卒中后PPC-M1功能连接"失平衡"及其调控机制研究

Visuospatial neglect is a frequent disability in stroke and adversely affects volitional movement. Our present studies revealed that the posterior parietal cortices (PPC) are involved not only in visuospatial attention but also in volitional movement. Indeed, the PPC is strongly interconnected not only with dorsolateral prefrontal regions, but also with ipsilateral motor cortex through distinct corticocortical connections. These corticocortical connections are thought to transfer crucial information relevant for planning movements in space and to integrate visuomotor transformations. However, the neural bases of these protracted changes are poorly understood. Noninvasive brain stimulation, a powerful tool for inducing transient disruptions of neural activity in the cerebral cortex, may be useful to investigate the interactions between the visuospatial attention and the volitional movement within PPC-M1 functional connections. The central aims of this proposal are to utilize multi-modal neuroimaging of functional magnetic resonance imaging (fMRI), structural MRI and diffusion tensor imaging (DTI), together with continuous theta burst stimulation (cTBS) to further study brain reorganization, not only for the interhemispheric connectivity between two hemispheres, but also for the intrahemispheric connectivity within PPC-M1 pathway, in patients with unilateral stroke, and to apply this understanding to test new methods for neurorehabilitation. We hypothesize that the recovery of spatial attention matched volitional movement (for example, hand movements to visual objects) should be associated with the structural or functional reorganization of PPC-M1 functional connectivity. Moreover, cTBS can be used to suppress cortical excitability. Following the real cTBS to suppress unaffected lateral PPC, there will be less overactivation on fMRI (better modulation) in the unaffected hemisphere, and new activation in the affected hemisphere. This will be associated with improved propositional spatial attention matched volitional movement ability post-real cTBS. In this project, we should use multi-modal neuroimaging address the brain connection. Indeed, we should demonstrate that cTBS-induced feature-specific effects on the spatial attention matched volitional movement recovery could point the way toward future therapeutic approaches that may be both more efficacious and better targeted than current therapies. The findings will be put in context by investigation of structural determinants of this relation through data-driven analysis and theoretical models.

脑卒中视空间忽略患者常伴有意向性运动障碍。我们前期研究发现意向性运动和视空间注意过程都需要后顶叶(PPC)的参与，两者功能预后也明显相关。然而意向性运动与视空间注意的交互作用和重塑机制还缺乏研究，PPC是否意向性运动和视空间注意的关键核心脑区尚未可知。皮层-皮层间交互作用或竞争"失平衡"是大脑皮层功能紊乱的重要神经机制。据此我们推测：PPC-M1功能连接"失平衡"是引发意向性定向运动障碍的重要因素，而PPC担任了中枢"闸门"的角色；采用持续θ爆发式刺激（cTBS）抑制对侧PPC的过度活动，有助于恢复PPC-M1功能连接的动态平衡，从而提高空间注意和意向性运动功能。为此，我们将利用TMS-MRI脑成像技术，结合运动和行为学数据，论证PPC在视空间注意和意向性运动调控中的中枢"闸门"作用；确立cTBS治疗空间忽略和意向性运动障碍的最佳刺激模式；揭示PPC-M1功能连接的中枢调控和重塑机制。

视空间忽略（Visuospatial neglect）是脑卒中患者常见的功能损害，有文献报道右侧和左侧卒中后空间忽略的发生率分别为43%和20%，并往往伴有意向性运动（Volitional movement）障碍，严重影响病人日常生活活动能力的恢复。意向性运动和视空间注意过程都需要后顶叶（PPC）的参与，然而意向性运动与视空间注意的交互作用和重塑机制还缺乏研究。因此，本课题以单侧脑卒中后视空间忽略和意向性定向运动障碍的脑机制研究为导向，利用TMS-MRI相结合的脑成像技术，结合运动和行为学数据，研究PPC在皮层-皮层间神经活动的交互作用及其兴奋-抑制平衡机制。研究结果发现PPC作为背侧环路的关键脑区参加并调控空间定向运动的执行，论证了PPC在背侧通路中的中枢“闸门”作用，说明PPC-M1功能连接兴奋-抑制“失平衡”与空间忽略和意向性定向运动障碍密切关联。此外，我们引入了神经定位导航系统并在此引导下进行TMS刺激点定位，使这种新的无创性刺激模式θ爆发式刺激（theta burst stimulation, TBS）能够准确地靶向调控PPC-M1功能连接兴奋-抑制平衡，从而可以确立为空间忽略和意向性运动障碍的最佳刺激模式。通过本课题的实施，我们建立了单侧脑卒中（局灶性脑损害）神经网络连接兴奋-抑制平衡机制研究与靶向调控技术创新和临床转化平台。使我们在此领域的临床基础与转化研究达到与国际接轨、国内领先水平。本研究按照课题设计有计划地完成了研究工作并达到了预期目标，研究成果已在Brain Stimul（IF=6.078）和Front Mol Neurosci（IF=5.076）等杂志上发表（论著12篇，SCI收录8篇）；也多次在国际和国内学术大会上交流并获奖。