Overview

The purpose of this study is to investigate the responses of the brain region known as the subgenual anterior cingulate cortex (sgACC) during transcranial magnetic stimulation (TMS) in individuals with depression. Specifically, investigators aim to determine whether the sgACC is engaged when TMS is delivered to specific targets and if the engagement of sgACC changes throughout a full TMS treatment intervention. To achieve this goal, the investigators will employ a combination of TMS and Magnetic Resonance Imaging (MRI) procedures.

Study participation will include completing various questionnaires, clinical assessments, receiving a full transcranial magnetic stimulation (TMS) treatment intervention (every weekday for 6 weeks), and undergoing MRI scans, both with and without concurrent TMS.

Eligibility

Inclusion Criteria

1. 18-65 years old
2. DSM-5 diagnosis of major depressive (at least 90%) or persistent depressive disorder (no more than 10%) as per SCID clinical interview.
3. Patient Health Questionnaire-9 (PHQ-9) score = or > than 10
4. Comprehension of instructions in the English language.
5. Capacity to provide informed consent and follow study procedures.
6. Availability for the duration of the study.

Exclusion Criteria

1. Implanted medical devices, metallic implants, or drug infusion pumps that are not MRI-safe (e.g., aneurysm clips, defibrillators, or cochlear implants)
2. History of significant medical events (e.g., stroke, seizures, brain scarring) or neurological/neurodevelopmental conditions (e.g., epilepsy) that are contraindications for TMS and MRI or may adversely affect brain function and data interpretation.
3. Current psychosis, mania, or substance use disorder
4. Prior failed response to full rTMS or ECT/MST trial. Any successful prior treatments are acceptable and support a prognosis that a new rTMS treatment would be worth attempting.
5. Inability to complete an MRI scan (e.g., claustrophobia, inability to remain still for extended periods).
6. Inability to tolerate TMS administration
7. Significant handicaps that would interfere with testing procedures
8. Acute systemic infection, high fever
9. Acute sleep deprivation or medication/substance intoxication or withdrawal (TMS seizure risk)
10. Current use of cyclosporine, tacrolimus, or others that can cause leukoencephalopathy.
11. Pregnancy
12. Dialysis
13. Suicide attempt in past 6 months (safety precaution)
14. Current use of Bupropion (Wellbutrin) above 300 mg, benzodiazepines, lithium, monoamine oxidase inhibitors (MAOIs), and/or high doses of stimulant medication is exclusionary. Note: Exclusionary dosages or medications may be reduced or discontinued under the supervision of a medical provider. Participants must provide documentation confirming that their medical provider has agreed to oversee any medication changes, as abrupt changes can lower the seizure threshold and are contraindicated for TMS.
15. Transportation limits or physical limits to attending daily M-F treatment sessions.
16. Per study physician discretion medications likely to interfere with blood flow or otherwise compromise functional imaging measures.
17. Any other factor that in the investigators' judgment may affect patient safety or compliance (e.g. distance greater than 100 miles from procedure site; unlikely to be able to schedule daily treatment sessions, etc.)

In addition, during this study participants will be asked to:

1. Refrain from substance use (including marijuana and illicit drugs) for the duration of the study
2. Abstain from alcohol for 24 hours before study visits.
3. Maintain a consistent level of caffeine consumption throughout the study period and avoid any significant increases.
4. Not initiate, discontinue, or adjust any psychiatric medications or therapy treatments during the study period.
5. Inform the study team of any new medical treatments or prescribed medications (e.g., antibiotics) to allow for safety review and determination of continued eligibility for the study.