TY - GEN A1 - Werder, Dina von A1 - Regnath, Franziska A1 - Schäfer, Daniel A1 - Jörres, Rudolf A1 - Lehnen, Nadine A1 - Glasauer, Stefan T1 - Post-COVID breathlessness: a mathematical model of respiratory processing in the brain T2 - European Archives of Psychiatry and Clinical Neuroscience N2 - Breathlessness is among the most common post-COVID symptoms. In a considerable number of patients, severe breathlessness cannot be explained by peripheral organ impairment. Recent concepts have described how such persistent breathlessness could arise from dysfunctional processing of respiratory information in the brain. In this paper, we present a first quantitative and testable mathematical model of how processing of respiratory-related signals could lead to breathlessness perception. The model is based on recent theories that the brain holds an adaptive and dynamic internal representation of a respiratory state that is based on previous experiences and comprises gas exchange between environment, lung and tissue cells. Perceived breathlessness reflects the brain’s estimate of this respiratory state signaling a potentially hazardous disequilibrium in gas exchange. The internal respiratory state evolves from the respiratory state of the last breath, is updated by a sensory measurement of CO2 concentration, and is dependent on the current activity context. To evaluate our model and thus test the assumed mechanism, we used data from an ongoing rebreathing experiment investigating breathlessness in patients with post-COVID without peripheral organ dysfunction (N = 5) and healthy control participants without complaints after COVID-19 (N = 5). Although the observed breathlessness patterns varied extensively between individual participants in the rebreathing experiment, our model shows good performance in replicating these individual, heterogeneous time courses. The model assumes the same underlying processes in the central nervous system in all individuals, i.e., also between patients and healthy control participants, and we hypothesize that differences in breathlessness are explained by different weighting and thus influence of these processes on the final percept. Our model could thus be applied in future studies to provide insight into where in the processing cascade of respiratory signals a deficit is located that leads to (post-COVID) breathlessness. A potential clinical application could be, e.g., the monitoring of effects of pulmonary rehabilitation on respiratory processing in the brain to improve the therapeutic strategies. KW - Pharmacology (medical) KW - Biological Psychiatry KW - Psychiatry and Mental health KW - General Medicine Y1 - 2024 U6 - https://doi.org/10.1007/s00406-023-01739-y SN - 0940-1334 ER - TY - GEN A1 - Schaefer, Daniel A1 - Jörres, Rudolf A1 - Nowak, Dennis A1 - Van Den Bergh, Omer A1 - Bogaerts, Katleen A1 - Glasauer, Stefan A1 - Lehnen, Nadine A1 - Von Werder, Dina T1 - Late breaking abstract : replication and validation of a rebreathing experiment to investigate post-COVID symptoms T2 - European Respiratory Journal Y1 - 2023 U6 - https://doi.org/10.1183/13993003.congress-2023.PA5072 VL - 62 IS - Suppl. 67 PB - European Respiratory Society ER - TY - GEN A1 - von Werder, Dina A1 - Aubele, Maria A1 - Regnath, Franziska A1 - Tebbe, Elisabeth A1 - Mladenov, Dejan A1 - von Rheinbaben, Victoria A1 - Hahn, Elisabeth A1 - Schäfer, Daniel A1 - Biersack, Katharina A1 - Adorjan, Kristina A1 - Stubbe, Hans C. A1 - Bogaerts, Katleen A1 - Jörres, Rudolf A. A1 - Nowak, Dennis A1 - Van den Bergh, Omer A1 - Glasauer, Stefan A1 - Lehnen, Nadine T1 - Increased breathlessness in post-COVID syndrome despite normal breathing patterns in a rebreathing challenge T2 - Scientific reports N2 - Severe symptoms in the absence of measurable body pathology are a frequent hallmark of post-COVID syndrome. From a Bayesian Brain perspective, such symptoms can be explained by incorrect internal models that the brain uses to interpret sensory signals. In this pre-registered study, we investigate whether induced breathlessness perception during a controlled CO2rebreathing challenge is reflected by altered respiratory measures (physiology and breathing patterns), and propose different computational mechanisms that could explain our findings in a Bayesian Brain framework. We analysed data from 40 patients with post-COVID syndrome and 40 healthy participants. Results from lung function, neurological and neurocognitive examination of all participants were within normal limits on the day of the experiment. Using a Bayesian repeated-measures ANOVA, we found that patients’ breathlessness was strongly increased (BF10,baseline =8.029, BF10,rebreathing =11636, BF10,recovery =43662) compared to controls. When excluding patients who hyperventilated (N = 8, 20%) during the experiment from the analysis, differences in breathlessness remained (BF10,baseline =1.283, BF10,rebreathing =126.812, BF10,recovery =751.282). For physiology and breathing patterns, all evidence pointed towards no difference between the two groups (0.307  BF10 < 0.704). In summary, we found intact breathing patterns and physiology but increased symptom perception in patients with post-COVID syndrome. Y1 - 2025 U6 - https://doi.org/10.1038/s41598-025-11728-x SN - 2045-2322 VL - 15 IS - 1 SP - 1 EP - 15 PB - Springer Nature CY - [London] ER -