The sham-tDCS intervention consist of a placebo 15 tDCS sessions distributed over 3 weeks (5 sessions per week, from Monday to Friday), at the same time each day, administered by the same operators and under identical experimental conditions. Each session last 30 minutes, with the Anode electrode placed on the left dorsal lateral prefrontal cortex (DLPFC) and the Cathode electrode on the right DLPFC. During the sessions only a 15-second initiation current is applied, providing the patient with the sensation of receiving an electric current on the scalp. Participants will also experience sounds and stimuli similar to those produced by active tDCS.

To investigate the effects of tDCS treatment on cognitive function in patients with depression, randomized into a "test" group and a "sham" group. Specifically, FAB is a tool used to evaluate frontal lobe functions, such as executive functioning. Lower scores suggest greater impairment of frontal lobe functions, while higher scores indicate better functioning. Below are the minimum and maximum scores and their meaning: 18-15: normal frontal lobe functioning; 14-12: mild impairment; 11-9: moderate impairment; 9-0: severe impairment.

To investigate the effects of tDCS treatment on cognitive function in patients with depression, randomized into a "test" group and a "sham" group. AS is a tool used to assess the presence of apathy in patients. Higher scores suggest greater severity of apathy, while lower scores indicate better motivation and engagement. Below are the minimum and maximum scores and their meaning: 18-27: no clinically significant apathy; 28-41: mild apathy; 42-55: moderate apathy; 56-72: severe apathy.

To investigate the effects of tDCS treatment on cognitive function in patients with depression, randomized into a "test" group and a "sham" group. Stroop Color Test is a neuropsychological tool used to assess cognitive flexibility, selective attention and processing speed. Performance is assessed by comparing raw scores to normative data adjusted for age, education and cultural background. Minimum score (0) indicates no ability to perform the task; on the other hand, there is no universal maximum score. Tipically, performance is categorized into a normal range when it is consistent with age-matched norms; mild impairment when the performance is slightly below expectations for age or education; moderate to severe impairment when patient shows significant difficulty with cognitive control or selective attention.

A blood sample is collected at enrollment and after tDCS/sham treatment to evaluate biomarkers, including BDNF, NGF, VEGF, IGF1, Ang, Nrg1, IL-6, and TNFα.

Concentrations will be reported in pg/mL or ng/mL, as appropriate for each biomarker.

A transcranial Doppler (TCD) exam is conducted to assess cerebral hemodynamics. Parameters including VPS (cm/s), EDV (cm/s), MBFV (cm/s), PI (unitless), and RI (unitless) are recorded bilaterally from the middle cerebral arteries and the basilar artery, both at rest and after breath-holding tests. Measurements will be reported in their respective units (e.g., cm/s for velocities, unitless for indices).

Cortical excitability is evaluated using transcranial magnetic stimulation (TMS) with single- and double-pulse protocols. Parameters include:

Resting motor threshold (rMT, % of maximum stimulator output); Cortical silent period (cSP, milliseconds); Motor evoked potential (MEP, µV); Paired-pulse stimulation (BiSTIM) is used to study inhibitory and excitatory circuits, including intracortical inhibition (ICI) and intracortical facilitation (ICF).

Results are reported in their respective units (e.g., % stimulator output for rMT, ms for cSP, µV for MEP).