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NCT Number: NCT07470099

The Role of Breathing Perception in Respiratory Control

Warfighters are frequently exposed to environments and life-support systems that increase breathing resistance and the work of breathing (WOB), such as aircraft on-board oxygen generation systems and underwater breathing apparatuses. Elevated WOB then increases the perception of breathing difficulty (dyspnea) and has been associated with impaired cognitive performance, including slower reaction time and reduced accuracy during attention-demanding tasks. These effects are particularly concerning in operational settings that require rapid decision-making and precise motor responses.

Despite growing recognition of this issue, critical gaps remain regarding strategies to mitigate the perceptual and cognitive consequences of elevated inspiratory resistance, especially under realistic operational stressors. The objective of this experiment is to determine whether modifying the sensory perception of breathing alters breathing perception and cognitive performance during inspiratory resistance. Auditory feedback of ventilation will be manipulated (normal, reduced, or amplified) to assess whether altering breathing-related sensory input affects breathing perception and cognitive performance without changing mechanical load.

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Key information

Conditions

Age range

18 year–40 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

In some instances, reducing inspiratory resistive loads (e.g., OBOGs, SCUBA) for Warfighters may not be feasible, but understanding how breathing perception is affected by resistance is essential. Auditory feedback of ventilation significantly influences breathing awareness, and as the WOB increases, this perception intensifies due to enhanced auditory input. This heightened awareness can distract and tax cognitive processing. Recent studies indicate that auditory distractions, like music during exercise, can lessen dyspnea and respiratory and whole-body discomfort in healthy individuals and those with chronic obstructive pulmonary disease. This effect may stem from reduced auditory feedback or improved emotional states linked to music. However, a key knowledge gap exists: it is unclear whether reducing auditory feedback of ventilation during increased inspiratory resistance affects breathing perception and cognitive function. The study will assess the impact of different auditory feedback of ventilation conditions (normal, eliminated via noise distraction, and amplified) on cognitive function under high inspiratory resistance. It's hypothesized that reducing auditory feedback of ventilation will not alter the WOB but will decrease breathing perception and enhance cognitive performance compared to standard or amplified feedback.

Participants will complete two study visits: a screening/familiarization visit (Study Day 0) followed by one experimental visit (Study Day 1). Participants will be instructed to avoid caffeine, alcohol, stimulant medication, pain/anti-inflammatory medication, cannabis and cannabis related products, and vigorous exercise for at least 24 hours prior to experimental visits. On Study Day 0, participants will complete a short familiarization breathing task in which they will breathe for 10 minutes through an 8-10mm hole at the end of a customized device, generating a pre-determined inspiratory resistance of 6-9.5 centimeters of water per liter per second (cmH2O/L/s). During the breathing task, cerebral vascular, cardiovascular and autonomic activity responses will be measured. Every 5 minutes during the breathing test, participants will be asked to rate breathing intensity and unpleasantness, and perform an inspiratory capacity maneuver. Cognitive assessments will be administered every 10 minutes. After the breathing task, participants will complete lung and respiratory muscle function tests.

Prior to Study Day 1 (the experimental visit), participants will be randomized to the order in which they are exposed to the interventional conditions (ambient/normal auditory feedback, enhanced auditory feedback, or removed auditory feedback with replacement of a self-selected music playlist). Upon arrival, an esophageal balloon will be placed to measure the pressure around the heart and lungs. Participants will then complete three full-length breathing tasks, in which they inspire against a predetermined resistive load for 60 minutes, with auditory conditions in the order of randomization. Biometric monitoring, cognitive tasks and participant ratings during the breathing tasks will be completed with the same frequency as Study Day 0. A 1-hour rest period will be observed between the breathing tasks.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Between the ages of 18-40 years old.
  • English speaking and reading.
  • Self-reported weekly activity of at least 120 minutes/week of high intensity exercise for the previous 2 years.
  • Normal pulmonary function assessed by a resting forced expiratory volume in 1 second over forced vital capacity (FEV1/FVC) > 75% of predicted.
  • Normal cognitive function assessed using the Montreal cognitive function test [18].
  • Body mass index (BMI) ≤ 35 kg/m2.
  • Females with a regular menstrual cycle that ranges from 21-35 days (eumenorrhea)

Exclusion criteria

  • History of smoking or recreational smoking, cardiovascular disease, renal disease, pulmonary disease (including asthma or exercise-induced asthma), neurological disease, and metabolic disease.
  • Are pregnant or could possibly be pregnant by self-report.
  • Are color blind.
  • Known allergy or hypersensitivity latex.
  • Take selective serotonin reuptake inhibitors, stimulant medication, antibiotics, and chronically consume pain medication (Aleve, Tylenol, etc.).
  • Resting blood pressure of > 130mmHg systolic or 90 mmHg diastolic and/or resting pulse rate of > 100 bpm.
  • Females with irregular menstrual cycles (oligomenorrhea) that ranges from 36-90 days, and females with the absence of a menstrual cycle (amenorrhea).
  • Taking birth control for the sole purpose of period cessation (eg., Mirena IUD)

Treatment and study plan

Ambient Noise

Other

Participants will complete the breathing task with ambient (or normal) auditory feedback (~10 decibels).

