Perturbative Seizure Prediction and Detection of a Seizure Permissive State

描述(申请人提供)：在200万患有癫痫的美国人中，近30%的人尽管接受了治疗，但仍有癫痫发作。现在，越来越多的人接受刺激设备作为治疗神经调节的手段。为了提供复杂的反馈刺激，一个人可以在癫痫发作的早期做出反应，以将其影响和传播降到最低，或者一个人可以在癫痫发作之前做出反应，以达到某种其他状态。很长一段时间以来，确定合适的潜伏期状态一直是一个中心主题，现在属于“癫痫发作预测”的范畴。对这种压力状态的识别既可以指示何时刺激以避免即将到来的癫痫发作。但是，癫痫发作预测界的经验是，迄今为止使用的所有衡量标准都会对显著水平的敏感度产生显著的误检率。这项工作将在破伤风毒素颞叶癫痫模型中进行。我们已经开发了一种系统，用于应用低频电刺激来调节神经元活动，而不会干扰我们记录长期植入动物的神经活动的能力(Sunderam等人，2006年)，因此可以应用反馈刺激。通过测量头部加速度，我们能够确定警戒状态(Sunderam等人，2007年)。这笔赠款的目的有三个方面。首先，研究增加警觉状态作为区分特征是否提高了对预适应状态的识别。第二，通过小幅度刺激实现和测试大脑状态的主动探头，以检测指示压力状态的大脑状态的变化。我们预计，在实施被动和主动预测方法后，我们仍将观察到显著的错误预测率。第三个目的是通过刺激来探索这些检测的性质：(A)错误的预测是否仅仅是错误分类，或者(B)如果识别的压力状态是癫痫发作允许的状态--一种仅有时过渡到癫痫发作的状态--并且“错误预测”是对这种状态的正确识别。从基础科学的角度来看，这应该让我们深入了解癫痫的发生过程和长期治疗。从更实际的短期应用的角度来看，检测癫痫发作允许状态和相关的转移概率将在开发有用的反馈干预措施方面具有很大的实用价值。具体地说，然后以干预为目标--例如电刺激--以响应对状态的检测来修改该转移概率。这项工作在未来几年的扩展将是测试一系列对预适应检测的反应刺激是否具有防止癫痫发作的能力。公共卫生相关性：这笔赠款的长期目标是改善神经刺激，以控制癫痫发作。通过解决压力状态的性质以及更重要的是错误发作预测的性质，我们将提高优化反馈刺激和制作微创刺激的能力。

DESCRIPTION (provided by applicant): Nearly 30% of the two million Americans suffering from epilepsy continue to have seizures despite treatment. There is now a growing acceptance of stimulation devices as a mean for therapeutic neuromodulation. To provide sophisticated feedback stimulation, one can either respond early into the seizure in order to minimize its impact and spread, or one can respond before the seizure to some other state. Identification of a suitable preseizure state has been a central theme for quite a while that now falls under the rubric of "seizure prediction." Identification of such a preseizure state could both indicate when to stimulate in order to avert an oncoming seizure. But, the experience in the seizure prediction community has been that all measures used so far yield a significant false detection rate for significant levels of sensitivity. This work will be performed in the tetanus toxin model for temporal lobe epilepsy. We have developed a system for applying low frequency electrical stimulation for modulation of neuronal activity without interfering with our ability to record neural activity in chronically implanted animals (Sunderam, et al, 2006), and therefore can apply feedback stimulation. With head acceleration measurements, we are able to determine state of vigilance (Sunderam, et al, 2007). The aims of this grant are three fold. First, to investigate if the addition of state of vigilance as a discrimination feature improves identification of preseizure states. Second, to implement and test an active probe of brain state through small amplitude stimulations to detect changes in brain state indicative of a preseizure state. We expect after implementing both the passive and active prediction methods that we will still observe significant false prediction rates. The third aim is to probe through stimulation the nature of these detections (a) if the false predictions are simply misclassifications OR (b) if the identified preseizure state is seizure permissive - a state that only sometimes transitions to seizure - and the 'false predictions' are correct identifications of this state. From a basic science standpoint, this should give insight into the seizure generation process and long-term treatment. From a more practical short-term application standpoint, detection of a seizure permissive state and the relevant transition probabilities will have great utility in the development of a useful feedback intervention. Specifically, one then targets intervention - for example electrical stimulation - in response to detection of the state to modify this transition probability. The extension of this work in future years will be to test a range of responsive stimuli to preseizure detections for their ability to prevent seizure. PUBLIC HEALTH RELEVANCE: The long term objectives of this grant are to improve neurostimulation for seizure control. By addressing the nature of the preseizure state and more importantly the nature of false seizure predictions, we will improve the ability to optimize feedback stimulation and to craft minimally invasive stimuli.