Altered functional connectivity in sensorimotor, emotional, and cognitive networks and changes of cerebellar volumes in Functional Movement Disorders
Autori
Elisabetta Sarasso (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, University of Genoa, Genoa, Italy) – Andrea Gardoni (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy) – Marialuisa Gandolfi (University of Verona, Verona, Italy) – Silvia Basaia (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy)
Elisa Canu (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy) – Elisa Sibilla (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy) – Chiara Tripodi (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy) – Angela Sandri (Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy)
Ilaria Antonella Di Vico (Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy) – Mirta Fiorio (University of Verona, Verona, Italy) – Giulia Pedrotti (University of Verona, Verona, Italy) – Anna Policelli (Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy)
Paolo Barone (University of Salerno, Salerno, Italy) – Maria Teresa Pellecchia (University of Salerno, Salerno, Italy) – Roberto Erro (University of Salerno, Salerno, Italy) – Sofia Cuoco (Neurological Clinic, AOU San Giovanni di Dio e Ruggi d’Aragona, Salerno, Italy)
Immacolata Carotenuto (Neurological Clinic, AOU San Giovanni di Dio e Ruggi d’Aragona, Salerno, Italy) – Claudia Vinciguerra (Neurological Clinic, AOU San Giovanni di Dio e Ruggi d’Aragona, Salerno, Italy) – Annibale Botto (Department of Neuroradiology, AOU San Giovanni di Dio e Ruggi d’Aragona, Salerno, Italy) – Marianna Amboni (Neurological Clinic, AOU San Giovanni di Dio e Ruggi d’Aragona, Salerno, Italy)
Michela Russo (Neurological Clinic, AOU San Giovanni di Dio e Ruggi d’Aragona, Salerno, Italy; Dipartimento di Ingegneria Elettrica e delle Tecnologie dell’Informazione, Università degli Studi di Napoli FEDERICO II, Naples, Italy) – Giancarlo Mansueto (University of Verona, Verona, Italy) – Francesca Benedetta Pizzini (University of Verona, Verona, Italy) – Marco Barillari (University of Verona, Verona, Italy)
Matteo Francesco Lauriola (Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy) – Maria Chiara Tozzi (Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy) – Francesca Rusciano (Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy) – Christian Geroin (University of Verona, Verona, Italy)
Melania Fasoli (University of Verona, Verona, Italy) – Angela Marotta (University of Verona, Verona, Italy) – Emanuela Pizzolla (University of Verona, Verona, Italy) – Francesca Salaorni (University of Verona, Verona, Italy)
Irene Lozzi (University of Verona, Verona, Italy) – Federica Bombieri (University of Verona, Verona, Italy) – Giovanna Maddalena Squintani (Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy) – Sara Mariotto (Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy) – Stefano Tamburin (University of Verona, Verona, Italy) – Fabio Paio (University of Verona, Verona, Italy) – Giuseppe De Biasi (Neurological Clinic, AOU San Giovanni di Dio e Ruggi d’Aragona, Salerno, Italy) – Giuseppe Piscosquito (Neurological Clinic, AOU San Giovanni di Dio e Ruggi d’Aragona, Salerno, Italy)
Michele Tinazzi (University of Verona, Verona, Italy) – Massimo Filippi (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy, Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy, Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy, Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy, Neurophysiology service, IRCCS San Raffaele Scientific Institute, Milan, Italy) – Federica Agosta (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy, Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy, Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy)
Background and aims
FMD remains a poorly understood phenomenon, characterized by inconsistent limb weakness, tremors, dystonia, and gait disturbances [1]. Preliminary evidence suggested that these symptoms might result from faulty neural processing, where disruptions in circuits integrating interoception, exteroception, and motor control lead to altered sensorimotor awareness [2]. The identification of neuroimaging biomarkers could enable earlier diagnosis and more effective management of FMD symptoms. This study aims to investigate alterations in brain functional connectivity (FC) and deep gray matter volume in patients with Functional Movement Disorders (FMD) compared to healthy controls. Specifically, it examines changes in resting-state FC networks and GM volume of areas involved in motor, exteroceptive and interoceptive domains.
Methods
Fifty-seven patients with FMD and 60 age- and sex-matched healthy controls underwent brain MRI. Brain MRI analyses included functional connectivity (FC) of the main resting-state networks using independent component analysis (MELODIC), cerebellar volumes using SUIT, and deep gray matter (GM) volumes using FMRIB’s Integrated Registration and Segmentation Tool and FreeSurfer. The study is funded by the European Union – Next Generation EU – NRRP M6C2 – Investment 2.1 Enhancement and strengthening of biomedical research in the NHS (PNRR-MAD-2022-12376826).
Results
FMD patients relative to healthy subjects exhibited an increased FC of bilateral putamen and caudate, right insula and inferior frontal gyrus within the basal ganglia network, an increased FC of bilateral precuneus within the ventral default-mode network, an increased FC of left cerebellum crus I within the primary visual network, and an increased FC of middle cingulate cortex in the precuneus network. Moreover, FMD patients showed increased volume of vermis crus II, VIIIa/b, and left lobules VIIIa/b.
Conclusion
The observed alterations of cerebellar volumes and of FC in the basal ganglia, default-mode, precuneus and primary visual networks may represent a mismatch between sensorimotor, emotional, and cognitive systems, leading to impaired self-awareness and motor intention, heightened attention to bodily signals, and compromised voluntary movement control mechanisms. These results support the neural basis of FMD, confirming that distinct mechanisms underlie the symptoms of this complex disorder.
REFERENCES
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