Universität zu Köln

Ruppert, Marina C., Greuel, Andrea, Tahmasian, Masoud ORCID: 0000-0003-3999-3807, Schwartz, Frank, Stuermer, Sophie, Maier, Franziska, Hammes, Jochen, Tittgemeyer, Marc, Timmermann, Lars, van Eimeren, Thilo, Drzezga, Alexander and Eggers, Carsten (2020). Network degeneration in Parkinson's disease: multimodal imaging of nigro-striato-cortical dysfunction. Brain, 143. S. 944 - 960. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2156

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Abstract

The spreading hypothesis of neurodegeneration assumes an expansion of neural pathologies along existing neural pathways. Multimodal neuroimaging studies have demonstrated distinct topographic patterns of cerebral pathologies in neurodegeneration. For Parkinson's disease the hypothesis so far rests largely on histopathological evidence of alpha-synuclein spreading in a characteristic pattern and progressive nigrostriatal dopamine depletion. Functional consequences of nigrostriatal dysfunction on cortical activity remain to be elucidated. Our goal was to investigate multimodal imaging correlates of degenerative processes in Parkinson's disease by assessing dopamine depletion and its potential effect on striatocortical connectivity networks and cortical metabolism in relation to parkinsonian symptoms. We combined F-18-DOPA-PET, F-18-fluorodeoxyglucose (FDG)-PET and resting state functional MRI to multimodally characterize network alterations in Parkinson's disease. Forty-two patients with mild-to-moderate stage Parkinson's disease and 14 age-matched healthy control subjects underwent a multimodal imaging protocol and comprehensive clinical examination. A voxel-wise group comparison of F-18-DOPA uptake identified the exact location and extent of putaminal dopamine depletion in patients. Resulting dusters were defined as seeds for a seed-to-voxel functional connectivity analysis. F-18-FDG metabolism was compared between groups at a whole-brain level and uptake values were extracted from regions with reduced putaminal connectivity. To unravel associations between dopaminergic activity, striatocortical connectivity, glucose metabolism and symptom severity, correlations between normalized uptake values, seed-to-cluster beta-values and clinical parameters were tested while controlling for age and dopaminergic medication. Aside from cortical hypometabolism, F-18-FDG-PET data for the first time revealed a hypometabolic midbrain cluster in patients with Parkinson's disease that comprised caudal parts of the bilateral substantia nigra pars compacta. Putaminal dopamine synthesis capacity was significantly reduced in the bilateral posterior putamen and correlated with ipsilateral nigral F-18-FUG uptake. Resting state functional MRI data indicated significantly reduced functional connectivity between the dopamine depleted putaminal seed and cortical areas primarily belonging to the sensorimotor network in patients with Parkinson's disease. In the inferior parietal cortex, hypoamnectivity in patients was significantly correlated with lower metabolism (left P= 0.021, right P = 0.018). Of note, unilateral network alterations quantified with different modalities corresponded with contralateral motor impairments. In conclusion, our results support the hypothesis that degeneration of nigrostriatal fibres functionally impairs distinct striatocortical connections, disturbing the efficient interplay between motor processing areas and impairing motor control in patients with Parkinson's disease. The present study is the first to reveal trimodal evidence for network-dependent degeneration in Parkinson's disease by outlining the impact of functional nigrostriatal pathway impairment on striatocortical functional connectivity networks and cortical metabolism.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ruppert, Marina C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Greuel, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Tahmasian, Masoud UNSPECIFIED orcid.org/0000-0003-3999-3807 UNSPECIFIED Schwartz, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Stuermer, Sophie UNSPECIFIED UNSPECIFIED UNSPECIFIED Maier, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Hammes, Jochen UNSPECIFIED UNSPECIFIED UNSPECIFIED Tittgemeyer, Marc UNSPECIFIED UNSPECIFIED UNSPECIFIED Timmermann, Lars UNSPECIFIED UNSPECIFIED UNSPECIFIED van Eimeren, Thilo UNSPECIFIED UNSPECIFIED UNSPECIFIED Drzezga, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Eggers, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-342567
DOI:	10.1093/brain/awaa019
Journal or Publication Title:	Brain
Volume:	143
Page Range:	S. 944 - 960
Date:	2020
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2156
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language POSITRON-EMISSION-TOMOGRAPHY; RESTING-STATE FMRI; FUNCTIONAL CONNECTIVITY; BASAL GANGLIA; ALZHEIMERS-DISEASE; SUBSTANTIA-NIGRA; HUMAN BRAIN; CIRCUITS; PATTERNS; TAU Multiple languages Clinical Neurology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34256