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This issue is crucial for several reasons: (i) increased respiratory loading is a major feature of several respiratory diseases, (ii) failure of the voluntary motor and cortical sensory processing drives is among the mechanisms that precede acute respiratory failure, (iii) several cerebral structures involved in responding to inspiratory loading participate in the perception of dyspnea, a distressing symptom in many disease. We studied functional connectivity and Granger causality of the respiratory network in controls and patients with chronic obstructive pulmonary disease (COPD), at rest and during inspiratory loading. Compared with those of controls, the motor cortex area of patients exhibited decreased connectivity with their contralateral counterparts and no connectivity with the brainstem. In the patients, the information flow was reversed at rest with the source of the network shifted from the medulla towards the motor cortex. During inspiratory loading, the system was overwhelmed and the motor cortex became the sink of the network. This major finding may help to understand why some patients with COPD are prone to acute respiratory failure. Network connectivity and causality were related to lung function and illness severity. We validated our connectivity and causality results with a mathematical model of neural network. Our findings suggest a new therapeutic strategy involving the modulation of brain activity to increase motor cortex functional connectivity and improve respiratory muscles performance in patients. <jats:italic>Hum Brain Mapp 37:2736\u20132754, 2016<\/jats:italic>. \u00a9 <jats:bold>2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.<\/jats:bold><\/jats:p>","DOI":"10.1002\/hbm.23205","type":"journal-article","created":{"date-parts":[[2016,4,10]],"date-time":"2016-04-10T12:35:28Z","timestamp":1460291728000},"page":"2736-2754","source":"Crossref","is-referenced-by-count":51,"title":["Functional connectivity and information flow of the respiratory neural network in chronic obstructive pulmonary disease"],"prefix":"10.1002","volume":"37","author":[{"given":"Lianchun","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Physics Matter and Complex Systems Research Laboratory, UMR 7057, CNRS Paris 7 University France"},{"name":"Institute of Theoretical Physics, Lanzhou University Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"De Mazancourt","sequence":"additional","affiliation":[{"name":"Department of Physics Matter and Complex Systems Research Laboratory, UMR 7057, CNRS Paris 7 University France"},{"name":"Ecole Normale Sup\u00e9rieure Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agathe","family":"Hess","sequence":"additional","affiliation":[{"name":"Neuroradiology Department APHP, H\u00f4pital Bichat  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fakhrul R.","family":"Ashadi","sequence":"additional","affiliation":[{"name":"Department of Physics Matter and Complex Systems Research Laboratory, UMR 7057, CNRS Paris 7 University France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Klein","sequence":"additional","affiliation":[{"name":"Neuroradiology Department APHP, H\u00f4pital Bichat  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Mal","sequence":"additional","affiliation":[{"name":"Respiratory Disease Department APHP, H\u00f4pital Bichat  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice","family":"Courbage","sequence":"additional","affiliation":[{"name":"Department of Physics Matter and Complex Systems Research Laboratory, UMR 7057, CNRS Paris 7 University France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Mangin","sequence":"additional","affiliation":[{"name":"Department of Physics Matter and Complex Systems Research Laboratory, UMR 7057, CNRS Paris 7 University France"},{"name":"Department of Physiology APHP, H\u00f4pital Bichat  France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4,5]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"AnderssonM JenkinsonM SmithSM(2007): Non\u2010Linear Registration Aka Spatial Normalization. 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