The investigators are conducting this research study to better understand how individuals with bipolar disorder regulate their emotions, and if the study can use a technique called "transcranial magnetic stimulation" or TMS to help improve emotion regulation for individuals with bipolar disorder.

Emotion dysregulation contributes to the development and maintenance of a wide range of psychopathology, but is especially relevant for individuals with bipolar mood disorders (BD). These individuals experience severe and episodic emotion dysregulation associated with maladaptive functioning, interpersonal problems, decreased work productivity, and suicidal ideation and behavior. To date, both pharmacological and psychosocial treatments fail to normalize emotion dysregulation for many bipolar patients. As a consequence, all too many experience poor outcomes. Thus, there is a significant need for new innovative approaches to target and improve emotion dysregulation in bipolar patients. Non-invasive neuromodulation using transcranial magnetic stimulation (TMS) may provide a viable strategy to help improve emotion dysregulation in bipolar mood disorders. As a first step to test this hypothesis, the current proposal seeks to experimentally identify specific neural target sites for improving emotion regulation using TMS. If the investigators can demonstrate target engagement of emotion regulation at the behavioral level using TMS, this will provide an important first step towards examining the potential utility of TMS as a viable strategy to help improve emotion dysregulation in bipolar mood disorders. While this is not a definitive clinical trial, the sham-controlled double-crossover design of this study will provide valuable information for target site selection for the development of TMS as an intervention strategy to improve emotion dysregulation in BD.

Inclusion Criteria:

• Patients

  • Men and women
  • Ages 18-50 years
  • Patients diagnosed with bipolar I disorder (BD-I), current mood state euthymic.
  • On a stable psychiatric medication regimen for at least a month prior to and during study participation

Healthy Controls:

• Men and women
• Ages 18-50 years
• Without major psychiatric illness

Exclusion Criteria:

• Patients

  • Any change in psychiatric medications within a month prior to and during study participation

  • Legal or mental incompetency

  • Intellectual disability

  • Current manic (YMRS > 12) or severe depressive episode (HAM-D-17 > 5)

  • Substance use disorder (abuse or dependence) with active use within the last 3 months

  • Significant medical or neurological illness

  • Prior neurosurgical procedure

  • History of seizures

  • History of ECT treatment or clinical TMS within the past three months

  • Implanted cardiac pacemakers

  • Patients who have conductive, ferromagnetic or other magnetic-sensitive metals implanted in their head or neck, or are non-removable and within 30 cm of the treatment coil. These include:

    • Aneurysm clips or coils
    • Carotid or cerebral stents
    • Metallic devices implanted in the head (e.g. Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit, or ventriculo-peritoneal shunt)
    • Magnetically active dental implants
    • Cochlear/otologic implants
    • CSF shunts
    • Ferromagnetic ocular implants
    • Pellets, bullets, fragments less than 30 cm from the coil
    • Facial tattoos with metallic ink, permanent makeup less than 30 cm from the coil

  • Pregnant women

Healthy Controls:

• History of major psychiatric illness, including psychosis

• Has a first-degree relative with psychosis

• Active use of neuropsychoactive medications

• Legal or mental incompetency

• Intellectual disability

• Substance use disorder (abuse or dependence) with active use within the last 3 months

• Significant medical or neurological illness

• Prior neurosurgical procedure

• History of seizures

• History of ECT treatment or clinical TMS within the past three months

• Implanted cardiac pacemakers

• Individuals who have conductive, ferromagnetic or other magnetic-sensitive metals implanted in their head or neck, or are non-removable and within 30 cm of the treatment coil. These include:

  • Aneurysm clips or coils
  • Carotid or cerebral stents
  • Metallic devices implanted in the head (e.g. Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit, or ventriculo-peritoneal shunt)
  • Magnetically active dental implants
  • Cochlear/otologic implants
  • CSF shunts
  • Ferromagnetic ocular implants
  • Pellets, bullets, fragments less than 30 cm from the coil
  • Facial tattoos with metallic ink, permanent makeup less than 30 cm from the coil

• Pregnant women

From enrollment until end of Visit 3, up to 4 weeks.

Adverse events are evaluated by the PI and actions are taken guided by the principles of Human Subjects research. An adverse event report is submitted to the IRB and regulatory officials using the Research Subject Report of Adverse Event form, according to the PHRC reporting guidelines, within 5 working days or 7 calendar days of the date they become aware of the problem.

The current study is intended to collect pilot data and therefore uses a small sample, which limits the interpretability of the results. All results from this study should thus be interpreted with caution.

Participants are blinded to whether they received active versus sham (placebo) TMS.