**2. TMS principles, parameters and mechanism of action**

The principle of the TMS method is based on Faraday's law of electromagnetic induction, formulated in 1831. This law states that around the primary coil through which a time‐varying current is flowing, a changing magnetic field is created that is able to induce a secondary current in conductors found within its reach. A patient's brain may be one such conductor. The secondary current induced is, according to Lenz's law, in the direction opposing the primary current. During TMS, an insulated metal coil is placed over the patient's head that delivers a changing electrical current producing a changing magnetic field perpendicular to the current passing through the coil. Magnetic pulses may be administered individually (single‐pulse TMS), or in pairs a few milliseconds apart (paired‐pulse TMS), or repeatedly in a sequence or "train" lasting from seconds to minutes (repetitive transcranial magnetic stimulation or rTMS). The first two options are used primarily for research and diagnostic purposes; rTMS is used mainly in the treatment of certain neuropsychiatric disorders, including schizophrenia [1, 3].

Repetitive transcranial magnetic stimulation is defined by the number of pulses per second or by frequency in Hertz (Hz). The frequency is categorized as "low‐frequency" ("slow") rTMS with 1 Hz or less and "high‐frequency" ("fast") rTMS with more than 1 Hz (usually between 5 and 25 Hz). Another parameter of stimulation is its intensity expressed as the percentage of the individual resting motor threshold (MT). The motor threshold is defined as the minimal intensity of the stimulus able to produce muscle contraction in at least 5 of 10 successive trials (usually in one of the small muscles of the hand, e.g., the abductor pollicis brevis) when the stimulation is applied to the motor cortex. The most commonly used stimulation intensity varies between 80% and 120% of the individual resting motor threshold. Other stimulation parameters include the length of the train of pulses, the duration of the pause between them ("intertrain"), the total number of pulses administered during one session, the total number of individual sessions, the stimulation coil localization, the type of coil (the most commonly used type in rTMS is the "figure‐of‐eight coil"; there are also oval coils, conical coils etc.; the double cone coil is one of the most innovative types), and the coil's position, and orientation on the patient's head. The most frequent stimulation site is the dorsolateral prefrontal cortex (DLPFC). This stimulation site is usually defined as the location 5 cm rostral to the area of the motor cortex, the stimulation of which determines the resting motor threshold. Another method for the localization of the stimulation site uses the international system of EEG electrode placement 10/20; the most precise localization method is performed by stereotactic neuronavigation. An interesting modification of standard rTMS is pattern stimulation, with theta burst stimulation (TBS) as the most important [1–3].

Although the specific effect of rTMS on neurotransmission is not entirely clear, it has been proven repeatedly that high‐frequency rTMS (10 to 20 Hz) increases brain excitability, and low‐ frequency rTMS (1 Hz and lower) decreases it. It has also been found that high‐frequency rTMS applied over the left prefrontal cortex (PFC) increases brain perfusion, and thus the metabolism of this region, whereas low‐frequency rTMS has the opposite effect [4].
