基于脑电的脑卒中患者运动想象认知过程的研究
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摘要
运动功能障碍是脑卒中后最主要的表现之一，运动功能的缺失或部分散失给患者的日常生活带来极大的痛苦，也给患者家属带来很大的不便。脑卒中后运动功能的恢复是解决患者生活不便和提高生活质量的首要任务和目标。最近有研究提出运动想象疗法有利于脑卒中患者运动功能的康复。运动想象是一种特殊的运动功能状态，它存在于运动记忆中，遵循中枢运动控制原则，激活运动记忆而没有任何明显的运动输出。运动想象可以作为一种激活运动神经网络的手段，可以运用在脑卒中的任何阶段以改善脑卒中患者的运动功能，此疗法不依赖于患者实际的残存功能，又与患者的主动运动密切相关。有研究表明，运动想象和实际运动同样可以激活双侧运动前区、顶叶、基底节和小脑。这些研究表明，脑卒中患者可利用运动想象部分活化损伤的运动网络。通过运动想象来促进瘫痪肢体的康复，较之被动运动肢体的康复更符合正常的由脑到肢体的兴奋传导模式，从而更有效地促进正常运动反射弧的形成。
运动想象在脑卒中患者运动功能康复中的应用是近几年研究的热点，其研究内容广泛但是没有深入，虽然运动想象的疗效得到一定的临床验证，但其治疗形式单一，尤其是停留在表层形式上，主要由治疗师说指导语，但是患者是否主动参与并不确定，没有定量描述患者参与程度以及疗效的手段；其次，脑卒中对运动想象的神经机制的影响尚不完全清楚。目前对脑卒中后运动想象神经机制的研究主要借助影像学，如功能磁共振等，探测相关皮层代谢水平(血氧饱和度)以衡量运动想象认知能力。但是这些影像学技术的时间分辨率很低(秒级别)，因此所探测的是整个运动想象过程中局部皮层活跃的总和，而不能实时观察运动想象的认知过程。另外，这些研究手段主要关注于局部皮层区域的活跃情况，而实际上大脑在完成一个任务时是以功能网络形式组织的，各个相关脑区功能上相互分离又相互整合。为了深入研究脑卒中后运动想象的认知神经机制，有必要借助高时间分辨率的技术手段实时观察脑卒中患者运动想象认知过程，并利用图论理论从功能网络的角度研究脑卒中对运动想象认知神经机制的影响。因此，我们借助行为学和具有高时间分辨率的事件相关脑电技术来解决如下科学问题：(1)脑卒中对运动想象认知宏观行为学的影响；(2)脑卒中对运动想象各个认知子阶段的严格锁时锁相皮层活动的影响；(3)脑卒中对运动想象各个认知子阶段的非锁相皮层活动的影响；(4)脑卒中对各个皮层区域之间相互作用关系以及皮层神经功能网络特性的影响。
在本论文中，采用了一种定量的运动想象认知任务，即对旋转到不同空间角度的左右手图片进行心理旋转的任务，利用行为学、事件相关电位、事件相关（去）同步以及相位同步、皮层神经网络技术，从功能分离和功能整合角度描述脑卒中对运动想象神经机制的影响，以给出脑卒中后运动想象对患者运动功能康复的作用机理,具体结果描述如下：
(1)首先，为了观察脑卒中对患者运动想象认知任务的宏观影响，对脑卒中患者的行为学进行分析。其结果表明临床评分越好的患者运动想象心理旋转认知任务完成的越好，说明此任务可以很好地衡量脑卒中患者的行为能力。左侧半球梗死脑卒中患者同样可以完成左右手图片的心理旋转任务，反应时间和正确率都会出现显著的“角度效应”，但其反应时间显著长于正常对照组而正确率则显著低于正常对照组。结果表明卒中病灶对患者运动想象能力造成一定的影响，脑卒中患者即使患侧（右手）的实际运动功能受损，但是对患侧手的心理想象也即对其表象运动的能力仍然保留，可以完成表象空间旋转的任务。
(2)其次，为了实时观察脑卒中患者的运动想象认知过程中的皮层锁相电活动，对脑卒中患者运动想象认知前两个子阶段的事件相关电位成分进行统计分析。正常对照组在视觉编码阶段中，其锁相的皮层活跃区域主要集中在双侧额叶、中央区和右侧顶叶。而脑卒中患者组则只有健侧半球（右半球）的额叶和顶叶活跃，其和运动相关的中央皮层以及受损半球的额叶（左半球）活跃缺失，表明在此阶段脑卒中患者组只对视觉刺激图片的物理属性进行编码而未激发和该图片相关的高级运动认知过程。正常对照组在心理旋转过程中出现了显著的“幅度调制”现象，其活跃区域集中在双侧顶叶。脑卒中患者其锁相的活跃区域则只集中在健侧半球的顶叶。左半球卒中的患者对视觉空间信息的编码和认知只由健侧半球的顶叶完成，由于缺失左半球顶叶的参与，卒中患者对空间信息编码的能力受损，不能准确区分和编码不同的视觉空间角度。
(3)皮层活跃除了严格锁相部分外，还有非严格锁相的皮层活跃，为了研究脑卒中对运动想象认知过程中的皮层非锁相活跃的影响，对脑卒中患者的beta波段的事件相关(去)同步进行分析。脑卒中患者组的beta波段事件相关去同步激活的皮层活跃程度显著小于正常对照组，表明脑卒中导致患者全局性皮层非锁相活跃程度减弱。类似于锁相的事件相关电位的结果，脑卒中患者组在视觉编码阶段同样表现出运动皮层区域非锁相活跃的不足。在心理旋转阶段，脑卒中患者组的枕叶、中央区和顶叶活跃，而额叶活跃较弱。在反应选择执行阶段，正常对照组的事件相关去同步的幅值出现“角度效应”，并且其非锁相活跃区域逐渐从左半球扩大到右半球。而脑卒中患者组在反应选择阶段的事件相关去同步的幅值则和空间角度无关，并且其活跃区域依旧集中在枕叶、中央区和顶叶，额叶的活跃相比正常对照组依然不足。脑卒中患者额叶的非锁相皮层活跃比较缺乏，其视觉空间角度信息的编码能力受损。
(4)上述技术手段主要是针对各个局部区域的皮层活跃进行考察，尚未描述各个皮层区域之间的相互关系。利用相位同步技术对脑卒中患者的皮层区域之间的相互关系进行分析，并利用图论理论构建皮层神经功能网络，从功能分离和功能整合的角度去理解脑卒中对运动想象认知神经机制的影响。脑卒中患者组的平均相位同步指数显著小于正常对照组的平均相位同步指数值。脑卒中患者组受损半球内（左半球）以及半球间的相位同步性显著降低，而健侧半球（右半球）内的同步性并未显著受损，说明卒中后病灶和病灶周围及其远距离皮层区域的同步性受损，其协调性下降。脑卒中患者的神经功能网络同样具有“小世界”特性，但是其特征路径长度变长表明脑卒中后脑区之间的信息传递所需要的路径变长，效率降低，尤其在心理旋转子阶段这种变化尤为显著。其次，聚类系数的降低表明脑区的功能分离能力受损，即脑区内的连接变得稀疏，紧密程度下降。节点聚类系数和介数的拓扑分析结果表明脑卒中患者组相比正常对照组在右半球顶叶的聚类系数、额叶的节点介数显著增大，表现出在运动想象认知过程中患者健侧半球的补偿效应。
