Altered Inter-Subregion Connectivity of the Default Mode Network in Relapsing Remitting Multiple Sclerosis: A Functional and Structural Connectivity Study

Background and PurposeLittle is known about the interactions between the default mode network (DMN) subregions in relapsing-remitting multiple sclerosis (RRMS). This study used diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) to examine alterations of long white matter tracts in paired DMN subregions and their functional connectivity in RRMS patients.MethodsTwenty-four RRMS patients and 24 healthy subjects participated in this study. The fiber connections derived from DTI tractography and the temporal correlation coefficient derived from rs-fMRI were combined to examine the inter-subregion structural-functional connectivity (SC-FC) within the DMN and its correlations with clinical markers.ResultsCompared with healthy subjects, the RRMS patients showed the following: 1) significantly decreased SC and increased FC in the pair-wise subregions; 2) two significant correlations in SC-FC coupling patterns, including the positive correlation between slightly increased FC value and long white matter tract damage in the PCC/PCUN-MPFC connection, and the negative correlations between significantly increased FC values and long white matter tract damage in the PCC/PCUN-bilateral mTL connections; 3) SC alterations [log(N track) of the PCC/PCUN-left IPL, RD value of the MPFC-left IPL, FA value of the PCC/PCUN-left mTL connections] correlated with EDSS, increases in the RD value of MPFC-left IPL connection was positively correlated to the MFIS; and decreases in the FA value of PCC/PCUN-right IPL connection was negatively correlated with the PASAT; 4) decreased SC (FA value of the MPFC-left IPL, track volume of the PCC/PCUN-MPFC, and log(N track) of PCC/PCUN-left mTL connections) was positively correlated with brain atrophy.ConclusionsIn the connections of paired DMN subregions, we observed decreased SC and increased FC in RRMS patients. The relationship between MS-related structural abnormalities and clinical markers suggests that the disruption of this long-distance “inter-subregion” connectivity (white matter) may significantly impact the integrity of the network's function.

背景与研究目的：目前对于复发缓解型多发性硬化（relapsing-remitting multiple sclerosis, RRMS）患者的默认模式网络（default mode network, DMN）子网区间的相互作用所知甚少。本研究采用弥散张量成像（diffusion tensor imaging, DTI）与静息态功能磁共振成像（resting-state functional MRI, rs-fMRI），探究复发缓解型多发性硬化患者配对DMN子网区的长白质纤维束改变及其功能连接特征。
研究方法：本研究共纳入24例复发缓解型多发性硬化患者与24例健康对照受试者。结合弥散张量纤维束追踪得到的纤维连接，与静息态功能磁共振得到的时间相关系数，分析DMN内部子网区间的结构-功能连接（structural-functional connectivity, SC-FC）模式，及其与临床标志物的相关性。
研究结果：与健康对照相比，复发缓解型多发性硬化患者表现出以下特征：1）两两子网区间的结构连接（structural connection, SC）显著降低，功能连接（functional connection, FC）显著升高；2）SC-FC耦合模式存在两项显著关联：后扣带回/楔前叶（posterior cingulate cortex/precuneus, PCC/PCUN）-内侧前额叶皮层（medial prefrontal cortex, MPFC）连接中，轻度升高的FC值与长白质纤维束损伤呈正相关；后扣带回/楔前叶-双侧内侧颞叶（medial temporal lobe, mTL）连接中，显著升高的FC值与长白质纤维束损伤呈负相关；3）多项SC指标与临床量表得分相关：后扣带回/楔前叶-左侧顶下小叶（inferior parietal lobule, IPL）的log(N纤维数)、内侧前额叶皮层-左侧顶下小叶的径向扩散系数（radial diffusivity, RD）值、后扣带回/楔前叶-左侧内侧颞叶的各向异性分数（fractional anisotropy, FA）值与扩展残疾状态量表（Expanded Disability Status Scale, EDSS）得分相关；内侧前额叶皮层-左侧顶下小叶的RD值升高与多发性硬化功能影响量表（Multiple Sclerosis Impact Scale, MFIS）得分呈正相关；后扣带回/楔前叶-右侧顶下小叶的FA值降低与步调听觉连续加法测验（Paced Auditory Serial Addition Test, PASAT）得分呈负相关；4）部分SC指标降低与脑萎缩呈正相关，包括内侧前额叶皮层-左侧顶下小叶的FA值、后扣带回/楔前叶-内侧前额叶皮层的纤维束体积、后扣带回/楔前叶-左侧内侧颞叶的log(N纤维数)。
研究结论：在配对的DMN子网区间连接中，复发缓解型多发性硬化患者的SC降低、FC升高。多发性硬化相关结构异常与临床标志物的关联提示，这种长距离“子网区间”（白质）连接的破坏可能显著影响网络功能的完整性。