Differential Brain Connectivity Patterns in Functional Movement Disorders: Evidence for Gait-Disorder-Specific Aberrations

Abstract

BackgroundThe clinical presentation of Functional Movement Disorders (FMD) is highly variable, encompassing gait disturbances and a wide range of hyper- and hypokinetic movement abnormalities. The neural correlates distinguishing different phenotypes, particularly functional gait disorders, remain poorly understood.ObjectiveTo investigate whether functional gait disorders are associated with specific patterns of brain connectivity that distinguish them from other FMD phenotypes.MethodsThirty-eight FMD patients (9 with isolated gait disorders, 9 with combined gait and other motor symptoms, 20 with non-gait motor symptoms) and 20 healthy controls underwent resting-state functional MRI. Using seed-based connectivity analysis with eight bilateral regions of interest of the motor network, we examined functional connectivity patterns across groups.ResultsSeed-based functional connectivity analysis revealed decreased connectivity between the left caudate nucleus and the left temporoparietal junction across gait disorder groups compared to both non-gait disorders and healthy controls. Patients with gait disorders showed decreased interhemispheric connectivity between primary sensorimotor areas compared to non-gait disorder patients, but partially increased connectivity compared to healthy controls. Both, isolated and combined gait disorder groups demonstrated characteristic alterations in premotor-sensorimotor connectivity patterns, with distinct profiles between these subgroups.ConclusionOur findings suggest distinct neural signatures in functional gait disorders compared to other functional movement phenotypes. These findings might reflect specific pathophysiological mechanisms underlying functional gait disorders, particularly involving sensory feedback integration and motor control. These results provide new insights into the neural basis of different functional movement disorder phenotypes and may contribute to the development of targeted therapeutic approaches.

Note:
Funding declaration: This work was supported by the Deutsche Forschungsgemeinschaft (DFG, grant number WE 5919/4-1).

Conflict of Interests: CAG was supported by the Faculty of Medicine, Christian-Albrechts-University Kiel. NB received honaria from Abbott, Abbvie, Biogen, Esteve, Ipsen, Merz, Teva, Zambon and was supported by the DFG (BR4328.2-2, GRK1957), the Michael J Fox Foundation, and the EU Joint Programme - Neurodegenerative Disease Research (JPND). KEZ has received research support from Strathmann and the German Research Council. She reports speaker’s honoraria from Bayer Vital GmbH, BIAL, AbbVie, Alexion, Allergan and Merz outside the submitted work. She has served as a consultant and received fees from Merz, Ipsen, Alexion, Bial and the German Federal Institute for Drugs and Medical Devices (BfArM). JSB has received consultancies/advisory board fees from Jazz Pharmaceuticals and Neuraxpharm, research support from Strathmann and speaker’s honoraria from Ipsen and Stadapharm.

Ethical Approval: All participants provided written informed consent. The study was approved by the Ethics Committees of the University Hospitals of Kiel and Lübeck and conducted in accordance with the approved guidelines.

Keywords: Movement Disorders, Functional, Gait Disorders, Neurologic, Magnetic Resonance Imaging, Functional, Motor Network, Temporoparietal Junction