Increased Auditory Feedback

Other

Participants will complete the breathing task with increased auditory feedback of ventilation (~70 decibels). Specifically, a small microphone will be placed in the device that participants breathe through to increase the sound of the participants breath.

Noise Distraction

Other

Participants will complete the breathing task without auditory feedback of ventilation. Specifically, participants will wear noise cancelling headphones and will listen to a self-selected music playlist at a constant volume (~80 decibels).

Primary outcomes

  1. Change in Stroop Color-Word Test Time Performance

    Time frame: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

    Time performance on the Stroop Color-Word Test (min:sec) will be measured every 10 minutes during each breathing task.

  2. Change in Stroop Color-Word Test Error Performance

    Time frame: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

    The number of errors on the Stroop Color-Word Test will be measured will be measured every 10 minutes during each breathing task.

  3. Change in Perception of Dyspnea Intensity

    Time frame: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

    Participants will rate perception of dyspnea (breathing) intensity on a visual analog scale (VAS) every 5 minutes during each breathing task. The participant will draw a vertical marker line on a horizontal line (100mm), indicating their breathing perception from "not noticeable" (0mm) to "maximal imaginable intensity" (100mm).

  4. Change in Perception of Dyspnea Unpleasantness

    Time frame: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

    Participants will rate perception of dyspnea (breathing) unpleasantness on a visual analog scale (VAS) every 5 minutes during each breathing task. The participant will draw a vertical marker line on a horizontal line (100mm), indicating their breathing perception from "not unpleasant" (0mm) to "maximal imaginable unpleasantness" (100mm).

Secondary outcomes

  1. Change in Diaphragm Thickness

    Time frame: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

    Diaphragm thickness will be measured via Doppler ultrasound of the 10th/11th rib space during functional residual capacity (FRC; rest) and end-inspiration, as well as during the maximal inspiratory pressure (MIP) test from FRC before and after each condition.

  2. Change in Heart Rate Variability

    Time frame: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

    Heart rate variability (beats per minute) will be measured continuously during each breathing task via 3-lead electrocardiograph (ECG).

  3. Change in Peripheral Oxygen Saturation

    Time frame: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

    Peripheral oxygen saturation will be measured continuously during each breathing task via pulse oximetry.

  4. Change in Blood Pressure - Brachial Artery

    Time frame: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

    Blood pressure will be measured every 10 minutes during each breathing task via a standard blood pressure cuff and auscultation of the brachial artery.

  5. Change in Blood Pressure - Finger Photoplethysmography

    Time frame: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

    Blood pressure will be measured continuously during each breathing task via finger photoplethysmography.

  6. Change in Heart Rate

    Time frame: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

    Heart Rate will be measured continuously during each breathing task by 3-lead electrocardiograph (ECG).

  7. Change in Cerebral Blood Oxygen Kinetics

    Time frame: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

    Oxyhemoglobin and deoxyhemoglobin (uptake/extraction, uM)will be measured continuously via near-infrared spectroscopy (NIRS) of the pre-frontal cortex during each breathing task.

  8. Change in Cerebral Blood Velocity

    Time frame: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

    Bilateral transcranial Doppler Ultrasound will be used to continuously measure middle and posterior cerebral artery blood velocity during each breathing task. The ultrasound transducers will be placed on both sides of the head at the temporal windows and the positions will be fixed using a transducer holder.

Study contacts

Contact information is provided by the study sponsor or research team.

Timothy D Mickleborough, PhD

CONTACT

[email protected]

812-855-0753

Sponsors and collaborators

Lead sponsor

Indiana University

Other

Collaborators

  • United States Department of Defense

Registry information

Official study title

Optimizing Mind-Body Interactions in Respiratory Control During Operationally Relevant Environmental Stressors

Important dates

Study start
2027
Primary completion
2027
Study completion
2028
First posted
Mar 13, 2026
Registry last updated
Mar 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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