Experimental evidence for a robust, transdiagnostic marker in functional disorders: Erroneous sensorimotor processing in functional dizziness and functional movement disorder.

OBJECTIVE: Recent neuroscientific models suggest that functional bodily symptoms can be attributed to perceptual dysregulation in the central nervous system. Evidence for this hypothesis comes from patients with functional dizziness, who exhibit marked sensorimotor processing deficits during eye-head movement planning and execution. Similar findings in eye-head movement planning in patients with irritable bowel syndrome confirmed that these sensorimotor processing deficits represent a shared, transdiagnostic mechanism. We now examine whether erroneous sensorimotor processing is also at play in functional movement disorder. METHODS: We measured head movements of 10 patients with functional movement disorder (F44.4, ICD-10), 10 patients with functional dizziness (F45.8, ICD-10), and (respectively) 10 healthy controls during an eye-head experiment, where participants performed large gaze shifts under normal, increased, and again normal head moment of inertia. Head oscillations at the end of the gaze shift served as a well-established marker for sensorimotor processing problems. We calculated Bayesian statistics for comparison. RESULTS: Patients with functional movement disorder (Bayes Factor (BF)10 = 5.36, BFincl = 11.16; substantial to strong evidence) as well as patients with functional dizziness (BF10 = 2.27, BFincl = 3.56; anecdotal to substantial evidence) showed increased head oscillations compared to healthy controls, indicating marked deficits in planning and executing movement. CONCLUSION: We replicate earlier experimental findings on erroneous sensorimotor processing in patients with functional dizziness, and show that patients with functional movement disorder show a similar impairment of sensorimotor processing during large gaze shifts. This provides an objectively measurable, transdiagnostic marker for functional disorders, highlighting important implications for diagnosis, treatment, and de-stigmatization.

Post-COVID breathlessness: a mathematical model of respiratory processing in the brain.

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.

Not a general, symptom-unspecific, transdiagnostic marker for functional symptoms: sensorimotor processing of head control is intact in chronic pain.

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. We discuss outcome parameter choice, organ system specificity, and selection of patient diagnoses as possible reasons for this result and recommend future avenues for research.

Altered sensorimotor processing in irritable bowel syndrome: Evidence for a transdiagnostic pathomechanism in functional somatic disorders.

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.