An implantable device to predict and prevent seizures

描述（由申请人提供）：经过我们生物工程研究伙伴关系的头四年，用于癫痫的植入式设备现在已经成为现实。这在一定程度上是由于我们集团开发的技术转化为工业。来自第一代反应性抗癫痫装置的多中心临床试验数据表明，这项新技术是安全的，并且有望为患者带来显著的益处。他们还证明，第一代设备很少能让患者免于癫痫发作。这是因为我们还不知道何时、何地以及如何通过电刺激来预防癫痫发作，也不知道癫痫网络中癫痫发作产生的潜在机制。这些挑战，并将其转化为更有效的第二代设备，是本提案的重点。具体来说，我们的目标是：(1)了解两种具有良好特征的、与难治性人类癫痫相似的自发癫痫动物模型的癫痫发作机制；(2)在癫痫网络中绘制癫痫发作图，以确定在何处放置传感电极和何时刺激以最大限度地抑制癫痫发作并减少副作用。(3)开发更有效的闭环刺激算法来控制癫痫发作。这些目标将通过由宾夕法尼亚大学、CHOP、佐治亚理工学院和BioQuantix公司在神经学、神经科学、生物工程和工业领域的知名合作者领导的一系列项目来实现。团队将通过在多个时间和空间尺度上进行详细的动物实验，专注于改进第一代人体设备的结果。这些包括：(1)细胞水平，通过宽带单元记录和生物物理精确的计算建模；(2)网络水平，采用电压敏感染料和多电极阵列对海马切片进行体外实验；(3)全脑水平，通过在体内同时进行微、大电极场记录和脑响应性刺激。这些实验将建立在我们的生物工程研究伙伴关系资助的第一个周期取得的实质性进展的基础上。我们团队的独特组成，成功技术转移的记录，以及我们从现有可编程设备中学习并立即将我们的发现传达给现有设备的能力，为进行尖端神经科学和生物工程研究提供了前所未有的机会，并立即将其转化为更好的治疗患者。

DESCRIPTION (provided by applicant): After the first four years of our Bioengineering Research Partnership, implantable devices for epilepsy are now a reality. This is due, in part, to translation of technology developed by our group to industry. Data from multi-center clinical trials of first generation responsive antiepileptic devices indicate that this new technology is safe, and that there is promise of significant benefit to patients. They also demonstrate that 1st-generation devices rarely make patients seizure free. This is because we do not yet understand when, where and how to deliver electrical stimulation to pre-empt seizures, or the mechanisms underlying seizure generation in epileptic networks. These challenges, and translating them into more effective second-generation devices, are the focus of this proposal. Specifically, our aims are: (1) To understand mechanisms underlying seizure generation in two well characterized, spontaneously seizing animal models of epilepsy with documented similarities to refractory human epilepsy, (2) To map seizure generation in the epileptic network to determine where to place sensing electrodes and when to stimulate to maximize seizure suppression and minimize side effects. (3) To develop more effective closed loop stimulation algorithms for controlling seizures. These Aims will be accomplished through a series of projects led by established collaborators in neurology, neuroscience, bioengineering and industry, at Penn, CHOP, Georgia Tech, and BioQuantix, Inc. Teams will focus on improving upon results from first-generation human devices through detailed animal experiments on multiple temporal and spatial scales. These include: (1) the cellular level, through broad-band unit recording and biophysically accurate computational modeling; (2) the network level, with in vitro experiments on hippocampal slices using voltage sensitive dyes and multi-electrode arrays; and (3) the whole brain level, through simultaneous micro and macroelectrode field recordings and responsive brain stimulation in vivo. These experiments will build upon the substantial progress made during the first cycle of our Bioengineering Research Partnership grant. The unique composition of our group, its track record of successful technology transfer, and our ability to learn from and immediately convey our discoveries to existing programmable devices, provide an unprecedented opportunity to perform cutting-edge neuroscience and bioengineering research and immediately translate it into better treatment for patients.