Epileptiform oscillations, EEG & seizure prediction

描述（由申请人提供）：全世界有5000万人患有癫痫，其中25%的患者癫痫发作无法通过任何现有的药物或手术治疗来控制。开发新的治疗方案和提高癫痫手术的疗效目前受到我们对癫痫大脑如何产生自发发作（ictogenesis）了解不足的限制。越来越多的证据表明，高频癫痫样振荡（60 - 500hz）是癫痫大脑的独特特征，在新皮层癫痫发作的形成中起着重要作用[1-3]。作为发展首席研究者（PI）作为临床研究者的职业生涯的一部分，我们建议梅奥诊所和宾夕法尼亚大学之间开展多学科合作，以了解新皮质ictogenesis和提高定位癫痫发脑区域的能力。这个项目是朝着更全面地了解一种常见且难以治疗的神经系统疾病迈出的第一步。我们将开发生物工程方法来检测和量化人类颅内脑电图记录中的高频癫痫状振荡（HFEO）。我们将探讨HFEO作为癫痫性脑特征在癫痫手术和癫痫发作预测中的临床应用价值。我们相信，了解HFEO的细胞和网络机制将提高我们定位局灶性癫痫脑区域的能力，这一区域目前限制了癫痫手术的成功，同时为合理开发新的治疗方法（如用于癫痫发作预测和预防的植入式设备）奠定基础。拟议的项目将继续合作，将宾夕法尼亚大学的神经科学和神经工程优势与梅奥诊所大型癫痫手术实践的临床优势结合起来，从而为发展中的临床研究者提供一个肥沃的环境。首席研究员已经证明了独立的以患者为基础的研究的潜力，并通过该项目提供的培训将开发一个独立的研究项目，将神经工程和临床研究的进展转化为临床实践。

DESCRIPTION (provided by applicant): Worldwide, 50 million people suffer from epilepsy, and for 25% of these patients the seizures are not controlled by any available medical or surgical treatments. Development of new treatment options and improving the efficacy of epilepsy surgery are presently limited by our poor understanding of how epileptic brain generates spontaneous seizures (ictogenesis). There is accumulating evidence that high-frequency epileptiform oscillations (60 - 500 Hz) are a unique signature of epileptic brain, and play an important role in neocortical seizure ictogenesis [1-3]. As part of a program to develop the principal investigator's (PI) career as a clinician-investigator, we propose a multidisciplinary collaboration between the Mayo Clinic and University of Pennsylvania directed at understanding neocortical ictogenesis and improving the ability to localize regions of epileptogenic brain. This project is an initial step toward a more complete understanding of a common, and difficult to treat, neurological disease. We will develop bioengineering methods to detect and quantify high-frequency epileptiform oscillations (HFEO) from human intracranial EEG recordings. We will investigate the clinical usefulness of HFEO as a signature of epileptogenic brain for epilepsy surgery and seizure prediction. We believe understanding the cellular and network mechanisms underlying HFEO will improve our ability to localize regions of focal epileptogenic brain, an area presently limiting the success of epilepsy surgery, while laying the foundation for the rational development of new therapies such as implantable devices for seizure prediction and prevention. The proposed project will continue a collaboration that combines the neuroscience and neuroengineering strengths of the University of Pennsylvania with the clinical strength of the Mayo Clinic's large surgical epilepsy practice, thus providing a fertile environment for a developing clinician-investigator. The principal investigator has demonstrated potential for independent patient-based research, and with the training provided by this project will develop an independent research program translating advances in neuroengineering and clinical research into clinical practice.