Cognitive neural prosthetics for clinical applications

描述（由申请人提供）：本申请的目的是在人类后顶叶皮层（PPC）中评估基于微丝的阵列技术和解码算法在神经假体应用中的有效性。这项工作的一个成果是人类批准的微线阵列技术，能够达到大脑皮层的深沟区。在动物中，我们已经证明，后顶叶皮层是一个区域，在点对点的手臂伸展任务中，它编码了到达目标（目标）的位置和真实的时间动态。我们的目的是表明，在人类中，这些特征也被编码，并且目标和动态信息可以结合起来，以更准确地解码运动意图。此外，我们对动物的研究表明，PPC编码了许多认知变量，这些变量可能对神经假体应用有潜在的帮助。任务将被设计成看看这些认知信号是否也可以从人类PPC中记录和解码。这些任务将检查1）运动序列的快速解码; 2）解码目标信息的符号和非空间的更高层次方面; 3）局部场电位，以提高解码准确性并为认知状态解码提供基础; 4）上下文解码; 5）学习作为目标和轨迹解码的实践函数，以及6）学习新的效应器动态。我们假设动物PPC的这些认知方面在相应的人类PPC中也是可用的。我们的五年目标是完成向美国食品药品监督管理局（FDA）提交的试验用器械豁免（IDE）的临床前测试，提交并获得IDE批准，获得IRB批准并设计将用于后续人体临床研究的行为任务和数据分析，并对两名受试者进行临床试验。为此，我们提出了五个具体目标：（1）根据推荐标准对技术进行生物相容性评估，（2）在长期植入后对技术进行组织学评估，（3）在非人灵长类动物模型中进行安全性和有效性评估，（4）测试将用于人类的解码算法的性能，以及（5）根据FDA批准的研究器械豁免临床试验，评估我们的技术和认知解码算法在瘫痪个体中的性能。

DESCRIPTION (provided by applicant): The objective of this application is to assess, in human posterior parietal cortex (PPC), the efficacy of both microwire-based array technology and decoding algorithms for neural prosthetic applications. An outcome of this work is a human-approved microwire array technology capable of reaching deep sulcal areas of the cortex. In animals, the posterior parietal cortex is an area that we have shown to encode both the reach target (goal) location and real time dynamics in point-to-point arm reaching tasks. It is our intention to show that, in the human, these features are also encoded and that goal and dynamic information can be combined for more accurate decoding of movement intentions. In addition, our research with animals has demonstrated that the PPC encodes a number of cognitive variables that could be potentially useful for neural prosthetic applications. Tasks will be designed to see if these cognitive signals can also be recorded and decoded from human PPC. These tasks will examine 1) rapid decoding of movement sequences; 2) decoding higher level aspects of goal information that are symbolic and non-spatial; 3) local field potentials to increase decode accuracy and provide a foundation for cognitive state decoding; 4) context decoding; 5) learning as a function of practice for goal and trajectory decoding and 6) learning novel effecter dynamics. We hypothesize that these cognitive aspects of animals' PPC are also available in the corresponding human PPC. Our five year goal for this grant is to complete the preclinical testing for an investigational device exemption (IDE) to the Food and Drug Administration, submit and gain approval for an IDE, obtain IRB approvals and design the behavioral tasks and data analysis that will be used in subsequent human clinical studies, and perform a clinical trial with two subjects. To this end, we have put forth five specific aims: (1) to perform a biocompatibility assessment of the technology per recommended standards, (2) to perform a histological assessment of the technology following chronic implantation, (3) to perform a safety and efficacy assessment in a non-human primate model, (4) to test the performance of decoding algorithms that will be used in humans, and (5) to assess the performance of our technology and cognitive decoding algorithms in paralyzed individuals under an FDA approved Investigational Device Exemption Clinical Trial.