Abstract: Objective To explore the changes of dynamic brain functional connectivity (FC) states in patients with cognitive impairment (CI) and no cognitive impairment (NCI) after minor ischemic stroke (MIS). Methods From December 1, 2014 to May 31, 2016, the consecutive patients with first acute MIS in Department of Neurology of Beijing Tiantan Hospital, Capital Medical University were

enrolled in this study. All patients underwent neuropsychological evaluation and multimodal

MRI, and were divided into the CI group (15 participants) and NCI group (11 participants). At the same time, participants with matched age and gender were recruited as healthy control (HC) (29 participants). Based on resting-state brain functional MRI images, a series of real-time dynamic FC networks were constructed by using the dynamic functional network connectivity method, which were divided into multiple representative dynamic FC states (modular connection state, strong connection state, local connection state and sparse connection state) by clustering method. The differences in dynamic characteristics of FC (fraction time and dwell time for each state, and the times of transition between states) were compared among HC, CI and NCI groups, and the changes of dynamic FC states at two time points (baseline and 3-month follow-up) were compared between CI and NCI groups. Results There was no statistical difference in fraction time of all connection states between HC, CI and NCI groups at baseline and 3-month follow-up. The dwell time of CI and NCI group at the baseline was lower than that of HC group, and the difference among the three groups was statistically significant (P =0.035), and the pairwise comparison by Bonferroni correction showed no statistical differences. During the follow-up, there was no statistical difference in dwell time among all connection states. In longitudinal comparison, compared with those at the baseline, fraction time in modular connection state decreased significantly (P =0.035) and increased significantly in sparse connection state (P =0.025) in CI group, and the dwell time in modular connection state reduced significantly (P =0.012) in CI group during the follow-up. However, there were no statistical differences in the fraction time and the dwell time of each connection state at two time points in NCI group. There were no statistical differences in times of transition between all the groups. Conclusions Compared with the healthy control, patients with MIS showed a trend of increasing local connection state and decreasing sparse connection state in the acute stage, but the differences were not statistically significant. For MIS patients with CI, modular connection state and sparse connection state improved significantly at 3-month follow-up compared with that in acute phase. The dynamic brain functional networks can objectively reflect the changes of brain function.

Key words: Stroke; Cognitive impairment; Dynamic functional network connectivity;Functional magnetic resonance imaging

摘要： 目的 探索轻型缺血性卒中后有认知障碍（cognitive impairment，CI）患者和无认知障碍（no cognitive impairment，NCI）患者脑动态功能连接（functional connectivity，FC）状态的变化。 方法 选择2014年12月1日-2016年5月31日首都医科大学附属北京天坛医院神经病学中心就诊的 轻型急性缺血性卒中患者为研究对象，对所有患者进行神经心理学评估和多模态MRI检查，分为CI 组（15例）和NCI组（11例），同时招募年龄、性别均匹配的志愿者作为健康对照（healthy control，HC）组 （29例）。基于静息态功能头颅MRI影像，利用动态功能网络连接方法构建一系列随时间变化的FC网络， 然后通过聚类方法划分为多个具有代表性的动态FC状态（分别为模块化连接状态、强连接状态、局 部连接状态和稀疏连接状态），比较HC组、CI组与NCI组的FC动态特征（各状态的时间比例、驻留时间 及各状态间的转换次数）差异，并在两个时间点（基线和3个月随访期）探索CI组与NCI组动态FC状态 的变化。 结果 HC组、CI组和NCI组在基线和随访期各连接状态的时间比例差异均无统计学意义。基线CI组 和NCI组在稀疏连接状态的驻留时间比HC组更低，三组差异有统计学意义（P =0.035），但两两比较 的结果均未通过Bonferroni校正；而在随访期，各连接状态的驻留时间差异均无统计学意义。纵向比 较中，与基线相比，CI组随访期在模块化连接状态的时间比例明显下降（P =0.035），在稀疏连接状 态的时间比例明显上升（P =0.025），在模块化连接状态的驻留时间明显降低（P =0.012）；而NCI 组 在两个时间点各连接状态的时间比例和驻留时间差异均无统计学意义。对于转换次数，所有组间的 差异均无统计学意义。 结论 轻型缺血性卒中患者急性期较对照人群有局部连接状态增多而稀疏连接状态减少的趋势， 但差异未达统计学意义；对于有认知障碍的轻型缺血性卒中患者，发病3个月时模块化连接状态和 稀疏连接状态均较急性期显著恢复；动态功能网络能够客观反映大脑功能的变化。

关键词: 卒中; 认知障碍; 动态功能网络连接; 功能磁共振成像