Emergent Functional Network Effects in Parkinson Disease

Abstract The hallmark pathology underlying Parkinson disease (PD) is progressive synucleinopathy, beginning in caudal brainstem that later spreads rostrally. However, the primarily subcortical pathology fails to account for the wide spectrum of clinical manifestations in PD. To reconcile these obser...

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Published in:Cerebral cortex (New York, N.Y. 1991) N.Y. 1991), 2019-06, Vol.29 (6), p.2509-2523
Main Authors: Gratton, Caterina, Koller, Jonathan M, Shannon, William, Greene, Deanna J, Maiti, Baijayanta, Snyder, Abraham Z, Petersen, Steven E, Perlmutter, Joel S, Campbell, Meghan C
Format: Article
Language:English
Subjects:
Aged
Brain - physiopathology
Connectome - methods
Female
Humans
Magnetic Resonance Imaging - methods
Male
Middle Aged
Neural Pathways - physiopathology
Original
Parkinson Disease - physiopathology
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Summary:Abstract The hallmark pathology underlying Parkinson disease (PD) is progressive synucleinopathy, beginning in caudal brainstem that later spreads rostrally. However, the primarily subcortical pathology fails to account for the wide spectrum of clinical manifestations in PD. To reconcile these observations, resting-state functional connectivity (FC) can be used to examine dysfunction across distributed brain networks. We measured FC in a large, single-site study of nondemented PD (N = 107; OFF medications) and healthy controls (N = 46) incorporating rigorous quality control measures and comprehensive sampling of cortical, subcortical and cerebellar regions. We employed novel statistical approaches to determine group differences across the entire connectome, at the network-level, and for select brain regions. Group differences respected well-characterized network delineations producing a striking “block-wise” pattern of network-to-network effects. Surprisingly, these results demonstrate that the greatest FC differences involve sensorimotor, thalamic, and cerebellar networks, with notably smaller striatal effects. Split-half replication demonstrates the robustness of these results. Finally, block-wise FC correlations with behavior suggest that FC disruptions may contribute to clinical manifestations in PD. Overall, these results indicate a concerted breakdown of functional network interactions, remote from primary pathophysiology, and suggest that FC deficits in PD are related to emergent network-level phenomena rather than focal pathology.
ISSN:1047-3211
1460-2199
DOI:10.1093/cercor/bhy121