# Neuroimaging the impact of respiration and respiratory-gated neuromodulation on human glymphatic physiology

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $783,130

## Abstract

Project summary:
 The flow of cerebrospinal fluid (CSF) through the brain is essential for maintaining brain health, and
clears metabolic waste products through the glymphatic system. Disruption of this clearance process is
associated with multiple neurodegenerative disorders, notably Alzheimer’s disease. Two key mechanisms
underlying CSF flow in humans are the respiratory cycle, and coherent neural activity. This project aims to
determine whether synergistic drive of respiration and neural activity enhances CSF flow in the human brain.
We will test how spontaneous respiration is associated with CSF flow and test whether slower breathing drives
higher flow. We will then use respiratory-gated transcutaneous vagal nerve stimulation, a noninvasive
neuromodulation technique to stimulate neural activity, integrating both respiratory and neural activity to
optimally drive CSF flow. Finally, we will test how respiration and respiratory-gated neurostimulation modulate
flow both in the large ventricles, and in the tiny perivascular spaces that are essential for brain clearance, using
a new fMRI-based imaging technique with high temporal resolution to measure rhythmic dynamics in
perivascular flow. Together, these studies will establish how modulation of respiration and neural activity in
concert drives CSF flow through the brain. This work will provide the foundation for future clinical investigations
testing whether noninvasive stimulation integrating neural and respiratory rhythms can improve clinical
outcomes and protect against development of neurological disorders such as Alzheimer’s disease.

## Key facts

- **NIH application ID:** 10600980
- **Project number:** 5R01AT011429-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Laura Diane Lewis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $783,130
- **Award type:** 5
- **Project period:** 2021-04-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10600980

## Citation

> US National Institutes of Health, RePORTER application 10600980, Neuroimaging the impact of respiration and respiratory-gated neuromodulation on human glymphatic physiology (5R01AT011429-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10600980. Licensed CC0.

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