Putting Priority Map Theory to the Test

描述(申请人提供)：尽管人们普遍认为前额叶和后顶叶皮质(PFC/PPC)对于灵活的行动和有效的感知是必要的，但在理解它们实现这些目标的控制机制方面存在着根本的差距。这种知识上的差距是一个关键问题，因为许多精神和神经疾病源于执行控制的原发功能障碍。长期目标是了解PFC和PPC控制运动和感觉系统的机制。目前提议的目标是测试一种新的模型，即PFC和PPC中的活动如何形成优先空间图，以标记视野中的显著和相关位置，然后将其用作执行控制信号的基础。偏向的机制可能涉及用于眼跳规划的机制。该项目的中心目标是测试人类PFC和PPC中的神经活动模式与优先图理论的预测相一致的程度，包括优先图的功能组织、优先排序的性质和表示 相互竞争的优先事项。提出这项研究的理由是，更好地理解控制是如何实施的，将导致一个强有力的理论框架，在这个框架内，将制定理解精神疾病的策略。本研究的目的将是测试、完善并可能驳斥优先图理论的原则，这将通过追求三个具体目标来实现：1)测试优先图中的活动不知道是什么导致优先排序的假设；2)测试优先图中的活动编码与多个优先项目相关联的激励的假设；以及3)测试优先图中的活动编码与多个优先项目相关联的线索概率的假设。强劲的初步数据证明了AIMS在申请者手中的可行性。使用新的地形图绘制方法，在额顶叶皮质确定了几个候选优先图。在目标1下，候选优先图中的延迟期活动和大脑活动的多变量模式在各种空间认知任务(如记忆、注意力、计划)中即使不能互换，也非常相似。在目标2下，额叶和顶叶皮质的行为测量和空间特定活动随着激励驱动的优先位置而扩大，这些优先位置保持在工作记忆中。在目标3下，工作记忆的表现随着维持的位置随后被探测的可能性而增加。这种方法是创新的，因为它具有高度的程序性；使用新的方法来对抗PFC和PPC的功能神经解剖学中的个体差异；用新的分析绕过过去的推理弱点；并使用强大的方法来严格测试关键假设。这项拟议的研究具有重要意义，因为它有望测试一种重要的执行控制新模型，并将提供对人脑施加控制的机制的详细了解，以便将这些机制的功能障碍模型作为神经病理的原因和潜在治疗方法。

DESCRIPTION (provided by applicant): Despite the widespread appreciation that the prefrontal and posterior parietal cortices (PFC/PPC) are necessary for flexible action and efficient perception, there is a fundamental gap in understanding the control mechanisms by which they accomplish these goals. This gap in knowledge is a critical problem because a host of psychiatric and neurologic disorders stem from a primary dysfunction of executive control. The long-term goal is to understand the mechanisms by which the PFC and PPC exert control over motor and sensory systems. The objective of the current proposal is to test a new model of how activity in the PFC and PPC form maps of prioritized space that tag salient and relevant locations in the visual field, which can then be used as the basis of executive control signals. The mechanisms of bias are likely to involve mechanisms used for saccade planning. The central aim of the project is to test the extent to which the patterns of neural activity in the human PFC and PPC are consistent with predictions from the priority map theory, including the functional organization of priority maps, the nature of what is prioritized, and the representation of competing priorities. The rationale for the proposed research is that a better understanding of how control is exerted will lead to a strong theoretical framework within which strategies for the understanding of mental disease will develop. The objective will be to test, refine, and possibly refute, tenets of the priority map theory which will be accomplished by pursuing three specific aims: 1) test the hypothesis that the activity in priority maps is agnostic about what led to prioritization; 2) test the hypothesis that the activity in priority maps encodes the incentives associated with multiple prioritized items; and 3) test the hypothesis that the activity in priorit maps encodes the cue probabilities associated with multiple prioritized items. Strong preliminary data demonstrate the feasibility of aims in the applicant's hands. Several candidate priority maps were identified in frontoparietal cortex using novel topographical mapping approaches. Under Aim 1, both delay period activity and multivariate patterns of brain activity in candidate priority maps were remarkably similar, if not interchangeable, across a variety of spatial cognition tasks (e.g., memory, attention, planning). Under Aim 2, behavioral measures and spatially specific activity in frontal and parietal cortex scaled with the incentive driven priorites of locations maintained in working memory. Under aim 3, working memory performance scaled with the likelihood that maintained locations would be later probed. The approach is innovative because it is highly programmatic; uses novel approaches to combat individual differences in the functional neuroanatomy of the PFC and PPC; sidesteps past inferential weaknesses with novel analyses; and uses powerful methods to rigorously test key hypotheses. The proposed research is significant because it is expected to test an important new model of executive control and will provide a detailed understanding of the mechanisms by which the human brain exerts control, such that models of dysfunction of these mechanisms can be targeted as causes of and potential treatments for neuropathology.