# Linking membrane voltage dynamics to fMRI measurement of functional connectivity in resting state and task related activities

> **NIH NIH F31** · EMORY UNIVERSITY · 2024 · $48,974

## Abstract

PROJECT ABSTRACT
Functional connectivity (FC) has been found to be altered in a wide range of otherwise indistinguishable disease
states. The most common tool to non-invasively study the organization of brain-wide FC networks is functional
magnetic resonance imaging (fMRI). fMRI relies on an indirect and indiscriminate measure of activity through
the blood oxygen level-dependent (BOLD) contrast mechanism. By capturing fluctuations in the BOLD signal
fMRI can detect distant synchronization between brain regions either at rest or during the performance of a
specific task. These regions are inferred to be functionally connected and are thought to involve the synchrony
of neuronal populations involved in a common function that are wired together through plasticity. Interpretation
of FC networks derived from BOLD fMRI studies is currently limited by 1) the dependence of fMRI BOLD signals
on hemodynamic changes as a proxy for neural activity and 2) a limited understanding of the mechanistic basis
for FC in the context of behaviorally relevant longitudinal reorganizations. My long-term goal is to better
understand the relationship between BOLD and neural activity in behaviorally relevant multi-regional circuits to
advance brain network analysis. Once we know how both vascular and neural changes influence FC, the basis
for network dysfunctions can be exploited with fMRI providing more robust fMRI-based disease detection.
In this proposed project, I will use EMX1-Cre mice expressing a novel JEDI-1P voltage fluorescent protein in
excitatory neurons across dorsal cortex. This voltage sensor has a large spectral band, allowing us to record
both slow, subthreshold voltage activity, and fast gamma band activity. Wide-field optical imaging will be
combined with fMRI to link neuronal changes in FC to hemodynamic changes measured with fMRI. In Aim 1 I
will image these JEDI-1P at resting state to establish the correspondence between membrane voltage dynamics
and fMRI for resting state functional connectivity networks. In Aim 2 I will train these mice to perform a
sensorimotor task. I will image them during task training to assess changes in FC due to learning. I hypothesize
that the correlation between fMRI BOLD and neural activity will be regionally specific for both resting state and
task training, the latter will result in a measurable strengthening of FC between task-relevant areas. Completion
of these aims will determine how functional networks observed with BOLD relate to neural activity and will provide
insights into how FC reflects behaviorally relevant changes in the learning of a sensorimotor task. This results in
a sharper understanding of the properties of neural network activity, its dependencies, and how to harness it in
future fMRI studies.

## Key facts

- **NIH application ID:** 11009493
- **Project number:** 5F31NS134314-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Lisa M Meyer-Baese
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11009493

## Citation

> US National Institutes of Health, RePORTER application 11009493, Linking membrane voltage dynamics to fMRI measurement of functional connectivity in resting state and task related activities (5F31NS134314-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11009493. Licensed CC0.

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