TY - GEN A1 - Schröder, Lena A1 - Werder, Dina von A1 - Ramaioli, Cecilia A1 - Wachtler, Thomas A1 - Henningsen, Peter A1 - Glasauer, Stefan A1 - Lehnen, Nadine T1 - Unstable Gaze in Functional Dizziness: A Contribution to Understanding the Pathophysiology of Functional Disorders T2 - Frontiers in Neuroscience N2 - Objective: We are still lacking a pathophysiological mechanism for functional disorders explaining the emergence and manifestation of characteristic, severely impairing bodily symptoms like chest pain or dizziness. A recent hypothesis based on the predictive coding theory of brain function suggests that in functional disorders, internal expectations do not match the actual sensory body states, leading to perceptual dysregulation and symptom perception. To test this hypothesis, we investigated the account of internal expectations and sensory input on gaze stabilization, a physiologically relevant parameter of gaze shifts, in functional dizziness. Methods: We assessed gaze stabilization in eight functional dizziness patients and 11 healthy controls during two distinct epochs of large gaze shifts: during a counter- rotation epoch (CR epoch), where the brain can use internal models, motor planning, and resulting internal expectations to achieve internally driven gaze stabilization; and during an oscillation epoch (OSC epoch), where, due to terminated motor planning, no movement expectations are present, and gaze is stabilized by sensory input alone. Results: Gaze stabilization differed between functional patients and healthy controls only when internal movement expectations were involved [F(1,17) = 14.63, p = 0.001, and partial η2 = 0.463]: functional dizziness patients showed reduced gaze stabilization during the CR (p = 0.036) but not OSC epoch (p = 0.26). Conclusion: While sensory-driven gaze stabilization is intact, there are marked, well- measurable deficits in internally-driven gaze stabilization in functional dizziness pointing at internal expectations that do not match actual body states. This experimental evidence supports the perceptual dysregulation hypothesis of functional disorders and is an important step toward understanding the underlying pathophysiology. Y1 - 2021 U6 - https://doi.org/10.3389/fnins.2021.685590 SN - 1662-453X SN - 1662-4548 VL - 15 ER - 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 -