Implantable Neurostimulators for Control of Oscillatory Brain Networks

我们建议开发一种植入式脑刺激系统来测量和控制局部振荡 场电位（LFP）同步在大脑网络。植入式神经技术，如脑深部 电刺激（DBS）已经彻底改变了运动障碍和癫痫的治疗。DBS有一些 精神病学的临床信号，但个体试验结果差异很大。我们认为这是一个 目标参与问题-高频恒定刺激用于帕金森或其他震颤 对精神疾病的治疗不是正确的方法。相反，我们认为正确的方法是 识别这些回路/网络中健康通信的特征，然后设计刺激方案 专门产生这些签名的LFP同步可能是那些通信之一 签名.在认知和情感功能的多个领域中，行为表现（读出） 当大脑区域显示同步（连贯）LFP时， 振荡此外，在运动和精神疾病中，临床有效的DBS与以下因素相关： LFP同步性的变化。Co-PI Widge开发了专门控制区域间 LFP同步，通过将一个区域中的电刺激脉冲锁定到一个区域中正在进行的振荡的相位， 另一个区域。翻译的挑战是，有效的，植入式实时同步监测和 锁相刺激需要在任何现有的或预期的设备中找不到的信号处理能力。 Co-PI Shoaran开发了高能效相位估计电路，专门针对DBS进行了优化， 比如植入物我们建议将这些方法联合收割机结合起来。目标1和2将开发新的应用程序- 集成Shoaran博士的测量和神经解码框架的特定集成电路（ASIC） 威奇博士的振荡控制方法我们将验证此电路的记录和锁相 在威奇博士的啮齿动物实验室里进行的实验在Aim 3中，世界领先的植入物合同制造商（Cirtec） 将把这种新的ASIC集成到一个包装好的、可植入的设备中，为大型动物安全测试做好准备。Cirtec 已经开发了一个DBS原型平台，该平台经过优化，可使新疗法更快地进入 人性化，使我们能够大大加快通往诊所的道路，降低监管风险。在5月底 几年后，我们要么准备好进行临床试验，要么只剩下少量的安全测试。 我们的团队在电子、医疗器械制造、临床脑刺激和技术方面拥有专业知识 商业化这项工作将总部设在明尼苏达州的“医疗巷”，一个震中的医疗 设备创新我们完全有资格执行这些目标，并将由此产生的技术推向市场。 成功将产生一种针对网络监测和治疗进行优化的新植入物，这是一种强大的新工具， 精神病治疗和尖端神经科学研究。

We propose to develop an implantable brain stimulation system to measure and control oscillatory local field potential (LFP) synchrony within brain networks. Implantable neurotechnologies like deep brain stimulation (DBS) have revolutionized the treatment of movement disorders and epilepsy. DBS has some clinical signal in psychiatry as well, but individual trial results are highly variable. We have argued that this is a target engagement problem – that the high-frequency constant stimulation used in Parkinson’s or other tremor disorders is not the right approach to the circuits of mental illness. Instead, we believe the correct approach is to identify signatures of healthy communication in these circuits/networks, then design stimulation protocols that specifically produce those signatures. LFP synchrony is likely one of those communication signatures. Across multiple domains of cognitive and emotional function, behavioral performance (a read-out of successful network communication) improves when brain regions show synchronous (coherent) LFP oscillations. Further, clinically effective DBS, in movement and psychiatric disorders, is associated with changes in LFP synchrony. Co-PI Widge has developed algorithms that specifically control inter-regional LFP synchrony, by locking electrical stimulation pulses in one region to the phase of an ongoing oscillation in another region. The translational challenge is that efficient, implantable real-time synchrony monitoring and phase-locked stimulation require signal processing capabilities not found in any existing or anticipated device. Co-PI Shoaran has developed power-efficient phase estimation circuits, specifically optimized for DBS- like implants. We propose to combine these approaches. Aims 1 and 2 will develop a new application- specific integrated circuit (ASIC) that integrates Dr. Shoaran’s measurement and neural decoding frameworks with Dr. Widge’s oscillation-control methods. We will validate this circuit’s recording and phase-locking capabilities in vivo in Dr. Widge’s rodent lab. In Aim 3, a world-leading contract implant manufacturer (Cirtec) will integrate that new ASIC into a packaged, implant-ready device ready for large animal safety testing. Cirtec has already developed a DBS prototyping platform optimized to get new therapies more quickly into first-in- human, allowing us to greatly accelerate the path to the clinic and reduce regulatory risk. At the end of 5 years, we will either be ready for that clinical pilot or have only modest safety testing remaining. Our team has expertise in electronics, medical device fabrication, clinical brain stimulation, and technology commercialization. The work will be headquartered in Minnesota’s “Medical Alley”, an epicenter of medical device innovation. We are well-qualified to execute these Aims and bring the resulting technology to market. Success would yield a new implant optimized for network monitoring and therapy, a powerful new tool for both psychiatric treatment and cutting-edge neuroscience research.