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Central Neck Dissection In Patients with Clinical Node Negative Thyroid Cancer
Funding Agency:
Principal Investigator:
Lab
Division:
Otolaryngology-Head & Neck Surgery
Project Summary:
RO1CA176911
The results of this research will lead to an increased understanding of the manner in which surgical management of thyroid cancer affects voice, swallowing, and perceptions of health quality.
Influence of Neuromuscular Pathology on Parkinsonian Communication Deficits
Funding Agency:
Principal Investigator:
Lab
Division:
Otolaryngology-Head & Neck Surgery
Project Summary:
RO1DC014358
Individuals with Parkinson disease (PD) experience devastating communication and swallowing deficits that negatively impact quality of life. Recent research has shown that PD pathology is widespread, including not only central nervous system regions, but also peripheral structures such as nerves and muscles involved in communication and swallowing. However, despite these recent data, very little is known about how peripheral pathologies contribute to communication and swallowing deficits and when in the disease process these deficits emerge. Furthermore, it is unknown how behavioral treatments used clinically, such as exercise-based voice and swallow therapies, affect the manifestation of these deficits. To develop more effective treatments, a clear understanding of the progression of peripheral pathologies and the manner in which these pathologies affect communication and swallowing must be obtained. These unknowns will be addressed in the proposed research by studying a progressive, novel genetic rat model of PD: homozygous knock-out (KO) of PINK1, a gene mutation known to cause PD, comparing these rats to non-affected controls (wild type; WT), and by manipulating exercise conditions. This approach provides a direct mechanistic link to PD in humans, insight into the effects of treatments in current clinical use, and knowledge of previously unexplored peripheral pathology in PD associated with vocalization and swallowing deficits. Employing tasks and behaviors analogous to those used in humans will maximize translation. Rats will be studied at ages that correspond to early, mid, and late stage PD (6, 10 and 14 months). Our central hypotheses are: (1) PINK1 KO rats will show behavioral deficits accompanied by peripheral pathologies that will progressively increase in severity by disease stage, (2) PINK1 KO rats that undergo exercise will show prevention or reversal of functional deficits and modulation of peripheral neuromuscular pathology. To address these hypotheses, this proposal has 3specific aims: (1) To quantify pathological changes to peripheral nerves and muscles that mediate vocalization and swallowing across stages of PD; (2) To determine how neuromuscular pathology relates to deficits in vocalization, tongue strength and functional eating across stages of PD; and (3) To determine how exercise of the tongue and larynx affects neuromuscular pathology. This proposal is timely and innovative because our understanding of PD now embodies widespread pathology that includes muscles and nerves. The proposed research will provide in-depth knowledge of neuromuscular pathology that is relatively unexplored in PD and will also be the first to examine how exercise can prevent or reverse biological changes within the tongue and larynx. Our systematic and controlled studies in the PINK1 KO rat combine techniques and theory from behavioral, anatomical, and physiological sciences and provide an opportunity to learn how neuromuscular pathologies inform observed behavioral changes in vocalization and swallowing. This translational research has a high likelihood of yielding meaningful findings related to important scientific and clinical issues. The proposed research examines how muscles and nerves involved in communication and swallowing may be affected by Parkinson disease. Experiments will determine how pathologies in muscles and nerves contribute to communication and swallowing deficits and when in the disease process these deficits emerge. Further, this work will examine how exercise-based voice and swallow therapies prevent or reverse muscle and nerve pathologies using a novel genetic rat model.
Lingual and Laryngeal Muscle Plasticity
Funding Agency:
Principal Investigator:
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.
