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

该项目涉及多变量反馈解耦控制器的发展，通过使用深部脑电刺激改变大脑动力学来抑制癫痫发作。关键的使能概念是癫痫状态和脑容量测量之间的可量化关系。S空间同步，以及通过电刺激破坏这种同步的能力。智力优势先前对癫痫患者和动物的脑电图（EEG）数据的研究表明，这种测量方法可以作为大脑癫痫状态的一致指标，电刺激虽然效果不完全一致，但总体上是有益的。提出的控制策略背后的新想法是将我们最近的癫痫焦点定位技术与以双相、脉冲序列调制的电信号形式实时传递的实际刺激相结合，以解除大脑的束缚。控制器的设计将依赖于面向控制的模型，描述电刺激和选择的空间大脑同步测量之间的关系。这些实验在慢性癫痫啮齿动物身上的成功，以及对被试的生理评估，将为定量评估癫痫发作控制的有效性和可能的副作用提供依据，并为癫痫发作发生机制的基础理论的有效性提供重要线索。更广泛的影响：预期的智力收益范围从混沌系统控制制度中的非标准问题的解决方案，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费用奠定基础。它还可能为医学和神经科学的新应用提供数据，例如帕金森病的治疗。震颤、偏头痛、睡眠障碍和其他脑动力障碍。

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.