利用高时间分辨率的事件相关脑电技术，观察到脑卒中对运动想象认知各个阶段的影响：对视觉刺激编码的影响主要表现在受损半球运动皮层活跃不足；而在心理想象运动过程中的影响主要表现在顶叶的不对称性，即，健侧半球主导；而在反应选择执行过程中则同样表现为受损半球运动皮层活跃不足。脑卒中后患者不同皮层区域之间的相互协调能力下降，其皮层神经功能网络的“小世界”性受损，整个网络信息传递效率下降，功能分离和功能整合能力受损，并在整个认知过程中出现了显著的健侧半球补偿效应。以上是作者这篇论文的主要工作。本文一方面从事件相关电位的锁相活动和事件相关（去）同步的的非锁相活动揭示卒中病灶对运动想象心理旋转认知任务各个阶段的局部皮层活跃的影响；另一方面利用图论理论研究卒中病灶对运动想象认知神经功能网络特性的影响，对揭示脑卒中后的运动想象认知神经机制和临床应用具有潜在的重大价值。
Motor impairment after stroke is a major cause of permanent disability. Loss of entirefunction or partial ability of movement brings lots of inconvenience to the stroke patientsand their families. Recovery of motor function in order to improve life quality of patients isa primary aim after stroke. Motor imagery was recently reported to be useful for recoveryof motor function in stroke patients. Motor imagery is a cognitive process in which therepresentation of a specific motor action is internally reactivated within working memorybut without an overt motor output. Motor imagery could be used as an additional trainingmethod during any stage after stroke to active movement network and it’s not dependent onpatients’ residual physical function and patients could participate actively. Neuroimagingstudies showed that cortical neural networks including posterior parietal and visual cortex,premotor cortex (BA6), supplementary motor areas (SMA) and primary motor cortex (M1)were activated during motor imagery. In addition, some subcortical structures, e.g., basalganglia, were also activated during motor imagery. Basal ganglia and motor cortices havebeen known to be involved in motor planning and execution, and their activation duringmotor imagery suggested that actual and mentally simulated movements largely share thesimilar neural structures. Compared with passive movement rehabilitation, motory imageryis more in line with the normal excitation mode of neural system, which is from centralneural system (e.g., brain structures) to extremes (e.g., limb), and more effective toregenerate the reflex neural arc of movement.
Although motor imagery training has justified some optimism in stroke rehabilitation,the majority of these studies to date were poorly controlled cases or with small samplesizes and the outcomes were inconsistent. Furthermore, the underlying neural mechanismsof motor rehabilitation by motor imagery have not been fully understood. The studies sofar have been mostly based on behavior assessment and overall neural