Minosse Silvia, Garaci Francesco, Martucci Alessio, Lanzafame Simona, Di Giuliano Francesca, Picchi Eliseo, Cesareo Massimo, Mancino Raffaele, Guerrisi Maria, Pistolese Chiara Adriana, Floris Roberto, Nucci Carlo, Toschi Nicola
Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy.
Neuroradiology Unit, Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy.
Front Neurol. 2019 Oct 25;10:1134. doi: 10.3389/fneur.2019.01134. eCollection 2019.
Resting-state functional magnetic resonance imaging (rs-fMRI) is commonly employed to study changes in functional brain connectivity. The recent hypothesis of a brain involvement in primary open angle Glaucoma has sprung interest for neuroimaging studies in this classically ophthalmological pathology. We explored a putative reorganization of functional brain networks in Glaucomatous patients, and evaluated the potential of functional network disruption indices as biomarkers of disease severity in terms of their relationship to clinical variables as well as select retinal layer thicknesses. Nineteen Glaucoma patients and 16 healthy control subjects (age: 50-76, mean 61.0 ± 8.2 years) underwent rs-fMRI examination at 3T. After preprocessing, rs-fMRI time series were parcellated into 116 regions using the Automated Anatomical Labeling atlas and adjacency matrices were computed based on partial correlations. Graph-theoretical measures of integration, segregation and centrality as well as group-wise and subject-wise disruption index estimates (which use regression of graph-theoretical metrics across subjects to quantify overall network changes) were then generated for all subjects. All subjects also underwent Optical Coherence Tomography (OCT) and visual field index (VFI) quantification. We then examined associations between brain network measures and VFI, as well as thickness of retinal nerve fiber layer (RNFL) and macular ganglion cell layer (MaculaGCL). In Glaucoma, group-wise disruption indices were negative for all graph theoretical metrics. Also, we found statistically significant group-wise differences in subject-wise disruption indexes in all local metrics. Two brain regions serving as hubs in healthy controls were not present in the Glaucoma group. Instead, three hub regions were present in Glaucoma patients but not in controls. We found significant associations between all disruption indices and VFI, RNFL as well as MaculaGCL. The disruption index based on the clustering coefficient yielded the best discriminative power for differentiating Glaucoma patients from healthy controls [Area Under the ROC curve (AUC) 0.91, sensitivity, 100%; specificity, 78.95%]. Our findings support a possible relationship between functional brain changes and disease severity in Glaucoma, as well as alternative explanations for motor and cognitive symptoms in Glaucoma, possibly pointing toward an inclusion of this pathology in the heterogeneous group of disconnection syndromes.
静息态功能磁共振成像（rs-fMRI）通常用于研究大脑功能连接的变化。最近关于大脑参与原发性开角型青光眼的假说引发了对这一经典眼科疾病进行神经影像学研究的兴趣。我们探究了青光眼患者功能性脑网络的假定重组，并根据功能网络破坏指数与临床变量以及选定视网膜层厚度的关系，评估其作为疾病严重程度生物标志物的潜力。19名青光眼患者和16名健康对照者（年龄：50 - 76岁，平均61.0 ± 8.2岁）接受了3T的rs-fMRI检查。预处理后，使用自动解剖标记图谱将rs-fMRI时间序列分割为116个区域，并基于偏相关性计算邻接矩阵。然后为所有受试者生成整合、分离和中心性的图论测量指标，以及组间和个体的破坏指数估计值（其使用跨受试者的图论指标回归来量化整体网络变化）。所有受试者还接受了光学相干断层扫描（OCT）和视野指数（VFI）量化。然后我们检查了脑网络测量指标与VFI之间的关联，以及视网膜神经纤维层（RNFL）和黄斑神经节细胞层（MaculaGCL）的厚度。在青光眼中，所有图论指标的组间破坏指数均为负值。此外，我们发现所有局部指标的个体破坏指数在组间存在统计学显著差异。青光眼组中不存在健康对照者中作为枢纽的两个脑区。相反，青光眼患者中有三个枢纽区域而对照者中没有。我们发现所有破坏指数与VFI、RNFL以及MaculaGCL之间存在显著关联。基于聚类系数的破坏指数在区分青光眼患者和健康对照者方面具有最佳判别能力[ROC曲线下面积（AUC）为0.91，敏感性为100%；特异性为78.95%]。我们的研究结果支持青光眼患者大脑功能变化与疾病严重程度之间可能存在的关系，以及对青光眼运动和认知症状的其他解释，这可能表明该疾病可归入异质性的分离综合征组。
