Individualized (fMRI-guided) TMS Treatment for Depression

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.

Interested subjects will be asked to complete multiple questionnaires, a clinical interview, and a TMS demonstration to determine eligibility following the informed consent process.

If determined eligible, participants will proceed to undergo an MRI scan to generate their individualized TMS targets.The subsequent visit will involve the first MRI scanning session with concurrent TMS (TMS/fMRI), referred to as Baseline TMS/fMRI, along with the completion of multiple questionnaires.

Following the Baseline TMS/fMRI session, participants will begin the TMS treatment phase. This phase comprises daily sessions (Monday to Friday) for 6 weeks, during which participants will receive rTMS treatments and complete various surveys.

Midway through and upon completion of the TMS treatment intervention, two additional TMS/fMRI sessions will replicate the procedures conducted during the initial Baseline TMS/fMRI.

Remote follow-up assessments at 1, 6, and 12 months post-treatment will evaluate any enduring improvements in clinical symptoms.

Participants will be compensated for completing study procedures.

Eligibility Criteria:
Inclusion Criteria

1. 18-65 years old
2. Diagnosis of major depressive or persistent depressive disorder 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. Current psychosis, mania, or substance use disorder
2. Prior failed response to full repetitive Transcranial Magnetic Stimulation (rTMS) treatment or Electroconvulsive Therapy/Magnetic Seizure Therapy (ECT/MST) trial.
3. While SSRI (Selective Serotonin Reuptake Inhibitors) and SNRI (Serotonin-Norepinephrine Reuptake Inhibitors) medications are permitted, specific guidelines apply:

   * Patients taking lithium, antipsychotics, TCAIs, MAOIs, or atypical antidepressants will be excluded.
   * Participants taking benzodiazepines must abstain from taking them 24 hours before visits.
   * Patients taking Bupropion (Wellbutrin) above 350 mg will be excluded.
4. History of neurological disorder or traumatic brain injury (other than mild).
5. Unable to have an MRI scan, or current or prior medical condition that could interfere with the collection or interpretation of MRI data
6. Unable to receive or tolerate TMS
7. Implanted devices, such as an aneurysm clip or cardiac pacemaker
8. History of stroke, epilepsy, or brain scarring
9. Pregnant, nursing, or trying to become pregnant (self-attestation alone)
10. Acute sleep deprivation or medication/substance intoxication or withdrawal (TMS seizure risk)
11. Current use of stimulants, cyclosporine, tacrolimus (or others that can cause leukoencephalopathy). Stimulants for ADHD/ADD will be considered on a case-by-case basis per PI discretion.
12. Dialysis
13. Transportation limits or physical limits to attending daily M-F treatment sessions
14. Per study physician discretion medications likely to interfere with blood flow or otherwise compromise functional imaging measures

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 the MRI scans
3. Abstain from increasing caffeine intake or beginning any new medications