activations byneuroimaging technology during motor imagery with few temporal details of the cognitiveprocess. Therefore, one interesting question is how stroke lesion would affect the neural mechanism of each sub-stage during the cognitive process of motor imagery. In this thesis,we aim to use event-related EEG recordings with high temporal resolution and behaviorperformance to find answers for those scientific questions:(1) stroke lesion effect onoverall behavior performance during motor imagery;(2) stroke impact on phase-lockedcortical activation in each sub-stage during motor imagery;(3) stroke impact onphase-unlocked cortical activation in each sub-stage during motor imagery;(4) strokeimpact on the interdependence between different brain areas and network properties fromfunctional segregation and integration perspective. We hope this study could reveal moreneural cognitive mechanism of motor imagery during rehabilitation after stroke which iscrucial for treatment planning and clinical outcome quantitative estimation.
In this thesis, a quantitative motor imagery cognitive process was employed, i.e.,identification task of hands pictures which were rotated to different spatial angles (mentalrotation task, MRT). Event-related electroencephalography (EEG) signal with hightimporal resolution was used to reveal temporal-spatial patterns of neural activation for twogroups in different cognitive sub-stages during MRT. Behavior performance, event-relatedpotential (ERP), event-related (de)synchronization (ERD/ERS), phase synchronization andcognitive functional network were investigated to illustrate neural mechanism of strokeeffect on cognitive process of motor imagery. Specific results were described as follow:
(1) In order to evaluate the overall impact of stroke on motor imagery, behaviorperformance of stroke patients was assessed. Behavior results showed that stroke patientswho with better clinical outcomes had better performance in MRT, which indicatedbehavior performance during MRT had good correlation with clinical outcomes in strokepatients. Patients with stroke lesion in left hemisphere could also accomplish MRT, showedsignificant “angle effect”. Although movement impairment of affected (right) hand wasobserved, representation of the affected hand movement was still intact or partly preserved,i.e., patients could accomplish the MRT with affected hand. Compared with controlsubjects, longer response time and lower accuracy rate were observed for stroke patients,which indicated that stroke lesion affected patients’ behavior performance in MRT.
