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

描述(申请人提供)：我的长期目标是阐明触觉行为背后的神经机制，并将这一科学知识应用于神经假体，以恢复截肢者和瘫痪患者的触觉。后顶叶皮质(PPC)和背侧运动前皮质(PMD)是位于顶额网络的解剖节点，与视觉引导的到达有关。最近，有证据表明，在这些地区有一个抽象的实现计划，在运动开始之前，可以从这两个地区读出实现目标。然而，目前还不清楚PPC和PMD在视觉引导到达中各自扮演的角色以及它们在功能上是如何相互联系的，对这些问题的回答可以帮助假肢设计者确定从哪里以及如何解码到达意图。为此，我打算用以下特定的假设来研究这些区域：对于视觉引导到达，PPC中的内侧顶内区(MIP)在视觉刺激信息到达时计算默认到达计划，即到达显著物体，该计划被传递给PMD，PMD使用强加的认知规则，在MIP中形成的默认到达计划和额区形成的非默认到达计划之间选择一个动作，例如，“绿色意味着开始，红色意味着停止”。一旦PMD确定动作选择并形成实际的伸展计划，该计划被反馈给MIP，然后MIP反映实际即将到来的伸展计划，以服务于眼手协调和在线控制伸展运动。我的假设基于以下观察。首先，MIP神经元代表刺激开始后短时间内偏心视觉刺激的位置。第二，PMD的失活会导致需要基于认知规则进行动作选择的任务出现选择性缺陷。第三，当时间接近运动开始时，MIP神经元代表即将到来的REACH目标的位置，而不是显著刺激的位置。根据我的假设，一个明确的实验预测是，将首先在MIP中检测到默认的到达计划(自下而上的信息流)，并且首先在PMD中检测到非默认的到达计划(自上而下的信息流)。我将通过比较每个计划在MIP和PMD中出现的时间来验证这一预测。另一种预测是，MIP的损害将干扰眼手协调和伸展运动的在线控制。在指导阶段，我将使用MIP的可逆灭活来测试第二个预测。在独立研究阶段，我将把重点扩大到包括PMD，并在完好无损的条件下使用多区域记录来测试第一个预测。此外，为了进一步证实MIP和PMD之间的方向性影响，我们将检查一个区域因另一个区域的失活而改变的神经反应。 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了解，还将为神经假体的应用提供必要的信息，例如，植入假体的理想靶脑区和解码到达意图的最佳信号处理方案。考虑到触觉在日常活动中的重要性，成功地将所获得的知识应用于神经假体将显著提高丧失触觉能力的患者的生活质量。

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.