Dopaminergic pathways and resting-state functional connectivity in Parkinson’s disease with freezing of gait

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-st...

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Autores principales:	Kenan Steidel, Marina C. Ruppert, Irina Palaghia, Andrea Greuel, Masoud Tahmasian, Franziska Maier, Jochen Hammes, Thilo van Eimeren, Lars Timmermann, Marc Tittgemeyer, Alexander Drzezga, David Pedrosa, Carsten Eggers
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Freezing of gait Multimodal imaging PET Functional connectivity Molecular connectivity Computer applications to medicine. Medical informatics R858-859.7 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/7029a6e36bca43fd9ca59b05ca98404c
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spelling	oai:doaj.org-article:7029a6e36bca43fd9ca59b05ca98404c2021-12-02T05:01:30ZDopaminergic pathways and resting-state functional connectivity in Parkinson’s disease with freezing of gait2213-158210.1016/j.nicl.2021.102899https://doaj.org/article/7029a6e36bca43fd9ca59b05ca98404c2021-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2213158221003430https://doaj.org/toc/2213-1582Freezing 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.Kenan SteidelMarina C. RuppertIrina PalaghiaAndrea GreuelMasoud TahmasianFranziska MaierJochen HammesThilo van EimerenLars TimmermannMarc TittgemeyerAlexander DrzezgaDavid PedrosaCarsten EggersElsevierarticleFreezing of gaitMultimodal imagingPETFunctional connectivityMolecular connectivityComputer applications to medicine. Medical informaticsR858-859.7Neurology. Diseases of the nervous systemRC346-429ENNeuroImage: Clinical, Vol 32, Iss , Pp 102899- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Freezing of gait Multimodal imaging PET Functional connectivity Molecular connectivity Computer applications to medicine. Medical informatics R858-859.7 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Freezing of gait Multimodal imaging PET Functional connectivity Molecular connectivity Computer applications to medicine. Medical informatics R858-859.7 Neurology. Diseases of the nervous system RC346-429 Kenan Steidel Marina C. Ruppert Irina Palaghia Andrea Greuel Masoud Tahmasian Franziska Maier Jochen Hammes Thilo van Eimeren Lars Timmermann Marc Tittgemeyer Alexander Drzezga David Pedrosa Carsten Eggers Dopaminergic pathways and resting-state functional connectivity in Parkinson’s disease with freezing of gait
description	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.
format	article
author	Kenan Steidel Marina C. Ruppert Irina Palaghia Andrea Greuel Masoud Tahmasian Franziska Maier Jochen Hammes Thilo van Eimeren Lars Timmermann Marc Tittgemeyer Alexander Drzezga David Pedrosa Carsten Eggers
author_facet	Kenan Steidel Marina C. Ruppert Irina Palaghia Andrea Greuel Masoud Tahmasian Franziska Maier Jochen Hammes Thilo van Eimeren Lars Timmermann Marc Tittgemeyer Alexander Drzezga David Pedrosa Carsten Eggers
author_sort	Kenan Steidel
title	Dopaminergic pathways and resting-state functional connectivity in Parkinson’s disease with freezing of gait
title_short	Dopaminergic pathways and resting-state functional connectivity in Parkinson’s disease with freezing of gait
title_full	Dopaminergic pathways and resting-state functional connectivity in Parkinson’s disease with freezing of gait
title_fullStr	Dopaminergic pathways and resting-state functional connectivity in Parkinson’s disease with freezing of gait
title_full_unstemmed	Dopaminergic pathways and resting-state functional connectivity in Parkinson’s disease with freezing of gait
title_sort	dopaminergic pathways and resting-state functional connectivity in parkinson’s disease with freezing of gait
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/7029a6e36bca43fd9ca59b05ca98404c
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Dopaminergic pathways and resting-state functional connectivity in Parkinson’s disease with freezing of gait

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