The purpose of this study is to investigate the effectiveness of accelerated intermittent theta-burst transcranial magnetic stimulation (aiTBS) in inducing anti-depressant responses in individuals with treatment-resistant depression of bipolar II disorder. This is a double-blind, randomized, sham-controlled trial that targets a single location on the left dorsolateral prefrontal cortex (LDLPFC) using the MagPro rTMS system.

The aim of this study is to assess the efficacy of aiTBS applied to the left dorsolateral prefrontal cortex (L-DLPFC) in reducing depressive symptoms in individuals with bipolar II disorder, and to determine the neural functional connectivity changes that underlie treatment response. A total of 60 individuals with bipolar II disorder who are currently experiencing a depressive episode will be recruited for the study.

The accelerated iTBS (aiTBS) treatment will consist of 10 sessions, administered daily over a period of 5 consecutive days. Before and after the stimulation, magnetic resonance imaging (MRI) scans, electroencephalograms (EEG), and heart rate variability (HRV) will be collected. The severity of depressive symptoms will be evaluated using both clinician-rated and self-report assessments.

Inclusion Criteria:

1. Participants aged 18 years old to 80 years old with a primary diagnosis of bipolar affective disorder II in a current major depressive episode, according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Fourth Edition, Text Revision (DSM-V).
2. Able to read, understand, and provide written, dated informed consent prior to screening. Participants will be deemed likely to comply with study protocol and communicate with study personnel about adverse events and other clinically important information.
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) or psychosis
5. In good general health, as ascertained by medical history.
6. Must have a stable psychiatrist during study enrollment, who confirms diagnosis of bipolar II disorder.
7. Must be on a mood stabilizer regimen for 6 weeks prior to study enrollment and agree to 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

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. Primary diagnosis other than bipolar II disorder
2. Any structural lesion e.g. structural neurological condition, more subcortical lesions than would be expected for age, stroke effecting stimulated area or connected areas or any other clinically significant abnormality that might affect safety, study participation, or confound interpretation of study results.
3. Metal implant in brain (e.g. deep brain stimulation), cardiac pacemaker, or cochlear implants
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's opinion might put the subject at risk or interfere with study results interpretation
9. Active substance abuse (<1 week) or intoxication verified by toxicology screen--of cocaine, 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 to interfere 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 acting antidepressant agent (i.e., ketamine or a course of ECT)

22. Any history of myocardial infarction, CABG, CHF, or other cardiac history

23. The presence or diagnosis of prominent anxiety disorder, personality disorder or dysthymia

24. History of intractable migraine

25. Hypomania in the past 6 months.

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

27. Unstable symptoms between screening and baseline as defined by a 30% change in MADRS-C score.

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

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