Objective: 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.

Background: 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.

Method: Thirty-eight patients with FMD and 43 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), and deep gray matter (GM) volumes using FMRIB’s Integrated Registration and Segmentation Tool and FreeSurfer.

This study was 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 the right caudate, putamen, insula and orbitofrontal gyrus within the basal ganglia network and an increased FC of the left precuneus within the ventral default-mode network. Moreover, FMD patients showed an increased volume of the left pallidum.

Conclusion: The observed alterations of basal ganglia and default-mode 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: [1] Tinazzi M, Morgante F, Marcuzzo E, Erro R, Barone P, Ceravolo R, Mazzucchi S, Pilotto A, Padovani A, Romito LM, Eleopra R, Zappia M, Nicoletti A, Dallocchio C, Arbasino C, Bono F, Pascarella A, Demartini B, Gambini O, Modugno N, Olivola E, Di Stefano V, Albanese A, Ferrazzano G, Tessitore A, Zibetti M, Calandra-Buonaura G, Petracca M, Esposito M, Pisani A, Manganotti P, Stocchi F, Coletti Moja M, Antonini A, Defazio G, Geroin C. Clinical Correlates of Functional Motor Disorders: An Italian Multicenter Study. Mov Disord Clin Pract. 2020 Sep 22;7(8):920-929. doi: 10.1002/mdc3.13077. PMID: 33163563; PMCID: PMC7604660.
[2] Hallett M, Aybek S, Dworetzky BA, McWhirter L, Staab JP, Stone J. Functional neurological disorder: new subtypes and shared mechanisms. Lancet Neurol. 2022 Jun;21(6):537-550. doi: 10.1016/S1474-4422(21)00422-1. Epub 2022 Apr 14. Erratum in: Lancet Neurol. 2022 Jun;21(6):e6. doi: 10.1016/S1474-4422(22)00179-X. PMID: 35430029; PMCID: PMC9107510.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/increased-basal-ganglia-and-default-mode-network-connectivity-and-altered-deep-gray-matter-volume-in-functional-movement-disorders/