抗N-甲基-D-天冬氨酸受体脑炎患者脑皮质厚度协变网络拓扑异常和功能连接改变

Abnormal topology of cortical thickness covariance network and altered functional connectivity in patients with anti-N-methyl-D-aspartate receptor encephalitis

目的:应用图论分析和功能连接(functional connectivity,FC)的方法,探究抗N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR)脑炎患者基于脑皮质厚度的结构协变网络拓扑属性和脑功能活动的改变,并探讨这些改变是否与认知相关。方法:纳入2018年7月至2021年11月于广西医科大学第一附属医院神经内科就诊的33例抗NMDAR脑炎患者(患者组)和35例性别、年龄及教育年限相匹配的健康对照(对照组),对所有被试行认知功能评估、结构和功能磁共振图像扫描。基于脑皮质厚度值分别构建两组的结构协变网络,计算并采用重复1000次的非参数置换检验比较两组网络的拓扑属性;以拓扑异常的脑区为感兴趣区,计算与全脑的FC值,使用SPM 12和RESTplus软件识别两组FC存在差异的脑区;提取差异脑区的FC值,利用SPSS 24.0软件进行FC值与认知功能评分Spearman相关分析。结果:抗NMDAR脑炎患者组的认知功能得分[27.0(23.5,28.0)分]低于对照组[29.0(27.0,30.0)分](Z=-3.029,P=0.002)。图论分析显示,与对照组相比,患者组皮质厚度协变网络的聚类系数升高(P=0.004),全局效率降低(P=0.004);此外,患者组左腹侧后扣带皮质和右背侧后扣带皮质的节点效率,左腹侧后扣带皮质和左侧颞上回极平面的度中心性均降低(均P<0.05,FDR校正)。FC分析结果发现,患者组左腹侧后扣带皮质与小脑后叶(MNI:x=6,y=-66,z=-21)的FC值,和左侧颞上回极平面与小脑前叶(MNI:x=6,y=-54,z=-12)的FC值均显著高于对照组(GRF校正,体素水平P<0.001,团块水平P<0.05),前者与认知功能评分呈负相关(r=-0.403,P=0.020)。结论:抗NMDAR脑炎患者的脑皮质厚度协变网络拓扑结构和脑功能连接发生改变,部分脑区的改变与认知下降程度相关,其可能是抗NMDAR脑炎患者认知障碍的潜在神经机制。

ObjectiveTo explore the changes in topological attributes of structural covariance network based on cortical thickness and the brain functional activities in patients with anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis by graph theory and functional connectivity(FC)analyses,and to investigate whether these changes were correlated to cognitive impairment.MethodsA total of 33 patients with anti-NMDAR encephalitis from Department of Neurology of the First Affiliated Hospital of Guangxi Medical University(patient group)and 35 healthy controls(control group)with matched gender,age,and education were included from July 2018 to November 2021.All subjects received cognitive function assessments,structural and functional magnetic resonance imaging scans.Structural covariance networks were constructed in the two groups based on cortical thickness values and topological characteristics of networks were computed.A non-parametric permutation test which repeated 1000 times was used to compare the characteristics of the networks between the two groups.Brain regions with abnormal topology were defined as region of interest(ROI),and FC values in global brain level were calculated.SPM 12 and RESTplus were used to identify the brain regions with significant differences in FC values between the two groups.Finally,Spearman correlation analysis between FC values of significant brain regions and cognitive scores were performed by SPSS 24.0.ResultsThe cognitive score of patients with anti-NMDAR encephalitis(27.0(23.5,28.0))was lower than that in control group(29.0(27.0,30.0))(Z=-3.029,P=0.002).Graph theory analysis found that the patients showed significantly increased clustering coefficients(P=0.004)and decreased global efficiency(P=0.004)compared with healthy controls.Moreover,the nodal efficiency of left ventral posterior cingulate cortex(vPCC)and right dorsal posterior cingulate cortex(dPCC),as well as the nodal degree centrality of left vPCC and left polar planum of superior temporal gyrus(ppSTG)in patient group were significantly decreased(P<0.05,FDR corrected)compared with control group.FC analysis showed the increased FC values between left vPCC and posterior cerebellum(MNI:x=6,y=-66,z=-21),as well as between left ppSTG and anterior cerebellum(MNI:x=6,y=-54,z=-12)(GRF corrected,voxel level P<0.001,cluster levelP<0.05)in patient grooup.The FC values between left vPCC and posterior cerebellum were negatively correlated with the cognitive scores(r=-0.403,P=0.020).ConclusionPatients with anti-NMDAR encephalitis show abnormal topology of structural covariance network based on cortical thickness and altered FC values,some of which are correlated to cognition and may be the underlying neural mechanism of cognitive impairment in patients with anti-NMDAR encephalitis.