Levodopa modulates small‐world architecture of functional brain networks in Parkinson's disease

Abstract

Background PD is associated with disrupted connectivity to a large number of distributed brain regions. How the disease alters the functional topological organization of the brain, however, remains poorly understood. Furthermore, how levodopa modulates network topology in PD is largely unknown. Objectives We used resting state functional MRI (rsfMRI) and graph theory to determine how small-world architecture is altered in PD and affected by levodopa administration. Methods Twenty-one PD patients and 20 controls underwent functional MRI scanning. PD patients were scanned off medication and one hour after 200mg levodopa. Imaging data were analyzed using 226 nodes comprising 10 intrinsic brain networks. Correlation matrices were generated for each subject and converted into cost thresholded, binarized adjacency matrices. Cost-integrated whole brain global and local efficiencies were compared across groups and tested for relationships with disease duration and severity. Results Data from two patients and four controls were excluded due to excess motion. Patients off medication showed no significant changes in global efficiency and overall local efficiency, but in a subnetwork analysis did show increased local efficiency in Executive (p=0.006), and Salience (p=0.018) networks. Levodopa significantly decreased local (p=0.039) efficiency in patients except within the Subcortical network where it significantly increased local efficiency (p=0.007). Conclusions Levodopa modulates global and local efficiency measures of small-world topology in PD suggesting that degeneration of nigrostriatal neurons in PD may be associated with a large-scale network reorganization, and that levodopa tends to normalize the disrupted network topology in PD.

Changes in functional organization and white matter integrity in the connectome in Parkinson's disease

“…In fact, a recent study investigated the functional reorganization of ten brain networks composed of 226 nodes in 19 cognitively intact PD patients on and off medication (Berman et al, 2016). PD patients off medication did not show a significant change in global efficiency or overall local efficiency compared to controls.…”

“…Relatively few studies have employed large-scale graph theory-based network methods using rs-fMRI in PD. These studies reported abnormalities in global and local network properties within the studied networks which also correlated with disease severity and cognitive deficits (Berman et al, 2016; Göttlich et al, 2013; Lebedev et al, 2014; Skidmore et al, 2011; Tinaz et al, 2016). …”

Cognitive Control and Brain Network Dynamics during Word Generation Tasks Predicted Using a Novel Event-Related Deep Brain Activity Method

“…By contrast, according to small-scale network architectures [77] [78], network connectivity is dependent on the modularity of neural systems. As the number of impulses pending processing increase at the synapse with decreasing the modularity, the network connectivity is improved at the cost of metabolic stress [77] [79]. Hence, connectivity and metabolic cost are counterbalanced.…”

Disrupted Brain Network Hubs in Subtype-Specific Parkinson's Disease

“…Using Rs-fMRI and graph theory, researchers have explored PD-related abnormal functional brain network in PD, including topological architecture [6,7] and spontaneous brain activity [8]. For example, PD patients exhibit marked decrease in nodal and global efficiency [9], local efficiency, and local clustering coefficient [10].…”