1985 — 1986 |
Davenport, Paul W |
R23Activity Code Description: Undocumented code - click on the grant title for more information. |
Reflex Response to High Frequency Ventilation
The study of high frequency ventilation (HFV) and its use as a clinical tool has centered primarily on gas exchange and respiratory mechanics. The effects of high frequency ventilation on the control of breathing has received much less attention. HFV produces a slowing of breathing and apnea in patients, normal adult and neonatal humans and experimental animals. The apnea during HFV in experimental animals has been shown to be vagally mediated. However, the role of particular vagal afferents and respiratory muscle afferents remains in question. A systematic study of the ventilatory parameters most likely involved in the reflex apnea during HFV (stroke volume, frequency, CO2 and resting lung volume) has not been done. The experiments proposed herein will investigate the interaction of these four parameters in the respiratory reflex response to HFV. This will be done by independently varying each of the parameters to test for their effect on the apneic threshold. Once an apneic threshold has been defined, the relative contribution of vagal and muscle afferents to the response to HFV will be assessed. The results of these experiments will provide information that will be predictive in choosing a HFV ventilator setting that will elicite or avoid apnea in patients depending on the therapeutic regimen. A better understanding of the role of vagal and muscle afferents in the control of respiration will also result from these experiments.
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1989 — 1991 |
Davenport, Paul W |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Respiratory Afferent Projections to the Cerebral Cortex
This project is designed to investigate neurogenic activity in the somatosensory regions of the cerebral cortex that is elicited by respiratory sensory systems. There is very little known about respiratory afferent activation of cortical neurons or the pathways to the cortex. Yet, it is intuitively sensible that respiratory afferents activate somatosensory regions of the cortex by the "common knowledge" that humans can sense and voluntarily control their breathing. It is, in fact, surprising that so little investigation of respiratory afferent activation of the cortex has been made. This project will not attempt to investigate all respiratory afferent input to the cerebral cortex, rather it will concentrate on respiratory muscle afferent projections that have been previously studied by these investigators. The general objectives of this project are to investigate the higher brain center processing of respiratory muscle afferent information. The specific goals are to determine the input coding of respiratory muscle mechanoreceptors using controlled intercostal muscle stretching as a model. The central processing of both this intercostal muscle and phrenic afferent information will be initially investigated in the sensorimotor cortex. The organization of the sites of respiratory muscle activation in this region will be studied functionally and anatomically. Potential afferent and efferent connections will be identified with neuronal labeling and thereby provide clues for the functional identification of the subcortical input pathways for respiratory muscle afferents. The thalamus, a highly probable relay site, will be studied and the thalamocortical connections of respiratory muscle afferent activated neurons determined. These functional and anatomical studies lay the foundation for future studies on the, as yet unknown subthalamic projection pathways for respiratory muscle afferents. Determination of the projection and processing of respiratory muscle afferents by higher brain centers provides a basis for continued study of the mechanism of respiratory sensation.
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1991 — 1992 |
Davenport, Paul |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
U.S.-New Zealand Cooperative Research: Mechanisms of Respiratory Sensation in Humans
This award supports a visit by Dr. Paul W. Davenport of the University of Florida to the University of Auckland, New Zealand, to work with Dr. Paul Hill to investigate mechanisms of respiratory sensation in humans. Respiratory sensations allow humans and animals to sense and adjust their ventilation to meet changing environmental demands. The sensation of increased inspiratory mechanical loads has been previously studied using psychophysical techniques, but very little is known about the sensory mechanisms mediating the sensation of mechanical loads. Recently an evoked potential technique was used to demonstrate the activation of somatosensory cortical regions by inspiratory loads. This new respiratory related evoked potential (RREP) technique has the potential to increase our understanding of the physiological mechanisms mediating respiratory load sensation. The researchers will use inspiratory occlusions to determine the cortical generator of the RREP early P1 peak. They will standardize the stimulus/ response paradigm and correlate the RREP with subjective measures of respiratory load sensation to begin the systematic investigation of the underlying physiological mechanisms. The results of these experiments will provide new information of the application of RREP's to the study of respiratory sensations.
