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Eliane Müller

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2 papers

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YNICL Journal 2025 Journal Article

Modulating the sense of agency in functional neurological disorder using real-time fMRI neurofeedback: a proof-of-concept study

Eliane Müller
Serafeim Loukas
Salome Häuselmann
Cristina Concetti
Dimitri Van De Ville
Nicolas Gninenko
Selma Aybek

BACKGROUND: Disrupted sense of agency (SoA), the perceived loss of control over one's actions, is common in functional neurological disorder (FND) and linked to abnormal activation in agency-related networks, particularly the right temporoparietal junction (rTPJ). This proof-of-concept study tested whether fMRI neurofeedback (NF) could enhance SoA in FND by targeting the rTPJ. METHODS: In this single-arm feasibility study, 18 patients with mixed FND symptoms completed three NF trainings during an adaptive visuomotor task, receiving intermittent visual feedback of their rTPJ activity. Pre- and post-training assessments included subjective agency ratings, neuroimaging during a transfer task, and clinical evaluations. RESULTS: Group-level subjective agency significantly increased after training (p = 0.0083), driven by responders (n = 8) who exhibited rTPJ (p = 0.042) and supplementary motor area (SMA) upregulation (p = 0.015) in the first session, alongside consistent task engagement. Behavioral gains coincided with trend-level decreases in rTPJ-dorsolateral prefrontal cortex (dlPFC) connectivity (p = 0.098), while non-responders showed reduced rTPJ-SMA connectivity (p = 0.008). No group-level clinical improvements were observed, but higher initial rTPJ (p = 0.03, ρ = -0.78) and dlPFC (p = 0.03, ρ = -0.75) activation were negatively associated with changes in self-reported core symptoms. CONCLUSION: NF from rTPJ activity is feasible in FND and may enhance explicit SoA in a subset of patients through early neural modulation and sustained engagement. High inter-individual variability underscores the need for sham-controlled trials with optimized, engaging feedback designs and longitudinal monitoring to identify patients who could benefit from NF.

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YNICL Journal 2025 Journal Article

Reduced microstructural white matter integrity is associated with the severity of physical symptoms in functional neurological disorder

Nicolas Gninenko
Eliane Müller
Selma Aybek

BACKGROUND: Functional neurological disorder (FND) is linked to functional changes in brain networks without an underlying brain lesion. However, the dichotomy between functional and structural changes has been challenged by research suggesting that not only functional but also anatomical alterations in the gray and white matter may underlie a subset of symptoms. This study aimed to characterize white matter microstructural integrity and its association with patient-reported and clinician-rated physical symptoms' severity in a large sample of FND patients. METHODS: Diffusion-weighted imaging data were collected from 85 FND patients with mixed symptoms and 75 healthy controls (HCs), together with illness duration, clinician-rated (S-FMDRS & CGI), and patient-reported (SF-36) symptom severity. Microstructural integrity was computed based on probabilistic tractography using the Desikan-Killiany parcellation. RESULTS: Compared to HCs, patients with FND presented widespread reduced microstructural integrity stemming from regions such as the right lateral orbitofrontal cortex, insula, putamen, and superior temporal regions. After adjusting for depression and anxiety, these differences were no longer significant. Within-group analysis revealed that reduced microstructural integrity, particularly in the left precuneus and left superior parietal cortex, was strongly correlated with both patient-reported and clinician-evaluated severity of physical symptoms in FND patients. CONCLUSION: Patients with FND present widespread reduced microstructural integrity in the brain, predominantly originating from temporoparietal, paralimbic and associated regions involved in emotion regulation and body awareness. These changes seem to be partly explained by comorbid mood disorders and the severity of physical symptoms, suggesting a plasticity phenomenon rather than trait biomarkers, which warrants further investigation in longitudinal study designs.

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