PROJECT SUMMARY/ABSTRACT Individuals with paradoxical vocal fold motion disorder(s) (PVFMD), which are classically understood as conditions involving trigger-induced abnormal vocal fold adduction during inspiration, are frequently missed or inaccurately diagnosed, resulting in protracted periods of ineffective, and at times dangerous, mismanagement.1?3 Much of this issue is due to the (1) paucity of diagnostic standards and (2) poor understanding of pathophysiological mechanisms driving heterogeneous clinical expression. Improved diagnostic procedures and a better understanding of PVFMD mechanisms are needed to more accurately identify individuals with PVFMD, improve management, and reduce personal and financial burden. Objectives of the current proposal are to address these gaps by (1) prospectively quantifying severity and identifying thresholds for pathology of cardinal features indicative of PVFMD, and (2) characterizing auxiliary features indicative of one variant of PVFMD: exercise-induced PVFMD, to begin to understand how features of this variant fit into the overarching spectrum of clinical characteristics. Objectives will be guided by a previously created taxonomic framework integrated from a comprehensive literature review,4 as well as validated quantitative methods to measure glottal configuration.5 Exploratory objectives will elucidate the theoretical merit of potential underlying mechanisms proposed in the PVFMD literature, providing a platform for future, in-depth investigation. Specifically, the primary aim (SA1) targets cardinal features in PVFMD axiomatic to the condition. The goal of this aim is to quantify magnitude of (A) inspiratory glottal obstruction and (B) two constructs of perceived dyspnea severity?intensity and appraisal of discomfort?during an attack-inducing exercise challenge in athletic adolescents with exercise-induced PVFMD, compared to findings for athletic control subjects, and identify thresholds for pathology. The hypothesis is that subjects with PVFMD will show a greater increase in inspiratory adduction and associated dyspnea from rest to exercise conditions compared to control subjects. The goal of the secondary aim (SA2) is to identify auxiliary (A) signs and (B) symptoms for exertion-induced PVFMD, and quantify their severity. Speculative results involve presence of stridor and arytenoid prolapse in the PVFMD group but not in controls, a hypothesis informed by expert opinion and retrospective case studies specific to the exertion variant of PVFMD.6?8 The exploratory aim (SA3) will investigate two potential mechanisms involved in PVFMD pathogenesis: (A) sympathovagal imbalance9,10 and (B) temperament. 8,11?20 The proposed research and training plan will provide the applicant with the necessary skills to continue to develop a programmatic line of research in aerodigestive and communicative laryngeal function and pathophysiology.