Universität zu Köln

Steidel, Kenan, Ruppert, Marina C., Palaghia, Irina, Greuel, Andrea ORCID: 0000-0002-0001-9225, Tahmasian, Masoud, Maier, Franziska, Hammes, Jochen, van Eimeren, Thilo ORCID: 0000-0002-6951-2325, Timmermann, Lars, Tittgemeyer, Marc, Drzezga, Alexander, Pedrosa, David and Eggers, Carsten (2021). Dopaminergic pathways and resting-state functional connectivity in Parkinson's disease with freezing of gait. NeuroImage-Clin., 32. OXFORD: ELSEVIER SCI LTD. ISSN 2213-1582

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Steidel, Kenan UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruppert, Marina C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Palaghia, Irina UNSPECIFIED UNSPECIFIED UNSPECIFIED Greuel, Andrea UNSPECIFIED orcid.org/0000-0002-0001-9225 UNSPECIFIED Tahmasian, Masoud UNSPECIFIED UNSPECIFIED UNSPECIFIED Maier, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Hammes, Jochen UNSPECIFIED UNSPECIFIED UNSPECIFIED van Eimeren, Thilo UNSPECIFIED orcid.org/0000-0002-6951-2325 UNSPECIFIED Timmermann, Lars UNSPECIFIED UNSPECIFIED UNSPECIFIED Tittgemeyer, Marc UNSPECIFIED UNSPECIFIED UNSPECIFIED Drzezga, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Pedrosa, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Eggers, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-596410
DOI:	10.1016/j.nicl.2021.102899
Journal or Publication Title:	NeuroImage-Clin.
Volume:	32
Date:	2021
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	2213-1582
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GRAY-MATTER ATROPHY; MOTOR; CONFLICT; DEFICITS; PET; PATHOGENESIS; STIMULATION; VALIDATION; PERFUSION; TEMPLATE Multiple languages Neuroimaging Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59641