基于fMRI分析脑结构-功能网络研究中风后抑郁"虚、瘀、郁"状态下脑区"失连接"及中药干预纵向追踪

The latest researches have shown that the occurrence of depression after stroke is associated with multiple abnormal brain regions and neural pathways. However, most of present studies are limited to a single brain region or a single neural circuit, the mechanism of interaction between different brain regions and neural pathways is still partial. Researches in multimodal fMRI study have found that brain structure-function network and the connection of fibers in patients with post-stroke depression appeared abnormal. Whether this "Abnormal connection mode" is the mechanism of post-stroke depression produced? Our previous studies have shown that stroke patients on the basis of "virtual、blood stasis、depression" will more easily complicated with depression , and protein microstructure extensive damage appeared in a number of brain regions, nerve fibers also exist abnormal connection mode. Effects of using traditional Chinese medicine to cure the disease are very obvious, but the knowledge of the mechanism is still unknown. This project will use the fMRI technology to detect brain structure, resting brain function and the connection of brain fibers. With advanced fiber tracking, independent component analysis and multimodal information fusion algorithm, longitudinal track the differences in the brain's structure, function, connection among the nerve fibers and brain spaces modal mode before and after the intervention of the Chinese medicine treatment. The analysis of above highly precised biological indicators will provide brain imaging evidence for the target of TCM treatment with the post-stroke depression. This project combing with the evidences of the imaging , biology and pharmacology will provide a new method for studying the mechanism of the Chinese medicine in the treatment of post-stroke depression.

最新研究表明，中风后抑郁的发生与多个脑区及神经通路异常有关。然而，目前的研究大多局限于单一的脑区或神经环路，对脑神经机制的认识局部化、片面化。课题组通过多模态fMRI研究发现中风后抑郁患者脑结构-功能网络及纤维连接出现异常连接方式，那么这种“失连接”是否是中风后抑郁产生的机制？我们前期研究显示，中风病在“虚、瘀、郁”的基础上易并发抑郁，在多个脑区出现白质纤维微结构的广泛损伤，神经纤维连接存在异常，中药干预疗效显著，但作用机制仍不明确。本项目拟采用fMRI技术检测脑结构、脑静息功能、脑纤维连接，进一步采用先进的纤维跟踪、独立成分分析、多模态信息融合等算法，纵向追踪中药干预前后脑结构、功能、纤维连接及脑空间模态的演变规律，获得具有高精度灵敏度的生物学指标，为中药干预中风后抑郁的作用靶点取得脑影像学证据。本项目将影像学、生物学、药理学证据相结合，为研究中药干预中风后抑郁作用机制提供新的方法。

国内外最新研究表明，中风后抑郁（PSD）严重影响中风患者的康复及预后。中风对于病人来讲不仅是肢体障碍，还会产生许多不良的心理暗示，从而不断产生悲观、失意等低落情绪，诱发抑郁。中风的基本病机是“虚、瘀”，中风后长期的肢体功能障碍更进一步刺激了患者，使肝气郁结，形成“虚、瘀、郁”， 进一步加重神经功能缺损。中风后抑郁的发生与多个脑区及神经通路异常有关。然而，目前的研究大多局限于单一的脑区或神经环路，对脑神经机制的认识局部化、片面化。中风后抑郁是典型的脑区“失连接”疾病，脑功能及纤维连接中出现异常的组织模式。本项目采用多模态MRI技术检测脑功能、脑静息功能、脑纤维连接，进一步采用先进的纤维跟踪、独立成分分析、多模态信息融合等算法，纵向追踪中药干预前后脑结构、功能、纤维连接及脑空间模态的演变规律。本研究发现卒中后抑郁症患者与正常人脑功能连接节点效率指标主要在楔前叶、丘脑区域存在差异；节点局部效率指标主要在脑岛、丘脑区域存在差异。卒中后抑郁症患者脑功能连接治疗前NE属性主要在基底神经节、丘脑、顶上小叶、脑岛区域存在差异。NLE属性主要在基底神经节、丘脑、顶上小叶存在差异。治疗后NE属性主要在基底神经节、丘脑、顶上小叶、脑岛、中央后回区域存在差异。卒中后抑郁大鼠脑区连接普遍减弱，涉及脑区有基底外侧杏仁核、下丘脑、纹状体、海马角、脚间核、左侧灰白色背侧导水管周围。主要表现为基底外侧杏仁核(中央)与脚间核连接减弱，下丘脑与脚间核连接减弱；纹状体与大脑皮层4区连接减弱，纹状体与左侧灰白色背侧导水管周围连接减弱；海马角、海马与左侧灰白色背侧导水管周围连接减弱。通过对患者与大鼠大脑核磁共振检测，发现患有卒中后抑郁症患者及大鼠均在楔前叶、丘脑、基底神经节、下丘脑、纹状体、海马角、中央后回、顶上小叶、脑岛区、脚间核等脑区出现连接减弱。患者损伤脑区主要在楔前叶、丘脑、基底神经节、顶上小叶、脑岛、中央后回；大鼠损伤脑区在基底外侧杏仁核、下丘脑、纹状体、海马角等区域。各功能脑区连接的减弱为进一步研究卒中后抑郁主要损伤脑区的功能、抑郁神经环路提供依据，为中药干预中风后抑郁的作用靶点取得脑影像学证据。