(2) Stroke impact on phase-locked activation of cortex during each sub-stage in motorimagery was assessed by event-related potential (ERP). Two significant ERP components(i.e., P200and P300) were observed during MRT, which were indicated visual stimuliencoding and mental rotation sub-stages respectively. During visual stimuli encodingsub-stage, stroke patients showed only frontal and parietal lobe in contralesionalhemisphere activated. Hypo-activation in bilateral central area and frontal lobe inipsilisonal hemisphere of stroke patients indicated that only physical property of handpictures were encoded and no higher movement related cognitive process were involved for stroke patients during visual stimuli encoding sub-stage. Significant “amplitudemodulation effect” in control subjects during mental rotation of visual stimuli wasobserved in bilateral parietal lobes which played an important role in spatial cognition.Stroke patients showed significant contralesional parietal lobe activation (i.e., lateralizationeffect), but no “amplitude modulation effect” was observed. All ERP results indicated thatstroke patients showed significant deficiency of movement-related areas activation inipsilesional hemisphere.
(3) In addition, event-related (de)synchronization (ERD/ERS) in beta band wasevaluated to assess the stroke impact on cortical phase-unlocked activation in eachcognitive sub-stage during motor imagery. Stroke patients had significantly smallerbeta-ERD values than control subjects. During visual stimuli encoding, only occipital andparietal lobes activated in stroke patients. Hypo-activation in movement related brain areasfor stroke patients might contribute to impairment of visual stimuli encoding ability.During mental rotation of visual stimuli, bilateral frontal, central and parietal lobes showedbeta-ERD for control subjects while stroke patients showed smaller beta-ERD valuesparticularly in frontal lobes. During response cognitive process, significant “angle effect”of beta-ERD was observed for control subjects, more activation particularly in righthemisphere was observed for more difficult task. No such effect was observed for strokepatients and the phase-unlocked activation was localized in parietal, central and occipitalareas. Hypo-activation in movement related brain areas in stroke patients might contributeto poor ability of spatial information encoding and impairment of movement executionability during MRT.
(4) Besides local phase-locked and phase–unlocked cortical activation was evaluated,interdependances between different brain cortical areas were assessed by phasesynchronization to investigate the stroke effect on cortical interactions. Furthermore, neuralfunctional network baesd on graphy theory was constructed to reveal cognitive networkalterations after stroke. Stroke patients showed significantly smaller phase synchronizationindex in ipsilesional hemisphere and interhemisphere. Stroke lesion might contribute to thesynchronization reduction in brain areas around lesion in the left hemisphere andsynchronization between brain areas with long distance in two hemispheres. Functionalnetwork of stroke patients also showed “small-worldness” property while with longercharacteristic path length and smaller clustering coefficient which indicated more pathswere needed to transfer information and the local interaction was sparse. All these resultsindicated that ability of functional segregation and functional integration after stroke wasimpaired significantly. Statistical results showed that patients showed significant largernodal clustering coefficient and betweenness in right (contralesional) hemisphere, particularly in mental rotation sub-stage, which showed compensation effect ofcontralesional hemisphere. These results revealed that functional network after strokereflected a lower capacity to integrate the communication between distance brain regionsand lower tendency to be modular. Patients’s network also showed contralesionalhemisphere compsenssation effect.
In summary, we investigated the cognitive alternations during MRT after the lefthemispheric stroke injury using both behavior and electrophysiological methods.Movement impairment after stroke would also accompanied by poor behaviorperformances in motor imagery. Hemispheric lateralization after stroke was observedwhich was due to the ipsilesional hypo-activation during visual stimuli perception andmental rotation. Furthermore, stroke lesion also resulted in the loss of “angle effect” due tothe impaired spatial information processing during response execution. Synchronization inipsilesional hemisphere was impaired significantly and the network of stroke patientsshowed lower ability to integrate the communication between brain areas and lowertendency to be modular, and contralesional hemisphere compensation effect. These resultsmight provide new insights into the understanding of cognitive process during mentalrotation, and could be referenced as a guide in stroke rehabilitation with motor imagerytraining. These were the major work in this thesis. On one hand, these studies investigatedstroke effect on cognitive process in motor imagery with time course from bothphase-locked and phase-unlocked event-related oscillations. On the other hand, strokeeffect on functional segregation and integration of the cognitive functional network wasalso investigated by graphy theory based on phase synchronization. This thesis would becrucial to reveal cognitive neural mechanism of motor imagery after stroke and potentiallyuseful for clinical application in rehabilitation training after stroke.
