The investigators are conducting this research study to better understand how individuals with bipolar disorder regulate their emotions, and if transcranial magnetic stimulation (TMS) can help improve emotion regulation for individuals with bipolar mood disorders.

The objective of this study protocol is to test whether intermittent theta-burst transcranial magnetic stimulation (iTBS-TMS) to ventrolateral prefrontal cortex (VLPFC) or inferior parietal lobule (IPL) can improve performance on emotion regulation tasks in patients with bipolar disorder. Results from this study will help inform future treatment development to improve emotion regulation in patients with bipolar disorder. The study will proceed in two phases: During Phase 1, a cohort of 30 healthy control subjects will be recruited in order to establish a normative sample from which to compare patient data. Functional magnetic resonance imaging (fMRI) data will be collected from healthy control participants during performance on two emotion regulation tasks (probing implicit and explicit emotion regulation). Data from these subjects will provide a normative distribution of VLPFC and IPL function from which to compare individual patients. During Phase 2, a cohort of 30 patients diagnosed with bipolar disorder will be recruited. Patient participants will perform the same two emotion regulation tasks during fMRI scanning. Data from individual patients will be analyzed to detect specific VLPFC and IPL subregions showing activation deviations from healthy controls (Phase 1 data). Patient-specific VLPFC and IPL subregions showing patterns of activation greater than two standard deviations from healthy controls will be used as individualized target sites for TMS stimulation. Patients will then receive high-dose iTBS-TMS (1800 pulses) of the VLPFC and IPL, and sham iTBS-TMS to the dorsomedial prefrontal cortex (dmPFC) across three separate study visits. Order of target stimulation will be randomized across participants. TMS sessions will take approximately 10 minutes and will be immediately followed by an fMRI scanning session, during which participants will again complete the implicit and explicit emotion regulation tasks. TMS sessions will take place in the scanning bay to enable quick transition to the fMRI task. Baseline scanning sessions and either active TMS-fMRI or sham TMS-fMRI sessions will occur on separate days, no more than two weeks apart. Effects of iTBS-TMS on emotion regulation will be evaluated by comparing pre-TMS versus post-TMS behavior, neural activation, and functional connectivity patterns during performance on implicit and explicit emotion regulation tasks.

Inclusion Criteria (Healthy Controls)

1. Male or female age 18-55
2. No history of psychiatric disorder, as assessed using the Mini-International Neuropsychiatric Interview (MINI).
3. Non-Clinical Levels of Emotion Dysregulation, as assessed using the Difficulties in Emotion Regulation Scale (DERS) Non-clinical levels of emotion dysregulation will be defined as a score < 80 on the DERS.

Exclusion Criteria (Healthy Controls)

1. Current or history of psychiatric disorders
2. Endorsement of clinical levels of emotion dysregulation
3. Current or history of: organic mental disorder; substance abuse within the past 12 months and/or history of substance abuse for > 1 year; past or current substance dependence (including alcohol); schizophrenia; delusional disorder; and psychotic disorders.
4. Current pregnancy.
5. Medical illness or non-psychiatric medical treatment that would likely interfere with study participation
6. Neurologic disorder, prior neurosurgical procedure, prior electroconvulsive therapy (ECT) or TMS, history of seizures or head trauma.
7. Presence of metallic implants that would interfere with safety during fMRI scanning.

Inclusion Criteria (Bipolar Disorder Group)

1. Male or female age 18-55

2. Diagnosis of Bipolar I Disorder (BD-I), as assessed through MINI.

3. Current mood state euthymic.

   a. Hamilton-Depression Rating Scale (HAM-D-17) and Young Mania Rating Scale (YMRS) will be used to assess current depressive and manic symptoms. Euthymia will be defined as a HAM-D-17 score <10 and YMRS score <12.

4. Clinical Levels of Emotion Dysregulation, as assessed using the DERS. Clinical levels of emotion dysregulation will be defined as a score > 80 on the DERS.

Exclusion Criteria (Bipolar Disorder Group)

1. Current symptoms of mania or depression (YMRS score >12, HAM-D-17 score >10).
2. Medication instability (<3 months).
3. Current or history of: organic mental disorder; substance abuse within the past 12 months and/or history of substance abuse for > 1 year; past or current substance dependence (including alcohol), verified by urine toxicology screen; schizophrenia; delusional disorder; and psychotic disorders.
4. Current pregnancy.
5. Medical illness or non-psychiatric medical treatment that would likely interfere with study participation
6. Neurologic disorder, prior neurosurgical procedure, prior ECT or TMS, history of seizures or head trauma.
7. Presence of metallic implants that would interfere with safety during fMRI scanning.

Masking will be implemented using a active-placebo TMS coil.