Top-Down vs Bottom-Up Information Flow in the Parietofrontal Network for Reaching

描述（由申请人提供）： 我的长期目标是阐明触及行为背后的神经机制，并将这些科学知识应用于神经假体，以恢复截肢者和瘫痪患者的触及。后顶叶皮层（PPC）和背侧运动前皮层（PMd）是位于顶叶-额叶网络中的解剖学节点，与视觉引导的到达有关。最近，研究表明，抽象的延伸计划在这些区域中表现出来，并且在运动开始之前，可以从这两个区域读出延伸目标。然而，目前还不清楚PPC和PMd各自的作用是什么，在视觉引导达到和它们是如何在功能上相互连接，答案可以帮助假肢设计师，以确定从哪里以及如何解码达到意图。为此，我的目标是用以下具体假设来研究这些区域：对于视觉引导的到达，PPC中的内侧顶内区（MIP）计算默认的到达计划，即，在视觉刺激信息到达时，到达显著对象，并且该计划被传递到PMd，PMd使用强加的认知规则在MIP中形成的默认到达计划和在额区中形成的非默认计划之间选择动作，例如，“绿色表示走，红色表示停”。一旦PMD解决了动作选择并形成实际的伸展计划，该计划被反馈到MIP，MIP然后反映实际的即将到来的伸展计划，以服务于眼手协调和伸展运动的在线控制。我的假设是基于以下观察。首先，MIP神经元代表刺激开始后短暂时间内偏心视觉刺激的位置。第二，PMd的失活诱导选择性赤字的任务，需要根据认知规则的行动选择。第三，MIP神经元代表即将到来的到达目标的位置，而不是随着时间接近运动开始的显著刺激的位置。一个明确的实验预测，从我的假设是，默认的到达计划（自下而上的信息流）将首先在MIP中检测到，而非默认的到达计划（自上而下的信息流）将首先在PMD中检测到。我将通过比较MIP和PMd中每个计划出现的时间来测试这个预测。另一种预测是MIP的病变会干扰眼手协调和对伸展运动的在线控制。在指导阶段，我将使用MIP的可逆失活来测试第二个预测。在独立调查阶段，我将扩大重点，包括PMd和测试的第一个预测使用多区域记录在完整的条件下。此外，为了进一步证实MIP和PMd之间的方向性影响，将检查一个区域中的神经反应因另一个区域失活而改变。 公共卫生相关性： 从这项研究中获得的科学知识不仅将促进我们对大脑的理解，还将为神经假体应用提供重要信息，例如，植入假肢的理想目标脑区和解码伸手意图的最佳信号处理方案。考虑到触及在我们日常活动中的重要性，将获得的知识成功应用于神经假体将为失去触及能力的患者带来生活质量的显着改善。

DESCRIPTION (provided by applicant): My long term goal is to elucidate the neural mechanism underlying reaching behavior and apply this scientific knowledge to a neural prosthesis to restore reaching for amputees and paralyzed patients. The posterior parietal cortex (PPC) and dorsal premotor cortex (PMd) are anatomical nodes located in the parieto-frontal network implicated in visually guided reaching. Recently, it was demonstrated that an abstract reaching plan is represented in these areas and that the reaching goal can be read out from both areas before the movement starts. However, it is still unclear what the respective roles of PPC and PMd are in visually guided reaching and how they are functionally interconnected, answers to which could help a prosthesis designer to determine from where and how to decode reaching intentions. To this end, I aim to investigate these areas with the following specific hypothesis: for visually guided reaching, the medial intraparietal area (MIP) in PPC computes a default reach plan, i.e., reaching for a salient object, upon arrival of the visual stimulus information, and this plan is passed to PMd which selects an action between the default reach plan formed in MIP and a non-default plan formed in the frontal area using imposed cognitive rules, e.g., 'green means go and red means stop'. Once PMd resolves the action selection and forms an actual reach plan, this plan is fed back to MIP which then reflects the actual impending reach plan to serve eye-hand coordination and online control of the reaching movement. My hypothesis is based on the following observations. First, MIP neurons represent the location of an eccentric visual stimulus for a brief period upon stimulus onset. Second, inactivation of PMd induces selective deficits in a task requiring action selection based on cognitive rules. Third, MIP neurons represent the location of the upcoming reach target instead of the location of the salient stimulus as time approaches the movement onset. One clear experimental prediction from my hypothesis is that a default reach plan (bottom-up information flow) will be detected in MIP first and a non-default reach plan (top-down information flow) will be detected in PMd first. I will test this prediction by comparing the time at which each plan arises in MIP and PMd. Another prediction is that lesion of MIP will disturb eye-hand coordination and online control of reaching movements. During the mentored phase, I will test the second prediction using a reversible inactivation of MIP. During the independent investigator phase, I will expand the focus to include PMd and test the first prediction using a multi-areal recording under an intact condition. In addition, to further confirm the directional influence between MIP and PMd, the altered neural response in one area by the inactivation of the other will be examined. PUBLIC HEALTH RELEVANCE: The scientific knowledge acquired from this study will not only advance our understanding of the brain but also provide essential information for neural prosthetic applications, e.g., the ideal target brain area to implant the prosthetics and the optimal signal processing scheme to decode the intention of reaching. Considering the importance of reaching in our daily activities, the successful application of the acquired knowledge to a neural prosthesis will bring a significant improvement to the quality of life for the patients who lost reaching abilities.