@misc{LehnenRamaioliHenningsenetal., author = {Lehnen, Nadine and Ramaioli, Cecilia and Henningsen, Peter and Glasauer, Stefan}, title = {An experimental litmus test of the emerging hypothesis that persistent physical symptoms can be explained as perceptual dysregulation}, series = {Journal of Psychosomatic Research}, volume = {114}, journal = {Journal of Psychosomatic Research}, issn = {1879-1360}, doi = {10.1016/j.jpsychores.2018.08.007}, pages = {15 -- 17}, language = {en} } @misc{LehnenSchroederHenningsenetal., author = {Lehnen, Nadine and Schr{\"o}der, Lena and Henningsen, Peter and Glasauer, Stefan and Ramaioli, Cecilia}, title = {Deficient head motor control in functional dizziness: Experimental evidence of central sensory-motor dysfunction in persistent physical symptoms}, series = {Progress in Brain Research}, volume = {249}, journal = {Progress in Brain Research}, issn = {1875-7855}, doi = {10.1016/bs.pbr.2019.02.006}, pages = {385 -- 400}, abstract = {Understanding the mechanisms of symptoms that are insufficiently explained by organic dysfunction remains challenging. Recently, it has been proposed that such "functional symptoms" are based on erroneous sensory processing in the central nervous system (CNS), with internal expectations dominating sensory inputs. In a pilot study, we used a head motor control set-up to assess the interplay between sensory input and expectation on the example of patients with functional dizziness. Eight patients and 11 age-matched healthy controls performed large active eye-head gaze shifts towards visual targets in the natural situation and with the head moment of inertia 3.3-fold increased. The latter induces head oscillations and the expected sensory outcome of the movement, estimated in the CNS, does not match the actual sensory input. Head oscillations were assessed in patients and in healthy subjects and compared to prior results from patients with organic disease (vestibular loss and cerebellar ataxia). Head oscillations in patients with functional dizziness were different from those of healthy subjects (F(1,17) = 27.26, P < 0.001, partial η2 = 0.62), and similar to those of patients with cerebellar ataxia, and with vestibular loss (F(2,19) = 0.56, P = 0.58). Even in the natural, unweighted, condition, head oscillations were higher in functional dizziness patients than in healthy subjects (P = 0.001). Since an extensive work-up failed to demonstrate any explanatory peripheral vestibular, motor, or cerebellar organic dysfunction, these motor control deficits are a first indication of erroneous interplay between expectations and sensory input in the CNS that could account for persistent physical symptoms.}, language = {en} } @misc{LehnenRadziejWeigeletal., author = {Lehnen, Nadine and Radziej, Katharina and Weigel, Angelika and K{\"a}nel, Roland von and Glasauer, Stefan and Pietron, Victor and Van den Bergh, Omer and L{\"o}we, Bernd and Lehmann, Marco and Henningsen, Peter}, title = {Complementing conceptual models of persistent somatic symptoms with mathematical formalization}, series = {Psychosomatic Medicine}, volume = {82}, journal = {Psychosomatic Medicine}, number = {5}, issn = {1534-7796}, doi = {10.1097/PSY.0000000000000801}, pages = {527 -- 528}, language = {en} } @misc{SchroederWerderRamaiolietal., author = {Schr{\"o}der, Lena and Werder, Dina von and Ramaioli, Cecilia and Wachtler, Thomas and Henningsen, Peter and Glasauer, Stefan and Lehnen, Nadine}, title = {Unstable Gaze in Functional Dizziness: A Contribution to Understanding the Pathophysiology of Functional Disorders}, series = {Frontiers in Neuroscience}, volume = {15}, journal = {Frontiers in Neuroscience}, issn = {1662-453X}, doi = {10.3389/fnins.2021.685590}, abstract = {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.}, language = {en} } @misc{SchroederRegnathGlasaueretal., author = {Schr{\"o}der, Lena and Regnath, Franziska and Glasauer, Stefan and Hackenberg, Anna and Hente, Juliane and Weilenmann, Sonja and Pohl, Daniel and K{\"a}nel, Roland von and Lehnen, Nadine}, title = {Altered sensorimotor processing in irritable bowel syndrome: Evidence for a transdiagnostic pathomechanism in functional somatic disorders}, series = {Frontiers in Neuroscience}, volume = {16}, journal = {Frontiers in Neuroscience}, issn = {1662-453X}, doi = {10.3389/fnins.2022.1029126}, abstract = {Objective A recent hypothesis suggests that functional somatic symptoms are due to altered information processing in the brain, with rigid expectations biasing sensorimotor signal processing. First experimental results confirmed such altered processing within the affected symptom modality, e.g., deficient eye-head coordination in patients with functional dizziness. Studies in patients with functional somatic symptoms looking at general, trans-symptomatic processing deficits are sparse. Here, we investigate sensorimotor processing during eye-head gaze shifts in irritable bowel syndrome (IBS) to test whether processing deficits exist across symptom modalities. Methods Study participants were seven patients suffering from IBS and seven age- and gender-matched healthy controls who performed large gaze shifts toward visual targets. Participants performed combined eye-head gaze shifts in the natural condition and with experimentally increased head moment of inertia. Head oscillations as a marker for sensorimotor processing deficits were assessed. Bayes statistics was used to assess evidence for the presence or absence of processing differences between IBS patients and healthy controls. Results With the head moment of inertia increased, IBS patients displayed more pronounced head oscillations than healthy controls (Bayes Factor 10 = 56.4, corresponding to strong evidence). Conclusion Patients with IBS show sensorimotor processing deficits, reflected by increased head oscillations during large gaze shifts to visual targets. In particular, patients with IBS have difficulties to adapt to the context of altered head moment of inertia. Our results suggest general transdiagnostic processing deficits in functional somatic disorders.