Translational Study of Vocal Exercise Dose-response

 描述(由申请人提供)：发声治疗对于改善一系列发声障碍的发声功能是必不可少的。对于与衰老相关的功能减退的嗓音障碍，声音疗法可以通过利用喉部固有肌肉的发声练习来改善发声质量和耐力，但这些改善的机制尚不清楚。根据肢体运动研究的结果，推测的机制是喉部肌肉生长(肥大)和力量增加，这些研究报告了这些因素的改善，以及渐进式阻力运动后功能的改善。了解发声训练是如何影响喉部肌肉结构和功能的，对于确定最合适的发声治疗剂量至关重要。这项研究的总体目标是确定发声训练对发声功能和喉肌肥大信号和生长的剂量-反应关系。我们的中心假设是，只有基于渐进式阻力训练原则的大剂量发声训练才能在老化的声音中导致发声功能和喉肌肥大的有益变化。我们将使用翻译方法验证这一假说，其中包括：(1)创新的行为动物模型，在该模型中，将训练大鼠增加超声发声的次数，使我们能够研究无法在人类身上研究的神经肌肉机制，包括肌肉纤维大小和类型、神经肌肉连接和调节骨骼肌生长的肥大信号对运动的反应；以及(2)人类发声训练，将传统的发声功能临床测量与新颖的喉部形态磁共振成像相结合。本研究有两个具体目的：(1)确定幼年和老年大鼠发声训练剂量对喉肥大神经肌肉反应；(2)确定老年男性和女性发声训练剂量-喉结构和功能的反应。这一职业发展奖的候选人在嗓音障碍的临床护理和使用翻译研究方法来研究喉部神经肌肉机制方面接受过强有力的培训。额外的培训和指导将使应聘者能够发展肌肉运动生理学和人类临床试验设计和实施方面的专业知识。组建的辅导团队拥有这些领域的研究专门知识以及成功和有效的辅导历史，以指导候选人完成上述研究项目和拟议的职业发展活动，包括运动学的正式课程、导师实验室的轮换、辅导补助金的撰写和同行评议出版物的准备。这项建议的结果不仅是了解发声锻炼剂量如何影响发声功能和结构，还将有助于候选人启动一项富有成效的独立研究计划，继续研究发声治疗和发声训练导致的喉部神经肌肉功能变化的潜在机制。

 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.