运动想象在脑卒中患者运动功能康复中的应用是近几年研究的热点，其研究内容广泛但是没有深入，虽然运动想象的疗效得到一定的临床验证，但其治疗形式单一，尤其是停留在表层形式上，主要由治疗师说指导语，但是患者是否主动参与并不确定，没有定量描述患者参与程度以及疗效的手段；其次，脑卒中对运动想象的神经机制的影响尚不完全清楚。目前对脑卒中后运动想象神经机制的研究主要借助影像学，如功能磁共振等，探测相关皮层代谢水平(血氧饱和度)以衡量运动想象认知能力。但是这些影像学技术的时间分辨率很低(秒级别)，因此所探测的是整个运动想象过程中局部皮层活跃的总和，而不能实时观察运动想象的认知过程。另外，这些研究手段主要关注于局部皮层区域的活跃情况，而实际上大脑在完成一个任务时是以功能网络形式组织的，各个相关脑区功能上相互分离又相互整合。为了深入研究脑卒中后运动想象的认知神经机制，有必要借助高时间分辨率的技术手段实时观察脑卒中患者运动想象认知过程，并利用图论理论从功能网络的角度研究脑卒中对运动想象认知神经机制的影响。因此，我们借助行为学和具有高时间分辨率的事件相关脑电技术来解决如下科学问题：(1)脑卒中对运动想象认知宏观行为学的影响；(2)脑卒中对运动想象各个认知子阶段的严格锁时锁相皮层活动的影响；(3)脑卒中对运动想象各个认知子阶段的非锁相皮层活动的影响；(4)脑卒中对各个皮层区域之间相互作用关系以及皮层神经功能网络特性的影响。
在本论文中，采用了一种定量的运动想象认知任务，即对旋转到不同空间角度的左右手图片进行心理旋转的任务，利用行为学、事件相关电位、事件相关（去）同步以及相位同步、皮层神经网络技术，从功能分离和功能整合角度描述脑卒中对运动想象神经机制的影响，以给出脑卒中后运动想象对患者运动功能康复的作用机理,具体结果描述如下：
(1)首先，为了观察脑卒中对患者运动想象认知任务的宏观影响，对脑卒中患者的行为学进行分析。其结果表明临床评分越好的患者运动想象心理旋转认知任务完成的越好，说明此任务可以很好地衡量脑卒中患者的行为能力。左侧半球梗死脑卒中患者同样可以完成左右手图片的心理旋转任务，反应时间和正确率都会出现显著的“角度效应”，但其反应时间显著长于正常对照组而正确率则显著低于正常对照组。结果表明卒中病灶对患者运动想象能力造成一定的影响，脑卒中患者即使患侧（右手）的实际运动功能受损，但是对患侧手的心理想象也即对其表象运动的能力仍然保留，可以完成表象空间旋转的任务。
(2)其次，为了实时观察脑卒中患者的运动想象认知过程中的皮层锁相电活动，对脑卒中患者运动想象认知前两个子阶段的事件相关电位成分进行统计分析。正常对照组在视觉编码阶段中，其锁相的皮层活跃区域主要集中在双侧额叶、中央区和右侧顶叶。而脑卒中患者组则只有健侧半球（右半球）的额叶和顶叶活跃，其和运动相关的中央皮层以及受损半球的额叶（左半球）活跃缺失，表明在此阶段脑卒中患者组只对视觉刺激图片的物理属性进行编码而未激发和该图片相关的高级运动认知过程。正常对照组在心理旋转过程中出现了显著的“幅度调制”现象，其活跃区域集中在双侧顶叶。脑卒中患者其锁相的活跃区域则只集中在健侧半球的顶叶。左半球卒中的患者对视觉空间信息的编码和认知只由健侧半球的顶叶完成，由于缺失左半球顶叶的参与，卒中患者对空间信息编码的能力受损，不能准确区分和编码不同的视觉空间角度。
(3)皮层活跃除了严格锁相部分外，还有非严格锁相的皮层活跃，为了研究脑卒中对运动想象认知过程中的皮层非锁相活跃的影响，对脑卒中患者的beta波段的事件相关(去)同步进行分析。脑卒中患者组的beta波段事件相关去同步激活的皮层活跃程度显著小于正常对照组，表明脑卒中导致患者全局性皮层非锁相活跃程度减弱。类似于锁相的事件相关电位的结果，脑卒中患者组在视觉编码阶段同样表现出运动皮层区域非锁相活跃的不足。在心理旋转阶段，脑卒中患者组的枕叶、中央区和顶叶活跃，而额叶活跃较弱。在反应选择执行阶段，正常对照组的事件相关去同步的幅值出现“角度效应”，并且其非锁相活跃区域逐渐从左半球扩大到右半球。而脑卒中患者组在反应选择阶段的事件相关去同步的幅值则和空间角度无关，并且其活跃区域依旧集中在枕叶、中央区和顶叶，额叶的活跃相比正常对照组依然不足。脑卒中患者额叶的非锁相皮层活跃比较缺乏，其视觉空间角度信息的编码能力受损。
(4)上述技术手段主要是针对各个局部区域的皮层活跃进行考察，尚未描述各个皮层区域之间的相互关系。利用相位同步技术对脑卒中患者的皮层区域之间的相互关系进行分析，并利用图论理论构建皮层神经功能网络，从功能分离和功能整合的角度去理解脑卒中对运动想象认知神经机制的影响。脑卒中患者组的平均相位同步指数显著小于正常对照组的平均相位同步指数值。脑卒中患者组受损半球内（左半球）以及半球间的相位同步性显著降低，而健侧半球（右半球）内的同步性并未显著受损，说明卒中后病灶和病灶周围及其远距离皮层区域的同步性受损，其协调性下降。脑卒中患者的神经功能网络同样具有“小世界”特性，但是其特征路径长度变长表明脑卒中后脑区之间的信息传递所需要的路径变长，效率降低，尤其在心理旋转子阶段这种变化尤为显著。其次，聚类系数的降低表明脑区的功能分离能力受损，即脑区内的连接变得稀疏，紧密程度下降。节点聚类系数和介数的拓扑分析结果表明脑卒中患者组相比正常对照组在右半球顶叶的聚类系数、额叶的节点介数显著增大，表现出在运动想象认知过程中患者健侧半球的补偿效应。
