Objective: To assess the relative importance of cortical and subcortical nodes and their connections in maintaining efficient structural connectome topology in Parkinson’s disease (PD).

Background: Dopaminergic degeneration in PD triggers a cascade of functional alterations in the extended basal ganglia network. This is associated with a redistribution of processing, which is reflected by relative hyper- or hypometabolism in subcortical and cortical regions. Less is known about the structural underpinnings of these alterations. Using a lesion simulation approach, we assessed the importance of subcortical and cortical nodes for maintaining the integrity of the structural connectome in PD.

Method: 28 PD patients without dementia (14 with mild cognitive impairment (PD-MCI)) and 20 controls underwent MRI. The grey matter was parcellated into 84 cortical and subcortical nodes. Whole-brain tractograms were represented as network graphs, weighted by the mean fractional anisotropy of each edge. Lesions of individual nodes were simulated by removing a node and its connections from the graph. The impact of simulated lesions was quantified as the proportional change in global efficiency after node removal. It was averaged for cortical and subcortical (caudate, putamen, pallidum, thalamus) nodes, and compared between groups controlling for demographic variables, grey matter atrophy and global efficiency of intact networks. Linear regression modelling was used to predict the global impact of simulated lesions.

Results: The global impact of removal of subcortical nodes was lower in PD, while the impact of cortical node removal was higher. In PD, lower topological value of subcortical nodes was the main predictor of an increased role of cortical nodes for maintaining efficient network structure. The relative importance of cortical compared to subcortical network elements was more pronounced in PD-MCI compared to PD without MCI.

Conclusion: The role of subcortical nodes and their connections in maintaining the integrational capacity of the connectome is decreased in PD. In contrast, the impact of cortical structures is increased, suggesting a compensatory role. Our study suggests a reorganisation of the structural connectome in PD which is more pronounced in PD-MCI. The rewiring of the connectome could be of interest for neuromodulation treatments and future precision-medicine interventions.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-role-of-cortical-and-subcortical-structures-in-maintaining-efficient-network-topology-in-parkinsons-disease/