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. 2024 Sep 26;19(9):e0309408.
doi: 10.1371/journal.pone.0309408. eCollection 2024.

A window into the mind-brain-body interplay: Development of diagnostic, prognostic biomarkers, and rehabilitation strategies in functional motor disorders

Marialuisa Gandolfi  1 , Angela Sandri  2 , Sara Mariotto  2 , Stefano Tamburin  1 , Anna Paolicelli  2 , Mirta Fiorio  1 , Giulia Pedrotti  1 , Paolo Barone  3 , Maria Teresa Pellecchia  3 , Roberto Erro  3 , Sofia Cuoco  4 , Immacolata Carotenuto  4 , Claudia Vinciguerra  4 , Annibale Botto  5 , Lucia Zenere  2   6 , Elisa Canu  6 , Elisa Sibilla  6 , Massimo Filippi  6   7   8   9   10 , Elisabetta Sarasso  6   7   11 , Federica Agosta  6   7   8 , Michele Tinazzi  1 ; Group Collaborators Consortium
Affiliations

A window into the mind-brain-body interplay: Development of diagnostic, prognostic biomarkers, and rehabilitation strategies in functional motor disorders

Marialuisa Gandolfi et al. PLoS One. .

Abstract

Background and aims: Functional motor disorders (FMD) present a prevalent, yet misunderstood spectrum of neurological conditions characterized by abnormal movements (i.e., functional limb weakness, tremor, dystonia, gait impairments), leading to substantial disability and diminished quality of life. Despite their high prevalence, FMD often face delayed diagnosis and inadequate treatment, resulting in significant social and economic burdens. The old concept of psychological factors as the primary cause (conversion disorder) has been abandoned due to the need for more evidence about their causal role. According to a predictive coding account, the emerging idea is that symptoms and disability may depend on dysfunctions of a specific neural system integrating interoception, exteroception, and motor control. Consequently, symptoms are construed as perceptions of the body's state. Besides the main pathophysiological features (abnormal attentional focus, beliefs/expectations, and sense of agency), the lived experience of symptoms and their resulting disability may depend on an altered integration at the neural level of interoception, exteroception, and motor control.

Methods and materials: Our proposal aims to elucidate the pathophysiological mechanisms of FMD through a three-stage research approach. Initially, a large cohort study will collect behavioral, neurophysiological, and MRI biomarkers from patients with FMD and healthy controls, employing eXplainable Artificial Intelligence (XAI) to develop a diagnostic algorithm. Subsequently, validation will occur using patients with organic motor disorders. Finally, the algorithm's prognostic value will be explored post-rehabilitation in one subgroup of patients with FMD.

Results: Data collection for the present study started in May 2023, and by May 2025, data collection will conclude.

Discussion: Our approach seeks to enhance early diagnosis and prognostication, improve FMD management, and reduce associated disability and socio-economic costs by identifying disease-specific biomarkers.

Trial registration: This trial was registered in clinicaltrials.gov (NCT06328790).

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Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: E. Sarasso and E. Canu have received research support from the Italian Ministry of Health. M. Filippi is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences, and Radiology, received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi, speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA, participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda, scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme, he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla. F. Agosta is Associate Editor of NeuroImage: Clinical, has received speaker honoraria from Biogen Idec, Italfarmaco, Roche, Zambon and Ely Lilli, and receives or has received research supports from the Italian Ministry of Health, the Italian Ministry of University and Research, AriSLA (Fondazione Italiana di Ricerca per la SLA), the European Research Council, the EU Joint Programme – Neurodegenerative Disease Research (JPND), and Foundation Research on Alzheimer Disease (France). The other authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. The schedule of enrolment, interventions, and assessments.
° in a sub-group of patients (n = 34); HC, Healthy Control; FMD, Functional Motor Disorder, MRI, Magnetic Resonance Imaging; T0 –assessment before rehabilitation; T1 –assessment at three months Follow-up.
Fig 2
Fig 2. An overview of the organization of the study program.
FMD, Functional Motor Disorder; HC, Healthy Control; MRI, Magnetic Resonance Imaging; XAI, eXplainable Artificial Intelligence.
See this image and copyright information in PMC

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