Alteration of Brain Functional Networks in Early-Stage Parkinson’s Disease: A Resting-State fMRI Study

<div><p>Although alterations of topological organization have previously been reported in the brain functional network of Parkinson’s disease (PD) patients, the topological properties of the brain network in early-stage PD patients who received antiparkinson treatment are largely unknown. This study sought to determine the topological characteristics of the large-scale functional network in early-stage PD patients. First, 26early-stage PD patients (Hoehn and Yahr stage:1-2) and 30 age-matched normal controls were scanned using resting-state functional MRI. Subsequently, graph theoretical analysis was employed to investigate the abnormal topological configuration of the brain network in early-stage PD patients. We found that both the PD patient and control groups showed small-world properties in their functional brain networks. However, compared with the controls, the early-stage PD patients exhibited abnormal global properties, characterized by lower global efficiency. Moreover, the modular structure and the hub distribution were markedly altered in early-stage PD patients. Furthermore, PD patients exhibited increased nodal centrality, primarily in the bilateral pallidum, the inferior parietal lobule, and the medial superior frontal gyrus, and decreased nodal centrality in the caudate nucleus, the supplementary motor areas, the precentral gyrus, and the middle frontal gyrus. There were significant negative correlations between the Unified Parkinson Disease Rating Scale motor scores and nodal centralities of superior parietal gyrus. These results suggest that the topological organization of the brain functional network was altered in early-stage PD patients who received antiparkinson treatment, and we speculated that the antiparkinson treatment may affect the efficiency of the brain network to effectively relieve clinical symptoms of PD.</p></div

Correlation between abnormal network properties and UPDRS motor scores.

<p>SPG.L: the left superior parietal gyrus.</p

Modules of the functional brain networks in each group.

<p>(A) Modules of the brain network in normal controls. (B) Modules of the brain network in PD patients. Colors in nodes and links correspond to different modules. Only intramodular edges are shown. The results were visualized using the BrainNet Viewer (NKLCNL, Beijing Normal University).</p

Demographic characteristics and clinical status of each group.

<p>Abbreviations: PD, Parkinson's disease; UPDRS, Unified Parkinson's Disease Rating Scale; H&Y, Hoehn and Yahr; MMSE, mini-mental state examination; LEDD, levodopa equivalent daily dose; NA, not available.</p><p>^a The P value was obtained using the two-tailed two-sample <i>t</i>-test.</p><p>^b The P value was obtained using the chi-squared test. The data are presented as the means ± SD.</p><p>Demographic characteristics and clinical status of each group.</p

Hubs of the functional brain networks in each group.

<p>The results were visualized using the BrainNet Viewer (NKLCNL, Beijing Normal University). The maps showed the hubs of the brain network in normal controls (top panel) and in PD patients (bottom panel). Colors in nodes indicate different modules. Detailed brain region information corresponding to the anatomical labels can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141815#pone.0141815.s002" target="_blank">S1 Table</a>.</p

Network modularity of functional brain networks as a function of sparsity among PD patients and normal controls.

<p>Network modularity of functional brain networks as a function of sparsity among PD patients and normal controls.</p

table_1.docx

<p>Cognitive impairment caused by subcortical ischemic vascular disease (SIVD) has been elucidated by many neuroimaging studies. However, little is known regarding the changes in brain functional connectivity networks in relation to the severity of cognitive impairment in SIVD. In the present study, 20 subcortical ischemic vascular cognitive impairment no dementia patients (SIVCIND) and 20 dementia patients (SIVaD) were enrolled; additionally, 19 normal controls were recruited. Each participant underwent a resting-state functional MRI scan. Whole-brain functional networks were analyzed with graph theory and network-based statistics (NBS) to study the functional organization of networks and find alterations in functional connectivity among brain regions. After adjustments for age, gender, and duration of formal education, there were significant group differences for two network functional organization indices, global efficiency and local efficiency, which decreased (NC > SIVCIND > SIVaD) as cognitive impairment worsened. Between-group differences in functional connectivity (NBS corrected, p < 0.01) mainly involved the orbitofrontal, parietal, and temporal cortices, as well as the basal ganglia. The brain connectivity network was progressively disrupted as cognitive impairment worsened, with an increased number of decreased connections between brain regions. We also observed more reductions in nodal efficiency in the prefrontal and temporal cortices for SIVaD than for SIVCIND. These findings indicated a progressively disrupted pattern of the brain functional connectivity network with increased cognitive impairment and showed promise for the development of reliable biomarkers of network metric changes related to cognitive impairment caused by SIVD.</p

Group comparison in the negative-diminish condition.

<p>The cold color indicates decreased activation. The color bar indicates T-score. L:left, R:right.</p

Group comparison in the negative-enhance condition.

<p>A warm color indicates increased activation, and cold color indicates decreased activation. The color bar indicates T-score. L:left, R:right.</p

Significant clusters identified in PTSD patients compared with controls.

<p>Significant clusters identified in PTSD patients compared with controls.</p