轻度脑外伤认知异质损伤的额叶-纹状体功能与结构连接分析及预后评价

Mild traumatic brain injury (mTBI) is the top medical costs associated with TBI. Cognitive problems are a major cause of this ongoing disability, and the heterogeneity of the injuries and the variability of the resulting cognitive problems make their management particularly problematic. On the basis of preliminary study, the current project concerns the key role identifying common underlying pathologies that enhances cognition regulation: prefrontal cortex and striatum interactions. The overarching of this project is overcome the method limit in cognitive heterogeneity analysis, such as cognitive nonlinear regulation, structural injury diffuse location and outcome variabilities. This project aims to investigate the prefontal- striatum functional connectivity modelling, individual white matter injury load analysis and outcome prediction by combining both individual imaging and trait features. Firstly, to overcome the limit in investigating cognitive brain injuries, we model the functional connectivity linking prefrontal cortex and striatum as well as its interaction with cognitive regulation. Secondly, to overcome the limitation in detecting the heterogeneity of the injuries in previous group-based analysis, we develop random resampling 1-N individual structural injury load method to investigate the coherence between functional and structural connectivity. Finally, this project overcomes the current limitation in subjective index in clinical cognitive treatment management. This project will develop pattern recognition and classification analysis by combining the above imaging and trait features, in order to predict the probability of risk patients.

认知障碍是医疗成本高居脑外伤首位的轻度脑外伤终身致残的首要原因，其损伤与预后的异质性一直是临床治疗的挑战性难题。本项目在前期研究基础上，聚焦于轻度脑外伤认知异质性调控核心网络前额叶-纹状体的脑连接建模，针对当前异质性分析面临的“认知调控非线性、结构损伤弥散性、预后结局多样性”等技术研究瓶颈，对应围绕”前额叶-纹状体功能连接分析、个体结构损伤负担检测、影像特征与个体特质的预后评估技术”的研发为关键科学问题。首先，区别于以往仅关注认知损伤脑区响应的局限，构建前额叶-纹状体脑连接认知调控模型；其次，区别于以往组分析框架对损伤分布弥散性的检测局限，研发随机无限抽样的个体损伤负担检测算法，并探讨功能连接与纤维束连接的损伤共变耦合性；最后，针对临床认知治疗决策缺乏客观指标的现状，研发模式特征识别分类方法，发展联合影像特征与个体特质因素的预后评估技术，为轻度脑外伤认知障碍高风险人群的预后评价提供客观指标

本项目聚焦于轻度脑外伤认知异质性调控核心辐射通路前额叶-纹状体，针对当前异质性分析所面临的“认知调控非线性、结构损伤弥散性、预后结局多样性”等技术研究瓶颈，重点围绕“前额叶-纹状体功能连接分析、个体结构损伤负担检测、影像特征与个体特质的预后评估技术”的研发为关键科学问题。首先，建立纹状体亚区精细分割的前额叶脑功能连接映射图谱，识别了脑创伤认知灵活与稳定性动态平衡的功能损伤基础。其次，聚焦创伤后头痛（PTH）高发但损伤机制不明的挑战，提出认知偏向致PTH发生理论假说，建构“中脑导水管周围灰质-默认脑网络”功能失连接模型实现了假说验证，并建立了创伤后慢性PTH高风险人群的准确预测技术。再次，研发脑白质功能网络的分割方法，建立了结构-功能耦合共变性分析方法，为创伤损伤的脑重塑机制提供可靠途径。最后，建构相关向量机回归的“脑龄”预测方法，为脑创伤加速认知老化的个体风险识别提供了客观指标，并在精神分裂症促老化研究及药物干预结局预测中获得临床再验证。项目执行期，在神经创伤学Top期刊等发表论文20篇（1篇IF>10，9篇IF>5,其中一篇为封面论文），研究工作得到J Headache Pain创始主编、国际头痛分类第三版临床指南总负责、Headache副主编等发表专题评述为“奠定了PTH发生病理机制的脑功能损伤基础”、“使PTH早期预测成为可能”的正面评价，部分成果已在神经外科国家重点专科得到初步临床应用。出版学术专著三部，申请国家发明专利3项、软著4项。项目执行期内培养博硕士共5名，1名研究人员获得国家自然科学基金优秀青年基金的资助；项目负责人协助推动了中国针灸学会脑科学产学研创新联盟等多个学会的学术交流工作，有效促进学科的发展与进步。课题组还与哈佛大学、佛罗里达大学、香港大学建立了长期的互访人员培养计划。