Focused Ultrasound Neuromodulation in Patients With Treatment-Resistant Depression

Inclusion Criteria: 1. Deemed to have the capacity to provide informed consent. 2. Aged between 18 and 65 years. 3. Diagnosis of major depressive disorder (MDD) according to DSM-5 criteria. 4. Total score \>20 on the Hamilton Depression Rating Scale (HAMD-17). 5. On a stable regimen of psychiatric medications for at least 30 days prior to enrollment. 6. Documented previous trial of at least two first-line antidepressant agents at adequate dose and duration, as assessed by two psychiatrists. 7. Documented previous trial of cognitive behavioral therapy (CBT) or psychotherapy for MDD, sustained for at least 6 weeks. Exclusion Criteria: 1. Pregnant or intending to become pregnant during the study period. 2. Diagnosis of a substance use disorder (excluding cannabis or nicotine) of moderate severity or greater, or when the substance is the primary focus of treatment, based on DSM-5 criteria. 3. Known active seizure disorder, significant head injury with an imaging-verified lesion 4. Unstable medical illness. 5. Not eligible for 3-Tesla MRI (i.e. MRI-incompatible pacemaker) 6. Inability to reliably attend required screening, treatment, or follow-up appointments. 7. Severe claustrophobia, as identified by the participant, that would prevent completion of MRI procedures.