Emergent Functional Network Effects in Parkinson Disease

Caterina Gratton, Jonathan M. Koller, William Shannon, Deanna J. Greene, Baijayanta Maiti, Abraham Z. Snyder, Steven E. Petersen, Joel S. Perlmutter, Meghan C. Campbell*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2509-2523
Number of pages15
JournalCerebral Cortex
Issue number6
StatePublished - Jun 1 2019


  • Parkinson disease
  • fMRI
  • functional connectivity
  • networks

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cognitive Neuroscience


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