基于大尺度皮层-丘脑回路模型的失神癫痫机制研究

Absence epilepsy is a subtype of idiopathic generalized epilepsy, mainly occurring in the childhood and adolescent years. Some absence epileptic patients have permanent cognitive impairments, affecting both of their physical and mental health, and thus seriously diminished their quality of life. As an electrophysiological hallmark of absence epilepsy, the bilaterally synchronous spike and wave discharges (SWDs) with a slow frequency at approximately 2–4 Hz is often observed on the electroencephalogram (EEG) of patients. It is believed that the generation of SWDs during absence seizures is highly associated with the abnormal interactions between cerebral cortex and thalamus, which together form the so-called corticothalamic system. As is well known, the thalamus comprises a group of interconnected subcortical nuclei, and recent experimental data have indicated that some thalamic nuclei are important for SWD occurrence and might have different functional roles in the generation, spreading and maintenance of SWDs. However, so far the exact functional roles of different thalamic nuclei and their corresponding regulation mechanisms for SWDs are not completely established. In this project, we propose to address this issue using the computational neuroscience approach. Here we first plan to establish a large-scale corticothalamic model based on the MRI and EEG data of absence epileptic patients. Then, using the high temporal-spatial neural signals generated by the large-scale corticothalamic model, we will systematically investigate the pathological mechanisms of absence seizures. In particular, we will explore the detailed roles of different thalamic nuclei in the generation, spreading and maintenance of SWDs during absence seizures, and elucidate the underlying regulation mechanisms of thalamus for absence epilepsy. The expected results of this project, on the first hand, will contribute to understand the generation and regulation mechanisms of absence epilepsy and, on the other hand, will provide new diagnosis and therapeutic strategies for absence epileptic patients.

失神癫痫是一种好发于儿童和青少年时期的特发全面性癫痫，部分患者存在一定认知功能障碍，严重地影响了患者的身心健康。失神癫痫脑电图特征是2-4Hz棘慢波放电（SWDs），其产生被高度怀疑与皮层-丘脑网络环路异常有关。已有证据表明，丘脑由于具有躯体特异性，其多个核团可能在SWDs的引发、播散及维持中扮演了不同角色。但迄今为止，丘脑精细结构在失神癫痫发作时的分功能作用和调控机制尚不明确。本项目基于计算神经科学研究手段，利用失神癫痫患者的磁共振、脑电数据构造和优化大尺度皮层-丘脑回路模型，通过计算机模拟的方法获得基于模型的高-时空分辨率的神经响应信号，并在此基础上深入研究失神癫痫的皮层-丘脑环路发病机理，重点阐明丘脑精细结构在SWDs的引发、播散及维持中可能所起的作用和调控机制。项目的研究成果将对最终阐明失神癫痫发生和调控的神经机制具有深刻的理论意义，并可能为临床失神癫痫的诊断和治疗提供全新的思路。

失神癫痫是一种好发于儿童和青少年时期的特发全面性癫痫，部分患者存在一定认知功能障碍，严重地影响了患者的身心健康。已有证据表明，丘脑的多个核团可能在SWDs的引发、播散及维持中扮演了不同角色，但迄今丘脑中的关键核团是如何调控失神放电的神经机制尚不明确。本项目基于计算神经科学研究手段，充分利用失神癫痫患者的磁共振和脑电数据构造覆盖全脑皮层脑区的大尺度皮层-丘脑回路模型，通过计算机模拟的方法获得基于模型的高时-空分辨率的神经响应信号，在此基础上深入研究失神癫痫的皮层-丘脑环路发病机理，重点探索丘脑不同区域、核团与不同皮层脑区间环路在SWDs的引发、播散及维持中所起的作用和失神癫痫的丘脑调控机制。在本项目执行期间，课题组成员认真开展相关研究工作，按计划进行了相关研究，取得了阶段性研究成果。在此基础上，进一步结合国际上的研究热点适当拓开了研究内容。目前，已在包括IEEE会刊在内的国际知名刊物和会议上发表论文22篇，其中SCI收录期刊论文20篇，影响因子大于5的论文3篇。在项目开展的四年中，项目负责人获英国物理学会“2018高被引中国作者奖”，作为主要成员(排名3)获得2019年度黄家驷生物医学工程奖二等奖。此外，在项目的支持下，课题组成员多次参加国内外重要学术会议，项目负责人受邀在多个学术会议上宣讲最新研究成果。