The proposed study is to evaluate the safety and initial efficacy of MRgFUS for patients with treatment-refractory Major Depression. This study is designed as a prospective, single arm, nonrandomized study. Assessments will be made before and after MRgFUS for adverse events related to treatment, for clinical symptom relief, and quality of life (QoL). The target in the brain chosen for ablation will be the anterior limb of the internal capsule (i.e 'capsulotomy').

Inclusion Criteria:

1. Men and women ≥20 and ≤80 years of age.

2. Patients who are able and willing to give consent and physically and practically able to attend study visits, as determined by both study Psychiatrist and the surgeon.

3. DSM-V diagnosis of major depressive episode, as a component of an Axis I disorder, such as Major Depressive Disorder, Bipolar Disorder, Anxiety Disorder, Eating Disorder, Substance Abuse/Dependence Disorder ,or Personality Disorder

4. At least 5-year illness history of the primary disorder and at least 6 months since the onset of the first episode of major depression.

5. A minimum score of 20 on the Hamilton Depression Rating Scale (HAMD) when depressed (patients with bipolar disorder may be rapid cycling, but have to have at least 2 weeks of major depression at the time the HAMD is conducted)

6. Medication-refractoriness as determined by an adequate dose and duration of standard psychiatric treatments (including psychotherapy and/or pharmacology) as determined by two psychiatrists associated with the study. Including specifically:

   1. Failed to respond or tolerate adequate trial of three or more medications accepted as first line in the treatment of depression
   2. Failed to respond or tolerate augmentation with or combination,of at least 2 medications known to be first line treatments for depression
   3. An adequate trial of cognitive behavioural therapy or other evidence-supported psychotherapy, delivered by a therapist experienced in treating depression

7. Able to communicate sensations during the ExAblate MRgFUS treatment

8. A consistent dose of any and all medications in the 30 days prior to study entry.

9. Women of childbearing potential must agree to use a contraception method throughout the study.

Exclusion Criteria:

1. Patients with unstable cardiac status [e.g. Unstable angina pectoris on medication, Patients with documented myocardial infarction within six months, Congestive heart failure requiring medication (other than diuretic), Patients on anti-arrhythmic drugs, Severe hypertension (diastolic BP > 100 on medication)]
2. Patients with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
3. Severely impaired renal function (estimated glomerular filtration rate < 30ml/min/1.73 m2) or receiving dialysis
4. Laboratory biochemical evidence of abnormal bleeding and/or coagulopathy, including risk factors for intraoperative or postoperative bleeding (platelet count less than 100,000 per cubic millimeter or abnormal INR)
5. Cerebrovascular disease (e.g. CVA within 6 months) or history of intracranial hemorrhage
6. Untreated, uncontrolled sleep apnea
7. Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage (e.g. Avastin) within one month of focused ultrasound procedure
8. Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment
9. Are participating or have participated in another clinical trial in the last 30 days
10. Patients unable to communicate with the investigator and staff.
11. Presence of significant cognitive impairment
12. Presence of psychosis on clinical evaluation.
13. Patients with brain tumors already known or revealed on pretreatment MRI
14. Currently pregnant (as determined by history and serum HCG) or lactating.