## 1 Introduction
### Structural Brain Abnormalities in Major Depressive Disorder  
Long-term MDD has been found to induce brain changes, with reduced volume or functionality observed in regions responsible for emotional processing and cognitive functions. Neuroimaging studies have shown that individuals with MDD exhibit decreased gray matter volumes in the prefrontal cortex, amygdala, hippocampus, and thalamus. These structural changes are thought to underline key symptoms of MDD, such as negative affect and difficulties in decision-making, as these regions play a critical role in mood regulation and the processing of emotional stimuli. In individuals with depression, functional and metabolic brain irregularities have been identified, and these changes often respond to treatment. Resting-state studies using positron emission tomography (PET) have revealed decreased cerebral blood flow and metabolism in the left dorsolateral prefrontal cortex (DLPFC), alongside increased metabolism in the right DLPFC in cases of MDD [11]. The hippocampus, a region commonly known to be involved in memory formation, is found to be affected by MDD, which can cause a reduction in total volume, which may lead to impairments in memory and cognitive functions of individuals [12]. Surface-based morphometry (SBM) highlights other structural nuances, such as cortical thickness and surface area changes. Studies have noted reduced cortical thickness in MDD, particularly in the ACC, superior temporal gyrus, and orbitofrontal cortex. Thinning in these areas may reflect neurodegenerative processes tied to depressive symptomatology, with implications for emotion regulation and social cognition [12]. There is increasing evidence of impaired neuroplasticity in MDD, such as the observation of widespread functional and structural abnormalities [13]. Brain plasticity has also been observed to be dysfunctional in terms of long-term potentiation and depression modification [9]. Compared to healthy individuals, depressed ones have lower levels of glutamate/glutamine (Glx) in the anterior cingulate compared to the same age control group [14]. Glx deficiency in patients with depression is probably an essential metabolic marker underlying hypotmetabolism. It reflects functional changes due to illness, most likely a reduced efficiency of the glutamatergic system and the associated occurrence of specific symptoms related to the affected brain areas. For example, psychomotor retardation and depressive mood may be symptoms associated with left DLPFC dysfunction [15; 16]. Low glutamate/glutamine levels in unipolar depressive patients are successfully restored after electroconvulsive therapy [17]. Research has shown that stimulating the left dorsolateral prefrontal cortex (DLPFC) using transcranial magnetic stimulation (tMS) can trigger increased dopamine release in the striatum [18]. The study by [PERSON] [19] demonstrates that rhythmic stimulation of the left DLPFC at 10 Hz facilitates the release of serotonin in limbic structures. Recent neuroimaging research has linked the left DLPFC to emotional judgment, while the right DLPFC is associated with anticipation and attention related to emotional judgment. The valence-lateralization theory, which suggests that the left prefrontal cortex is dominant for positive emotions and the right for negative emotions, is supported by fMRI studies in healthy individuals. These studies demonstrate a linear or parametric relationship between negative and positive emotional judgment and neural activity in the left and right DLPFC. Specifically, reduced activity in the left DLPFC is associated with impaired emotional judgment and abnormal modulation by positive and negative emotional valence. Conversely, increased activity in the right DLPFC appears to correlate with the attentional regulation of emotional judgment. Most tDCS studies reveal the anode targeting at left DLPFC and cathode targeting at right DLPFC, modulating the neurotransmitters released that regulate synaptic plasticity of this region frequently affected in MDD.