Uncovering the Internal Representation of Actions in Posterior Parietal Cortex

项目总结 神经损伤和疾病对美国数百万人的生活质量产生了负面影响。特别是， 对后顶叶皮质(PPC)的损害会导致各种视觉和眼动病理，包括 视性共济失调，动眼失用和失语。非人灵长类动物和人类研究阐明 PPC如何集成视觉和运动信息来计划和执行移动决策。然而，很多 关于购买力平价如何以及在哪里代表未来的决定和行动，仍然是未知的。在这 提议，我们将使用两种互补的技术，功能超声神经成像(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 移动效应器、目标位置和动作合意性。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 以卓越的时空分辨率测量脑血流动力学的神经成像技术 (&lt；100微米；~100毫秒)和大视场(几厘米)-非常适合记录详细的 整个皮质区域的活动是平行的。此外，我们将使用电生理学，这是 神经元记录，以在单个神经元水平上验证FUS发现。在具体目标1中，我们将调查 恒河猴完全性FUS数据对PPC内运动位置的解剖组织 眼睛和手的运动到视觉目标。这将提供PPC中响应场的详细皮质图 根据效应器和运动位置。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(努力和奖励)以购买力平价编码。就像《特殊目标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更换液体来改变奖励和努力 奖励金额和每个动作所需的精确度(即努力)。在具体目标3中，我们将调查 脑血流动力学与潜在神经活动之间的联系 宽带电生理学(单单元、多单元和LFP)。我们将使用这些数据1)验证我们的FU 发现和2)探索在单个神经元水平上有趣的活动斑块。如果成功，这一贡献 将进一步验证FUS作为一种强大和可访问的神经成像技术，用于未来的研究和临床 电生理学难以达到和/或难以规模化的应用。这些具体目标加在一起，将 阐明运动和决策变量在PPC中从微尺度(电生理学)到 中尺度(FUS)。通过了解影响视觉运动决定的神经元回路，我们可以更好地 了解视觉运动障碍，例如视性共济失调和动眼失用症。这一项目将被实施 通过加州大学洛杉矶分校-加州理工学院MSTP在安德森和夏皮罗博士的指导下进行。所描述的研究 将构成我博士论文的基础，并为我灌输成为一名有成就的内科科学家的技能。

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.