利用高时间分辨率的事件相关脑电技术，观察到脑卒中对运动想象认知各个阶段的影响：对视觉刺激编码的影响主要表现在受损半球运动皮层活跃不足；而在心理想象运动过程中的影响主要表现在顶叶的不对称性，即，健侧半球主导；而在反应选择执行过程中则同样表现为受损半球运动皮层活跃不足。脑卒中后患者不同皮层区域之间的相互协调能力下降，其皮层神经功能网络的“小世界”性受损，整个网络信息传递效率下降，功能分离和功能整合能力受损，并在整个认知过程中出现了显著的健侧半球补偿效应。以上是作者这篇论文的主要工作。本文一方面从事件相关电位的锁相活动和事件相关（去）同步的的非锁相活动揭示卒中病灶对运动想象心理旋转认知任务各个阶段的局部皮层活跃的影响；另一方面利用图论理论研究卒中病灶对运动想象认知神经功能网络特性的影响，对揭示脑卒中后的运动想象认知神经机制和临床应用具有潜在的重大价值。
Motor impairment after stroke is a major cause of permanent disability. Loss of entirefunction or partial ability of movement brings lots of inconvenience to the stroke patientsand their families. Recovery of motor function in order to improve life quality of patients isa primary aim after stroke. Motor imagery was recently reported to be useful for recoveryof motor function in stroke patients. Motor imagery is a cognitive process in which therepresentation of a specific motor action is internally reactivated within working memorybut without an overt motor output. Motor imagery could be used as an additional trainingmethod during any stage after stroke to active movement network and it’s not dependent onpatients’ residual physical function and patients could participate actively. Neuroimagingstudies showed that cortical neural networks including posterior parietal and visual cortex,premotor cortex (BA6), supplementary motor areas (SMA) and primary motor cortex (M1)were activated during motor imagery. In addition, some subcortical structures, e.g., basalganglia, were also activated during motor imagery. Basal ganglia and motor cortices havebeen known to be involved in motor planning and execution, and their activation duringmotor imagery suggested that actual and mentally simulated movements largely share thesimilar neural structures. Compared with passive movement rehabilitation, motory imageryis more in line with the normal excitation mode of neural system, which is from centralneural system (e.g., brain structures) to extremes (e.g., limb), and more effective toregenerate the reflex neural arc of movement.
