大脑皮层褶皱形成“共推理论”研究

Cerebral cortical folding is an important feature of brain structure. Exploring the mecha-nism of cortical folding may bring new insights into exploring the developmental mechanism of brain structure and function. However, works available in literature barely considered more than one possible factor (i.e., neuronal proliferation and projection, neuronal axon development) that contributes to cortical folding. Also, few of them have conducted joint analysis by using data of multiple modalities. Therefore, the hypotheses proposed in those works are limited to one aspect or another. This project will be proposed based on our previous hypothesis that cortical folding is caused by the pushing force of neuronal axons, defined as “single-cause pushing hypothesis”. We will propose promotion to this hypothesis by incorporating two factors, the pushing effect of neu-ron growth and the pushing force of neuronal axon, and come up with a novel “joint pushing hy-pothesis”. Technically, we will develop joint analysis methods to use and take the most advantages of macro-scale and micro-scale data. Based on the methods, we will quantify the three elements: cortical folding, neurons and neuronal axons, and further quantify the relationship between cortical folding and neuronal axons and the relationship between cortical folding and neurons, so that more “comprehensive” data-based evidence can be provided to the novel hypothesis. Also, we will use longitudinal data to study how the two factors alternately and jointly contribute to cortical folding, so that “dynamic” evidence to the novel hypothesis can be obtained. This project will provide a new way of studying the cerebral cortical folding mechanism. The results may hold the clue to brain evolution and brain diseases.

皮层褶皱是大脑的一个重要特征。对大脑皮层褶皱形成机理的研究本质上是对大脑结构以及功能形成机理的研究。然而已有的理论很少同时考虑多个因素，也很少使用多种数据，因此在一定程度上具片面性。本项目拟在前期神经元轴突“单推理论”基础上，增加神经元细胞体的作用，提出皮层褶皱形成新理论：神经元轴突和神经元细胞体的“共推理论”。在方法上，我们拟使用宏观和微观数据联合分析的方法，发挥各数据模态的优势，分别量化神经元轴突与皮层褶皱之间关系以及神经元细胞体与皮层褶皱之间关系，尝试为“共推理论”提供尽可能“全面”的量化证据。另外，为了更好的研究神经元轴突和神经元细胞体这两个因素是如何在时间轴上交替或者共同对影响皮层褶皱形成，我们拟对多时间点数据进行量化分析，尝试为“共推理论”提供“动态”证据。本项目将为研究大脑皮层褶皱形成机理开辟新的研究途径，其结果将为大脑认知原理、物种间的进化和脑疾病病理等的研究提供新的思路。

皮层褶皱是大脑的一个重要特征。对大脑皮层褶皱形成机理的研究本质上是对大脑结构以及功能形成机理的研究。然而已有的理论很少同时考虑多个因素，也很少使用多种数据，因此在一定程度上具片面性。本项目的研究目标是将轴突，细胞体同时纳入考量而提出新的皮层褶皱形成“共推理论”。本项目以宏观微观联合分析方法以及多时间点数据分析方法为研究手段，量化细胞体，轴突和皮层褶皱这三者之间的关系，为“共推理论”提供全面和动态的证据。为了实现这一目标，项目组在理论上深入分析了皮层、纤维束和褶皱三者之间的结构关系，并用脑功能数据对其进行了验证。在方法上，完成了多种模态数据下白质纤维束的量化方法，如dMRI数据下纤维束形态量化表达方法、概率性纤维束通路的全局连接性和形状量化表达方法，髓鞘染色数据轴突的局部走向量化表达方法，以及束路追踪数据纤维束的连接模式表达方法等。我们还完成了多种模态数据联合分析的方法开发。这些方法都被用于上述的理论研究中。另外，项目组还完成了多时间点数据的处理、联合分析和量化，为 “共推理论”提供“动态”分析手段。最后，还将提出的理论应用于自闭症褶皱异常成因的探索中。