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      A Joint Computational Respiratory Neural Network-Biomechanical Model for Breathing and Airway Defensive Behaviors

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          Abstract

          Data-driven computational neural network models have been used to study mechanisms for generating the motor patterns for breathing and breathing related behaviors such as coughing. These models have commonly been evaluated in open loop conditions or with feedback of lung volume simply represented as a filtered version of phrenic motor output. Limitations of these approaches preclude assessment of the influence of mechanical properties of the musculoskeletal system and motivated development of a biomechanical model of the respiratory muscles, airway, and lungs using published measures from human subjects. Here we describe the model and some aspects of its behavior when linked to a computational brainstem respiratory network model for breathing and airway defensive behavior composed of discrete “integrate and fire” populations. The network incorporated multiple circuit paths and operations for tuning inspiratory drive suggested by prior work. Results from neuromechanical system simulations included generation of a eupneic-like breathing pattern and the observation that increased respiratory drive and operating volume result in higher peak flow rates during cough, even when the expiratory drive is unchanged, or when the expiratory abdominal pressure is unchanged. Sequential elimination of the model’s sources of inspiratory drive during cough also suggested a role for disinhibitory regulation via tonic expiratory neurons, a result that was subsequently supported by an analysis of in vivo data. Comparisons with antecedent models, discrepancies with experimental results, and some model limitations are noted.

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          Most cited references67

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          Measurement of the separate volume changes of rib cage and abdomen during breathing.

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            Global physiology and pathophysiology of cough: ACCP evidence-based clinical practice guidelines.

            F McCool (2005)
            The anatomy and neurophysiology of cough has been reviewed in the preceding section. The objective of this section is to describe how the varied anatomic components of the respiratory system work in concert to produce an effective cough. This was accomplished by reviewing (1) the factors needed to produce effective cough pressures and gas velocity in the airways, and (2) the salient features of the interaction between the airflow generated during a cough and the mucus that lines the tracheobronchial tree. The MEDLINE database was searched for this review, and the search consisted of studies published in English between 1960 and April 2004. Search terms were "cough mechanics" and "cough physiology." Inhaling to high lung volumes and glottic closure prior to the expiratory phase of cough facilitate the generation of high intrathoracic pressures. These high intrathoracic pressures (1) provide the driving force for airstream flow during cough and (2) dynamically compress the central airways, which further enhances the cough airstream velocity. High intrathoracic pressures are needed to generate the requisite cough expiratory flows and airstream velocities. However, cough may be effective in individuals with mild-to-moderate degrees of respiratory muscle weakness, as only modest increases in intrathoracic pressure are needed to dynamically compress the large intrathoracic airways and increase cough flow velocity.
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              Peak flow and peak cough flow in the evaluation of expiratory muscle weakness and bulbar impairment in patients with neuromuscular disease.

              To study the expiratory muscle force and the ability to cough estimated by the peak expiratory flow and peak cough flow in patients with Duchenne muscular dystrophy and amyotrophic lateral sclerosis. A total of 27 patients with amyotrophic lateral sclerosis and 52 patients with Duchenne muscular dystrophy were studied. From the group of 144 normal subjects of this laboratory, we selected 38 for comparison. The maximal inspiratory pressure in patients with Duchenne muscular dystrophy and amyotrophic lateral sclerosis was 64.5 +/- 24.7% and 37.8 +/- 21.8%, respectively, and maximal expiratory pressure was 64.2 +/- 32.5% and 37.7 +/- 21.6%, respectively. Patient groups showed a significant lower peak expiratory flow than normal subjects. Higher peak cough flow than peak expiratory flow was found in all groups. The peak cough flow-peak expiratory flow difference was 46 +/- 18% in normal subjects, 43 +/- 23% in patients with Duchenne muscular dystrophy, and 11 +/- 17% in patients with amyotrophic lateral sclerosis. The peak expiratory flow and peak cough flow were not different in bulbar onset amyotrophic lateral sclerosis. In patient groups, the dynamic and static behavior correlated positively. These results suggest that peak cough flow-peak expiratory flow is useful to monitor expiratory muscle weakness and bulbar involvement and to assess its evolution in these patients.
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                Author and article information

                Journal
                Front Physiol
                Front Physiol
                Front. Physio.
                Frontiers in Physiology
                Frontiers Research Foundation
                1664-042X
                20 April 2012
                23 July 2012
                2012
                : 3
                : 264
                Affiliations
                [1] 1simpleDepartment of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida Tampa, FL, USA
                [2] 2simpleDepartment of Physiological Sciences, College of Veterinary Medicine, University of Florida Gainesville, FL, USA
                Author notes

                Edited by: Raimond L. Winslow, The Johns Hopkins University, USA

                Reviewed by: Raimond L. Winslow, The Johns Hopkins University, USA; Silvina Ponce Dawson, Universidad de Buenos Aires, Argentina

                *Correspondence: Bruce G. Lindsey, Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612-4799, USA. e-mail: blindsey@ 123456health.usf.edu

                This article was submitted to Frontiers in Computational Physiology and Medicine, a specialty of Frontiers in Physiology.

                Article
                10.3389/fphys.2012.00264
                3429040
                22934020
                3bc2d2cd-3e92-41ba-aca3-057425a57865
                Copyright © 2012 O’Connor, Segers, Morris, Nuding, Pitts, Bolser, Davenport and Lindsey.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 14 March 2012
                : 24 June 2012
                Page count
                Figures: 8, Tables: 5, Equations: 55, References: 86, Pages: 28, Words: 19264
                Categories
                Physiology
                Original Research

                Anatomy & Physiology
                breathing,chest wall dynamics,cough,neuromechanical model simulation,biomechanical model,inspiratory drive,brainstem,computational neural network model

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