Perturbative Seizure Prediction and Detection of a Seizure Permissive State

项目摘要 在200万患有癫痫的美国人中，近30%的人尽管接受了治疗，但仍继续癫痫发作。 现在越来越多的人接受刺激装置作为治疗性神经调节的手段。到 提供复杂的反馈刺激，人们可以在癫痫发作早期做出反应，以最大限度地减少 它的影响和传播，或者一个人可以在癫痫发作之前对其他状态做出反应。确定一个适当 癫痫前状态一直是一个中心主题，现在福尔斯属于“癫痫发作”的范畴 预测.“识别这种先兆状态既可以表明何时刺激，以避免 即将发作但是，癫痫发作预测界的经验是， 到目前为止，对于显著灵敏度水平产生显著的错误检测率。 这项工作将在颞叶癫痫的破伤风毒素模型中进行。我们已经开发出一种 用于施加低频电刺激以调节神经元活动而不干扰的系统 我们能够记录长期植入动物的神经活动（Sunderam等人，2006年），因此 可以应用反馈刺激。通过头部加速度测量，我们能够确定 警惕（Sunderam等人，2007）。 这笔赠款的目的有三个方面。首先，调查是否将警戒状态作为一种歧视 特征改进了对预振状态的识别。 第二，实现并测试了一种通过小幅度刺激来检测大脑状态的主动探头， 指示癫痫前状态的大脑状态的变化。 我们期望在实现被动和主动预测方法之后， 严重的错误预测率。 第三个目的是通过刺激来探测这些检测的性质（a）如果错误的预测是 或者（B）如果所识别的癫痫前状态是癫痫发作许可状态-仅 有时转变为癫痫发作-而“错误的预测”是对这种状态的正确识别。 从基础科学的角度来看，这应该可以深入了解癫痫发作的产生过程和长期的 治疗从更实际的短期应用的观点来看，检测癫痫发作许可状态和 相关的转移概率在开发有用的反馈干预中将具有很大的效用。 具体地，然后响应于检测到电刺激，将干预（例如电刺激）作为目标。 改变这种转移概率。今后几年这项工作的扩展将是测试一系列 响应刺激以检测其防止癫痫发作的能力。

Project Summary 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.