Imaging Brain Fluids During Breathing

Study Overview
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Brief Summary
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This study will perform magnetic resonance imaging (MRI) measurements of hemodynamics and cerebrospinal fluid flow across breathing tasks and during breath-locked neuromodulation.

Detailed Description
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Cerebrospinal fluid (CSF) flow is essential for brain health, as it clears waste products from the brain. This study will investigate how breathing affects the flow of CSF around the brain. The investigators will perform high resolution magnetic resonance imaging (MRI) scans in participants who are breathing in specific patterns or performing simple tasks and test the effects on CSF flow. Participants will complete an imaging study visit in which the investigators will image their brain activity while they perform simple tasks, including paced breathing tasks. The participants will be split into two arms: (1) paced breathing (25 participants low resolution, 15 participants high resolution), (2) transcutaneous vagal nerve stimulation (25 participants low resolution, 15 participants high resolution). The MRI scans will take place in the 7 Tesla MRI scanner at Massachusetts General Hospital.

Official Title
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Neuroimaging the Impact of Respiration and Respiratory-gated Neuromodulation on Human Glymphatic Physiology

Conditions
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Healthy

Intervention / Treatment
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* Device: Transcutaneous vagal nerve stimulation
* Behavioral: Breathing task


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult age 18-70 years Exclusion Criteria: No ferrous metal implanted in head or body No history of major head trauma No neurological or psychiatric disorder Not using medication that affects brain function No implanted electronic devices (e.g. pacemaker) No implant that poses an MR contraindication Not pregnant, suspect they are pregnant, or seeking to become pregnant Not claustrophobic No piercings or jewelry that cannot be removed Does not weigh more than 250 pounds Normal or contact-corrected normal vision Exclusion for transcutaneous vagus nerve stimulation (tVNS) arm: Conditions of skin or anatomy that affect left auricle or forehead skin and could impact placement of electrodes for tVNS or forehead stimulation Diagnosis of significant cardiovascular or cerebrovascular disease [e.g. congestive heart failure, stroke, cardiac conduction disorders (including: bundle branch block, heart block, long Q-T syndrome), history of asystole or non-sustained ventricular tachycardia. Bradycardia (defined as resting heart rate <50 bpm) Hypotension defined as blood pressure <90/60 mmHg

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Breath task<br>Participants will breathe in specific patterns. | Behavioral: Breathing task<br>* Participants will be asked to breathe in specific patterns.<br>|
| Experimental: Transcutaneous vagal nerve stimulation<br>Participants will receive transcutaneous vagal nerve stimulation in specific patterns. | Device: Transcutaneous vagal nerve stimulation<br>* Noninvasive stimulation vs sham stimulation will be delivered via an auricular device.<br>Behavioral: Breathing task<br>* Participants will be asked to breathe in specific patterns.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| functional magnetic resonance imaging (fMRI) signals | fMRI measures of hemodynamic responses. Units: percent signal change | During study (2 hours) | 
| Cerebrospinal fluid (CSF) signals | MR-based measures of CSF signals. Units: percent signal change | During study (2 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate | Heart rate variability will be calculated. Units: milliseconds (ms) | During study ( 2 hours) | 
| Pulse oximetry | Amplitude of pulse oximetry signal. Units: arbitrary (no physical units are output by this system) | During study ( 2 hours) | 
| Respiratory physiology timing | Breath timing. Units: Hertz (Hz) | During study (2 hours) | 
| Respiratory physiology amplitude | Breath amplitude. Units: arbitrary (no physical units output by this sensor) | During study (2 hours) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glymphatics, Cerebrospinal fluid