The habenula (Hb) is an ancient structure, located at the center of the dorsal diencephalic conduction system, a pathway involved in linking forebrain to midbrain regions. An increasing number of studies indicated that the lateral habeluna (LHb) is overactivity during depressive behaviors in rats, where it could drive the changes in midbrain monoamine neurotransmitter linked to depression. However, the efficiency and mechanism of deep brain stimulation (DBS) of the LHb and/or its major afferent bundle (i.e., stria medullaris thalami) could treat treatment-resistant major depression (TRD) is still unclear. This research will investigate the effectiveness and mechanism of bilateral MRI Compatible and Long-term LFP Recordable DBS to habenula and/or its major afferent bundle for treatment TRD patients.

Inclusion Criteria:

• Age 18-70 years old;
• DSM-IV diagnosis of Major depression disorder of psychiatrists;
• More than 3 year's history of depression and failure to respond to a minimum of three different antidepressant treatments;
• Failure or intolerance or unwilling of an adequate course of electroconvulsive therapy (ECT) during any episode;
• HAMD-17≥20;
• GAF≤50；
• Capacity to provide informed consent (understanding of the study purpose and methods);

Exclusion Criteria:

• Obvious medical and psychiatric comorbidities;
• Alcohol or substance abuse/dependence within 12 months;
• Antisocial personality disorder, dementia, current tic disorder;
• Subject has a history of 2 or more suicide attempts < 12 months prior to the screening testing;
• Pregnancy and/or lactation;
• There are contraindications for DBS surgery and chronic stimulation.