基于运动学习环路的脑卒中后吞咽障碍发生机制及tDCS调控研究

The incidence of dysphagia following stroke is high, its complications such as aspiration pneumonia and malnutrition seriously affect the prognosis. So far, however, the neural mechanism of the occurrence and rehabilitation in post-stroke dysphagia is still vague. Our preliminary experimental results showed that dysphagia after stroke may damage the motor programming process using high-resolution manometry (HRM) and also found transcranial direct current stimulation (tDCS) can bi-directional regulate the excitability of swallowing primary motor cortex (M1). To this end, we propose the hypothesis: maladaptive motor learning circuits may be involved in the occurrence of dysphagia after stroke. tDCS modulate the key node of motor learning circuit, which facilitate the excitability of motor cortex and improve the efficiency of circuit. In order to verify the hypothesis, we use dynamic digital image analysis technology, HRM, multi-channel electromyography to explore the specific biomechanical effects. Furthermore, cortical inhibition by cathodal tDCS pre-condition to healthy volunteers and cortical excitation by anodal tDCS to dysphagia patients after stroke. From the neural level, we observe the activated swallowing brain regions and their connectivity in motor learning circuits by task functional magnetic resonance (fMRI) and resting-fMRI. We also detect the excitability of neural pathway by transcranial magnetic stimulation motor evoked-potential (TMS-MEP) to clarify the mechanism of dynamic change of various stage of motor learning.This study from the new viewpoint of motor learning circuit and the new method of tDCS will lay a good foundation to reveal the mechanism of occurrence and recovery of dysphagia and provide us a new treatment strategy.

脑卒中后吞咽障碍（DFS）发生率高，导致的吸入性肺炎和营养不良严重影响患者预后，但其发生和康复的神经机制仍不明确。我们前期研究提示DFS可能损害运动学习的编程过程，并发现经颅直流电刺激（tDCS）可双向调节吞咽皮质M1区。为此，我们提出假说：运动学习环路功能异常是DFS发生的重要因素。通过tDCS调控该环路的关键节点有助于诱导吞咽皮质可塑性，提高环路效率，改善吞咽运动学习。为验证该假说，我们采用数字化动态吞咽影像分析、高分辨率咽腔测压、表面肌电从外周层面提取其生物力学的特异性特征；通过抑制性tDCS虚拟损伤和兴奋性tDCS干预其关键节点，借助TMS-MEP和任务/静息态fMRI从中枢层面检测神经通路的活性和运动学习脑区的激活及环路功能连接，并阐明不同学习阶段的动态变化机制。本研究将从吞咽运动学习环路的新视点和tDCS调控新方法，为揭示吞咽障碍的神经重塑机制奠定基础，为治疗策略提供新的思路。

本研究从全新的吞咽运动学习角度探讨脑卒中后吞咽障碍的发生机制。先采用高分辨率测压HRM技术从外周生物力学角度探讨不同部位电刺激时咽肌/UES功能变化。后应用吞咽造影定量分析技术剖析不同食品质构参数对吞咽动作时间学参数和食团形变率的影响。研究期间屡次受挫，最终探索了一个适合脑卒中后吞咽障碍患者的吞咽运动学习范式。接着，我们采用fMRI/DTI从中枢水平检测卒中后吞咽脑区的神经活动，结合阳极tDCS干预，探讨脑卒中后吞咽障碍运动特征与相关的吞咽、学习脑区关键节点间关系。研究发现左右两侧大脑半球在吞咽系列动作中承担不同的角色。脑卒中后吞咽障碍的受累半球insula脑区活性降低，与DTI纤维束减少呈正相关性。健侧半球insula脑区活性增强。健侧半球阳极tDCS干预可以增强双侧insula脑区的活性。提示insula脑区是脑卒中后吞咽障碍中的关键脑区，也许可以成为今后治疗和判断预后的靶点。研究部分成果已发表在Scientific Reports，中华物理医学与康复杂志，中国中医急症杂志发表（发表论著3篇，其中SCI 收录1篇，IF=4.01）；课题负责人多次在国内学术会议上受邀做学术汇报。