and investigating its application for the treatment of bipolar disorder and addictions, especially to cocaine.

At this latter point, they have observed that dependence is related to the brain’s reward circuit. In general, everything points to it working quite well to reduce the strength of dependence; however, “as a therapy to prevent relapses must be accompanied by pharmacological and psychological treatment,” says López-Ibor. Its efficacy is also being demonstrated with alcoholic patients, since “it acts on the prefrontal cortex on the right side, to decrease the craving,” says Prieto.

They are also testing it to attack sleep disorders that often have a background of anxiety and depression. And it has given very good results in reducing auditory hallucinations of a certain type of schizophrenia, although a 2015 study by the prestigious Cochrane Collaboration on International Health Promotion Policy found that there is not enough evidence to determine its effectiveness in treating this disorder as a whole. “However, without a doubt, where we have more experience and where there is more evidence of its effectiveness at the moment is treatment-resistant depression,” emphasizes López-Ibor. In particular, in these cases of chronic pathological sadness, “the stimulation of the left dorsolateral prefrontal cortex achieves an improvement in 50% to 60% of patients who do not achieve it with drugs. In some cases, it can even replace the medication,” says Prieto.

OCD

Another disorder addressed with this strategy is obsessive-compulsive disorder (OCD). In this particular condition, TMS has been shown to be helpful in relieving compulsions in patients. “Although it is not so much to treat the obsessive part, it responds better to the drugs,” he adds. On the other hand, TMS “allows us to evaluate the state of neuronal connections and the effectiveness of brain plasticity mechanisms, which give us a measure of your health,” says Pascual-Leone, leader of the Barcelona Brain Health Initiative project, which aims to study three thousand healthy brains in order to find biological markers and mechanisms to protect against diseases.

For two decades, hospitals such as the Gregorio Marañón have been using TMS as a diagnostic method in the detection of spinal diseases, a case of myelopathies. “It is a diagnostic complement to the CT scan and the clinic,” explains Prieto. “By doing a stimulation in the motor area, the integrity of the motor system can be analyzed. This information helps the neurosurgeon to know the current situation of the patient before dealing with the surgery,” he continues.

It is also used to check the state in which neuronal circuits are in certain patients, for example, the analysis of the connections between the motor zones of the brain and the muscles, and allows the evaluation of damage caused by heart attacks, multiple sclerosis, amyotrophic lateral sclerosis, movement disorders and other injuries affecting the cranial nerves or spinal cord. In the same way, it can be used to explore the brain and the state of excitability and connectivity of its cortex.

This is one of the research lines of the same hospital in Madrid, which seeks to know if certain diseases have a marker of excitability. “It is very useful because it also allows us to find out if a certain pharmacological treatment is producing modifications. It helps us to learn which circuits are affected by various neurological and psychiatric ailments and whether a drug normalizes dysfunctions,” says Prieto.

A promising future 

When asked about the future, Dr López-Ibor states the following: “It is a technique that will help a lot in psychiatric and neurological pathologies, such as attention deficit disorder (ADD) and multiple sclerosis.” He also considers it promising to treat autism, “as it is a non-invasive and painless technique, easy to apply to people suffering from this neurobiological disorder because they are comfortable, sitting quietly, talking to the therapist while the magnet is applied,” says this specialist.

There is no doubt that this is a fertile field for research and much remains to be discovered. For now, it is proven to have an effect on neurotransmitters, such as dopamine and serotonin. It also produces changes in plasticity. “There is scientific evidence that it stimulates dendritic growth and synaptic buttons that bind neurons. However, we do not yet know how this is achieved,” acknowledges Dr Prieto. It is not yet clear what effects it has in other areas related to the stimulation. “The effects combine, because it doesn’t just work at the point where the magnet is applied, nothing else on those neurons, but it also affects other areas at a distance. We continue to learn about which areas will be stimulated or affected by stimulating a particular point,” adds the neurophysiologist. “It is not known which is the ultimate mechanism by which it works, but I can assure you that it does work,” he concludes.