基于静息态fMRI的重复经颅磁刺激促进脑卒中下肢运动功能恢复的神经重塑机制研究

关键词：重复经颅磁刺激  脑卒中  静息态功能磁共振成像  下肢运动功能  功能连接

Keywords:repetitive transcranial magnetic stimulation  stroke  resting-state functional magnetic resonance imaging  lower limbs motor function  functional connectivity

摘要：

      摘要 目的：基于静息态功能磁共振（functional magnetic resonance imaging， fMRI）探究重复经颅磁刺激（repetitive transcranial magnetic stimulation，rTMS）对脑卒中患者下肢运动功能的影响及脑重塑机制。 方法：招募24例脑卒中患者随机分为rTMS组（n=12）和假刺激组（n=12）。两组均接受常规康复治疗。rTMS组给予患者下肢皮质功能区10Hz的高频重复经颅磁刺激，每天1次，每周5次，共3周。假刺激组使用假线圈，治疗时可以听到声音，但无磁刺激效果。在治疗前后采用Fugl-Meyer下肢运动功能评定量表（Fugl-Meyer assessment of the lower extremity， FMA-LE）量表评估患者下肢运动功能，并进行fMRI扫描检查。采用低频振幅（amplitude of low-frequency fluctuations， ALFF）和功能连接（functional connectivity， FC）分析脑卒中患者干预前后的自发活动水平和网络连接特征，并与患者的下肢运动功能进行相关性分析。 结果：治疗后，rTMS组的FMA-LE评分的改善明显优于假刺激组（P=0.003）。治疗3周后，slow-5波段的ALFF值在患侧大脑半球的中央前回和中央后回存在显著的交互效应，且两组患者slow-5波段ALFF值与FMA-LE的变化值呈显著正相关性。FC分析显示患侧半球M1与健侧大脑半球的辅助运动区和小脑后叶上部、与患侧大脑半球的枕中回之间的FC值存在显著的交互效应，且rTMS组FC值的增高显著优于假刺激组，FC的改变值与FMA-LE的变化量呈显著正相关性。 结论：rTMS促进脑卒中患者下肢功能恢复机制是提高患侧M1和S1的自发活动水平，以及通过强化患侧M1与健侧SMA和小脑以及患侧枕叶皮层的FC以修复运动网络。

Abstract:

      Abstract Objective： To explore the effects of repetitive transcranial magnetic stimulation （rTMS） on lower limb motor function and brain remodeling mechanism in stroke patients using resting state functional magnetic resonance imaging (rs-fMRI). Method： Twenty-four patients with stroke were recruited and randomly divided into rTMS group （n=12） and sham-stimulation group （n=12）. Both groups received routine rehabilitation treatment. The rTMS group received 10Hz high-frequency rTMS treatment on the cortical functional area of the lower limb using the validated TMS coil， once daily for five days per week for three weeks. The sham stimulation group used a pseudostimulus coil that produced sounds without magnetic stimulation effect. The amplitude of low-frequency fluctuations (ALFF) values and functional connectivity (FC) Z-maps of the rTMS and sham groups were analyzed using a two-factor repeated measures ANOVA. Pearson correlation analysis was used to investigate the relationship between lower limb function scores, ALFF values and FC values. Result： After treatment， the FMA-LE score of the rTMS group was significantly better than that in the sham group （P=0.025）. The ALFF values in the slow-5 band in primary motor cortex (M1) and primary somatosensory cortex (S1) of the affected hemisphere showed a significant interaction effect between group and intervention time， and the improvement in ALFF values was significantly higher in the rTMS group than in the sham group after intervention. There was a significant interaction effect in the FC values between the affected M1 and the unaffected hemisphere's supplementary motor area， the upper posterior lobe， and the posterior cingulate gyrus. Moreover， the rTMS group showed a significantly greater increase in FC values compared to the sham group after intervention. The changes of the slow-5 band ALFF and FC values before and after intervention were significantly positively correlated with the changes of FMA-LE in the two groups. Conclusion： rTMS promotes lower limb functional recovery in stroke patients by enhancing the spontaneous activity of M1 and S1 on the affected hemisphere. The motor network is further repaired by strengthening the FC between the affected M1 , the unaffected SMA and cerebellum, and the affected occipital cortex.