非认知损害复发缓解型多发性硬化患者默认模式网络子系统的MRI研究

A MRI study of the default mode network subsystems in relapsing-remitting multiple sclerosis patients with preserved cognitive function

目的探讨非认知损害复发缓解型多发性硬化(RRMS)患者默认模式网络(DMN)的子系统灰质体积、子系统内部及之间功能连接的变化情况。方法该研究为前瞻性研究。收集2020年4月至2021年1月在复旦大学附属华山医院诊治的37例非认知损害RRMS患者(RRMS组),并同期纳入的43名健康志愿者(HC组)。RRMS组患者均接受临床认知功能量表评分。所有受检者均接受大脑结构三维T1WI和静息态功能MRI。DMN被划分为核心(CORE)、背内侧前额叶(DMPFC)、内侧颞叶(MTL)3个子系统。通过空间标准化生成的灰质体积图提取3个子系统的灰质体积;根据Yeo′s 17网络定义DMN的24个兴趣区(ROI)并计算其功能连接值,从而获取子系统内部和子系统间的功能连接平均值。采用独立样本t检验比较RRMS组和HC组的灰质体积和功能连接的差异,采用Spearman偏相关分析子系统灰质体积与功能连接,以及子系统功能连接与临床相关量表评分的相关性。结果与HC组相比,RRMS组DMN 3个子系统的灰质体积均显著降低(P<0.05),而3个子系统内部及其之间的功能连接在HC组与RRMS组间差异均无统计学意义(P>0.05)。基于ROI水平,与HC相比,RRMS组患者DMN子系统内功能连接值显著减低的脑区主要集中在DMPFC左背内侧前额叶皮层、DMPFC右外侧颞叶皮层和MTL左内侧颞叶皮层(P<0.01)。HC组的DMPFC灰质体积与DMPFC内部功能连接呈正相关(r=0.326,P=0.040);RRMS组CORE灰质体积与CORE和DMPFC之间的功能连接呈正相关(r=0.363,P=0.038),CORE内部功能连接与记忆与执行筛查量表评分呈正相关(r=0.430,P=0.036)。结论非认知损害的RRMS患者DMN的3个子系统均出现灰质萎缩。子系统DMPFC的结构与功能无相关性。子系统CORE的功能连接可反映记忆执行状态,DMPFC和CORE可能是非认知损害的RRMS患者神经变性和脑功能改变的重要脑区。

Objective To investigate the changes in gray matter volume of the subsystems as well as intra-subsystem and inter-subsystem functional connectivity in the default mode network(DMN)of relapsing-remitting multiple sclerosis(RRMS)patients with preserved cognitive function.Methods In this prospective study,thirty-seven RRMS patients with preserved cognitive function who were admitted to Huashan Hospital of Fudan University from April 2020 to January 2021(RRMS group)and 43 healthy volunteers(HC group)were recruited.Patients in the RRMS group received the cognitive assessment using a clinical cognitive functioning scale.Three-dimensional T1WI and resting-state functional MRI were performed to obtain the brain structural and functional data.The DMN was divided into three subsystems:CORE,dorsal medial prefrontal cortex(DMPFC),and medial temporal lobe(MTL).The gray matter volume of the three subsystems were extracted from the gray matter volume map generated by spatial normalization;24 regions of interest(ROIs)of the DMN were defined based on Yeo′s 17 networks,and their functional connectivity values were calculated to derive the mean intra-subsystem and inter-subsystem functional connectivity values.Differences in gray matter volume and functional connectivity between the RRMS and HC groups were compared using independent sample t-tests;Spearman′s partial correlation was used to analyze the correlation between subsystems′gray matter volume and functional connectivity,as well as between subsystems′functional connectivity and clinical scale scores.Results Compared to the HC group,the gray matter volume of the three subsystems of the DMN were considerably reduced in the RRMS group(P<0.05).The functional connectivity within and between the three subsystems were not statistically significantly different between the HC and RRMS groups(P>0.05).Based on the ROI analysis,patients with RRMS the brain regions with significantly reduced DMN intra-subsystem functional connectivity values were mainly located in the left dorsomedial prefrontal cortex of the DMPFC,the right lateral temporal cortex of the DMPFC,and the left medial temporal cortex of the MTL,as compared with the HC group(P<0.01).The gray matter volume of DMPFC was positively correlated with the functional connectivity within DMPFC in the control group(r=0.326,P=0.040).In the RRMS group,the gray matter volume of CORE was positively correlated with the functional connectivity between CORE and DMPFC(r=0.363,P=0.038),and the functional connectivity within CORE was positively correlated with scores on the memory and executive screening scale(r=0.430,P=0.036).Conclusions RRMS patients with preserved cognitive function exhibit gray matter atrophy in all three DMN subsystems.There is no correlation between the structure and function of the DMPFC subsystem.The functional connectivity within CORE subsystem may reflect memory and execution status;DMPFC and CORE may be critical encephalic regions for neurodegeneration and brain functional changes in RRMS patients with preserved cognitive function.