镜像治疗患肢痛的脑功能影像学研究

Following limb amputation, most patients continue to experience the presence of the missing limb, a sense of being able to move it, and pain emanating from it. Phantom limb pain (PLP) is one of the major complications after amputation. It has recently demonstrated that the use of “mirror therapy” can relieve PLP in amputees, but the physiological basis for this effect remains unknown. The appearance of functional magnetic resonance imaging (fMRI) and diffusion tensor imaging(DTI)make it possible to study the PLP mechanism in the cortex. The goal of this study is to explore the mechanism of PLP through comparing the differences of the structural and functional connectivity changes in the large-scale brain networks and the structural and effective connectivity changes in the local network among the cortical areas involved in fMRI tasks, among the PLP patients，the healthy controls and the PLP free amputees;to analyze the brain structure and function data in the process of mirror therapy, to explore the relationship of cortical reorganization patterns and phantom limb pain, and the dynamic effect of mirror therapy on brain structure and function of cortical reorganization, reveal the biological mechanisms of mirror therapy on phantom limb pain, and analyze the relationship between the consistency of the mirror limbs and phantom limb with the treatment of mirror therapy, providing objective indicators and morphological evidence for the best time long-term effectiveness of the situation, indications choose of the mirror therapy. The study will not only enable us to better understand the physiological basis of the interaction of the mirror therapy, cortical reorganization, and the development of PLP but also contribute to the development of a functional measure of the response of PLP to treatment and may result in the development of additional treatments for PLP.

幻肢痛(phantom limb pain, PLP) 是截肢后的主要并发症之一，发生率高，治疗困难。已有的研究表明镜像疗法（mirror therapy，MT）可以有效的缓解幻肢痛，但是镜像治疗究竟是通过何种机制来发挥其作用的，目前尚不清楚。本项目拟应用fMRI及DTI技术获取幻肢痛患者、截肢后无幻肢痛者及健康对照组大脑结构和功能数据，对不同组被试的大尺度结构网络连接、功能网络连接、网络拓扑属性以及fMRI任务激活的脑区构建的局部结构和效应网络连接进行对比分析，探索研究幻肢痛大脑皮质功能重组形成过程，揭示截肢后发生幻肢痛的神经病理机制；获取幻肢痛镜像治疗过程中脑结构与功能的动态影像学数据，深入研究镜像治疗对脑皮层功能及结构连接的动态影响，阐明镜像疗法缓解幻肢痛的神经生物学机制，并为镜像疗法的最佳适用时机、长期效用情况、适应症选择等提供客观有效的形态学依据。

幻肢痛是截肢后最常见的并发症，发病率高、难以治愈、对患者身心健康影响很大，但其神经病理机制仍不清楚。本课题综合运用高分辨率的结构MRI、DTI和静息态fMRI技术，研究下肢截患者大脑结构和功能的异常影像学特征，并在此基础上结合多种脑网络分析方法，对幻肢痛的发生机制进行深入系统的研究。研究结果显示，幻肢痛患者在多个功能子网络内及网络之间功能连接模式发生改变；同时幻肢痛患者多个与疼痛相关的脑区局部和远程信息传输能力异常，尤其是背外侧前额叶与多个疼痛相关脑区表现为一致性的功能连接的增强，提示该脑区可能在疼痛环路的调控中起到重要作用；研究还发现幻肢痛患者的大脑网络rich-club组织的结构和功能连接出现特异性变化，且rich-club组织结构和功能连接与病程呈现明显的负相关，即病程越长幻肢痛患者的rich-club组织连接强度越低，预示着幻肢痛患者异常的功能输出与进程性的rich-club组织紊乱具有密切关系。这些结果从脑网络的角度为解释幻肢痛的神经病理机制提供了客观的影像学依据，为幻肢痛临床治疗提供了潜在的治疗靶点。同时本课题还采用fNIRS技术对镜像运动时大脑的激活模式和血氧信号的时程特点进行了初步研究，发现镜像运动能够显著激活镜像肢体对侧大脑感觉运动皮层，且与运动执行具有相似的时间特性曲线。这些结果从影像学的角度肯定了镜像运动中镜像肢体对于其对侧大脑感觉运动环路的作用，为镜像运动疗法应用于临床幻肢痛的干预治疗提供了新的依据。本项目资助发表SCI论文5篇，核心期刊论文2篇，待发表SCI论文1篇。指导一名本科生完成毕业设计。培养博士研究生1名，已取得博士学位。