Uncovering the Internal Representation of Actions in Posterior Parietal Cortex

项目摘要 神经损伤和疾病对美国数百万人的生活质量产生负面影响。特别是， 后顶叶皮层（PPC）的损伤引起各种视觉和眼科病理，包括 视神经共济失调、眼神经失用症和同时性失认症。非人类灵长类动物和人类的研究已经阐明了 PPC如何整合视觉和运动信息来计划和执行运动决策。然而，许多 PPC如何以及在哪里代表未来的决策和行动仍然是未知的。在这 我们将使用两种互补的技术，功能性超声神经成像（fUS）和 电生理学，探索PPC如何代表决策和运动变量。这些变量包括 运动效应器、目标位置和动作期望。迄今为止，神经记录技术已经牺牲了 视场的空间和时间分辨率，反之亦然。现在，fUS作为一种创新的 一种神经成像技术，以卓越的时空分辨率测量脑血流动力学 （<100 µm; ~100 ms）和大视场（几cm）--非常适合记录详细信息的规格 整个皮层区域的活动平行。此外，我们将使用电生理学，黄金标准， 神经元记录，以验证单神经元水平的fUS结果。在具体目标1中，我们将研究 恒河猴完整运动过程中fUS数据对PPC运动部位的解剖学组织学研究 眼睛和手移动到视觉目标。这将提供PPC中反应场的详细皮质图 根据效应器和运动位置来确定运动轨迹。在具体目标2中，我们将确定如何以及在何处做出决定 变量（努力和回报）被编码在PPC中。与特定目标1一样，我们将在动物 进行眼睛和手的运动，但我们也会通过独立改变液体来改变奖励和努力 奖励金额和每个动作所需的准确性（即努力）。在第三章中，我们将研究 脑血流动力学和潜在的神经活动之间的联系，通过同时fUS和 宽带电生理学（单单位、多单位和LFP）。我们将使用这些数据1）验证我们的FUS 研究结果和2）探索单个神经元水平上有趣的活动区域。如果成功，这一贡献 将进一步验证fUS作为未来研究和临床的强大和可访问的神经成像技术 电生理学难以实现和/或扩展的应用。这些具体目标将 阐明运动和决策变量在PPC中编码的位置，从微观尺度（电生理学）到 中尺度（fUS）。通过了解影响视觉运动决策的神经元回路，我们可以更好地 了解视觉运动障碍，例如视神经共济失调和眼神经失用症。该项目将在 通过UCLA-Caltech MSTP在Andersen和Shapiro博士的指导下。所描述的研究 将构成我的博士论文的基础，并灌输我成为一名有成就的医生科学家的技能。

PROJECT SUMMARY Neurological injuries and diseases negatively affect quality of life for millions of people in the US. In particular, damage to the posterior parietal cortex (PPC) causes various visual and oculomotor pathologies, including optic ataxia, oculomotor apraxia, and simultagnosia. Nonhuman primate and human studies have elucidated how PPC integrates visual and motor information to plan and execute movement decisions. However, much still remains unknown about how and where PPC represents future decisions and actions. In this proposal, we will use two complementary techniques, functional ultrasound neuroimaging (fUS) and electrophysiology, to explore how PPC represents decision and motor variables. These variables include movement effector, target location, and action desirability. To date, neural recording techniques have sacrificed spatial and temporal resolution for field of view or vice-versa. Now, fUS is available as an innovative neuroimaging technique that measures cerebral hemodynamics with exceptional spatiotemporal resolution (<100 µm; ~100 ms) and a large field of view (several cm) – specifications ideally suited to recording detailed activity of entire cortical regions in parallel. In addition, we will use electrophysiology, the gold standard for neuronal recordings, to verify fUS findings at the single-neuron level. In Specific Aim 1, we will investigate the anatomical organization of movement location in PPC by recording fUS data as rhesus macaques complete eye and hand movements to visual targets. This will provide a detailed cortical map of response fields in PPC according to effector and movement location. In Specific Aim 2, we will identify how and where decision variables (effort and reward) are encoded in PPC. Like Specific Aim 1, we will record fUS data while animals perform eye and hand movements, but we will also vary reward and effort by independently changing the liquid reward amount and required accuracy (i.e. effort) for each movement. In Specific Aim 3, we will investigate the link between cerebral hemodynamics and the underlying neural activity through simultaneous fUS and broad-band electrophysiology (single-unit, multi-unit, and LFP). We will use these data to 1) validate our fUS findings and 2) explore interesting patches of activity at the single neuron level. If successful, this contribution will further validate fUS as a robust and accessible neuroimaging technique for future research and clinical applications where electrophysiology is difficult to attain and/or scale. Together, these Specific Aims will elucidate where motor and decision variables are encoded in PPC from the micro-scale (electrophysiology) to the meso-scale (fUS). By understanding the neuronal circuits influencing visual-motor decisions, we can better understand visual-motor disorders, e.g. optic ataxia and oculomotor apraxia. This project will be conducted through the UCLA-Caltech MSTP under the mentorship of Drs. Andersen and Shapiro. The described research will form the basis of my PhD thesis and instill the skills for me to become an accomplished physician scientist.