This pilot study aims to identify the area of the brain best suited for the treatment of Borderline Personality disorder (BPD). The study investigators will test whether repetitiveTranscranial Magnetic Stimulation (rTMS), a gentle non-invasive brain stimulation method, can improve regulation of emotions and impulsivity in individuals with BPD.

This study will enroll up to 20 participants. Participant will be consented for the study remotely via a secure internet platform called Zoom. Participants will undergo 1 Magnetic Resonance Imaging or MRI scan and up to 3 brain stimulation of transcranial magnetic stimulation or TMS sessions, and cognitive behavioral testing on a computer.

Participants will complete 4 in-person visits over the course of up to 3 weeks.

Borderline personality disorder (BPD) is a serious neuropsychiatric illness with a prevalence of 1-5% in the general population. Two core symptoms of BPD are emotional dysregulation and increased impulsivity. These dysfunctions are associated with depression, anxiety, and impulsive acts, particularly acts of self-harm that may include suicide. Current treatment options for BPD include specialized psychotherapies and pharmacotherapy, which are of limited benefit for many patients. There is an urgent need for development of novel and more effective treatments.

BPD may arise from dysfunction of brain circuits involved in emotional regulation. A circuit-based treatment such as repetitive Transcranial Magnetic Stimulation (rTMS) holds promise for treatment of BPD. Several recent studies examined rTMS treatment in BPD and found it was well tolerated with encouraging signs of clinical efficacy. Advances in affective neuroscience, combined with progress in brain imaging and neuromodulation technology, make it possible to develop new circuit-based approaches to rTMS that could enhance efficacy for treatment for BPD. Evidence from task- based neuroimaging in BPD showed hyperactivity in the amygdala (a brain structure implicated in the generation of negative emotions) along with diminished top-down prefrontal-amygdala circuit control. These findings suggest that neuroimaging-guided rTMS stimulation of this circuit could enhance emotional regulation and behavioral control in patients with BPD and have greater therapeutic benefit.

This project aims to explore a novel circuit-based rTMS treatment protocol for BPD. 20 subjects with BPD will be recruited and undergo resting-state functional Magnetic Resonance Imaging (fMRI) to identify regions in the right and left ventrolateral prefrontal cortex (VLPFC) having strongest connectivity with the right and left amygdala. These will be used as individualized targets for neuronavigated excitatory intermittent theta burst (iTBS) rTMS of right, left, and bilateral VLPFC. Change in measures of impulse control and emotion regulation will be examined pre-post single rTMS sessions to determine which stimulation target(s) show the greatest VLPFC-amygdala circuit engagement.

The study investigators will examine the effects of right-sided, left-sided, and bilateral VLPFC stimulation in 20 subjects to determine which target(s) show the greatest signal of engagement of the VLPFC-amygdala network.

Inclusion Criteria:

• Age of 18-65
• DSM-5 Diagnosis of Borderline Personality Disorder (BPD) based upon a psychiatric evaluation and ZAN-BPD scale
• Fluent English speaker
• Ability to give informed consent

Exclusion Criteria:

• Medical conditions that prevent TMS or MRI to be performed safely upon evaluation by the study psychiatrist
• Active alcohol or drug abuse of such severity that it would pose a risk for TMS administration (i.e., unstable motor thresholds or increased risk for seizure)
• Active suicidal plan
• Current diagnosis of Psychotic or Bipolar disorders