基于人脑发育轨迹的癫痫异常神经网络瓦解的机制及靶点研究

Interference of brain self-maintenance and subsequently forming of abnormal neural network is a key scientific issue in epilepsy research. Rolandic epilepsy (RE) is the most common pediatric epilepsy syndrome related to brain development, which is characterized by self-limited course: as the brain develops, epileptic seizures gradually decreased to self-cure. It demonstrates a full picture of process for abnormal epileptic network development to disruption, providing the best model to study the disruption of epileptic network. Through our preliminary cross-sectional work, we’ve already depicted the structural, functional and metabolic feature of RE network by multimodal neuroimaging techniques to target the hypothetical seizure and comorbid subnetworks. In this project, we intend to detailed depict the dynamic evolution and complex behavior of the RE abnormal neural network in a prospective manner by taking advantage of our longitudinal multi-modality database of RE cohort. Furthermore, we plan to apply optimized algorithms of connectome and texture analysis to construct the abnormal brain network model of RE in a directional and weighted pattern along with the developmental trajectory of brain. By tracing the evolution, especially disruption of the RE network, we are going to precisely extract the temporal and spatial hub of the abnormal brain network. We hope the study will shed light on the mechanism of the disruption of the epileptic neural network and offer possible new clues to future precise therapy in individualized treatment of epilepsy.

脑自稳态网络系统的破坏，异常神经网络的形成和衍变是癫痫学科研究中公认的重要科学问题。Rolandic癫痫（RE）是最常见的与脑发育相关的儿童癫痫综合征，病程具特征性的自限性：癫痫发作随脑发育逐渐减少至自愈，为我们完整地呈现了癫痫异常神经网络发展至瓦解的全过程，是研究癫痫异常神经网络瓦解的最佳切入点。在前期工作中，我们应用多模态影像学技术对RE异常神经网络的结构、功能和代谢特征进行了横断面研究，初步锁定其痫性发作及共病的目标子网络。本次项目拟以RE异常神经网络的瓦解机制及靶点为主攻方向，继续扩充已建立的RE多模态影像学纵向队列资源，引入先进的脑连接组学和纹理分析技术，有向加权地构建完整的RE异常神经网络疾病模型，并着力纵向追踪循脑发育轨迹的网络发展特别是瓦解过程，力求精准提取和分离出异常网络动态衍变过程中时间与空间的关键节点，为突破癫痫异常神经网络的瓦解及其机制提供全新的思路和靶点。

癫痫是一种具有持续致痫倾向的脑部疾病，严重影响大脑发育和功能，具有神经生物、认知、心理和社会的广泛不良后果。癫痫的异常神经网络的固化被认为是造成患者癫痫持续发作及共病的主要原因。而阐明癫痫异常神经网络如何固化及瓦解靶点是精准防控癫痫的关键所在，故癫痫的异常神经网络一直是癫痫学科的研究热点。前颞叶切除术是难治性颞叶内侧癫痫最有效的治疗手段，我们拟借助于颞叶内侧癫痫手术干预前后，探讨手术干预前后癫痫异常结构和功能网络重塑机制，纵向追踪癫痫异常神经网络瓦解过程，寻找瓦解靶点。通过对比颞叶内侧手术前及手术后多个时间点结构及功能网络改变，结果提示颞叶内侧癫痫患者存在术后的皮层增厚，提示成功的癫痫手术后的皮层重塑。对侧海马与同侧岛叶的功能连接在术后3个月时明显减弱，在术后24个月时保持相对稳定；对侧海马与双侧内侧前额叶皮层和额上回的功能连接在术后3个月时明显增强，随后保持相对稳定。提示成功的前颞叶切除术可能不会导致对侧海马明显的结构重塑。对侧海马与双侧前额叶皮层和额上回的功能连接增强可能与术后的功能重塑有关，证明了颞叶内侧癫痫手术干预后结构和功能重塑过程，为未来探究癫痫异常神经网络固化及瓦解的脑源性机制研究提供了新的线索。