Establishing a Dose-response Relationship With Accelerated Transcranial Magnetic Stimulation

Inclusion Criteria:

   1. Male or Female, between the ages of 22 and 65 at the time of screening.

   2. Able to read, understand, and provide written, dated informed consent prior to
   screening. Proficiency in English sufficient to complete questionnaires / follow
   instructions during fMRI assessments and aiTBS interventions. Stated willingness to
   comply with all study procedures, including availability for the duration of the
   study, and to communicate with study personnel about adverse events and other
   clinically important information.

   3. Currently diagnosed with Major Depressive Disorder (MDD) and meets criteria for a
   Major Depressive Episode, according to the criteria defined in the Diagnosis and
   Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).

   4. Medical records confirming a history of moderate to severe treatment-resistance as
   defined by a score of 7-14 on the Maudsley Staging Method (MSM3).

   5. MADRS score of ≥20 at screening (Visit 1).

   6. TMS naive.

   7. Access to ongoing psychiatric care before and after completion of the study.

   8. Access to clinical rTMS after study completion.

   9. Must be on a stable antidepressant therapeutic regimen for 6 weeks prior to study
   enrollment and agree to continue this regimen throughout the study period.

10. In good general health, as evidenced by medical history.

11. For females of reproductive potential: use of highly effective contraception for at
   least 1 month prior to screening and agreement to use such a method during study
   participation.

12. Agreement to adhere to Lifestyle Considerations throughout study duration.

Lifestyle considerations:

   1. Abstain from becoming pregnant from the screening visit (Visit 1) until after the
   final study visit (Visit 9).

   2. Continue usual intake patterns of caffeine- or xanthine-containing products (e.g.,
   coffee, tea, cola drinks, and chocolate) without significant change for the duration
   of the study.

   3. Abstain from alcohol for at least 24 hours before the start of each MRI and TMS
   session. Participants who use tobacco products will be informed that use will be
   allowed only in between intervention sessions.

Exclusion Criteria:

   1. Pregnancy

   2. Primary psychiatric condition other than MDD requiring treatment except stable
   comorbid anxiety disorder

   3. History of or current psychotic disorder or bipolar disorder

   4. Severe borderline personality disorder.

   5. Diagnosis of Intellectual Disability or Autism Spectrum Disorder

   6. Current moderate or severe substance use disorder or demonstrating signs of acute
   substance withdrawal

   7. Urine screening test positive for illicit substances

   8. Active suicidal ideation (defined as an MSSI > 8) or a suicide attempt (as defined by
   the C-SSRS) within the past one year

   9. Any history of ECT (greater than 8 sessions) without meeting responder criteria

10. Recent (within 4 weeks of any clinical effect) or concurrent use of rapid acting
   antidepressant agent (i.e., ketamine or a course of ECT)

11. History of significant neurologic disease, including dementia, Parkinson's or
   Huntington's disease, brain tumor, seizure disorder, subdural hematoma, multiple
   sclerosis, or history of significant head trauma

12. Untreated or insufficiently treated endocrine disorder.

13. Contraindication to receiving rTMS (e.g., metal in head, history of seizure, known
   brain lesion)

14. Contraindication to MRI (ferromagnetic metal in their body)

15. Treatment with another investigational drug or other intervention within the study
   period

16. Depth-adjusted aiTBS treatment dose > 65% maximum stimulator output (MSO)

17. Unstable symptoms between screening and baseline as defined by a ≥ 30% change in
   MADRS-S score.

18. Any other condition deemed by the PD to interfere with the study or increase risk to
   the participant