Personalized Therapeutic Neuromodulation for Anhedonic Depression

Inclusion Criteria:

   1. Male or Female, between the ages of 18 and 80 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) or Bipolar Disorder type II
   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 (MSM).

   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. 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.

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

10. 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.

Exclusion Criteria:

   1. Pregnancy

   2. Primary psychiatric condition other than MDD requiring treatment except stable
   co-morbid anxiety disorder

   3. History of or current psychotic disorder or bipolar disorder

   4. Diagnosis of Intellectual Disability or Autism Spectrum Disorder

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

   6. Urine screening test positive for illicit substances

   7. Active suicidal ideation (defined as an MSSI > 8) or a suicide attempt within the past
   90 days

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

   9. Recent (during the current depressive episode) or concurrent use of rapid acting
   antidepressant agent (i.e., ketamine or a course of ECT)

10. 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

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

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

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

14. Any other condition deemed by the PI to interfere with the study or increase risk to
   the participant