PECASE: Modeling and Control of Neuronal Networks

目的：拟议的职业生涯计划涉及脑内神经元网络的建模和控制及其在脑深部刺激治疗帕金森-S病(PD)中的应用。具体的目标是：(I)构建一种通用的方法来建模复杂的神经元网络，其中不同的大脑核团之间发生相互作用，(Ii)为这类网络设计计算上有效的控制策略，以及(Iii)将这些方法应用于用DBS恢复帕金森病引起的病理网络动力学的问题。该项目的成功将从根本上影响控制系统和神经科学之间的接口，并为神经疾病的医疗创造新的机会。智力价值：这项工作介绍了一个系统的理论框架，以(I)了解神经网络的电生理学和病理生理学以及DBS控制的影响，以及(Ii)设计和探索新的DBS策略，在动物实验和转换到患者之前，通过广泛的模拟来治疗PD。该建模框架最终将为帕金森病带来更安全和潜在更具治疗性的DBS。最终的愿景是将这一变革性的方法应用于其他神经系统疾病(肌张力障碍、抑郁症、强迫症)，影响全球数百万患者。更广泛的影响：拟议的计划还将影响各级教育。它包括为高年级本科生和研究生开发一门关于神经系统建模和DBS控制的新课程，并通过独特的研讨会和实习机会接触所有年龄段的女性。最后，工科学生将有机会在克利夫兰诊所与合作者一起进行电生理实验。

Objective: The proposed CAREER program involves modeling and control of neuronal networks in the brain and its application to the treatment of Parkinson?s disease (PD) using deep brain stimulation (DBS). Specific objectives are to: (i) construct a general approach for modeling complex neuronal networks where interactions occur between different brain nuclei, (ii) design computationally efficient control strategies for such networks, and (iii) apply these methodologies to the problem of restoring pathological network dynamics arising from PD with DBS. Success of the program will fundamentally impact the interface between control systems and neuroscience and create new opportunities for medical treatment of neurological disorders. Intellectual Merit: The work introduces a systems theoretic framework to (i) understand electrophysiology and pathophysiology of neuronal networks and the impact of DBS control, and (ii) design and explore new DBS strategies to treat PD with extensive simulation before experimenting on animals and translating to patients. The modeling framework will eventually lead to safer and potentially more therapeutic DBS for PD. The ultimate vision is to apply this transformative methodology to other neurological disorders (Dystonia, Depression, Obsessive Compulsive Disorders), impacting millions of patients worldwide. Broader Impact: The proposed plan will also impact education at all levels. It includes developing a new course for senior undergraduate and graduate students on modeling and DBS control of neural systems, and reaching out to women of all ages with unique workshops and internship opportunities. Finally, engineering students will be given the opportunity to perform electrophysiological experiments with collaborator at the Cleveland Clinic.