# Neuroinflammation and Executive Function in Bipolar Disorder: A PET-fMRI Study

> **NIH NIH K23** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $199,768

## Abstract

Individuals with bipolar disorder (BD) experience severe and persistent difficulties with executive functions, such
as inhibitory control. Inhibitory control difficulties in BD could be related to inflammation via its effects on brain
functioning. However, direct measurement of brain inflammation markers (i.e. glial activation) in BD is limited
and further understanding of how glial activation contributes to inhibitory brain dysfunction in BD is needed. The
goal of this proposal is to study the neuroinflammatory basis of inhibitory control and identify novel neuroimmune
treatment targets for executive dysfunction in mood disorders. To this end, the candidate proposes: (1) training
objectives to establish expertise in the use of simultaneous PET-MRI as a research tool, an interdisciplinary
knowledge base in psychoneuroimmunology, and full independence with fMRI methodology, which together will
further career development into an expert clinical translational researcher in bipolar disorder; (2) a research
objective to examine glial activation as a mechanism of inhibitory control brain dysfunction and cognitive
performance in BD; (3) a team of mentors and advisors to ensure the candidate’s success, with expertise in
bipolar disorder (Dr. Andrew Nierenberg), multi-modal psychiatric neuroimaging (Dr. Darin Dougherty), molecular
imaging and simultaneous PET-fMRI (Dr. Jacob Hooker), psychiatric neuroimmunology (Dr. Beth Stevens), fMRI
inhibitory control paradigms (Dr. Scott Langenecker), and neuroimaging statistics (Dr. Mark Vangel). The
rationale for the proposed project is that despite evidence for inflammatory alterations in BD, interrogation of
brain inflammatory markers in-vivo and their role in executive functioning is limited. Human imaging with novel
radiopharmaceuticals to visualize glial activation and its role in inhibitory brain function is needed. The central
hypothesis of the proposal is that glial activation adversely impacts frontostriatal brain circuitry and, in turn,
inhibitory control in BD. The proposed specific aims are to determine the: (1) difference in glial activation
between BD (n = 20) and healthy controls (HC; n = 20); (2) association between glial activation and inhibitory
control neural circuitry in BD; (3) association between glial activation and inhibitory control performance on
cognitive testing in BD. This proposed research is innovative for examining markers of brain inflammation as a
novel mechanism of the understudied burden of executive function in BD using cutting edge simultaneous PET-
fMRI technology. The proposed research is significant because it could yield novel neuroimmune treatment
targets and crucial pilot data towards the use of PET-fMRI for understanding the unmet clinical problem of
inhibitory dysfunction in BD. Overall, this project and training plan will promote the candidate’s career
development by facilitating an independent program of program of research at the interface of psychiatric
neuroimaging ...

## Key facts

- **NIH application ID:** 10319012
- **Project number:** 5K23MH122676-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Amy Peters
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $199,768
- **Award type:** 5
- **Project period:** 2020-12-15 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10319012

## Citation

> US National Institutes of Health, RePORTER application 10319012, Neuroinflammation and Executive Function in Bipolar Disorder: A PET-fMRI Study (5K23MH122676-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10319012. Licensed CC0.

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