Epileptogenic Focus Localization and Closed-loop Control of Brain Dynamics in Epilepsy

癫痫病灶定位和脑动力学闭环控制

• 批准号: 1102390
• 负责人: Konstantinos Tsakalis
• 金额: $ 36万
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1102390&HistoricalAwards=false
• 关键词: Epileptogenic; Focus; Localization; Closed; loop

This project deals with the development of multivariable feedback decoupling controllers for the suppression of epileptic seizures by altering the brain dynamics through the use of deep-brain electrical stimulation. The key enabling concepts are a quantifiable relationship between the epileptic state and measures of brain?s spatial synchronization, and the ability to disrupt this synchronization by means of electrical stimulation. Intellectual MeritPrior work with electroencephalographic (EEG) data from epileptic patients and animals has indicated that such measures can be consistent indicators of the epileptic state of the brain and that electrical stimulation has generally beneficial, though not quite consistent effects. The novel idea behind the proposed control strategy is to combine our recent epileptogenic focus localization techniques with real-time delivery of practical stimuli in the form of biphasic, pulse-train-modulated, electrical signals to disentrain the brain. The controller design will rely on control-oriented models, describing the relationships between electrical stimuli and selected measures of spatial brain synchronization. The success of these experiments in rodents with chronic epilepsy, together with the physiological evaluation of the subjects, will provide a quantitative assessment of the effectiveness and possible side effects in the control of seizures, as well as important clues on the validity of the underlying theory about the mechanisms of seizure generation (ictogenesis).Broader Impacts:Expected intellectual benefits range from the solution of nonstandard problems in the regime of control of chaotic systems, to yet untapped engineering applications to biological systems. This research, if successful, will contribute to the new treatment modalities of neuromodulation for epilepsy and form a basis for economic growth and reduction of associated medical costs. It may also provide data for new applications in medicine and neuroscience, such as the treatment of Parkinson?s tremors, migraines, sleep disorders and other brain dynamical disorders.

本项目致力于开发多变量反馈解耦控制器，通过使用脑深部电刺激改变脑动力学来抑制癫痫发作。关键的使能概念是癫痫状态和大脑测量指标之间的可量化关系-S空间同步，以及通过电刺激破坏这种同步的能力。智力价值先前对癫痫患者和动物的脑电(EEG)数据的研究表明，这种测量可以作为大脑癫痫状态的一致指标，电刺激通常是有益的，尽管效果并不完全一致。提出的控制策略背后的新想法是将我们最近的致痫灶定位技术与实时传送实际刺激的形式相结合，以脉冲序列调制的两相电信号的形式来分离大脑。控制器的设计将依赖于面向控制的模型，这些模型描述了电刺激和选定的大脑空间同步措施之间的关系。在患有慢性癫痫的啮齿动物上的这些实验的成功，以及对受试者的生理评估，将提供对癫痫发作控制的有效性和可能的副作用的定量评估，以及关于癫痫发作产生机制(细胞发生)的潜在理论有效性的重要线索。广泛的影响：预期的智力收益从解决混沌系统控制制度中的非标准问题，到尚未开发的生物系统的工程应用。这项研究如果成功，将有助于癫痫神经调节的新治疗方式，并为经济增长和降低相关医疗成本奠定基础。它还可能为医学和神经科学的新应用提供数据，如治疗帕金森氏症、S震颤、偏头痛、睡眠障碍和其他脑动力学障碍。