The Role of Breathing Perception in Respiratory Control

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Work of Breathing
• Intervention / Treatment: Other: Ambient Noise; Other: Increased Auditory Feedback; Other: Noise Distraction

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Timothy D Mickleborough, PhD; Phone Number: 812-855-0753; Email: tmickleb@iu.edu

Study Locations

• United States
  • Indiana
    • Bloomington, Indiana, United States, 47405
      • Multidisciplinary Engineering and Sciences Hall (MESH)
      • Contact: Scott M Clarke; Phone Number: 812-856-3244; Email: scotclar@iu.edu
      • Contact: Zachary J Schalder, PhD; Phone Number: 812-855-6953; Email: zschlade@iu.edu
      • Principal Investigator: Timothy D Mickleborough, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ambient noise, then music distraction, then increased ventilation auditory feedback; Participants will complete 3 full length breathing tasks, one under each auditory condition. The order of condition exposure will be assigned via randomization.	Other: Ambient Noise; Participants will complete the breathing task with ambient (or normal) auditory feedback (~10 decibels).; Other: Increased Auditory Feedback; 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.; Other: Noise Distraction; 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).
Active Comparator: Ambient noise, then increased ventilation auditory feedback, then music distraction; Participants will complete 3 full length breathing tasks, one under each auditory condition. The order of condition exposure will be assigned via randomization.	Other: Ambient Noise; Participants will complete the breathing task with ambient (or normal) auditory feedback (~10 decibels).; Other: Increased Auditory Feedback; 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.; Other: Noise Distraction; 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).
Active Comparator: Music distraction, then ambient noise, then increased ventilation auditory feedback; Participants will complete 3 full length breathing tasks, one under each auditory condition. The order of condition exposure will be assigned via randomization.	Other: Ambient Noise; Participants will complete the breathing task with ambient (or normal) auditory feedback (~10 decibels).; Other: Increased Auditory Feedback; 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.; Other: Noise Distraction; 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).
Active Comparator: Increased ventilation auditory feedback, then ambient noise, then music distraction; Participants will complete 3 full length breathing tasks, one under each auditory condition. The order of condition exposure will be assigned via randomization.	Other: Ambient Noise; Participants will complete the breathing task with ambient (or normal) auditory feedback (~10 decibels).; Other: Increased Auditory Feedback; 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.; Other: Noise Distraction; 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).
Active Comparator: Increased ventilation auditory feedback, then music distraction, then ambient noise; Participants will complete 3 full length breathing tasks, one under each auditory condition. The order of condition exposure will be assigned via randomization.	Other: Ambient Noise; Participants will complete the breathing task with ambient (or normal) auditory feedback (~10 decibels).; Other: Increased Auditory Feedback; 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.; Other: Noise Distraction; 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).
Active Comparator: Music distraction, then increased ventilation auditory feedback, then ambient noise; Participants will complete 3 full length breathing tasks, one under each auditory condition. The order of condition exposure will be assigned via randomization.	Other: Ambient Noise; Participants will complete the breathing task with ambient (or normal) auditory feedback (~10 decibels).; Other: Increased Auditory Feedback; 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.; Other: Noise Distraction; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Stroop Color-Word Test Time Performance	Time performance on the Stroop Color-Word Test (min:sec) will be measured every 10 minutes during each breathing task.	Before and after each Day 1 breathing task (approximately 60 minutes in duration)
Change in Stroop Color-Word Test Error Performance	The number of errors on the Stroop Color-Word Test will be measured will be measured every 10 minutes during each breathing task.	Before and after each Day 1 breathing task (approximately 60 minutes in duration)
Change in Perception of Dyspnea Intensity	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).	Before and after each Day 1 breathing task (approximately 60 minutes in duration)
Change in Perception of Dyspnea Unpleasantness	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).	Before and after each Day 1 breathing task (approximately 60 minutes in duration)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cerebral Blood Velocity	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.	Before and after each Day 1 breathing task (approximately 60 minutes in duration)
Change in Heart Rate	Heart Rate will be measured continuously during each breathing task by 3-lead electrocardiograph (ECG).	Before and after each Day 1 breathing task (approximately 60 minutes in duration)
Change in Blood Pressure - Finger Photoplethysmography	Blood pressure will be measured continuously during each breathing task via finger photoplethysmography.	Before and after each Day 1 breathing task (approximately 60 minutes in duration)
Change in Blood Pressure - Brachial Artery	Blood pressure will be measured every 10 minutes during each breathing task via a standard blood pressure cuff and auscultation of the brachial artery.	Before and after each Day 1 breathing task (approximately 60 minutes in duration)
Change in Diaphragm Thickness	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.	Before and after each Day 1 breathing task (approximately 60 minutes in duration)
Change in Heart Rate Variability	Heart rate variability (beats per minute) will be measured continuously during each breathing task via 3-lead electrocardiograph (ECG).	Before and after each Day 1 breathing task (approximately 60 minutes in duration)
Change in Peripheral Oxygen Saturation	Peripheral oxygen saturation will be measured continuously during each breathing task via pulse oximetry.	Before and after each Day 1 breathing task (approximately 60 minutes in duration)
Change in Cerebral Blood Oxygen Kinetics	Oxyhemoglobin and deoxyhemoglobin (uptake/extraction, uM)will be measured continuously via near-infrared spectroscopy (NIRS) of the pre-frontal cortex during each breathing task.	Before and after each Day 1 breathing task (approximately 60 minutes in duration)

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: United States Department of Defense

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2027
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: March 10, 2026
• First Submitted That Met QC Criteria: March 10, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cognitive Performance; Dyspnea Perception; Auditory Distraction
• Other Study ID Numbers: 28381- Aim 2; FOAAFRLAFOSR20240007 (Other Grant/Funding Number: Air Force Office of Scientific Research)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The plan to share individual participant data (IPD) is still unknown. However, if other researchers request IPD, we will evaluate that request and determine to share IPD.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes