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)在大脑网络中的同步性。像深脑这样的植入式神经技术 刺激(DBS)使运动障碍和癫痫的治疗发生了革命性变化。星展银行有一些 精神病学的临床信号也是如此，但个人试验结果高度不同。我们辩称，这是一个 目标交战问题-帕金森氏症或其他震颤中使用的高频持续刺激 精神障碍不是治疗精神疾病循环的正确方法。相反，我们认为正确的方法是 识别这些电路/网络中健康通信的特征，然后设计刺激协议 专门产生这些签名的人。LFP同步很可能是这些通信之一 签名。在认知和情绪功能的多个领域，行为表现(读出 当大脑区域显示同步(一致)LFP时)会得到改善 震荡。此外，临床上有效的DBS，在运动和精神障碍方面，与 LFP同步的变化。Co-Pi Widge开发了专门控制区域间的算法 LFP同步，通过将一个区域中的电刺激脉冲锁定到 另一个地区。转换的挑战是高效、可植入的实时同步监控和 锁相刺激需要任何现有或预期的设备所没有的信号处理能力。 Co-Pi Shoaran开发了省电的相位估计电路，专门针对DBS进行了优化- 就像植入物。我们建议将这些方法结合起来。AIMS 1和AIMS 2将开发一个新的应用程序- 集成了肖兰博士的测量和神经解码框架的专用集成电路(ASIC) 威奇博士的振荡控制方法。我们将验证该电路的录音和锁相 在Widge博士的啮齿动物实验室中的体内能力。在Aim 3，世界领先的植入物合同制造商(Cirtec) 将把这种新的ASIC集成到一种封装的、可植入的设备中，为大型动物安全测试做好准备。CIRTEC 已经开发了一个星展银行原型平台，优化后的平台可以更快地将新疗法引入第一流的 人类，使我们大大加快了通往诊所的道路，并降低了监管风险。在第五年的末尾 几年后，我们要么为临床试验做好准备，要么只剩下适度的安全性测试。 我们的团队在电子、医疗设备制造、临床脑刺激和技术方面拥有专业知识 商业化。这项工作的总部将设在明尼苏达州的“医疗小巷”，这是一个医疗中心 设备创新。我们完全有资格实现这些目标，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，这是一种对两者都有效的新工具 精神病学治疗和前沿神经科学研究。

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.