Dopaminergic pathways and resting-state functional connectivity in Parkinson’s disease with freezing of gait
| Autor: | Masoud Tahmasian, Marina C. Ruppert, Carsten Eggers, Kenan Steidel, Irina Palaghia, Thilo van Eimeren, Marc Tittgemeyer, Alexander Drzezga, Andrea Greuel, Jochen Hammes, David J. Pedrosa, Lars Timmermann, Franziska Maier |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Parkinson's disease
Dopamine ROI region of interest Medizin Striatum FOG freezing of gait Functional connectivity MC Molecular connectivity Neural Pathways diagnostic imaging [Parkinson Disease] DMN Default mode network BDI-II Beck’s depression inventory II PGS postural instability and gait score Freezing of gait Molecular connectivity PET Multimodal imaging Medical sciences Medicine Gait Default mode network rs-fMRI resting state functional magnetic resonance tomography MMSE Mini-Mental Status Examination PDQ-39 Parkinson’s disease questionnaire Dopaminergic Regular Article Parkinson Disease Magnetic Resonance Imaging diagnostic imaging [Neural Pathways] Ventral tegmental area UPDRS-III Unified Parkinson’s disease Rating Scale part III medicine.anatomical_structure FDOPA-PET 6-[18F]fluoro-L-Dopa-PET Neurology Dopaminergic pathways NMS non-motor symptom scale complications [Parkinson Disease] medicine.drug Cognitive Neuroscience Computer applications to medicine. Medical informatics R858-859.7 FOG-Q freezing-of-gait questionnaire VTA ventral tegmental area etiology [Gait Disorders Neurologic] diagnostic imaging [Gait Disorders Neurologic] DU dopaminergic uptake medicine Humans Radiology Nuclear Medicine and imaging ddc:610 RC346-429 Gait Disorders Neurologic ComputingMethodologies_COMPUTERGRAPHICS Resting state fMRI business.industry BPd FDOPA-binding potential medicine.disease Neurology (clinical) Neurology. Diseases of the nervous system business Neuroscience |
| Zdroj: | NeuroImage: Clinical 32, 102899-(2021). doi:10.1016/j.nicl.2021.102899 Publikationen im Open Access gefördert durch die UB NeuroImage: Clinical, Vol 32, Iss, Pp 102899-(2021) NeuroImage: Clinical 32, 102899 (2021). doi:10.1016/j.nicl.2021.102899 NeuroImage : Clinical |
| DOI: | 10.1016/j.nicl.2021.102899 |
| Popis: | Graphical abstract Highlights • Freezers exhibited a dopaminergic deficit in the left caudate. • The dopamine depleted caudate shows altered striatocortical functional connectivity. • Ventral tegmental area displays increased coupling with regions of the DMN. • Molecular connectivity revealed a specific impairment in mesocorticolimbic pathways. Freezing of gait is a common phenomenon of advanced Parkinson’s disease. Besides locomotor function per se, a role of cognitive deficits has been suggested. Limited evidence of associated dopaminergic deficits points to caudatal denervation. Further, altered functional connectivity within resting-state networks with importance for cognitive functions has been described in freezers. A potential pathophysiological link between both imaging findings has not yet been addressed. The current study sought to investigate the association between dopaminergic pathway dysintegrity and functional dysconnectivity in relation to FOG severity and cognitive performance in a well-characterized PD cohort undergoing high-resolution 6-[18F]fluoro-L-Dopa PET and functional MRI. The freezing of gait questionnaire was applied to categorize patients (n = 59) into freezers and non-freezers. A voxel-wise group comparison of 6-[18F]fluoro-L-Dopa PET scans with focus on striatum was performed between both well-matched and neuropsychologically characterized patient groups. Seed-to-voxel resting-state functional connectivity maps of the resulting dopamine depleted structures and dopaminergic midbrain regions were created and compared between both groups. For a direct between-group comparison of dopaminergic pathway integrity, a molecular connectivity approach was conducted on 6-[18F]fluoro-L-Dopa scans. With respect to striatal regions, freezers showed significant dopaminergic deficits in the left caudate nucleus, which exhibited altered functional connectivity with regions of the visual network. Regarding midbrain structures, the bilateral ventral tegmental area showed altered functional coupling to regions of the default mode network. An explorative examination of the integrity of dopaminergic pathways by molecular connectivity analysis revealed freezing-associated impairments in mesolimbic and mesocortical pathways. This study represents the first characterization of a link between dopaminergic pathway dysintegrity and altered functional connectivity in Parkinson’s disease with freezing of gait and hints at a specific involvement of striatocortical and mesocorticolimbic pathways in freezers. |
| Databáze: | OpenAIRE |
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