Abstract

Aim: The aim of the present study is to investigate the relationship between both functional connectivity and brain networks with cognitive decline, in patients with Parkinson's disease (PD). Introduction: PD phenotype is not limited to motor impairment but, rather, a wide range of non-motor disturbances can occur, with cognitive impairment being one of the most common. However, how the large-scale organization of brain activity differs in cognitively impaired patients, as opposed to cognitively preserved ones, remains poorly understood. Methods: Starting from source-reconstructed resting-state magnetoencephalography data, we applied the phase linearity measurement (PLM) to estimate functional connectivity, globally and between brain areas, in PD patients with and without cognitive impairment (respectively PD-CI and PD-NC), as compared with healthy subjects (HS). Further, using graph analysis, we characterized the alterations in brain network topology and related these, as well as the functional connectivity, to cognitive performance. Results: We found reduced global and nodal PLM in several temporal (fusiform gyrus, Heschl's gyrus, and inferior temporal gyrus), parietal (postcentral gyrus), and occipital (lingual gyrus) areas within the left hemisphere, in the gamma band, in PD-CI patients, as compared with PD-NC and HS. With regard to the global topological features, PD-CI patients, as compared with HS and PD-NC patients, showed differences in multi-frequencies bands (delta, alpha, gamma) in the Leaf fraction, Tree hierarchy (Th) (both higher in PD-CI), and Diameter (lower in PD-CI). Finally, we found statistically significant correlations between the Montreal Cognitive Assessment test and both the Diameter in delta band and the Th in the alpha band. Conclusion: Our work points to specific large-scale rearrangements that occur selectively in cognitively compromised PD patients and are correlated to cognitive impairment. Impact statement In this article, we want to test the hypothesis that the cognitive decline observed in Parkinson's disease (PD) patients may be related to specific changes of both functional connectivity and brain network topology. Specifically, starting from magnetoencephalography signals and by applying the phase linearity measurement (PLM), a connectivity metric that measures the synchronization between brain regions, we were able to highlight differences in the global and nodal PLM values in PD patients with cognitive impairment as compared with both cognitively unimpaired patients and healthy subjects. Further, using graph analysis, we analyzed alterations in brain network topology that were related to cognitive functioning.

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