# Cerebellar metabolism, neural circuits, and symptoms in bipolar disorder

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2020 · $544,605

## Abstract

Abstract
Bipolar disorder (BD) is a frequently devastating psychiatric illness that is challenging to diagnose and treat.
Identifying the underlying mechanisms of this illness may provide a foundation for better evidence-based
diagnostic and therapeutic techniques. For the first time in the context of psychiatric illness, we recently
explored the utility of a magnetic resonance imaging (MRI) strategy called T1 relaxation in the rotating frame
(T1ρ), which is highly sensitive to brain pH. We tested patients with BD in the euthymic state and found
prominent T1ρ differences compared to matched controls. More recently, we also imaged participants with BD
in depressed and manic states. These studies suggest that the brain area with the most prominent T1ρ
changes in bipolar disorder is the cerebellum, a structure has been previously suggested to contribute to BD
but has received relatively little attention compared to forebrain structures. Neuroanatomical models of BD
have largely overlooked the cerebellum despite compelling evidence that the cerebellum is strongly connected
to brain regions involved in the emotional control network that has been put forth as a model of the disorder.
We hypothesize that cerebellar activity plays a critical role in regulating mood in BD, which will be tested in this
proposal using a cross-sectional design and recruiting BD subjects across the mood spectrum as well as
matched controls. Participants will undergo psychiatric symptom assessment and brain imaging. Psychiatric
symptom assessments will include, the Montgomery-Asberg Depression Rating Scale (MADRS) and Young
Mania Rating Scale (YMRS). Brain imaging will include quantitative whole-brain T1ρ mapping, 31P- and 1H-
MRS of the cerebellar vermis, as well as diffusion imaging (DWI) and resting state fMRI. Medications will be
assessed and used as covariates in analyses. This data will be used to assess the following aims: Aim 1) Does
cerebellar activity play a significant role in mood regulation in BD? We hypothesize that the cerebellum plays a
significant role in maintaining a euthymic mood state (i.e., plays a compensatory role). We reason that if
cerebellar activity normalizes mood, then its activity should be greatest when BD participants are euthymic and
decrease with increasing mood symptom severity. Alternatively, if cerebellar activity drives abnormal moods,
then it is likely to be greatest in patients who are manic or depressed. Aim 2) Does connectivity of the
cerebellar vermis with the emotional control network differ with mood symptoms in BD? We hypothesize that
functional connectivity between the vermis and nodes of the emotional control network will vary with mood
state with increased connectivity in the euthymic state and decreased connectivity during exaggerated mood
states (depression/mania). We also expect that BD participants in the euthymic state will exhibit increased
connectivity relative to healthy controls. These results would provide further evi...

## Key facts

- **NIH application ID:** 9942506
- **Project number:** 5R01MH111578-04
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** VINCENT A MAGNOTTA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $544,605
- **Award type:** 5
- **Project period:** 2017-09-20 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9942506

## Citation

> US National Institutes of Health, RePORTER application 9942506, Cerebellar metabolism, neural circuits, and symptoms in bipolar disorder (5R01MH111578-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9942506. Licensed CC0.

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