**2. Basic principle of TMS and cortical reactivity**

Since its introduction by Barker in the 1980s [1], who first discovered the induction of finger and foot movements through the use of a magnetic coil placed on the motor cortex, TMS has greatly advanced our ability to explore and understand neural circuitry in neurology, psychiatry, and neuropsychological research.TMS uses principles of electromagnetic induction [2]. According to the principle whenever an electric current is passed through a coil, a transient magnetic field is generated, which induces a current in the corresponding neural tissue, consistent with Faraday's law. When the induced current is sufficient (several mA/cm<sup>2</sup> ), depolarization of neuronal membranes occurs, and hence generation of action potentials, which is recorded peripherally using electromyography (**Figure 1**). Based on which area of the cortex is stimulated, different functions can be assessed. In the case of the stimulation of the primary motor cortex, TMS is thought to predominantly activate the pyramidal cells transynaptically through excitatory intraneuronal elements. The corticospinal tract (CST) is the main descending motor pathway from the cerebral cortex to the spinal cord that can be activated by TMS. The CST originates from large pyramidal cells predominantly in the fifth layer of the cerebral cortex. The descending corticospinal tract is known to make monosynaptic connections with spinal motoneurons in humans. This organized electrical activity in the corticospinal tract is also regulated by the balance of GABAergic inhibitory postsynaptic firing and excitatory glutamate receptor activations. This contrasting cortical modulation by GABAergic vs. Glutamatergic fibers in neural tissue can be studied non-invasively in the human brain through TMS parameters. Cortical inhibition by GABAergic neurons mediates the balance between the excitatory and inhibitory systems of the nervous system. TMS has been used to study a variety of neuropsychiatric disorders including anxiety, obsessive–compulsive disorder, attention deficit hyperkinetic disorder, post-traumatic stress disorder, schizophrenia, and mood disorder by assessing

#### **Figure 1.**

*TMS figure explaining the procedure from TMS machine to recording of motor evoked potential from hand; figure depicts TMS machine, figure of 8 coil(green), generation of the magnetic field through the coil, induced current in the cortex and finally TMS elicited motor potential recording of the event through hand muscle. Magnetic pulses activate cortical pyramidal neurons, leading to a corticospinal output that can be measured peripherally as a motor-evoked potential (MEP) using electromyography.*
