The purpose of this research is to understand how a neurostimulation technique, transcranial electrical stimulation (tES), affects brain function in adults with major depression measured with functional magnetic resonance imaging (fMRI). This study targets a specific kind of tES called transcranial direct current stimulation (tDCS), where a mild, constant current is passed between electrodes placed on the scalp.

This is an investigator-initiated MRI research study of a noninvasive neurostimulation technique, transcranial direct current stimulation (tDCS) using focal "high definition" (HD) electrodes positioned using pre-treatment MRI. Primary objective is to measure changes in brain function during MRI-guided HDtDCS with MRI. Secondary objective is to measure changes in depressive symptoms after five consecutive days of MRI-guided tDCS (20 minutes per session).

Inclusion Criteria:

• 1. Ages between 18 and 65
• 2. Race/ethnicity: all races and ethnic groups
• 3. Sex/Gender: all
• 4. Capacity to provide informed consent
• 5. Diagnosis of Major Depressive Disorder made by volunteer's physician at least one year prior (confirmed by patient self-report)
• 6. Currently under the care of a clinician for depression (psychiatrist, psychologist, or other clinician)
• 7. Currently experiencing symptoms of depression (Patient Health Questionnaire 9, PHQ9 >4 at screening; Hamilton Depression Rating Scale 17-item, HDRS-17, score >8 at Visit 1)
• 8. Stable or no pharmacological antidepressant regimen (SSRI, SNRI, MOAI, or tricyclic/TCA) with no change in treatment 6 weeks prior to study start

Exclusion Criteria:

• 1. Ages below 18 (neurobiology is quite different in children vs. adults)
• 2. Ages above 65 (cortical excitability changes with age)
• 3. Active suicidal thoughts, ideation, or behavior with plan within the past month (HDRS-17 item 3 score 3-4)
• 4. Change in antidepressant medication within 6 weeks of study start
• 5. Diagnosis of any medical condition potentially affecting brain function: neuropsychiatric or mental disorders, other mood disorders (bipolar disorder, primary anxiety disorder, PTSD), psychotic states or disorders, developmental disorders, neurological disorders, including mild cognitive impairment, significant head injury, significant history of alcohol/substance abuse or dependence within past 12 months, chronic pain (current, or for more than one year within the past one year), other major medical conditions (e.g., cancer, stroke).
• 6. MRI contraindications: metal or other implants that are not MR-safe, claustrophobia, pregnancy or suspected pregnancy
• 7. tES contraindications: skin conditions or injuries on the scalp hair extensions, wigs, braids, etc. that cannot be removed prior to the study, metal implants or pacemakers (also contraindicated for MRI)
• 8. Non-English speakers (due to written consent and questionnaires administered)
• 9. Neurostimulation or neuromodulation treatment for any reason within the past 3 months
• 10. Current medication use potentially affecting brain function, including decongestants, antihistamines, benzodiazepines or other anticonvulsants, anti-psychotics.
• 11. Prisoners will not participate in this study.