Accelerating Dissemination of Implantable Neurotechnology for Clinical Research

总结 侵入性神经刺激是治疗运动障碍和癫痫的一种成熟技术， 显示出改善精神和认知障碍的希望。最近，几个植入式 神经刺激硬件平台已经开始结合皮层和皮层下场的感测 潜在的活动，具有从内部设备到外部计算机的无线流传输能力， 年这些高时间和空间分辨率的信号可用于揭示大脑的电路基础 疾病，开发新的疗法，合理地从电路分析，并发展适应性（反馈 受控的）神经刺激范例，其中设备根据改变的大脑需求自动调整。 最近的“第二代”植入式装置，例如Summit RC+S（Medtronic）， 大大提高了性能，并为新用途提供了很大的灵活性， 复杂性然而，有效利用这一平台和相关平台需要学术研究人员开发 以前不熟悉的能力，包括使用“应用程序”对所需设备功能进行编程 编程接口”，并根据FDA的要求记录软件的性能和确认 设备法规。虽然许多BRAIN计划资助的赠款打算使用这些第二代 双向接口，这四个机构的建议，共同努力，是唯一的团体， 克服了技术和监管障碍，推出了具有第二代传感功能的临床方案 装置.我们已经成立了“开放思维”神经通信联盟， 监管基础设施与对方和新的调查人员，并开始传播这方面的知识 在2018年4月和2019年4月的大脑倡议会议上，新研究人员的公开会议上。通过这个 建议，我们将大大扩大这些技术传播活动，为调查人员提供 启动自己的临床研究的关键要素：一个“交钥匙”用户界面， 包括用于家庭神经感测和自适应刺激的开源软件元素， 简化了FDA批准研究方案的监管途径，我们称之为“开源 质量管理体系”。我们将通过一年两次的讲习班传播教育和资源， 基于网络的法规文件、软件和质量管理体系库。我们的团队 代表神经调节的主要临床领域：运动障碍（UCSF）、癫痫 (Mayo诊所）和精神病学（布朗/贝勒），并包括设计和传播 可植入器械（Oxford）。该联盟将促进已经获得资助的提案，以及新的项目的进入。 研究人员，在快速发展的生态系统植入式无线神经接口。两个新的临床 团队已经开始使用我们的神经传感接口，为他们自己的临床试验做准备， 适应性刺激，表明传播工具的准备就绪。

Summary Invasive neurostimulation is an established technique in the therapy of movement disorders and epilepsy, and shows promise for amelioration of psychiatric and cognitive disorders. Recently, several implantable neurostimulation hardware platforms have begun to incorporate sensing of cortical and subcortical field potential activity, with the capability for wireless streaming from the internal device to external computers over years. These high temporal and spatial resolution signals may be used for discovering the circuit basis of brain disorders, developing new therapies rationally derived from circuit analysis, and developing adaptive (feedback controlled) neurostimulation paradigms in which the device auto-adjusts according to changing brain needs. The most recent “second generation” implantable devices, such as Summit RC+S (Medtronic), have substantially improved capabilities and offer great flexibility for novel uses, at the expense of increased complexity. However, effective use of this and related platforms requires academic investigators to develop previously unfamiliar capabilities, including programming of the desired device functions using an “application programming interface”, and documenting the performance and validation of software according to FDA device regulations. While many BRAIN Initiative funded grants intend to use these second generation bidirectional interfaces, the four institutions on this proposal, working together, are the only groups that have surmounted the technical and regulatory barriers to launching clinical protocols with second generation sensing devices. We have formed the “Open Mind” neural communications consortium to share technical and regulatory infrastructure with each other and with new investigators, and begun to disseminate this knowledge at open meetings for new investigators, at the April 2018 and 2019 Brain Initiative Meetings. Through this proposal, we will greatly expand these technology dissemination activities, to provide investigators with elements critical to the launch of their own clinical studies: A “turnkey” user interface to get started that includes open source software elements for neural sensing at home and for adaptive stimulation, and a streamlined regulatory pathway for FDA approval of investigational protocols, which we call the “Open Source Quality Management System”. We will disseminate education and resources through biannual workshops and a web-based library of regulatory documents, software, and the Quality Management System. Our team represents the major clinical areas of interest in neuromodulation: movement disorders (UCSF), epilepsy (Mayo Clinic), and psychiatry (Brown/Baylor), and includes experts in the design and dissemination of implantable devices (Oxford). This consortium will facilitate already funded proposals, as well as entry of new investigators, in the rapidly evolving ecosystem of implantable wireless neural interfaces. Two new clinical teams have already begun to work with our neural sensing interface in preparation for their own clinical trials of adaptive stimulation, demonstrating readiness of tools for dissemination.