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

BACKGROUND: Autonomic nervous system (ANS) dysregulation is increasingly linked to concussion. However, studies examining the relationship between concussion and ANS measures, such as heart rate (HR), HR variability (HRV), and pupillary light reflex (PLR), are limited by small sample sizes, inconsistent control of confounders, and methodological heterogeneity, thereby limiting clinical translation. OBJECTIVE: The Measuring Autonomic Nervous System in Warfighters Following Exertion and Resting Stressors (ANSWERS) study aims to address these limitations by incorporating adequate sample sizes, using appropriate ANS recording protocols, and controlling for confounders. METHODS: This 2-aim study integrates cross-sectional and longitudinal observational designs to clarify the relationship between ANS measures and commonly used symptom- and clinical performance-based assessments and to track how these measures change over time. In aim 1 (cross-sectional), we will evaluate differences and associations between ANS function and performance on standard postconcussion 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 as well as a battery of cognitive, balance, vestibular, oculomotor, and symptom assessments. In aim 2 (longitudinal), we will track 50 athletes with concussion and 50 age-, sex-, and sport-matched controls using the same assessments across 3 time points: within 7 days of injury, at participant-reported symptom resolution, and 1 to 2 weeks following clearance for return to activity. RESULTS: The Measuring ANSWERS study was funded in August 2023, with participant recruitment initiated in November 2023 and expected to continue through August 2027. As of July 2026, a total of 122 (48.8%) of the planned 250 participants have been enrolled, with data collection ongoing and study findings anticipated to be disseminated in late 2027. CONCLUSIONS: The Measuring ANSWERS study will provide a reproducible, standardized framework for assessing ANS function after concussion and may inform the integration of physiological markers into return-to-activity decision-making in both athlete and military populations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/103400.