# Targeting Emotion Regulation in Bipolar Disorder with Intermittent Theta Burst Stimulation: A Mechanistic Study

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $808,186

## Abstract

PROJECT SUMMARY/ABSTRACT
Individuals with bipolar disorder (BD) experience severe and episodic disruptions in regulatory control of
emotion (emotion regulation, ER) that exacerbate symptoms in BD across depressed, manic, and euthymic
states and interfere with mood stability over time. Emotion dysregulation in BD is associated with maladaptive
functioning, interpersonal problems, decreased work productivity, and suicidal ideation and behavior. The
development of rapid-acting alternative treatment options that improve ER are important to help achieve and
sustain remission and improve long-term functioning in individuals with BD. In this mechanistic study, we will
test whether stimulating the inferior parietal lobule (IPL), a key region within the neurocircuitry supporting ER,
with a rapid and robust form of transcranial magnetic stimulation (accelerated intermittent theta-burst
stimulation, aiTBS), will increase ER in depressed patients with BD, as indexed by increased IPL-ER
neurocircuit functional connectivity and improved performance on ER-related behavioral tasks. Using functional
magnetic resonance imaging (fMRI) and ER-related computer tasks before and after active versus sham
aiTBS, Aim 1 of the project will examine ER-related brain network changes following aiTBS using resting
state functional magnetic resonance imaging (fMRI) before and after aiTBS. Aim 2 of the project will examine
ER behavior-based changes following aiTBS and the relationship to brain network changes using ER-related
behavioral tasks measured before and after aiTBS. We will additionally examine changes in brain activation
associated with ER behavior during an in-scanner task pre and post aiTBS; changes in functional connectivity
within the broader ER-related neurocircuitry (e.g. ventrolateral prefrontal cortex, amygdala) following aiTBS;
and the effects of baseline patient characteristics relevant to ER on outcomes (emotion reactivity, executive
function, impulsivity, approach/avoidance, interoceptive awareness). Patients will be randomized to either
active or sham aiTBS and will receive 6 sessions of high dose (1800 pulses) iTBS per day over a course of 4
days. Patients will be scanned at baseline and 3 days post aiTBS to measure the neuroplastic effects of
aiTBS. To increase the potential clinical utility of findings from this study, we will examine the effects of aiTBS
to the IPL in a sample of BD patients who are currently depressed, the most common and chronic mood state
in this population. If we can show stimulation of the IPL engages the broader neurocircuitry supporting adaptive
ER and affects ER-related behavior in depressed patients with BD, this will be an important first step towards
validating this target for the treatment of ER deficits in BD, and towards future validation of this approach in
maintaining mood stability in BD.

## Key facts

- **NIH application ID:** 10856350
- **Project number:** 1R01MH136276-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Kristen K Ellard
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $808,186
- **Award type:** 1
- **Project period:** 2024-06-05 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10856350

## Citation

> US National Institutes of Health, RePORTER application 10856350, Targeting Emotion Regulation in Bipolar Disorder with Intermittent Theta Burst Stimulation: A Mechanistic Study (1R01MH136276-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10856350. Licensed CC0.

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