Objective: To investigate topological organization of the functional brain connectome in Parkinson’s disease (PD) patients with freezing of gait (FOG).

Background: The cumulative evidence of neuroimaging studies suggested that PD FOG may be related to a network-wide dysfunction. Up to date, the topological architecture of the functional brain connectome in PD patients with FOG remain unknown.

Method: The functional brain connectome was constructed for 37 PD patients with FOG and 38 matched patients without FOG by using resting-state functional magnetic resonance imaging (MRI) data, and the topologic properties were analyzed by using graph theory approaches. Nonparametric permutation tests were used for group comparisons of topological properties. The Network-based statistic (NBS) was further employed to investigate functional connectivity alteration in PD patients with FOG.

Results: Both groups showed efficient small-world topology in the functional brain connectome. However, compared with patients without FOG, those with FOG showed altered values in the global properties, characterized by lower normalized clustering coefficient and marginally higher global efficiency, implying a shift toward randomization in their functional brain connectome. In addition, Patients with FOG showed increased nodal centralities and increased functional connectivity of widely distributed subnetworks involving the sensorimotor network (supplementary motor area), frontoparietal network, visual network and subcortical regions (caudate and thalamus) and decreased nodal centralities in the triangular part of inferior frontal and parahippocampal cortices. Notably, the altered nodal centralities in the right hippocampus were positively correlated with FOG severity.

Conclusion: These results suggest that PD FOG is associated with disruptions in the topological organization of the functional brain connectome and this disruption in widely distributed neural networks may contribute to systems-level impairments in PD patients with FOG.

References: 1. Ehgoetz Martens KA, Hall JM, Georgiades MJ, et al. The functional network signature of heterogeneity in freezing of gait. Brain 2018; 141(4): 1145-60. 2. Mitchell T, Potvin-Desrochers A, Lafontaine AL, Monchi O, Thiel A, Paquette C. Cerebral metabolic changes related to freezing of gait in Parkinson’s disease. J Nucl Med 2018. 3. Fasano A, Herman T, Tessitore A, Strafella AP, Bohnen NI. Neuroimaging of Freezing of Gait. J Parkinsons Dis 2015; 5(2): 241-54.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/disrupted-functional-brain-connectome-in-parkinsons-disease-patients-with-freezing-of-gait/