常规MRI阴性的儿童及青少年特发性全面性癫痫脑动态功能连接研究

李清会; 张体江

doi:10.12182/20241160108

常规MRI阴性的儿童及青少年特发性全面性癫痫脑动态功能连接研究

Brain Dynamic Functional Connectivity in Children and Adolescents With Conventional MRI-Negative Idiopathic Generalized Epilepsy

摘要

摘要:
目的探讨常规MRI阴性的儿童及青少年特发性全面性癫痫（idiopathic generalized epilepsy, IGE）脑动态功能连接（dynamic functional connectivity, dFC）变化及其与临床变量的相关性。
方法收集颅脑常规MRI阴性的IGE患儿40例，对照组37例。所有受试者均采集T₂-液体衰减反转恢复序列（T₂ -fluid attenuated inversion recovery, T₂-FLAIR）、三维T₁加权成像（three-dimensional T₁ weighted imaging, 3D-T₁WI）及静息态功能磁共振成像（resting-state fMRI, rs-fMRI）图像，通过独立成分分析（independent component analysis, ICA）、滑动时间窗及k-means聚类法得到6个功能连接状态及dFC指标（时间分数、平均停留时间及转换次数）。基于SPSS18.0及GIFT软件Stats模块分析dFC组间差异及其与临床变量的相关性。通过改变滑动窗口大小验证dFC结果的可靠性及稳定性。
结果 IGE组与对照组临床一般资料差异无统计学意义（P>0.05）。与对照组相比，在state 5中，IGE组默认模式网络（default mode network, DMN）内部、DMN与额顶网络（frontoparietal network, FPN）间dFC增强；DMN与视觉网络（visual network, VN）间dFC降低（P<0.001）。在state 6中，DMN与VN、基底节网络（basal ganglia network, BGN）与感觉运动网络（sensorimotor network, SMN）间dFC增强；DMN与注意网络（attention network, ATTN）间、VN内部dFC降低（P<0.001）。state 1时间分数（Z=－2.192，P=0.028）及平均停留时间（Z=－2.144，P=0.032）、state 4时间分数（Z=－2.444，P=0.015）及平均停留时间（Z=－2.368，P=0.018）和state 6时间分数（Z=－2.047，P=0.041）在两组间差异有统计学意义。IGE组state 1时间分数与病程呈负相关（r=－0.421，P=0.007，Bonferroni校正）。在验证分析中，当滑动窗口的大小及聚类数目改变时，IGE组与对照组之间的dFC指标仍然存在差异。
结论常规MRI阴性的儿童及青少年IGE患者存在全脑功能连接的动态属性异常，且IGE患者state 1时间分数与临床变量具有相关性，为儿童及青少年IGE患者神经机制研究提供新的影像学依据。

Abstract:
Objective To investigate the changes in brain dynamic functional connectivity (dFC) in children and adolescents with idiopathic generalized epilepsy (IGE) who have negative findings for conventional magnetic resonance imaging (MRI) and to explore the correlation between dFC indicators and clinical variables.
Methods A total of 40 children and adolescents with IGE who have negative findings for routine brain MRI and 37 healthy controls were enrolled. T₂-fluid attenuated inversion recovery (T₂-FLAIR) was performed for all subjects. They also uinderwent 3-dimensional T₁ weighted imaging (3D-T₁WI) and resting-state functional MRI (rs-fMRI). Using independent component analysis (ICA), sliding time windows, and k-means clustering, we identified 6 functional connectivity states and derived dFC indicators, including fraction of time, mean dwell time, and the number of transitions. Then, SPSS18.0 and GIFT software Stats module were used to analyze the intergroup differences in dFC and its correlation with clinical variables. The reliability and stability of the dFC results were validated by changing the size of the sliding window.
Results There were no significant differences in the general clinical data between the IGE group and the control group (P>0.05). Compared with the control group, the IGE group showed in state 5 increased dFC within the default mode network (DMN), increased dFC between DMN and the frontoparietal network (FPN), and decreased dFC between DMN and the visual network (VN) (P<0.001). In state 6, the IGE group showed increased dFC between DMN and VN, increased dFC between the basal ganglia network (BGN) and the sensorimotor network (SMN), decreased dFC between the DMN and the attention network (ATTN), and decreased dFC within the VN (P<0.001). There were statistically significant differences between the two groups in the fraction of time (Z=－2.192, P=0.028) and the mean dwell time (Z=－2.144, P=0.032) in state 1, in the fraction of time (Z=－2.444, P=0.015) and the mean dwell time (Z=－2.368, P=0.018) in state 4, and in the fraction of time (Z=－2.047, P=0.041) in state 6. There was a negative correlation between the duration of the disease and the fraction of time of state 1 in the IGE group (r=－0.421, P=0.007, Bonferroni correction). In the validation analysis, significant differences in dFC indicators between the IGE group and the control group persisted when the size of the sliding window and the number of clusters were changed.
Conclusion Children and adolescents with IGE and negative findings for conventional MRI exhibit abnormal dynamic properties of whole-brain functional connectivity, and the fraction of time of state 1 in IGE patients is correlated with clinical variables, providing new imaging evidence for research in the neural mechanisms of children and adolescents with IGE.

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