Translational Study of Vocal Exercise Dose-response

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 DESCRIPTION (provided by applicant): Voice therapy is essential for improving vocal function across a range of voice disorders. For hypofunctional voice disorders associated with aging, voice therapy can improve vocal quality and stamina using vocal exercises that engage the intrinsic laryngeal musculature, but the mechanisms underlying these improvements are unknown. Putative mechanisms are laryngeal muscle growth (hypertrophy) and increased strength based on findings from limb exercise studies that report improvement of these factors along with functional improvements following progressive resistance exercise. Understanding how vocal exercise impacts laryngeal muscle structure and function is critical for determining the most appropriate dose of voice therapy. The overall objective of this research is to determine the dose-response relationship of vocal exercise to both vocal function and laryngeal muscle hypertrophic signaling and growth. Our central hypothesis is that only a high dose of vocal exercise based on progressive resistance training principles will result in beneficial changes in both vocal function and laryngeal muscle hypertrophy in the aging voice. We will test this hypothesis using a translational approach that includes: (1) an innovative behavioral animal model, in which rats will be trained to increase the number of ultrasonic vocalizations, allowing us to investigate neuromuscular mechanisms that are not possible to study in humans, including changes in muscle fiber size and type, neuromuscular junctions, and hypertrophic signaling regulating skeletal muscle growth in response to exercise; and (2) vocal training in humans incorporating traditional clinical measures of vocal function with novel magnetic resonance imaging of laryngeal morphology. This research has two specific aims: (1) To determine the laryngeal hypertrophic neuromuscular response to vocal exercise dosage in young adult and old rats; and (2) To determine the vocal exercise dose-response of laryngeal structure and function in aged men and women. The candidate for this career development award has strong training in the clinical care of voice disorders and in using translational research methods to investigate laryngeal neuromuscular mechanisms. Additional training and mentorship will allow the candidate to develop expertise in muscle exercise physiology and human clinical trial design and implementation. The assembled mentoring team has research expertise in these areas as well as a history of successful and effective mentoring to guide the candidate through the research project described above and the proposed career development activities, including formal coursework in kinesiology, rotations in the mentors' laboratories, and mentored grant writing and peer-review publication preparation. The outcome of this proposal will not only be an understanding of how vocal exercise dose impacts vocal function and structure, but will also help the candidate launch a productive and independent research program to continue investigating laryngeal neuromuscular mechanisms underlying functional changes resulting from voice therapy and vocal training.