Uncovering the Internal Representation of Actions in Posterior Parietal Cortex

揭示后顶叶皮层动作的内部表征

• 批准号: 10507756
• 负责人: Whitney Scott Griggs
• 金额: $ 5.18万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10507756
• 关键词: Anatomy; Animals; Anterior; Apraxias; Area; Ataxia; Bilateral; Brain region; Complex; Cues; Data; Doctor of Philosophy; Electrophysiology (science); Exhibits; Eye; Fingers; Functional Magnetic Resonance Imaging; Functional disorder; Future; Gold; Hand; Human; Image; Knowledge; Link; Liquid substance; Location; Macaca mulatta; Maps; Measures; Mentorship; Methods; Motor; Movement; Music; Nervous System Trauma; Neurons; Optics; Parietal; Parietal Lobe; Pathology; Patients; Pattern; Persons; Physicians; Play; Population; Probability; Quality of life; Reporting; Research; Resolution; Rewards; Role; Saccades; Scientist; Signal Transduction; Techniques; Technology; Testing; Validation; Visual; Visual Motor Coordinations; cerebral hemodynamics; clinical application; cortex mapping; environmental change; hemodynamics; in vivo; innovation; lateral intraparietal area; motor disorder; multisensory; negative affect; nervous system disorder; neuroimaging; neuronal circuitry; neurovascular; neurovascular coupling; nonhuman primate; novel; oculomotor; relating to nervous system; response; skills; spatiotemporal; temporal measurement; ultrasound; ventral intraparietal area; visual motor

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.

项目概要 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。尤其， 后顶叶皮层 (PPC) 损伤会导致各种视觉和动眼神经病变，包括 视神经共济失调、动眼神经失用症和同时失认症。非人类灵长类动物和人类研究已阐明 PPC 如何整合视觉和运动信息来计划和执行运动决策。然而，很多 PPC 如何以及在何处代表未来的决策和行动仍然未知。在这个 建议，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 如何表示决策和运动变量。这些变量包括 运动效应器、目标位置和动作需求。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 （<100 µm；~100 ms）和大视场（几厘米）——非常适合记录详细信息的规格 整个皮质区域的活动是并行的。此外，我们将使用电生理学这一黄金标准 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，我们将调查 通过记录恒河猴完整的 fUS 数据来对 PPC 中的运动位置进行解剖学组织 眼睛和手部运动到视觉目标。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。在具体目标 2 中，我们将确定决策的方式和地点 变量（努力和奖励）在 PPC 中编码。与具体目标 1 一样，我们将记录动物时的 fUS 数据 执行眼睛和手的运动，但我们也会通过独立改变液体来改变奖励和努力 每个动作的奖励金额和所需的准确性（即努力程度）。在具体目标 3 中，我们将调查 通过同时进行 fUS 和 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来 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片段。如果成功的话，这个贡献 将进一步验证 fUS 作为一种强大且易于使用的神经影像技术，用于未来的研究和临床 电生理学难以实现和/或扩展的应用。这些具体目标共同将 阐明运动和决策变量在 PPC 中从微观尺度（电生理学）到编码的位置 中观尺度（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动眼神经失用。该项目将进行 在博士的指导下通过加州大学洛杉矶分校-加州理工学院 MSTP。安徒生和夏皮罗。所描述的研究 将构成我的博士论文的基础，并为我灌输成为一名出色的医师科学家的技能。