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质(PPC)评估基于微线阵列技术和解码算法用于神经假体应用的有效性。这项工作的一个成果是人类批准的微线阵列技术，能够到达大脑皮层的深层沟区。在动物中，我们已经证明，在点对点手臂到达任务中，顶叶后皮质是编码到达目标(目标)位置和实时动态的区域。我们的意图是表明，在人类身上，这些特征也是编码的，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被记录下来，并从人类PPC中解码出来。这些任务将考察1)运动序列的快速解码；2)解码目标信息的象征性和非空间的高级方面；3)局部场势以提高解码精度并为认知状态解码提供基础；4)上下文解码；5)学习作为练习的函数的目标和轨迹解码以及6)学习新的效应器动力学。我们假设，动物PPC的这些认知方面也适用于相应的人类PPC。我们这笔赠款的五年目标是完成向食品和药物管理局提供的研究设备豁免(IDE)的临床前测试，提交并获得IDE的批准，获得IRB的批准并设计将用于后续人类临床研究的行为任务和数据分析，以及对两个受试者进行临床试验。为此，我们提出了五个具体目标：(1)根据推荐的标准对该技术进行生物兼容性评估，(2)对长期植入后的技术进行组织学评估，(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，以及(5)根据FDA批准的研究装置豁免临床试验，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.