{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T05:29:08Z","timestamp":1761629348635,"version":"build-2065373602"},"reference-count":110,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T00:00:00Z","timestamp":1761436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009104","name":"University of Modena and Reggio Emilia,","doi-asserted-by":"crossref","award":["FAR-DIP2024-GANDOLFI E93C24000500005"],"award-info":[{"award-number":["FAR-DIP2024-GANDOLFI E93C24000500005"]}],"id":[{"id":"10.13039\/100009104","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Italian National Recovery and Resilience Plan (NRRP), M4C2"},{"name":"European Union\u2014NextGenerationEU","award":["IR0000011","CUP B51E22000150006"],"award-info":[{"award-number":["IR0000011","CUP B51E22000150006"]}]},{"name":"Ministry of University and Research","award":["PRIN 2022ZY5RXB CUP E53D2301172"],"award-info":[{"award-number":["PRIN 2022ZY5RXB CUP E53D2301172"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>The human respiratory Central Pattern Generator (CPG) is a complex and tightly regulated network of neurons responsible for the automatic rhythm of breathing. Among the brain nuclei involved in respiratory control, excitatory neurons within the PreBotzinger Complex (PreB\u00f6tC) are both necessary and sufficient for generating this rhythmic activity. Although several models of the PreB\u00f6tC circuit have been proposed, a comprehensive analysis of network behavior in response to physiologically relevant external inputs remains limited. In this study, we present a computational model of the PreB\u00f6tC consisting of 1000 excitatory neurons, divided into two functional subgroups: the rhythm-generating population and the pattern-forming population. To enable real-time closed-loop simulations, we employed parallelized multi-process computing to accelerate network simulation. The network, composed of asynchronous neurons, could produce bursting activity at a eupneic breathing frequency of 0.22 Hz, which could also reproduce the rapid and stable chemoreception of breathing activated in response to hypercapnia. Additionally, it successfully replicated rapid and stable respiratory responses to elevated carbon dioxide levels (hypercapnia), mediated through simulated chemoreception. External inputs from a carbon dioxide sensor were used to modulate the network activity, allowing the implementation of a real-time respiratory control system. These results demonstrate that a network of asynchronous, non-bursting neurons can emulate the behavior of the respiratory CPG and its modulation by external stimuli. The proposed model represents a step toward developing a closed-loop controller for breathing regulation.<\/jats:p>","DOI":"10.3390\/bioengineering12111163","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:51:42Z","timestamp":1761526302000},"page":"1163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Computational Model of the Respiratory CPG for the Artificial Control of Breathing"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3890-3061","authenticated-orcid":false,"given":"Lorenzo","family":"De Toni","sequence":"first","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, I-41125 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6693-493X","authenticated-orcid":false,"given":"Federica","family":"Perricone","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, I-41125 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9976-7786","authenticated-orcid":false,"given":"Lorenzo","family":"Tartarini","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, I-41125 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia Maria","family":"Boiani","sequence":"additional","affiliation":[{"name":"Institute of Biophysics, National Research Council (CNR), I-90146 Palermo, Italy"},{"name":"Department of Engineering \u201cEnzo Ferrari\u201d, University of Modena and Reggio Emilia, I-41125 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7466-9629","authenticated-orcid":false,"given":"Stefano","family":"Cattini","sequence":"additional","affiliation":[{"name":"Department of Engineering \u201cEnzo Ferrari\u201d, University of Modena and Reggio Emilia, I-41125 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1743-3043","authenticated-orcid":false,"given":"Luigi","family":"Rovati","sequence":"additional","affiliation":[{"name":"Department of Engineering \u201cEnzo Ferrari\u201d, University of Modena and Reggio Emilia, I-41125 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2496-2311","authenticated-orcid":false,"given":"Dimitri","family":"Rodarie","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, I-27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Egidio","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, I-27100 Pavia, Italy"},{"name":"Brain Connectivity Center, IRCCS Mondino Foundation, I-27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0381-1576","authenticated-orcid":false,"given":"Jonathan","family":"Mapelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, I-41125 Modena, Italy"},{"name":"Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, I-41125 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Gandolfi","sequence":"additional","affiliation":[{"name":"Department of Engineering \u201cEnzo Ferrari\u201d, University of Modena and Reggio Emilia, I-41125 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R986","DOI":"10.1016\/S0960-9822(01)00581-4","article-title":"Central pattern generators and the control of rhythmic movements","volume":"11","author":"Marder","year":"2001","journal-title":"Curr. 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