Precision Closed-loop Brain-Computer Interface Neuromodulation for Treatment-Resistant Depression

Inclusion Criteria: * Age 18 to 70 years, regardless of sex. * At least primary school education and able to understand the content of the assessment scales. * Meet the diagnostic criteria for depressive disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). * Have a history of depression lasting at least 24 months and have received adequate-dose and adequate-duration treatment with at least 2 antidepressants for 8 weeks or longer, including electroconvulsive therapy without anesthesia, with a reduction rate in the HAMD-17 score of 20% or less after treatment. * Have a HAMD-17 score greater than 17 at baseline. * Have been on a stable regimen of the current antidepressant medication for at least 1 month before enrollment. * Meet at least one of the following three criteria: 1. Depression with onset before 18 years of age. 1. The age at first depressive episode was younger than 18 years, confirmed by a psychiatrist at the attending physician level or above according to the DSM-5 or International Classification of Diseases, 11th Revision (ICD-11) diagnostic criteria for depressive disorders. 2. The age at onset can be supported by at least one of the following sources: the participant's medical history report, previous medical records, or information about age at onset provided by a guardian. 3. If the onset age is unclear, confirmation requires consistency between at least two independent sources of information. 2. A clear history of self-injurious or suicidal behavior: 1. As confirmed by a guardian or through review of previous medical records, the participant has had clinically significant self-injurious behavior, such as cutting, burning, hitting oneself, involving intentional self-harm without the intent to die; or suicidal behavior or tendencies, such as recurrent suicidal ideation, suicidal planning, or a suicide attempt. 2. Such behavior or tendencies must be documented in, but not limited to, outpatient or inpatient medical records, psychological assessment records, or school or community referral records. Alternatively, they may be clearly described by a guardian and documented and confirmed in writing by the investigator. 3. A clear history of traumatic stress: 1. As confirmed by a guardian or through review of previous medical records, before the onset or worsening of depression, the participant experienced a situation meeting the DSM-5 definition of traumatic events, including but not limited to: actual or threatened death; serious injury; sexual violence; abuse; neglect; bullying; major accidents; war; natural disasters; intimate partner violence. 2. The traumatic event must have a clearly documented time of occurrence, type of event, and temporal relationship with the onset or worsening of depressive symptoms. 3. Standardized instruments such as life event questionnaires may be used as supplementary assessments. However, final eligibility determination must be made by the investigator based on comprehensive evaluation of: information provided by the legal guardian; previous medical records; clinical judgment. * Participants or their legal guardians must voluntarily sign the informed consent form and must be capable of completing follow-up assessments; * Participants assigned to the DBS group must pass preoperative evaluation for DBS surgery and must have no contraindications for neurosurgical procedures; * Participants assigned to the taVNS group must pass taVNS eligibility assessment, including: no recent facial or auricular injuries; no metallic implants in the head or heart; no active gastrointestinal symptoms; no acute exacerbation of respiratory disorders; no personal or family history of epilepsy; no frequent or severe headaches. Exclusion Criteria: * Previous diagnosis of: schizophrenia; schizoaffective disorder; substance dependence or drug addiction; mental disorders secondary to other medical conditions; or presence of significant psychotic symptoms, including delusions and hallucinations. * Presence of severe or unstable disorders involving the: central nervous system; cardiovascular system; respiratory system; liver; kidney; endocrine system; hematological system; or other major organ systems, which, in the investigator's judgment, make the participant unsuitable for enrollment. * Female participants who are: pregnant; breastfeeding; planning pregnancy during the study period or within 8 weeks after the last medication administration; or male participants with plans for reproduction during the study period. * Participation in another clinical trial within the previous 3 months. * Inability to undergo MRI examination. * MRI findings indicating any of the following: more than two lacunar infarcts; regional infarction lesions with a volume \>1 cm³; significant white matter lesions; a total Fazekas score of 3. * Severe aphasia, visual impairment, hearing impairment, or other conditions preventing completion of study procedures. * Any condition that, in the investigator's opinion, makes the participant unsuitable for participation in this study. * Contraindications to DBS surgery or chronic vagus nerve stimulation (VNS). * High suicide risk determined using the Columbia-Suicide Severity Rating Scale (C-SSRS). Participants will be excluded if any of the following criteria are met: 1. A suicide attempt within the previous 3 months; 2. Persistent active suicidal ideation with intent to act, as indicated by the C-SSRS assessment; 3. Emergency department visit or hospitalization due to suicide risk within 1 month prior to enrollment; 4. Baseline C-SSRS assessment indicates non-persistent active suicidal ideation, but the investigator determines, based on the intensity of suicidal intent score (C-SSRS Item 5) and clinical evaluation, that the participant has severely impaired impulse control and immediate suicide risk, confirmed by a psychiatric specialist.