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Accepted for/Published in: JMIR Research Protocols

Date Submitted: Jun 2, 2026
Date Accepted: Jun 29, 2026

The final, peer-reviewed published version of this preprint can be found here:

Autonomic Nervous System Responses to Rest and Exertion Following Concussion (the Measuring ANSWERS Study): Protocol for a 2-Aim Cross-Sectional and Longitudinal Observational Study

Cole WR, Finegan AE, Kiefer AW, Sinnott AM, Mann M, Zou B, Xiao M, Heikke BL, Willoughby D, MacPherson R, Holter-Soerensen KA, Campbell CD, Chandler MC, Register-Mihalik JK, Mihalik JP

Autonomic Nervous System Responses to Rest and Exertion Following Concussion (the Measuring ANSWERS Study): Protocol for a 2-Aim Cross-Sectional and Longitudinal Observational Study

JMIR Res Protoc 2026;15:e103400

DOI: 10.2196/103400

PMID: 42600155

Autonomic Nervous System Responses to Rest and Exertion Following Concussion: Protocol for the Measuring ANSWERS Study

  • Wesley R. Cole; 
  • Aidan E. Finegan; 
  • Adam W. Kiefer; 
  • Aaron M. Sinnott; 
  • Meredith Mann; 
  • Baiming Zou; 
  • Meisheng Xiao; 
  • Brittany L. Heikke; 
  • Dominic Willoughby; 
  • Ryan MacPherson; 
  • Katelyn A. Holter-Soerensen; 
  • Chloe D. Campbell; 
  • Madison C. Chandler; 
  • Johna K. Register-Mihalik; 
  • Jason P. Mihalik

ABSTRACT

Autonomic nervous system (ANS) dysregulation is increasingly linked to concussion. However, studies examining links between concussion and ANS measures, such as heart rate (HR), heart rate variability (HRV), and pupillary light reflex (PLR), are limited by small sample sizes, inconsistent control of confounders, and methodological heterogeneity limiting clinical translation. The Measuring Autonomic Nervous System in Warfighters following Exertion and Resting Stressors (Measuring ANSWERS) study aims to address these limitations by incorporating adequate sample sizes, appropriate ANS recording protocols, and controlling for confounders. This two-aim protocol integrates cross-sectional and longitudinal observational designs to clarify the relationship between ANS measures and commonly used symptom- and clinical performance-based assessments, and track how these change over time. In Aim 1 (cross-sectional), we will evaluate differences and associations between ANS function and performance on standard post-concussion clinical performance and symptom measures in 150 participants (50 military service members (SMs) and 100 collegiate club athletes, analyzed separately), stratified by concussion history. Participants will complete resting and exertional ANS measures in addition to a battery of cognitive, balance, vestibular, oculomotor, and symptom assessments. In Aim 2 (longitudinal), we will track 50 concussed athletes and 50 age-, sex-, and sport-matched controls on the same assessments across three time points: within 7 days of injury, at participant-reported symptom resolution, and 1-2 weeks following clearance for return to activity. Measuring ANSWERS provides a reproducible, standardized framework for assessing ANS function after concussion and potentially informs the integration of physiological markers into return-to-activity decision-making in both athlete and military populations.


 Citation

Please cite as:

Cole WR, Finegan AE, Kiefer AW, Sinnott AM, Mann M, Zou B, Xiao M, Heikke BL, Willoughby D, MacPherson R, Holter-Soerensen KA, Campbell CD, Chandler MC, Register-Mihalik JK, Mihalik JP

Autonomic Nervous System Responses to Rest and Exertion Following Concussion (the Measuring ANSWERS Study): Protocol for a 2-Aim Cross-Sectional and Longitudinal Observational Study

JMIR Res Protoc 2026;15:e103400

DOI: 10.2196/103400

PMID: 42600155

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