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Background Current models on functional neurological disorders (FND) propose a multifactorial origin. Recent studies identified potential biological vulnerability factors such as a reduced limbic volume or an altered stress response. These findings highlight the need to investigate a potential genetic contribution to the biological vulnerability to FND. Method Eighty-five mixed FND patients and seventy-six healthy controls (HC) were genotyped for ten single nucleotide polymorphisms within seven genes associated with the stress system. For the genetic variant that was found associated with FND, further associations to structural brain alterations were investigated using a region-of-interest approach. Regions were previously selected based on their biological involvement and as vulnerability for FND. Results A significant association between the diagnosis of FND and the rs53576 of the oxytocin receptor (OXTR) gene was found. A significant association between decreased right insular volumes and rs53576 (OXTR) was identified in FND patients. In female patients, the rs53576 (OXTR) was associated with a reduced bilateral amygdalar volume. Conclusion These preliminary results suggest a genetic contribution to the biological vulnerability for FND involving the oxytocinergic system, and (sex-specific) structural changes in insula and amygdala.
Background Current models on functional neurological disorders (FND) propose a multifactorial origin. Recent studies identified potential biological vulnerability factors such as a reduced limbic volume or an altered stress response. These findings highlight the need to investigate a potential genetic contribution to the biological vulnerability to FND. Method Eighty-five mixed FND patients and seventy-six healthy controls (HC) were genotyped for ten single nucleotide polymorphisms within seven genes associated with the stress system. For the genetic variant that was found associated with FND, further associations to structural brain alterations were investigated using a region-of-interest approach. Regions were previously selected based on their biological involvement and as vulnerability for FND. Results A significant association between the diagnosis of FND and the rs53576 of the oxytocin receptor (OXTR) gene was found. A significant association between decreased right insular volumes and rs53576 (OXTR) was identified in FND patients. In female patients, the rs53576 (OXTR) was associated with a reduced bilateral amygdalar volume. Conclusion These preliminary results suggest a genetic contribution to the biological vulnerability for FND involving the oxytocinergic system, and (sex-specific) structural changes in insula and amygdala.
BACKGROUND Functional Neurological Disorder (FND), including Functional Movement Disorders (FMD), arises from disruptions in the perception-action cycle, where maladaptive cognitive learning processes reduce agency and motor control. FND significantly impacts quality of life, with patients often experiencing physical disability and psychological distress. Extended reality (XR) technologies present a novel therapeutic opportunity by leveraging biofeedback training to target sensory attenuation and amplification mechanisms, aiming to restore motor function and agency. OBJECTIVE Current study proposes to co-produce and evaluate the usability of an XR technology platform for FND rehabilitation, focusing on functional limb weakness. The platform integrates biofeedback training with haptic and visual feedback to support motor relearning and control. METHODS An Experience-Based Co-Design (EBCD) framework is proposed to engage FND patients, caregivers, and healthcare professionals in collaboratively designing the XR platform. Stakeholders share their experiences through narrative interviews and co-design workshops, which can identify emotional touchpoints and prioritized patient-centered needs. Insights will be synthesized using qualitative analysis and guided the development of system requirements through Quality Function Deployment (QFD), ensuring the platform aligned with user needs. Three XR training tasks—VR relaxation, XR position feedback, and XR force feedback—will be iteratively refined through 4-week Agile sprints. Usability will be assessed using the System Usability Scale (SUS) and qualitative feedback, with themes analyzed in NVivo to identify areas for platform improvement. RESULTS High usability scores (above 85) were recorded for the VR relaxation and XR position feedback tasks in pre-design phase, reflecting excellent usability and participant satisfaction. However, the XR force feedback task exhibited variability, particularly among participants with functional dystonia, underscoring the need for task-specific personalization. Key themes included customization, comfort, accessibility, and XR technological quality, ensuring the platform effectively addressed diverse patient needs. Pre-design study also highlighted the potential of XR technology for FMD rehabilitation by integrating biofeedback training into a patient-centered design framework. The EBCD and QFD approaches can facilitate co-production, ensuring that usability and accessibility challenges were systematically addressed. While high usability was achieved for most tasks in pre-design phase, the variability in force feedback usability emphasizes the importance of tailored interventions to accommodate individual needs. Current study will leverage dynamic functional connectivity within key brain regions for personalization and integrating the XR platform into the FND stepped care framework for scalable and sustainable rehabilitation. CONCLUSIONS Through co-production and iterative refinement, the current study proposes to demonstrate the promise of XR technology as a scalable at-home solution for FMD rehabilitation. Personalization and accessibility remain critical for optimizing usability and clinical outcomes, paving the way for at-home implementation within the FND stepped care model. CLINICALTRIAL N/A
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