Neuromodulation for Enhancement of Emotion Regulation in Bipolar Mood Disorders
Neuromodulation for Enhancement of Emotion Regulation in Bipolar Mood Disorders
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) 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 function from which to compare individual patients.
 During Phase 2, a cohort of 60 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 subregions showing
 activation deviations from healthy controls (Phase 1 data). Patient-specific VLPFC 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 be
 randomized to receive either low-dose iTBS-TMS (600 pulses; n=20), high-dose iTBS-TMS (1800
 pulses; n=20), or sham iTBS-TMS (n=20). Post-TMS fMRI scans will be acquired during
 performance on identical implicit and explicit emotion regulation tasks from baseline.
 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.