## 3 Brain Stimulation Techniques
tMS is another noninvasive brain stimulation technique that uses a magnetic coil to generate a local electric current by electromagnetic induction. This is applied to a focal region of the brain, resulting in depolarization or hyperpolarization, neuronal excitation, or inhibition [34]. When the motor cortex is stimulated, the electric current travels to the descending fibers of the spinal cord and causes muscle contraction. tMS depolarizes myelinated axons in the stimulated cortex, initiating a cascade of neural events propagating locally and to distant brain regions via cortico-cortical and cortico-subcortical connections. The brain's current state influences the extent and duration of both local and remote tMS effects and involves a balance of excitatory (glutamatergic) and inhibitory (GABA-ergic) neurotransmission [35]. In clinical practice, high-frequency or low-frequency rTMS is most used, while tMS-theta-burst (TBS) treats depression [36]. Other invasive brain stimulation methods are Deep brain stimulation (DBS) and Vagus nerve stimulation (VNS). VNS involves delivering electrical signals to the vagus nerve using a device implanted under the skin, while DBS involves placing electrodes in targeted regions of the brain. Figure 1: (**A**) Example of electrode placement (anode, blue; reference electrode, orange) in transcranial direct current stimulation applied for a patient with depression/anxiety. The exact area for stimulation is determined based on the International 10/20 EEG system. (**B**) In MDD or BD, the stimulating electrodes can be positioned in different configurations: anode—F3 (left dorsolateral prefrontal cortex), reference electrode—F4 (right dorsolateral prefrontal cortex), Fp2 (right orbitofrontal cortex), or F8 (right inferior frontal gyrus) (generated with Biorender). Electroconvulsive therapy (ECT) involves placing electrodes on the scalp to induce generalized convulsive activity, resulting in a seizure, and is performed under general anesthesia. While it could be considered a noninvasive form of brain stimulation, ECT is generally categorized as more invasive than methods like tDCS and TMS, as it induces a seizure and requires anesthesia, even though it does not involve surgery (see Figure 2). All these techniques fall under the broader category of transcranial electrical stimulation (TES). tDCS offers several advantages, including cost-effectiveness, portability, and a relatively low risk of side effects. In terms of efficacy, ECT remains highly effective for severe, treatment-resistant depression (TRD) and is often the \"gold standard\", showing quicker and more robust effects than other neuromodulation therapies. Research results reveal more significant results in reducing depressive symptoms, as measured by tests such as the Hamilton Depression Scale (HDRS) or Beck Depression Inventory (BDI). However, effects on anxiety symptoms or suicidal ideation are more pronounced with ECT compared to tDCS and rTMS. Magnetic stimulation is effective, especially in resistant depression, but the effect is smaller compared to ECT. Despite this, it remains more tolerable for patients and is beneficial for those with mild-to-moderate MDD. Recent evidence suggests that rTMS may be well-tolerated among those who have experienced adverse reactions to medication. In patients with mild to moderate MDD, studies have shown encouraging results with tDCS, and several studies show it to be beneficial when integrated alongside medication-based treatments. However, the evidence for its benefit in treatment-resistant depression is still inconclusive. The variability in findings across different studies underscores the importance of establishing standardized protocols to ensure more reliable outcomes [37]. ECT is by far the most effective and rapid treatment for major depressive disorder (MDD). It has the best results in reducing suicidality and alleviating severe MDD, making it particularly valuable when other treatments have failed.