目的:新的证据表明脑小血管病(CSVD)病理改变了脑结构连接(SC)和功能连接(FC)网络。尽管网络级SC和FC在健康人群中紧密耦合,在具有不同CSVD负担的患者中,SC-FC偶联如何与神经认知结局相关,目前尚不清楚.
方法:使用多模态MRI,我们重建了54例严重CSVD负担(CSVD-s)患者的全脑SC和FC网络,106例轻度CSVD负荷(CSVD-m)患者,和79个健康对照。然后,我们研究了CSVD中异常的SC-FC耦合和功能网络拓扑及其与认知功能障碍的相关性。
结果:与对照组相比,CSVD-M患者在任何SC-FC偶联中均无明显变化,但CSVD-s患者表现出明显的全脑下降(p=0.014),听觉/运动(p=0.033),和边缘模块化(p=0.011)SC-FC耦合。对于功能网络拓扑,尽管全球效率没有变化,CSVD患者的双侧杏仁核(p=0.024和0.035)和海马回(p=0.001和0.005)的淋巴结效率显着降低。值得注意的是,对于CSVD患者,全脑SC-FC耦合与MoCA(r=0.327,p=0.020)和SDMT(r=0.373,p=0.008)评分呈显著正相关,边缘/皮质下模块化SC-FC耦合与SCWT评分呈负相关(r=-0.316,p=0.025),整体/局部有效率(r=0.367,p=0.009,r=0.353,p=0.012)与AVLT评分呈正相关。对于CSVD-m组,全脑和听觉/运动模块化SC-FC耦合与SCWT(r=0.217,p=0.028和r=0.219,p=0.027)和TMT(r=0.324,p=0.001和r=0.245,p=0.013)得分呈显着正相关,全球/局部效率与AVLT(r=0.230,p=0.020和r=0.248,p=0.012)和SDMT(r=0.263,p=0.008和r=0.263,p=0.007)评分呈正相关。
结论:我们的研究结果表明,与功能效率降低相关的全脑和模块依赖性SC-FC偶联降低可能是CSVD更严重的负担和更严重的认知功能下降的基础。SC-FC偶联可能作为CSVD负担的更敏感的神经影像学生物标志物,并为CSVD临床发展的病理生理机制提供了新的见解。
OBJECTIVE: Emerging evidence suggests that cerebral small vessel disease (CSVD) pathology changes brain structural connectivity (SC) and functional connectivity (FC) networks. Although network-level SC and FC are closely coupled in the healthy population, how SC-FC coupling correlates with neurocognitive outcomes in patients with different CSVD burdens remains largely unknown.
METHODS: Using multimodal MRI, we reconstructed whole-brain SC and FC networks for 54 patients with severe CSVD burden (CSVD-s), 106 patients with mild CSVD burden (CSVD-m), and 79 healthy controls. We then investigated the aberrant SC-FC coupling and functional network topology in CSVD and their correlations with cognitive dysfunction.
RESULTS: Compared with controls, the CSVD-m patients showed no significant change in any SC-FC coupling, but the CSVD-s patients exhibited significantly decreased whole-brain (p = 0.014), auditory/motor (p = 0.033), and limbic modular (p = 0.011) SC-FC coupling. For functional network topology, despite no change in global efficiency, CSVD-s patients exhibited significantly reduced nodal efficiency of the bilateral amygdala (p = 0.024 and 0.035) and heschl gyrus (p = 0.001 and 0.005). Notably, for the CSVD-s patients, whole-brain SC-FC coupling showed a significantly positive correlation with MoCA (r = 0.327, p = 0.020) and SDMT (r = 0.373, p = 0.008) scores, limbic/subcortical modular SC-FC coupling showed a negative correlation (r = -0.316, p = 0.025) with SCWT score, and global/local efficiency (r = 0.367, p = 0.009 and r = 0.353, p = 0.012) showed a positive correlation with AVLT score. For the CSVD-m group, whole-brain and auditory/motor modular SC-FC couplings showed significantly positive correlations with SCWT (r = 0.217, p = 0.028 and r = 0.219, p = 0.027) and TMT (r = 0.324, p = 0.001 and r = 0.245, p = 0.013) scores, and global/local efficiency showed positive correlations with AVLT (r = 0.230, p = 0.020 and r = 0.248, p = 0.012) and SDMT (r = 0.263, p = 0.008 and r = 0.263, p = 0.007) scores.
CONCLUSIONS: Our findings demonstrated that decreased whole-brain and module-dependent SC-FC coupling associated with reduced functional efficiency might underlie more severe burden and worse cognitive decline in CSVD. SC-FC coupling might serve as a more sensitive neuroimaging biomarker of CSVD burden and provided new insights into the pathophysiologic mechanisms of clinical development of CSVD.