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伸手行为背后的神经机制，并将这一科学知识应用于神经义肢，以恢复截肢者和瘫痪患者的伸手能力。后顶叶皮层（PPC）和背侧运动前皮层（PMd）是位于顶叶-额叶网络的解剖节点，与视觉引导到达有关。最近，一项研究表明，在这些区域中有一个抽象的到达计划，并且在运动开始之前，可以从这两个区域中读出到达目标。然而，目前还不清楚PPC和PMd在视觉引导下的作用，以及它们在功能上是如何相互联系的，这些问题的答案可以帮助假肢设计师确定从哪里以及如何解码到达意图。为此,我的目标是调查这些领域使用以下具体的假设:视觉引导达到,内侧壁内的区域(MIP) PPC计算违约达成计划,即,一个显著的对象,抵达后的视觉刺激信息,这计划是传递给PMd选择默认实现之间的行动计划中形成MIP和非计划形成的锋面使用实施认知规则,例如,绿色意味着去红色意味着停止。一旦PMd解决了动作选择并形成实际的到达计划，该计划将反馈给MIP， MIP将反映实际即将到达的到达计划，为到达运动提供眼手协调和在线控制。我的假设是基于以下观察。首先，MIP神经元在刺激发生后的短时间内代表偏心视觉刺激的位置。第二，PMd的失活导致了基于认知规则的行动选择任务的选择性缺陷。第三，随着运动开始时间的临近，MIP神经元代表即将到达目标的位置，而不是显著刺激的位置。从我的假设中得出的一个明确的实验预测是，默认的到达计划（自下而上的信息流）将首先在MIP中被检测到，而非默认的到达计划（自上而下的信息流）将首先在PMd中被检测到。我将通过比较每个计划在MIP和PMd中出现的时间来测试这个预测。另一种预测是，MIP病变将干扰眼手协调和对伸手动作的在线控制。在指导阶段，我将使用可逆的MIP失活来测试第二个预测。在独立研究者阶段，我将扩展重点，包括PMd，并在完整条件下使用多面记录测试第一个预测。此外，为了进一步确认MIP和PMd之间的定向影响，将检查一个区域因另一个区域失活而改变的神经反应。

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.