A variety of neuromuscular diseases result in impaired cough (dystussia) and/or impaired swallow (dysphagia). The long-term goal of this project is to determine brainstem mechanisms that control and coordinate cough and swallow. Our central hypothesis is that a """"""""core"""""""" respiratory network is reconfigured by neuronal assemblies dynamically organized into regulatory elements (BCAs-behavioral control assemblies) necessary for the expression of airway protective behaviors. The pharyngeal phase of swallow has an important airway protective component, and this mechanism along with airflows generated by cough combine to prevent aspiration and to eject materials that penetrate the airway. The operational features, identity, and specific neural mechanisms which regulate and coordinate cough and swallow to optimize airway protection are unknown. The currently accepted model for cough proposes that the central pattern generating network for breathing is rapidly reconfigured to produce the cough motor pattern. There are no published models that explain how cough is coordinated with swallow to protect the airway from aspiration. BCAs exert a critical controlling function of the respiratory CPG, allowing it to a) reconfigure to generate widely variant motor patterns associated with cough and swallow, and b) impart novel regulatory characteristics to the system such that each behavior can be controlled by afferent systems in a manner that is functionally appropriate. The rationale for the proposed research is that once the organization and regulation of the brainstem airway protection system is established, the mechanisms responsible for aspiration in neurologic disease can be identified.
The Specific Aims of this project are: 1) Identify the operational principles that govern the coordination of the cough and swallow motor patterns to protect the airway from aspiration. 2) Determine the functional role of caudal medial column neurons in the neurogenesis of the cough and swallow motor patterns. 3) Develop a predictive computational distributed network model with known regulatory mechanisms in the neurogenesis of cough and swallow. The project is expected to yield the following outcomes. First, the role of a newly identified population of neurons in the caudal medial medulla in the neurogenesis of airway protection will become known. This information will allow us to test a unified model of airway protection and elucidate the functional organization of this system. Second, this organization will be studied during challenges that promote the simultaneous expression of breathing, cough and swallow. In doing so, we also will enhance our understanding of the central mechanisms responsible for behavior selection. Third, the resultant model of the airway protection network will allow us to predict elements of the network that may be affected neurologic disease, resulting in dystussia and/or dysphagia. These outcomes will define the central mechanisms responsible for the regulation of airway protection and provide fundamental new information that will advance our understanding of the central organization of breathing, cough, and swallow.

Public Health Relevance

A variety of neuromuscular diseases result in impaired cough (dystussia) and/or impaired swallow function (dysphagia). Impairment of these airway protective behaviors results in an increase in pulmonary infections due to aspiration. Pulmonary complications related to inadequate airway defense are the leading cause of death in patients with spinal cord injuries and Parkinson's Disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL103415-04
Application #
8539069
Study Section
Special Emphasis Panel (ZRG1-VH-D (50))
Program Officer
Laposky, Aaron D
Project Start
2010-09-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2013
Total Cost
$528,073
Indirect Cost
$113,794
Name
University of Florida
Department
Physiology
Type
Schools of Veterinary Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Pitts, Teresa; Hegland, Karen Wheeler; Sapienza, Christine M et al. (2016) Alterations in oropharyngeal sensory evoked potentials (PSEP) with Parkinson's disease. Respir Physiol Neurobiol 229:11-6
Gibson, Peter; Wang, Gang; McGarvey, Lorcan et al. (2016) Treatment of Unexplained Chronic Cough: CHEST Guideline and Expert Panel Report. Chest 149:27-44
Mondal, Pritish; Abu-Hasan, Mutasim; Saha, Abhishek et al. (2016) Effect of laparotomy on respiratory muscle activation pattern. Physiol Rep 4:
Pitts, Teresa; Morris, Kendall F; Segers, Lauren S et al. (2016) Feed-forward and reciprocal inhibition for gain and phase timing control in a computational model of repetitive cough. J Appl Physiol (1985) 121:268-78
French, Cynthia T; Diekemper, Rebecca L; Irwin, Richard S et al. (2015) Assessment of Intervention Fidelity and Recommendations for Researchers Conducting Studies on the Diagnosis and Treatment of Chronic Cough in the Adult: CHEST Guideline and Expert Panel Report. Chest 148:32-54
Pitts, Teresa; Gayagoy, Albright G; Rose, Melanie J et al. (2015) Suppression of Abdominal Motor Activity during Swallowing in Cats and Humans. PLoS One 10:e0128245
Poliacek, I; Rose, M J; Pitts, T E et al. (2015) Central administration of nicotine suppresses tracheobronchial cough in anesthetized cats. J Appl Physiol (1985) 118:265-72
Nuding, Sarah C; Segers, Lauren S; Iceman, Kimberly E et al. (2015) Functional connectivity in raphé-pontomedullary circuits supports active suppression of breathing during hypocapnic apnea. J Neurophysiol 114:2162-86
Segers, L S; Nuding, S C; Ott, M M et al. (2015) Peripheral chemoreceptors tune inspiratory drive via tonic expiratory neuron hubs in the medullary ventral respiratory column network. J Neurophysiol 113:352-68
Boulet, Louis-Philippe; Coeytaux, Remy R; McCrory, Douglas C et al. (2015) Tools for assessing outcomes in studies of chronic cough: CHEST guideline and expert panel report. Chest 147:804-14

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