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Funding Agency:

NIH

Principal Investigator:

Nadine P Connor, PhD

Lab

Dr. Connor's Lab

Division:

Otolaryngology-Head & Neck Surgery

Project Summary:

RO1DC0008149

Skeletal muscles, including those of the tongue and larynx, are capable of considerable plasticity based on changing demands and levels of activity. The biological mechanisms that influence lingual and laryngeal muscular plasticity are not well defined or well-studied. This limits our ability to design and carry-out effective rehabilitation for voice and swallowing disorders. Aging allows examination of naturally occurring muscular plasticity and how to intervene towards prevention or reversal of suboptimal sensorimotor changes throughout the adult lifespan. Senescent individuals exhibit a pattern of structural and functional adaptations within muscles and the vascular system that may contribute to fatigue and weakness, such as alterations in microvascular geometry and blood flow, accelerated programmed cell death (apoptosis), and impaired regenerative capacity via muscle stem cells (satellite cells). We will use and extend a tongue exercise-water swallow paradigm developed in our lab to examine lingual and laryngeal musculoplasticity as a function of aging and exercise. Because muscles involved in the control of vocalization and swallowing share many neuromuscular control properties, tongue exercise paired with a water swallow may theoretically benefit both lingual and laryngeal functions. However, the manner in which this type of cranial cross-system exercise is manifested at the muscle level is unclear, and it is not known how musculoplastic adaptations affect vocalization and swallowing behaviors. Our hypothesis is that lingual and laryngeal muscle structure and physiology are altered throughout the adult lifespan and that age-related cranial musculoplasticity contributes to deficits observed in vocalization and deglutition. We hypothesize that mechanisms are alterations in lingual and laryngeal muscle regenerative capacity, programmed cell death, microvascular geometry and blood flow, and that these variables can be positively influenced by tongue exercise. We will test these hypotheses in rats of different ages that have undergone tongue exercise versus control conditions. We have 3 specific aims. In young adult, middle-aged and old rats, we will: (1) Quantify mechanisms of lingual and laryngeal muscle plasticity using an aging rat tongue exercise model; (2) Quantify changes in lingual and laryngeal muscle microvascular geometry and red blood cell (RBC) velocity with aging and exercise; (3) Determine how aging and tongue exercise affect vocalization and deglutition behavior. This work is innovative and significant because the mechanisms by which exercise impacts protective effects in the lingual and laryngeal sensorimotor systems are largely unexplored. Our neuromuscular model is the first to evaluate the effects of a behavioral exercise program on lingual and laryngeal muscle plasticity and on causal pathways. Further, this work is highly significant in providing a basis for understanding mechanisms underlying the potential benefits of exercise as a therapeutic intervention for muscular adaptation in cranial muscles. Translation of findings will assist within creasing effectiveness and efficiency of exercise-based voice and swallow treatments. Muscles can undergo substantial deterioration in structure and function when they are compromised by aging and disease and can make positive changes with rehabilitation. However, biological factors under lying these processes have been largely undefined in muscles of the tongue and larynx. Our research uses a rat model to determine how exercise tasks may change tongue and larynx muscles. This work is highly relevant to human voice and swallowing rehabilitation because we need specific scientific data to help make behavioral therapies more effective and efficient.

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