Perturbative Seizure Prediction and Detection of a Seizure Permissive State

扰动癫痫发作预测和癫痫允许状态检测

• 批准号: 8059573
• 负责人: BRUCE J GLUCKMAN
• 金额: $ 32.52万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-15 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8059573
• 关键词: Acceleration; Address; Algorithms; American; Animals; Back; Basic Science; Brain; Communities; Detection; Development; Devices; Discrimination; Electric Stimulation; Epilepsy; Feedback; Frequencies; Future; Generations; Grant; Head; Health; Implant; Intervention; Measurement; Measures; Methods; Modeling; Morphologic artifacts; Nature; Neurons; Probability; Process; Seizures; Sensitivity and Specificity; Specificity; Stimulus; System; Temporal Lobe Epilepsy; Testing; Tetanus Toxin; Therapeutic; Work; experience; falls; improved; insight; minimally invasive; neuroregulation; prevent; relating to nervous system; response; vigilance

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.

描述（由申请人提供）：尽管有治疗，但在患有癫痫病的两百万美国人中，近30％仍有癫痫发作。现在，人们越来越接受刺激装置作为治疗性神经调节的平均值。为了提供复杂的反馈刺激，一个人可以提早响应癫痫发作，以最大程度地减少其影响和传播，或者可以在癫痫发作之前响应其他状态。相当长一段时间以来，对合适的preseirure国家的识别一直是一个核心主题，现在属于“癫痫发作预测”。识别这种率状态既可以表明何时刺激以避免迎面癫痫发作。但是，在癫痫发作预测界的经验是，到目前为止使用的所有措施都为显着敏感性提供了显着的错误检测率。这项工作将在颞叶癫痫的破伤风毒素模型中进行。我们已经开发了一种用于应用低频电刺激的系统，以调节神经元活动，而不会干扰我们记录慢性植入动物中神经活动的能力（Sunderam等，2006），因此可以应用反馈刺激。通过头部加速度测量，我们能够确定警惕状态（Sunderam等，2007）。这笔赠款的目的是三倍。首先，要调查是否增加警惕状态作为歧视特征是否可以改善对Preseizure国家的识别。其次，通过小振幅刺激实施和测试大脑状态的主动探针，以检测脑状态的变化，指示质量状态。我们希望在实施被动和主动预测方法之后，我们仍将观察到明显的错误预测率。第三个目的是通过刺激这些检测的性质进行探测（a）如果错误的预测仅仅是错误的分类，或者（b）如果已确定的preseizure态是癫痫发作的 - 这种状态有时只有有时转变为癫痫发作，而“错误的预测”是对该状态的正确识别。从基础科学的角度来看，这应该深入了解癫痫发作过程和长期治疗。从更实际的短期应用的角度来看，检测癫痫发作状态和相关的过渡概率将在开发有用的反馈干预措施方面具有很大的实用性。具体而言，然后将干预措施（例如电刺激）靶向检测状态以修改这种过渡概率。在未来几年中，这项工作的扩展将是测试一系列响应性刺激，以防止其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癫痫发作控制的神经刺激。通过解决preseizure状态的性质，更重要的是，我们将提高优化反馈刺激和制作微创刺激的能力。