Chaos Control of Nonlinear Electrical Activity in the Brain

癫痫发作是一种常见的疾病，折磨着超过250万美国人。 这些癫痫发作代表了大脑电状态的紊乱，有时可以通过药物治疗来预防;然而，超过25%的癫痫患者无法通过抗癫痫药物得到帮助。 对于这些癫痫发作足够严重的患者，唯一剩下的选择是手术切除脑组织，这有时会导致严重的神经功能缺损。 本提案中描述的研究的最终目标是了解大脑的这些非线性电状态，以便有可能设计出一种侵入性较小且潜在损害性小得多的替代手术治疗药物难治性癫痫患者。 总体目标是设计一种在概念上类似于植入式心脏除颤器的设备，因为它可以检测癫痫发作的最早阶段，并使用电刺激来防止或恢复癫痫发作。 这项研究需要在不同但相关的领域进行探索，如非线性混沌理论和计算机编程以及实验生物学方面的专业知识。 实验将集中在海马体上，海马体是大脑的一个区域，是产生癫痫样电活动的频繁病灶。 最初的实验将对大鼠海马切片进行非线性数学分析和控制算法的测试，其可以被诱导产生类似于在整个动物中观察到的癫痫行为的自发放电。 将根据控制算法通过电极施加电刺激以恢复爆发。 随后的实验将采用这些发现并将其应用于大鼠的体内研究，以观察是否与切片中相同的动力学和控制原理，如果不是，则如何适当修改这些控制算法。 最近在理解和控制混沌系统方面的进展为将这些原理应用于操纵大脑中的病理性电活动提供了宝贵的机会。 它最终将允许预防或恢复大脑中的癫痫发作，这将对公共卫生以及社会整体成本节约产生巨大效益。

9900350MogulEpileptic seizures are a common disease that afflicts over 2.5 million Americans. These seizures represent a disorder of the electrical state of the brain that can sometimes be prevented with pharmaceutical treatment; however, over 25% of epilepsy patients cannot be helped by antiepileptic drugs. For these patients in whom seizures are sufficiently severe, the only remaining option is surgical removal of brain tissue which can sometimes result in severe neurological deficits. The ultimate goal of the research described in this proposal is to understand these nonlinear electrical states of the brain such that it would be possible to engineer a less invasive and potentially far less damaging alternative to surgery for drug-refractory epilepsy patients. The overall goal is to engineer a device similar in concept to an implantable cardiac defribrillator in that it would detect the earliest stages of a seizure and prevent or revert it using electrical stimulation. This research requires exploration in diverse but related fields such as nonlinear chaos theory and computer programming as well as expertise in experimental biology. Experiments will be focused on the hippocampus, a region of the brain that is a frequent foci for generation of epileptiform electical activity. Initial experiments will perform nonlinear mathematical analysis and testing of control algorithms on rat hippocampal slices which can be induced to produce spontaneous discharges analogous to epileptic behavior seen in whole animals. Electrical stimulation will be applied via an electrode according to control algorithms to revert the bursting. Subsequent experiments will then take these findings and apply them to in vivo studies in rats to see whether the same dynamics and control principles apply as in the slice and, if not, how these control algorithms could be modified appropriately. Recent advances in understanding and controlling chaotic systems have provided an invaluable opportunity to apply these principles toward manipulation of pathological electrical activity in the brain. It would ultimately permit the ability to prevent or revert seizures in the brain which would have enormous benefits to public health as well as overall cost savings to society.