}, language = {en} } @misc{WerderRegnathSchaeferetal., author = {Werder, Dina von and Regnath, Franziska and Sch{\"a}fer, Daniel and J{\"o}rres, Rudolf and Lehnen, Nadine and Glasauer, Stefan}, title = {Post-COVID breathlessness: a mathematical model of respiratory processing in the brain}, series = {European Archives of Psychiatry and Clinical Neuroscience}, journal = {European Archives of Psychiatry and Clinical Neuroscience}, issn = {0940-1334}, doi = {10.1007/s00406-023-01739-y}, abstract = {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.}, language = {en} } @misc{SchaeferJoerresNowaketal., author = {Schaefer, Daniel and J{\"o}rres, Rudolf and Nowak, Dennis and Van Den Bergh, Omer and Bogaerts, Katleen and Glasauer, Stefan and Lehnen, Nadine and Von Werder, Dina}, title = {Late breaking abstract : replication and validation of a rebreathing experiment to investigate post-COVID symptoms}, series = {European Respiratory Journal}, volume = {62}, journal = {European Respiratory Journal}, number = {Suppl. 67}, publisher = {European Respiratory Society}, doi = {10.1183/13993003.congress-2023.PA5072}, language = {en} } @misc{RegnathBiersackSchroederetal., author = {Regnath, Franziska and Biersack, Katharina and Schr{\"o}der, Lena and Stainer, Marie-Christin and von Werder, Dina and P{\"u}rner, Dominik and Haslinger, Bernhard and Lehnen, Nadine}, title = {Experimental evidence for a robust, transdiagnostic marker in functional disorders: Erroneous sensorimotor processing in functional dizziness and functional movement disorder}, series = {Journal of Psychosomatic Research}, volume = {183}, journal = {Journal of Psychosomatic Research}, editor = {Glasauer, Stefan}, publisher = {Elsevier BV}, issn = {0022-3999}, doi = {10.1016/j.jpsychores.2024.111694}, pages = {10}, language = {en} } @misc{RegnathBiersackJaegeretal., author = {Regnath, Franziska and Biersack, Katharina and J{\"a}ger, Nina and Glasauer, Stefan and Lehnen, Nadine}, title = {Not a general, symptom-unspecific, transdiagnostic marker for functional symptoms: sensorimotor processing of head control is intact in chronic pain}, series = {Frontiers in Neurology}, volume = {14}, journal = {Frontiers in Neurology}, issn = {1664-2295}, doi = {10.3389/fneur.2023.1294702}, abstract = {Introduction: Functional disorders are prevalent in all medical fields and pose a tremendous public health problem, with pain being one of the most common functional symptoms. Understanding the underlying, potentially unifying mechanism in functional (pain) disorders is instrumental in facilitating timely diagnosis, stigma reduction, and adequate treatment options. Neuroscientific models of perception suggest that functional symptoms arise due to dysregulated sensorimotor processing in the central nervous system, with brain-based predictions dominating the eventual percept. Experimental evidence for this transdiagnostic mechanism has been established in various functional symptoms. The goal of the current study was to investigate whether erroneous sensorimotor processing is an underlying transdiagnostic mechanism in chronic (functional) pain. Method: A total of 13 patients with chronic (functional) pain [three patients with chronic (functional) pain disorder, F45.40, ICD-10; 10 patients with chronic pain disorder with somatic and psychological factors, F45.41, ICD-10]; and 15 healthy controls performed large combined eye-head gaze shifts toward visual targets, naturally and with increased head moment of inertia. We simultaneously measured participants' eye and head movements to assess head oscillations at the end of the gaze shift, which are an established indicator of (transdiagnostic) sensorimotor processing deficits of head control. Results: Using a Bayesian analysis protocol, we found that patients with chronic (functional) pain and control participants stabilized their heads equally well (Bayes Factor 01 = 3.7, Bayes Factor exclusion = 5.23; corresponding to substantial evidence) during all sessions of the experiment. Conclusion: Our results suggest that patients with chronic (functional) pain do not show measurable symptom-unspecific sensorimotor processing deficits.}, language = {en} } @misc{vonWerderAubeleRegnathetal., author = {von Werder, Dina and Aubele, Maria and Regnath, Franziska and Tebbe, Elisabeth and Mladenov, Dejan and von Rheinbaben, Victoria and Hahn, Elisabeth and Sch{\"a}fer, Daniel and Biersack, Katharina and Adorjan, Kristina and Stubbe, Hans C. and Bogaerts, Katleen and J{\"o}rres, Rudolf A. and Nowak, Dennis and Van den Bergh, Omer and Glasauer, Stefan and Lehnen, Nadine}, title = {Increased breathlessness in post-COVID syndrome despite normal breathing patterns in a rebreathing challenge}, series = {Scientific reports}, volume = {15}, journal = {Scientific reports}, number = {1}, publisher = {Springer Nature}, address = {[London]}, issn = {2045-2322}, doi = {10.1038/s41598-025-11728-x}, pages = {1 -- 15}, abstract = {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.}, language = {en} }