颞叶内侧癫痫中海马-前岛叶通路异常重塑对执行功能损害的作用

Mesial temporal lobe epilepsy (mTLE) is a common epileptic syndrome based on formation of abnormal neural circuit. It is often accompanied by significant cognitive impairment, including executive dysfunction. However, there are few studies about executive dysfunction in mTLE, and the specific neural loop mechanism has not been illustrated yet. In preliminary experiment, the applicant has found that the functional connectivity of the hippocampal-anterior insular pathway is significantly and positively correlated with executive function in mTLE. Thus, we propose a hypothesis that the abnormal reorganization of the hippocampal-anterior insular pathway is a critical path leading to executive dysfunction in mTLE. In the present study, we aimed to depict the dynamic characterization model of the abnormal reorganized hippocampal-anterior insular pathway in mTLE from the perspectives of brain structure, function and electrophysiology, using magnetic resonance imaging (MRI) and neuro-electrophysiological techniques. Further, the relationship between the abnormal reorganization of the hippocampal-anterior insular pathway and executive dysfunction will be verified. The results of this program will provide a new perspective for clarifying the mechanism of executive dysfunction and a theoretical basis for the new strategy to treat comorbidity in mTLE.

颞叶内侧癫痫以异常神经环路形成为基础的一种常见癫痫综合征，常伴随明显的认知功能损害，其中包括执行功能损害。然而，关于颞叶内侧癫痫中执行功能损害的研究并不多，其神经环路机制尚未阐明。申请人通过预实验发现，颞叶内侧癫痫中海马-前岛叶通路的功能连接强度与执行功能呈显著正相关。据此我们提出假说：颞叶内侧癫痫中海马-前岛叶通路异常重塑是导致执行功能损害的关键途径。本项目拟采用磁共振成像技术与神经电生理手段相结合的方法，从脑结构、功能、电生理多个维度描绘颞叶内侧癫痫中海马-前岛叶通路异常重塑的动态表征模型，并验证其与执行功能损害的关联。本项目的研究成果将为明确执行功能损害的机制提供新视角，并为开发治疗颞叶内侧癫痫共病的新策略提供理论依据。

执行功能是目标导向行为的认知基础，包括工作记忆、优先级排序、注意分配、行为决策和校正错误等；但其潜在神经机制尚未阐明。本项目以癫痫患者为研究窗口，结合高空间分辨率的功能磁共振技术和高时间分辨率的颅内电生理技术对执行功能的潜在神经机制展开了系列研究。在海马-前岛叶通路异常重塑方面，我们明确了内侧颞叶癫痫中海马-前岛叶的功能连接受损，且功能连接强度与执行功能明显正相关。这项研究提示癫痫放电会通过认知网络的慢性重塑损害认知功能；为后续靶向神经调控技术干预认知功能障碍提供了理论基础。在执行功能的神经机制方面，我们发现前岛叶中的相位进动样表征参与了奖赏预期，同时还揭示了前额叶中工作记忆表征在记忆编码和维持阶段发生的转变参与了调控工作记忆的优先顺序。这两项研究提示前岛叶、前额叶能够根据任务需求“自上而下”地编码刺激的优先级顺序，从而保证在多重任务下高效切换显著性信息和认知网络；为深入理解执行功能的神经机制提供了电生理证据，为阐明其他疾病中执行功能损害及其生物标志物指明了方向。