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: 7736366
• 负责人: BRUCE J GLUCKMAN
• 金额: $ 34.24万
• 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/7736366
• 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; 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; public health relevance; 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）：在 200 万患有癫痫症的美国人中，近 30% 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装置作为治疗性神经调节的手段。为了提供复杂的反馈刺激，人们可以在癫痫发作早期做出反应，以尽量减少其影响和扩散，或者可以在癫痫发作之前对某种其他状态做出反应。识别合适的癫痫发作前状态长期以来一直是一个中心主题，现在属于“癫痫发作预测”的范畴。对这种癫痫发作前状态的识别可以指示何时进行刺激以避免即将发生的癫痫发作。但是，癫痫预测界的经验是，迄今为止使用的所有措施都会产生显着的错误检测率和显着的灵敏度水平。这项工作将在颞叶癫痫的破伤风毒素模型中进行。我们开发了一种系统，用于应用低频电刺激来调节神经元活动，而不干扰我们记录长期植入动物的神经活动的能力（Sunderam 等人，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）。这笔赠款的目的有三个。首先，研究将警戒状态添加为区分特征是否可以改善癫痫前状态的识别。其次，通过小幅度刺激实施和测试大脑状态的主动探针，以检测指示癫痫发作前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，我们仍然会观察到显着的错误预测率。第三个目标是通过刺激来探究这些检测的本质（a）错误预测是否只是错误分类，或者（b）所识别的癫痫发作前状态是否是允许癫痫发作的状态（一种仅有时会转变为癫痫发作的状态），并且“错误预测”是对该状态的正确识别。从基础科学的角度来看，这应该可以深入了解癫痫发作的发生过程和长期治疗。从更实际的短期应用的角度来看，癫痫发作许可状态和相关转换概率的检测将在开发有用的反馈干预方面具有很大的用处。具体来说，然后响应于检测到的状态而瞄准干预（例如电刺激）以修改这一转变概率。这项工作在未来几年的扩展将是测试一系列对癫痫发作前检测的响应刺激，以了解其预防癫痫发作的能力。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。通过解决癫痫发作前状态的本质，更重要的是解决错误癫痫预测的本质，我们将提高优化反馈刺激和制作微创刺激的能力。