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0.915 |
1993 — 2004 |
Davenport, Paul W |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Respiratory Sensation in Normal and Asthmatic Children
DESCRIPTION (Adapted from the applicant's abstract): Asthma is the most common cause of respiratory disability in children. One of the common factors associated with asthma fatality is failure to recognize the severity of the asthma attack. This project has demonstrated that children with a history of life threatening asthma attacks (LTA) have a significantly decreased perceptual sensitivity to increased extrinsic loads and an increased threshold for detection of an increased extrinsic load. The absence of an early component, the P1 peak, or the respiratory related evoked potential (RREP) is indicative that there may be an intrinsic neural processing deficit in some children with LTA. The studies performed to date in this project demonstrate that one component of the child's failure to recognize an asthmatic attack in its early stages may be a reduced perceptual sensitivity to an increased load. The primary goal of this project is to continue the investigation of the neurophysiologic and behavioral mechanisms which may be mediating this failure of some asthmatics to recognize the severity of their asthma. Specifically, the sensory processes mediating bronchoconstriction, respiratory load perception and subsequent behavioral responses in asthmatic children. These studies will test the hypothesis that the sensation of mechanical loads is related to the components of the RREP. It is further hypothesized that the late components of the RREP are correlated with cognitive processing of respiratory loads. The significance of the work lies in the fact that impaired perception of intrinsic and extrinsic loaded breathing may put some asthmatic patients at risk of underestimation of the severity of an attack, delay in awareness of onset, inadequate self-assessment and delay in seeking medical attention. The RREP is a unique measure of cortical neural activity elicited by breathing against a mechanical load. This technique will be used, in combination with established psychophysical measures, to test for differences in the neural processing of respiratory load information between LTA, non-LTA asthmatic and non-asthmatic children. The perceptual sensitivity and interaction of different types of stimuli will be investigated. An investigation of the relationship between neural measures of mechanical load afferent activation and subjective measures of load perception will be performed. Bronchoconstriction and resistive loads will be used to test for the correlation between intrinsic and extrinsic perception. The relationship between the component peaks of the RREP and respiratory loads will be determined. The cortical activation by loads will be measured and the RREP recorded with the inclusion and exclusion of the different mechanoreceptor populations. The results of this project will provide new information on the sensory mechanisms mediating respiratory sensation in LTA asthmatic and non-asthmatic children. These results will be used to develop a better physiological understanding of self-assessment mechanisms in these children and used to provide enhanced treatment.
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2010 — 2013 |
Bolser, Donald C [⬀] Davenport, Paul W Lindsey, Bruce G Morris, Kendall Francis (co-PI) [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Central Mechanisms of Airway Protection
DESCRIPTION (provided by applicant): 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.
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2012 — 2015 |
Davenport, Paul W Morris, Kendall Francis (co-PI) [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Mechanisms of Swallow Control of Breathing
DESCRIPTION (provided by applicant): The goal of this project is to determine (i) how the respiratory neural network generates the swallow-breathing pattern during the pharyngeal phase of swallowing, (ii) iterative computational modeling and simulation analysis testing model-based predictions on the recruitment, reconfiguration and output pattern of the neural elements that mediate the swallow-breathing pattern and (iii) mechanisms for induced load compensation modulation and coordination of neural elements that control breathing and swallow. Our central hypothesis is that induced reflex pharyngeal swallow generates a specific swallow-breathing pattern by swallow central pattern generator (sCPG) reconfiguration of the respiratory central pattern generator (rCPG). It is further hypothesized that current breathing-related treatments for dysphagia are effective by compensation induced reconfiguration and activation of convergent neural elements in sCPG and rCPGs that control upper airway, pharyngeal and respiratory muscles. The sCPG must reconfigure the respiratory neural network because many of the muscles used for control of the pharynx and larynx during breathing are also used during swallow. We propose that the swallow-respiratory pattern is controlled by neuronal assemblies dynamically organized into regulatory elements required for the expression of airway defensive behaviors. These behavioral control assemblies for swallow are composed of recruited sCPG neurons that exhibit recruited connectivity with the rCPG and reconfigure the respiratory neural network to generate the swallow-breathing pattern. Our overall approach will be to simultaneously record multiple brainstem neurons using our well established cat model of airway defensive reflexes. Our custom network modeling and simulation analysis will enable us to determine and predict the recruitment, reconfiguration and output pattern of the sCPG and rCPG neural elements mediating the swallow breathing pattern as well as load compensation modulation of swallow. There are 3 Specific Aims. In Specific Aim 1, multiple neurons in the dorsal and ventral swallow and respiratory groups will be recorded simultaneously during breathing and swallow. Advanced spike train analysis and metrics will be used to determine cooperative discharge patterns among these neurons specific to the rCPG, sCPG and swallow control of breathing. In Specific Aim 2, we will revise and test our model of the swallow network. We will incorporate inferred functional interactions among specific brainstem swallow and respiratory neuronal populations identified from analyses of spike trains simultaneously recorded with multiple electrode arrays. In Specific Aim 3, we will use our neural network model simulation to predict the effect of increased respiratory loads on recruited and reconfigured neural elements generating the swallow-breathing pattern. This research project will provide new and directly relevant insights into the control and coordination of swallow breathing pattern, predictions necessary to understand these control systems and potential neural mechanisms that may rehabilitate the failure of these control systems in disease.
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