Accelerated Intermittent Theta-Burst Stimulation (aiTBS) in Treatment-Resistant Depression of Bipolar II Disorder

Inclusion Criteria:

1. Participants aged 18 years old to 80 years old with a primary diagnosis of bipolaraffective disorder II in a current major depressive episode, according to the criteriadefined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth FourthEdition, Text Revision (DSM-V).
2. Able to read, understand, and provide written, dated informed consent prior toscreening. Participants will be deemed likely to comply with study protocol andcommunicate with study personnel about adverse events and other clinically importantinformation.
3. Meet the criteria by Maudsley Staging Method score >=7
4. Not in a current state of hypomania (as assessed by the Young Mania Rating Scale) orpsychosis
5. In good general health, as ascertained by medical history.
6. Must have a stable psychiatrist during study enrollment, who confirms diagnosis ofbipolar II disorder.
7. Must be on a mood stabilizer regimen for 6 weeks prior to study enrollment and agreeto continue this regimen during study period
8. Meet the threshold on the MADRS, with a total score of >/=20 at screening/baseline.
9. TMS Naive
10. For females of reproductive potential: use of highly effective contraception for atleast 1 month prior to screening and agreement to use such a method during studyparticipation.
11. Agreement to adhere to Lifestyle Considerations throughout study duration. Lifestyle considerations:
12. Abstain from becoming pregnant from the screening visit (Visit 1) until after thefinal study visit (Visit 9).
13. Continue usual intake patterns of caffeine- or xanthine-containing products (e.g.,coffee, tea, cola drinks, and chocolate) without significant change for the durationof the study.
14. Abstain from alcohol for at least 24 hours before the start of each MRI and TMSsession. Participants who use tobacco products will be informed that use will be allowed only inbetween intervention sessions.

Exclusion Criteria:

1. Primary diagnosis other than bipolar II disorder
2. Any structural lesion e.g. structural neurological condition, more subcortical lesionsthan would be expected for age, stroke effecting stimulated area or connected areas orany other clinically significant abnormality that might affect safety, studyparticipation, or confound interpretation of study results.
3. Metal implant in brain (e.g. deep brain stimulation), cardiac pacemaker, or cochlearimplants
4. History of epilepsy or seizures
5. Shrapnel or any ferromagnetic item in the head
6. Pregnancy
7. Autism Spectrum disorder
8. Any current or past history of any physical condition which in the investigator'sopinion might put the subject at risk or interfere with study results interpretation
9. Active substance abuse (<1 week) or intoxication verified by toxicology screen--ofcocaine, amphetamines, benzodiazepines
10. Cognitive impairment (including dementia)
11. Current severe insomnia (must sleep a minimum of 5 hours the night before stimulation)
12. Current hypomania or psychosis
13. Showing symptoms of withdrawal from alcohol or benzodiazepines
14. A diagnosis of intellectual disability
15. Parkinsonism or other movement disorder determined by Principal Investigator tointerfere with treatment
16. Any other indication the Principal Investigator feels would comprise data.
17. Current active suicidal ideation or suicide attempt or suicidal behaviors in the last 6 months
18. Any history of psycho surgery for depression
19. Any history of ECT (greater than 8 sessions) without meeting responder criteria
20. Recent (within 4 weeks of any clinical effect) or concurrent use of rapid actingantidepressant agent (i.e., ketamine or a course of ECT)
21. Any history of myocardial infarction, CABG, CHF, or other cardiac history
22. The presence or diagnosis of prominent anxiety disorder, personality disorder ordysthymia
23. History of intractable migraine
24. Hypomania in the past 6 months.
25. Depth-adjusted aiTBS treatment dose > 65% maximum stimulator output (MSO)
26. Unstable symptoms between screening and baseline as defined by a 30% change in MADRS-Cscore.
27. Any other condition deemed by the PI to interfere with the study or increase risk tothe participant