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

研究启动奖为传统黑人学院和大学的教师提供支持，他们正在建立一个研究项目。期望该奖项有助于进一步提高教师的研究能力和效率，改善其所在机构的研究和教学，并使本科生参与研究经验。北卡罗来纳农工州立大学获得的这一奖项在许多领域具有潜在的更广泛和社会影响。该项目的重点是开发一个数学模型，以了解深层脑刺激的机制，这是一种用于治疗帕金森病的疗法。本科生和高中生将获得研究经验。脑深部刺激治疗帕金森病的有效性与基底节区病理性节律性的破坏有关。为了找到一个更有效的深部脑刺激程序，关键是要使用适当的神经元网络模型，能够产生间歇性同步振荡动力学，观察帕金森病患者。作为基底节区唯一的兴奋性核，丘底核在基底节区的动力学中起着重要作用，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，负责各种有节奏的爆发模式在丘脑下核神经元。本研究将建立由关键电流组成的新的丘脑下核计算模型，并建立网络模型，即更新的基底神经节网络模型和扩展的皮层-基底神经节-丘脑模型。通过数值和数学分析，本研究将研究基底神经节的内在神经元特性和网络特性是如何结合起来产生间歇性同步节律的。本项目将加强对帕金森病基底神经节病理节律机制和深部脑刺激程序的理解。这项研究还可能导致发现更有效的方法，用最少的刺激干预来打破帕金森状态下的间歇性同步节律。

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.