基于逆行调控皮层振荡的深部脑刺激作用机理研究

项目名称： 基于逆行调控皮层振荡的深部脑刺激作用机理研究

项目编号： No.61501330

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 无线电电子学、电信技术

项目作者： 卢梅丽

作者单位： 天津职业技术师范大学

项目金额： 21万元

中文摘要： 以丘脑底核为靶点的深部脑刺激通过抑制基底核病理性振荡能有效地改善帕金森症状。最近实验证实刺激的有效靶点实际位于从皮层投射至丘脑底核的传入轴突上，并引起刺激对皮层振荡的逆行调控。然而，其调控机理以及皮层活动在刺激调制基底核病理性振荡中的关键作用仍不清楚。轴突是动作电位产生及传播的重要区域，我们认为传入轴突的兴奋性以及皮层-丘脑底核耦合特性是刺激影响皮层-基底核网络振荡的关键因素。因此，项目提出从轴突动力学角度阐释深部脑刺激逆行调控皮层振荡的生物物理机制，通过皮层-丘脑底核耦合特性揭示刺激抑制皮层-基底核网络病理性振荡的作用机理。.项目首次建立包含传入轴突离子通道的皮层-丘脑底核耦合神经元模型，研究刺激调制皮层放电模式对传入轴突动力学的依存性，以及该过程对皮层-基底核网络病理性振荡的影响，揭示深部脑刺激的作用机理，为优化刺激靶点以及以皮层振荡为反馈的深部脑刺激闭环控制研究提供理论基础。

中文关键词： 深部脑刺激；逆行调控；皮层-基底核网络；同步振荡；传入轴突

英文摘要： Deep brain stimulation (DBS) targeting on the subthalamic nucleus (STN) can effectively alleviate the symptoms of Parkinson’s disease (PD) by mitigating the abnormal synchronous oscillations in basal ganglia. Recent experimental researches verified that the actual stimulation target located on the STN afferent axons originating from the cortex and the stimulation antidromically regulated the cortical oscillations by activating the axons. However, it is not clear about the underlying biophysical mechanism of this antidromic modulation and the key role of cortical activities play in regulating the abnormal synchronous oscillations in basal ganglia. The neural axon is an important region where the action potentials are generated and propagated. It is suggested that the excitabilities of STN afferent axons and the coupling connections between cortical and STN neurons are the critical factors in the process of stimulation influencing the oscillations in cortico-basal ganglia network. Therefore, the biophysical mechanism of the antidromic regulation of cortical oscillations by the stimulation is explained in this project from the view of the dynamics of afferent axons, and then the mechanism about the inhibiting action of the stimulation on the abnormal oscillations in cortico-basal ganglia network is revealed based on the features of coupled cortico-STN neurons..In this project, we for the first time establish the model of coupled cortico-STN neurons which can characterize the ion channels of the STN afferent axons. We research how the modulation of firing patterns of cortical neurons by the stimulation depends on the dynamics of afferent axons, and how the process influences the abnormal synchronous oscillations in cortico-basal ganglia network. This project will help to clarify the mechanism of action of DBS and provide the theoretical bases for the researches on the optimization of stimulation targets and close-loop control of DBS utilizing the cortical oscillations as feedback signals.

英文关键词： Deep brain stimulation;antidromic modulation ;cortico-basal ganglia network;synchronous oscillation;afferent axon