N. Piramide1,2, E. Sarasso1,2, A. Tomic3, E. Canu1, I. Petrovic3, M. Svetel3, S. Basaia1, N. Dragasevic Miskovic3, V.S. Kostic3, M. Filippi1,4,5,2, F. Agosta1,2
1IRCCS San Raffaele Scientific Institute, Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Milan, Italy, 2Vita-Salute San Raffaele University, Milan, Italy, 3University of Belgrade, Clinic of Neurology, Faculty of Medicine, Belgrade, Serbia, 4IRCCS San Raffaele Scientific Institute, Neurology Unit, Milan, Italy, 5IRCCS San Raffaele Scientific Institute, Neurophysiology Unit, Milan, Italy

Background: The pathophysiological mechanisms underlying functional dystonia (FD) are poorly understood, making FD management a challenge for clinicians. Recent studies showed structural alterations of the sensorimotor and emotional circuits in FD patients. To date, no functional MRI (fMRI) studies investigated functional connectivity (FC) alterations in patients with FD.

Purpose: To explore the functional connectivity (FC) of the primary motor (M1) cortex in functional dystonia (FD) patients relative to healthy controls, with a focus on different clinical phenotypes.

Methods: Forty FD patients (12 fixed [FixFD]; 28 mobile [MobFD]) and 43 healthy controls (14 young FixFD-age-matched [yHC]; 29 old MobFD-age-matched [oHC]) were recruited.FD patients and controls underwent resting state fMRI. A seed-based FC analysis was performed using bilateral M1 as regions of interest.

Results: Compared to controls, FD patients showed reduced FC between left M1 and left dorsal anterior cingulate cortex, and between right M1 and left M1, premotor/supplementary motor area (SMA), dorsal posterior cingulate cortex (PCC), and bilateral precuneus. Relative to yHC, FixFD patients showed reduced FC between M1 and precuneus bilaterally. Compared to oHC, MobFD patients revealed reduced FC between right M1 and left M1, premotor/SMA, dorsal-PCC, bilateral primary sensory cortices and parieto-occipital areas, and increased FC of right M1 with right associative visual cortex and bilateral ventral-PCC. FixFD patients, relative to MobFD, showed lower FC between the right M1 and right associative visual area, and bilateral precuneus and ventral-PCC.

Conclusion(s): Our study confirm previous findings in the whole FD group, suggesting a disconnection between motor areas and regions involved in sense of agency (precuneus), emotional regulation and inhibitory function (cingulate cortex). In addition, our results point toward different FC changes in the two FD phenotypes, with FixFD patients having abnormalities mainly in areas related to sense of agency, while MobFD in regions involved in sensorimotor functions (reduced FC) and emotional processing (increased FC). The different FC alterations we found in the two groups of FD patients sustained the presence of FixFD and MobFD clinical phenotypes, supporting previous clinical and structural MRI findings.

Implications: Improving our knowledge on the pathophysiological mechanisms underlying FD could help clinicians to better manage motor manifestations that are typical for FD.

Funding, acknowledgements: This study was supported by the Ministry of Education, Science, and Technological Development of the Republic of Serbia (project #175090).

Keywords: functional dystonia, sensorimotor networks, functional connectivity

Topic: Neurology: Parkinson's disease

Did this work require ethics approval? Yes
Institution: Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia
Committee: Human Research Ethics Committee of University of Belgrade, Serbia
Ethics number: Belgrade project #175090

All authors, affiliations and abstracts have been published as submitted.

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