Research Initiation Award: Investigation of mechanisms underlying pathological rhythms in parkinsonian basal ganglia - A mathematical modeling study

研究启动奖为历史悠久的黑人学院和大学的教职员工提供支持，他们正在建立一个研究项目。预计该奖项有助于进一步提高教师的研究能力和有效性，改善其所在机构的研究和教学，并让本科生参与研究经验。授予北卡罗来纳A&T；州立大学的奖项可能在许多领域产生更广泛的社会影响。该项目的重点是开发一个数学模型，以了解脑深部刺激的潜在机制，这是一种用于治疗帕金森氏症的疗法。本科生和高中生都将获得研究经验。脑深部刺激治疗帕金森氏病的有效性与破坏基底节的病理节律性有关。为了找到一种更有效的脑深部刺激程序，使用适当的神经网络模型是至关重要的，该模型能够产生在帕金森患者中观察到的间歇性同步振荡动力学。丘脑底核作为基底节中唯一的兴奋性核团，在基底节的运动中起着重要作用，是帕金森病深部脑刺激的标准靶点。最近的实验已经确定了一组离子电流，这些电流负责丘脑底核神经元的各种节律性爆发模式。本研究将开发一种新的包含关键电流的丘脑底核计算模型，并在此基础上建立网络模型，即更新的基底节网络模型和扩展的皮质-基底节-丘脑模型。通过进行数值和数学分析，这项研究将研究基底节的固有神经元特性和网络特性如何结合起来产生间歇性同步节律。这个项目将加强对帕金森氏症基底神经节和脑深部刺激过程中潜在的病理节律的机制的理解。这项研究还可能导致发现更有效的方法来打破帕金森状态下的间歇性同步节律，只需最少的刺激干预。

Research Initiation Awards provide support for faculty at Historically Black Colleges and Universities who are building a research program. It is expected that the award helps to further the faculty member's research capability and effectiveness, improves research and teaching at his home institution, and involves undergraduate students in research experiences. The award to North Carolina A&T State University has potential broader and societal impact in a number of areas. The project focuses on developing a mathematical model to understand the mechanisms underlying deep brain stimulation, a therapy used in the treatment of Parkinson's disease. Undergraduate students as well as high school students will gain research experiences. The effectiveness of deep brain stimulation in Parkinson's disease has been linked to the destruction of pathological rhythmicity in basal ganglia. To find a more effective deep brain stimulation procedure, it is crucial to use appropriate neuronal network models that are able to produce intermittently synchronized oscillatory dynamics observed in parkinsonian patients. As the only excitatory nucleus in the basal ganglia, the subthalamic nucleus plays an important role in the dynamics of basal ganglia and is a standard target for deep brain stimulation in Parkinson's disease. Recent experiments have identified a set of ionic currents that are responsible for various rhythmic bursting patterns in subthalamic nucleus neurons. This research will develop a new computational model for the subthalamic nucleus that comprises key currents and then set up network models, namely an updated basal ganglia network model and an extended cortex-basal ganglia-thalamus model. By performing numerical and mathematical analyses, the research will study how intrinsic neuronal properties and network properties in basal ganglia incorporate to generate intermittently synchronized rhythms. This project will enhance the understanding of the mechanisms underlying pathological rhythms in parkinsonian basal ganglia and deep brain stimulation procedures. The research may also lead to the discovery of more effective methods to break the intermittently synchronized rhythms in parkinsonian states with a minimal amount of stimulation intervention.