Large-scale network dysfunction in a-Synucleinopathy: A meta-analysis of resting-state functional connectivity

Background Although dysfunction of large-scale brain networks has been frequently demonstrated in patients with a-Synucleinopathy (alpha-Syn, i.e., Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy), a consistent pattern of dysfunction remains unclear. We aim to investigate network dysfunction in patients with alpha-Syn through a meta-analysis.& nbsp;Methods Whole-brain seed-based resting-state functional connectivity studies (published before September 1st, 2020 in English) comparing alpha-Syn patients with healthy controls (HC) were retrieved from electronic databases (PubMed, Web of Science, and EMBASE). Seeds from each study were categorized into networks by their location within a priori functional networks. Seed-based effect size mapping with Permutation of Subject Images analysis of between-group effects identified the network systems in which alpha-Syn was associated with hyperconnectivity (increased connectivity in alpha-Syn vs. HC) or hypoconnectivity (decreased connectivity in alpha-Syn vs. HC) within and between each seed-network. This study was registered on PROSPERO (CRD42020210133).& nbsp;Findings In total, 136 seed-based voxel-wise resting-state functional connectivity datasets from 72 publications (3093 alpha-Syn patients and 3331 HC) were included in the meta-analysis. We found that alpha-Syn patients demonstrated imbalanced connectivity among subcortical network, cerebellum, and frontal parietal networks that involved in motor functioning and executive control. The patient group was associated with hypoconnectivity in default mode network and ventral attention network that involved in cognition and attention. Additionally, the patient group exhibited hyperconnectivity between neural systems involved in top-down emotion regulation and hypoconnectivity between networks involved in bottom-up emotion processing.& nbsp;Interpretation These findings supported neurocognitive models in which network dysfunction is tightly linked to motor, cognitive and psychiatric symptoms observed in alpha-Syn patients.& nbsp;Funding This study was partially supported by the Research Grants Council of Hong Kong (Grant No. RGC14116121). Copyright (C)& nbsp;2022 The Author(s). Published by Elsevier B.V.

Automated summary

A meta-analysis on network dysfunction in patients with alpha-Synucleinopathy revealed imbalanced connectivity in subcortical networks, cerebellum, and frontal networks related to motor functioning and cognitive control. Patients also exhibited hypoconnectivity in networks involved in cognition and attention, as well as abnormal connectivity between networks related to emotion regulation and processing.