Translational Study of Vocal Exercise Dose-response

 描述（由申请人提供）：语音治疗对于改善一系列语音障碍的语音功能至关重要。对于与衰老相关的功能减退的声音障碍，声音治疗可以通过使用喉内肌肉组织的发声练习来改善声音质量和耐力，但这些改善的机制尚不清楚。假定的机制是喉肌生长（肥大）和力量增加，这是基于肢体运动研究的结果，这些研究报告了这些因素的改善，沿着渐进式抗阻运动后的功能改善。了解发声练习如何影响喉部肌肉结构和功能对于确定最合适的声音治疗剂量至关重要。本研究的总体目标是确定发声锻炼对发声功能和喉肌肥大信号传导和生长的剂量-反应关系。我们的中心假设是，只有一个高剂量的发声练习的基础上渐进阻力训练原则将导致在两个发声功能和喉肌肉肥大的声音老化的有益变化。我们将使用一种转化方法来验证这一假设，包括：（1）一种创新的行为动物模型，其中大鼠将被训练以增加超声发声的数量，使我们能够研究在人类中不可能研究的神经肌肉机制，包括肌肉纤维大小和类型的变化，神经肌肉接头，以及调节骨骼肌生长的肥大信号对运动的反应;以及（2）将传统的发声功能临床测量与喉部形态的新型磁共振成像相结合的人类发声训练。本研究有两个具体的目的：（1）确定青年和老年大鼠喉肥大神经肌肉对发声运动剂量的反应;（2）确定老年男性和女性喉结构和功能的发声运动剂量反应。该职业发展奖的候选人在嗓音疾病的临床护理和使用转化研究方法调查喉神经肌肉机制方面接受了很强的培训。额外的培训和指导将使候选人能够发展肌肉运动生理学和人体临床试验设计和实施方面的专业知识。组建的指导团队拥有这些领域的研究专业知识，以及成功和有效的指导历史，以指导候选人完成上述研究项目和拟议的职业发展活动，包括运动机能学的正式课程，导师实验室的轮换，以及指导资助写作和同行评审出版物的准备。该提案的结果不仅是了解声乐运动剂量如何影响声乐功能和结构，而且还将帮助候选人启动一个富有成效的独立研究计划，以继续研究嗓音治疗和声乐训练引起的功能变化的喉神经肌肉机制。

 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.