Although motor imagery training has justified some optimism in stroke rehabilitation,the majority of these studies to date were poorly controlled cases or with small samplesizes and the outcomes were inconsistent. Furthermore, the underlying neural mechanismsof motor rehabilitation by motor imagery have not been fully understood. The studies sofar have been mostly based on behavior assessment and overall neural activations byneuroimaging technology during motor imagery with few temporal details of the cognitiveprocess. Therefore, one interesting question is how stroke lesion would affect the neural mechanism of each sub-stage during the cognitive process of motor imagery. In this thesis,we aim to use event-related EEG recordings with high temporal resolution and behaviorperformance to find answers for those scientific questions:(1) stroke lesion effect onoverall behavior performance during motor imagery;(2) stroke impact on phase-lockedcortical activation in each sub-stage during motor imagery;(3) stroke impact onphase-unlocked cortical activation in each sub-stage during motor imagery;(4) strokeimpact on the interdependence between different brain areas and network properties fromfunctional segregation and integration perspective. We hope this study could reveal moreneural cognitive mechanism of motor imagery during rehabilitation after stroke which iscrucial for treatment planning and clinical outcome quantitative estimation.
In this thesis, a quantitative motor imagery cognitive process was employed, i.e.,identification task of hands pictures which were rotated to different spatial angles (mentalrotation task, MRT). Event-related electroencephalography (EEG) signal with hightimporal resolution was used to reveal temporal-spatial patterns of neural activation for twogroups in different cognitive sub-stages during MRT. Behavior performance, event-relatedpotential (ERP), event-related (de)synchronization (ERD/ERS), phase synchronization andcognitive functional network were investigated to illustrate neural mechanism of strokeeffect on cognitive process of motor imagery. Specific results were described as follow:
(1) In order to evaluate the overall impact of stroke on motor imagery, behaviorperformance of stroke patients was assessed. Behavior results showed that stroke patientswho with better clinical outcomes had better performance in MRT, which indicatedbehavior performance during MRT had good correlation with clinical outcomes in strokepatients. Patients with stroke lesion in left hemisphere could also accomplish MRT, showedsignificant “angle effect”. Although movement impairment of affected (right) hand wasobserved, representation of the affected hand movement was still intact or partly preserved,i.e., patients could accomplish the MRT with affected hand. Compared with controlsubjects, longer response time and lower accuracy rate were observed for stroke patients,which indicated that stroke lesion affected patients’ behavior performance in MRT.
