Altered Functional Brain Connectomes between Sporadic and Familial Parkinson's Patients

Abstract

Familial Parkinson's disease (PD) is often caused by mutation of a certain gene, while sporadic PD is associated with variants of genes which can influence the susceptibility to PD. The goal of this study was to investigate the difference between the two forms of PD in terms of brain abnormalities using resting-state functional MRI and graph theory. Thirty-one familial PD patients and 36 sporadic PD patients underwent resting-state functional MRI scanning. Frequency-dependent functional connectivity was calculated for each subject using wavelet-based correlations of BOLD signal over 246 brain regions from Brainnetome Atlas. Graph theoretical analysis was then performed to analyze the topology of the functional network, and functional connectome differences were identified with a network-based statistical approach. Our results revealed a frequency-specific (0.016 and 0.031 Hz) connectome difference between familial and sporadic forms of PD, as indicated by an increase in assortativity and decrease in the nodal strength in the left medial amygdala of the familial PD group. In addition, the familial PD patients also showed a distinctive functional network between the left medial amygdala and regions related to retrieval of motion information. The present study indicates that the medial amygdala might be most vulnerable to both sporadic and familial PD. Our findings provide some new insights into disrupted resting-state functional connectomes between sporadic PD and familial PD.

Keywords: assortativity; familial PD; functional brain connectome; small-worldness; sporadic PD.

Figure 1

Group comparisons of global topological metrics across four wavelet scales. These metrics include clustering coefficient (upper left), characteristic path length (upper right) and assortativity (lower left).

Figure 2

Brain regions showing the decreased nodal degree in familial PD group compared with sporadic PD group (p = 3 × 10⁻⁵) on the fourth wavelet scale.

Figure 3

Compared with sporadic PD, familial PD group showed a decreased functional networks strength according to the network-based statistical (NBS) analysis method, under a liberal primary threshold of (p < 1 × 10⁻³). The line represents the functional connection.