Collaborative Research: Analysis and Control of Nonlinear Oscillatory Networks for the Design of Novel Cortical Stimulation Strategies

据估计，1.2%的美国人患有活动性癫痫，每年治疗这些病例的费用估计为125亿美元。虽然脑刺激在临床实践中是常规使用的，但刺激信号和参数通常是经验性地应用和调整的，并且可以通过大脑网络动力学的定量模型来显著改进。事实上，人脑功能是由动态丰富的神经成分复杂而时变的相互联系之间的复杂动力学产生的，而多种神经功能障碍与这些网络机制的中断有关。该项目将开发新的理论和工具来预测癫痫发作的发生和蔓延，并为使用新的大脑电刺激策略治疗神经疾病提供信息。通过构建包含癫痫数据和动态分析的数学模型，这项工作旨在揭示癫痫事件背后的现象，并将它们与大脑的解剖特征联系起来。这一预期结果将为分析和优化实用的非侵入性脑网络刺激提供新的理论基础。该项目还将在研究生和本科生层面开展教育活动，以促进数量庞大和多样化的STEM劳动力的增长，开展与当地社区接触的外展活动，以及促进多学科方法解决神经科学问题的传播活动。该项目将开发新的方法来分析复杂网络中振荡的传播，并得出控制机制来调节网络动力学的时空演变，如神经振荡。具体地说，这项研究的目标是(I)描述一组新的动态生物标记物，它们解释了癫痫事件期间神经记录的质量变化--这些生物标记物提供了非线性、联网的神经团模型的结构和参数与癫痫记录特征之间的定量联系；(Ii)揭示了允许健康的、局部的神经振荡级联成全脑病理性癫痫的结构特性；以及(Iii)开发时空控制策略来调节振荡动力学在网络上的传播，这将为分析和优化实用的非侵入性脑刺激提供坚实的理论基础。除了在网络控制和动力系统领域做出贡献外，该项目还将有助于将这些学科与计算神经科学相结合，并促进控制理论工具的转化，以设计新的、有针对性的、非侵入性的和高效的神经疾病治疗方法。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

It is estimated that 1.2 percent of Americans have active epilepsy, and the annual cost for treating these cases is estimated at $12.5 billion. While brain stimulation is routinely used in clinical practice, stimulation signals and parameters are often applied and tuned empirically, and can be substantially improved by a quantitative model of the brain network dynamics. Indeed, human brain function function arises from complex dynamics between intricate and time-varying interconnection of dynamically rich neural components, and multiple neurological disorders are linked to disruptions of these network mechanisms. This project will develop new theories and tools to predict the onset and spreading of epileptic seizures and to inform the use of novel electrical brain stimulation strategies to treat neurological disorders. By constructing mathematical models that incorporate epileptic data and dynamical analysis, this work aims at uncovering the phenomena that underlie epileptic events and linking them to features of the anatomy of the brain. The intended outcome will be a novel theoretical basis to analyze and optimize practical noninvasive stimulation of brain networks. This project will also pursue educational initiatives at the graduate and undergraduate levels that will contribute to the growth of a large and diverse STEM workforce, outreach activities to engage the local community, and dissemination activities to promote multi-disciplinary approaches to problems in neuroscience.The project will develop novel methods to analyze the spreading of oscillations in complex networks and derive control mechanisms to regulate the spatiotemporal evolution of network dynamics, such as neurological oscillations. In particular, the research will aim to (i) characterize a novel set of dynamical biomarkers that explain qualitative changes in neurological recordings during epileptic events -- these biomarkers provide a quantitative link between the structure and parameters of nonlinear, networked, neural mass models and the features of epileptic recordings; (ii) reveal the structural properties that allow healthy, localized neural oscillations to cascade into brain-wide pathological seizures, and (iii) develop spatiotemporal control strategies to regulate the spreading of oscillatory dynamics over networks, which will provide a solid theoretical basis to analyze and optimize practical noninvasive brain stimulation. In addition to contributing to the fields of network control and dynamical systems, this project will also contribute to the integration of these disciplines with computational neuroscience and promote the translation of control-theoretic tools towards the design of novel, targeted, non-invasive, and highly effective treatments for neurological disorders.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.