(2) Stroke impact on phase-locked activation of cortex during each sub-stage in motorimagery was assessed by event-related potential (ERP). Two significant ERP components(i.e., P200and P300) were observed during MRT, which were indicated visual stimuliencoding and mental rotation sub-stages respectively. During visual stimuli encodingsub-stage, stroke patients showed only frontal and parietal lobe in contralesionalhemisphere activated. Hypo-activation in bilateral central area and frontal lobe inipsilisonal hemisphere of stroke patients indicated that only physical property of handpictures were encoded and no higher movement related cognitive process were involved for stroke patients during visual stimuli encoding sub-stage. Significant “amplitudemodulation effect” in control subjects during mental rotation of visual stimuli wasobserved in bilateral parietal lobes which played an important role in spatial cognition.Stroke patients showed significant contralesional parietal lobe activation (i.e., lateralizationeffect), but no “amplitude modulation effect” was observed. All ERP results indicated thatstroke patients showed significant deficiency of movement-related areas activation inipsilesional hemisphere.
(3) In addition, event-related (de)synchronization (ERD/ERS) in beta band wasevaluated to assess the stroke impact on cortical phase-unlocked activation in eachcognitive sub-stage during motor imagery. Stroke patients had significantly smallerbeta-ERD values than control subjects. During visual stimuli encoding, only occipital andparietal lobes activated in stroke patients. Hypo-activation in movement related brain areasfor stroke patients might contribute to impairment of visual stimuli encoding ability.During mental rotation of visual stimuli, bilateral frontal, central and parietal lobes showedbeta-ERD for control subjects while stroke patients showed smaller beta-ERD valuesparticularly in frontal lobes. During response cognitive process, significant “angle effect”of beta-ERD was observed for control subjects, more activation particularly in righthemisphere was observed for more difficult task. No such effect was observed for strokepatients and the phase-unlocked activation was localized in parietal, central and occipitalareas. Hypo-activation in movement related brain areas in stroke patients might contributeto poor ability of spatial information encoding and impairment of movement executionability during MRT.
(4) Besides local phase-locked and phase–unlocked cortical activation was evaluated,interdependances between different brain cortical areas were assessed by phasesynchronization to investigate the stroke effect on cortical interactions. Furthermore, neuralfunctional network baesd on graphy theory was constructed to reveal cognitive networkalterations after stroke. Stroke patients showed significantly smaller phase synchronizationindex in ipsilesional hemisphere and interhemisphere. Stroke lesion might contribute to thesynchronization reduction in brain areas around lesion in the left hemisphere andsynchronization between brain areas with long distance in two hemispheres. Functionalnetwork of stroke patients also showed “small-worldness” property while with longercharacteristic path length and smaller clustering coefficient which indicated more pathswere needed to transfer information and the local interaction was sparse. All these resultsindicated that ability of functional segregation and functional integration after stroke wasimpaired significantly. Statistical results showed that patients showed significant largernodal clustering coefficient and betweenness in right (contralesional) hemisphere, particularly in mental rotation sub-stage, which showed compensation effect ofcontralesional hemisphere. These results revealed that functional network after strokereflected a lower capacity to integrate the communication between distance brain regionsand lower tendency to be modular. Patients’s network also showed contralesionalhemisphere compsenssation effect.
In summary, we investigated the cognitive alternations during MRT after the lefthemispheric stroke injury using both behavior and electrophysiological methods.Movement impairment after stroke would also accompanied by poor behaviorperformances in motor imagery. Hemispheric lateralization after stroke was observedwhich was due to the ipsilesional hypo-activation during visual stimuli perception andmental rotation. Furthermore, stroke lesion also resulted in the loss of “angle effect” due tothe impaired spatial information processing during response execution. Synchronization inipsilesional hemisphere was impaired significantly and the network of stroke patientsshowed lower ability to integrate the communication between brain areas and lowertendency to be modular, and contralesional hemisphere compensation effect. These resultsmight provide new insights into the understanding of cognitive process during mentalrotation, and could be referenced as a guide in stroke rehabilitation with motor imagerytraining. These were the major work in this thesis. On one hand, these studies investigatedstroke effect on cognitive process in motor imagery with time course from bothphase-locked and phase-unlocked event-related oscillations. On the other hand, strokeeffect on functional segregation and integration of the cognitive functional network wasalso investigated by graphy theory based on phase synchronization. This thesis would becrucial to reveal cognitive neural mechanism of motor imagery after stroke and potentiallyuseful for clinical application in rehabilitation training after stroke.
引文
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