Depression is a common mood disorder globally, and there is a need for additional forms of therapy. Transcranial magnetic stimulation (TMS) is a form of brain stimulation that does not require intervention (non-invasive). It has been investigated over the past fifteen years whether this form of stimulation effectively treats patients with a major depressive disorder.
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History:
The effects of applying electric current were already demonstrated around 45 BC. Scribonius Largus described this in his Compositions (1983 edition). Largus was the regular physician of the Roman emperor Claudius, and he was familiar with the electric ray that stuns its prey with powerful electrical discharges. He treated a patient suffering from a headache by placing such an electric ray on the patient’s head. The electric discharge from the ray eliminated the headache of the patient.
Mechanism:
In 1985, neurologist Anthony Barker et al. (1985) introduced a method to generate an electrical current in the head without physical intervention and thus activate the large cerebral cortex. This method later became known as transcranial magnetic stimulation (TMS) and is based on the physical laws of Hans Christian Ørsted (1820) and Michael Faraday (1831). When a short-term electric current flows through a coil (an electrical element) on the head, a magnetic field is generated (Ørsted’s law). The magnetic field locally generates an electric current in the outermost layer of the cerebral cortex (Faraday’s law).
Barker et al. (1985) demonstrated the principle of TMS by placing a coil 7-10 cm in the center of the head and causing involuntary finger movement using a magnetic pulse. When an electrical charge moves rapidly across a stimulating cellular membrane (a kind of membrane), an electrical voltage is created, explaining the finger movement. This electrical voltage increases the tension present in the nerve cells of the brain. Ultimately, the so-called corticospinal pathway is activated.
The maximum magnetic field generated by a standard machine directly under the coil is between 1.5 and 2.5 Tesla. It is equivalent to approximately 40,000 times the intensity of the Earth’s magnetic field.
Because the magnetic field’s strength decreases, only the nerve cells in the outer layer of the brain are activated. But because the brain is connected in many ways, the effects can also be measured in other areas of the brain (figure 2) (Komssi et al. 2002). It allows researchers to investigate the functional networks in the brain.
If TMS is applied for a longer period (15-20 minutes), changes can occur in the brain that lasts longer than the stimulation itself (Hallett 2007). Based on the frequency and intensity of the TMS pulses, the excitability of the stimulated area can be influenced.
Frequency:
Research has shown that stimulation frequencies of around 1 Hz reduce the excitability of the large cerebral cortex. A stimulation frequency of 10 Hz or higher, on the other hand, shows an increase in the excitability of this brain area (Maeda et al., 2000). It shows similarities with the ‘long-term depression’ and ‘long-term potentiation’ effects found in animals after low (1 Hz) and high frequency (25-100 Hz) electrical stimulation (Shepherd 1998; Thickbroom 2007).
Transfer substances such as glutamate and gamma-aminobutyric acid also influence the effects of TMS (Hallett 2000). The type of effect can also depend on the area’s basic condition to be stimulated (Silvanto et al. 2008). For example, an increase in excitability of 1 Hz-TMS has been observed in patients with migraines (Brighina et al. 2002).
Intensity:
In addition to the frequency, the intensity of the stimulation is also important. The intensity is determined based on the amount of energy required to derive a muscle response of 50 μV with TMS across the primary motor cortex in 5 out of 10 cases (Wassermann 1998). The main reason for determining this motor threshold is safety and ethics. There are considerable individual differences in motor thresholds. These can be partly explained by the physical distance between the skull and the brain and partly by neurophysiology variation (Wassermann 2002). Determining everyone’s threshold ensures that someone is not unnecessarily exposed to high intensities during stimulation.
The effects of one TMS session are short-lived and usually no longer noticeable an hour after stimulation. Researchers say that it takes daily TMS for a few weeks to achieve effects that last for longer. In addition to the number of sessions, a higher intensity would also be positively related to the effect’s duration (Avery et al. 2006).
Safety:
The TMS technique is harmless and has no adverse effects on health. The condition is that no epilepsy occurs in the first degree of the patient’s family. There should also be no metal in the patient’s head. The possibility of influencing the brain without physical intervention offers possibilities for thorough research and applications in clinics.
Treatment of depression:
In the early 1990s, a group of German researchers described the positive effects of high-frequency TMS on the left frontal cerebral cortex in two patients with severe depression. This study was the start of a series of controlled studies of the effectiveness of treatment with TMS. Previous studies have shown a link between depression and a hypoactive left frontal cortex. These studies have led to the use of high-frequency stimulation (Baxter et al. 1989). TMS treatment in patients with severe depression consists of an average of ten to twenty daily sessions. Patients who do not respond sufficiently to other treatments and antidepressants also need so many sessions to continue.
Effectiveness:
Recently, research has been conducted into the antidepressant effect of high-frequency TMS, as described in 30 high-quality treatment studies with 1120 patients (Schutter 2009). The frequencies used for stimulation were between 5 and 20 Hz. The number of sessions per treatment was between 5 and 20 (μ = 11). The mean stimulation intensity was 97% of the motor threshold, and the mean number of simulations was 1194 pulses per session. This research clearly shows that a real treatment works much better than undergoing a fake treatment. However, the therapeutic effect is of moderate magnitude (cohen’s d = 0.39; 95% confidence interval: 0.25-0.54).
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