Cognitive neural prosthetics for clinical applications

描述（由申请人提供）：本申请的目的是评估在人类后顶叶皮层（PPC）中，基于微线的阵列技术和解码算法在神经假肢应用中的功效。这项工作的一个成果是人类认可的微线阵列技术能够到达皮层的深沟区域。在动物中，我们已经证明，后顶叶皮层是一个编码点对点手臂到达任务中到达目标（目标）位置和实时动态的区域。我们的目的是表明，在人类中，这些特征也被编码，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肢的应用有潜在的用处。将设计一些任务，看看这些认知信号是否也能从人类的PPC中被记录和解码。这些任务将检查1)快速解码的运动序列；2)解码更高层次的目标信息，这些信息具有符号性和非空间性；3)局部场电位提高解码精度，为认知状态解码提供基础；4)语境解码；5)学习作为目标和轨迹解码练习的功能；6)学习新的效应动力学。我们假设动物PPC的这些认知方面也存在于相应的人类PPC中。我们的五年目标是完成研究器械豁免（IDE）的临床前测试，向食品和药物管理局提交并获得IDE的批准，获得IRB批准，设计行为任务和数据分析，将用于后续的人体临床研究，并进行两名受试者的临床试验。为此，我们提出了五个具体目标：(1)按照推荐标准对该技术进行生物相容性评估，(2)对该技术进行慢性植入后的组织学评估，(3)在非人类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，(5)在FDA批准的研究性器械豁免临床试验中评估我们的技术和认知解码算法在瘫痪患者中的表现。

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.