Neural mechanisms of spatial representations beyond the self

项目摘要/摘要 空间导航是人类的一种基本行为，导航功能缺陷是 阿尔茨海默病等严重神经系统疾病的标志性症状。了解如何将 因此，人脑对空间信息的处理和编码对于 对受影响患者的治疗。先前的研究表明，大脑形成对空间的神经表征 信息，通过单个神经元的空间调谐活动(例如，放置单元、网格单元或头部方向单元)，以及 通过细胞群体的协调振荡活动。这些研究中的绝大多数都集中在 对自我相关的空间信息进行编码，如自己的位置、方向和运动。然而， 社交环境中的日常任务不仅需要为自己编码空间信息，也需要为他人编码空间信息 环境中的人。目前，很大程度上还不清楚人脑是如何完成这一重要任务的 功能，以及人类认知的各个方面如何影响这些空间编码机制。这个项目 因此，旨在阐明空间信息编码的神经机制和 对他人的认识。具体地说，拟议的研究计划将确定人类大脑深部振荡是如何 单神经元活动使我们能够跟踪其他个体在我们环境中移动的情况。 接下来，该项目将确定这些空间编码机制是否特定于 另一个人，或者是否可以更灵活地使用它们来支持对运动的无生命物体进行编码 甚至还有更抽象的认知功能，比如想象中的导航。最后，该项目将决定如何 空间信息在更复杂的真实世界场景中编码，当多个信息源(例如， 多人)出席。为了解决这些问题，颅内内侧颞叶活动将 记录自两个罕见的参与者组：(1)永久植入深度电极的参与者 通过反应性神经刺激(RNS)治疗局灶性癫痫，提供了一个独特的机会 记录自由活动和自然行为中的脑深部振荡；以及(2)住院癫痫 在癫痫监测单元(EMU)中临时植入颅内电极的患者，从谁关节 可以记录到振荡和单个神经元的活动。 此外，这个奖项将让我完成一个多方面的职业发展计划：因为我目前 电生理记录的经验仅限于RNS参与者的振荡活动，我会学到的 记录和分析临床环境下EMU患者的人类单个神经元活动。我的训练将是 在这一研究领域的先驱的指导下，将在加州大学洛杉矶分校举行，加州大学洛杉矶分校是世界领先的 临床和研究工作涉及这些患者群体。我将进一步参加研讨会、课程作业和 会议，不仅要发展为一名实验者，而且要发展为一名独立的领导者和科学 通信器。总而言之，这将为我提供向独立过渡所需的一套技能。

PROJECT SUMMARY/ABSTRACT Spatial navigation is a fundamental human behavior, and deficits in navigational functions are among the hallmark symptoms of severe neurological disorders such as Alzheimer’s disease. Understanding how the human brain processes and encodes spatial information is thus of critical importance for the development of therapies for affected patients. Previous studies have shown that the brain forms neural representations of spatial information, via spatially-tuned activity of single neurons (e.g., place cells, grid cells, or head direction cells), and by the coordinated oscillatory activity of cell populations. The vast majority of these studies have focused on the encoding of self-related spatial information, such as one’s own location, orientation, and movements. However, everyday tasks in social settings require the encoding of spatial information not only for oneself, but also for other people in the environment. At present, it is largely unknown how the human brain accomplishes this important function, and how aspects of human cognition may affect these spatial encoding mechanisms. This project therefore aims to elucidate the neural mechanisms that underlie the encoding of spatial information and awareness of others. Specifically, the proposed research plan will determine how human deep brain oscillations and single-neuron activity allow us to keep track of other individuals as they move through our environment. Next, the project will determine whether these spatial encoding mechanisms are specific to the encoding of another person, or whether they can be used more flexibly to support the encoding of moving inanimate objects and even more abstract cognitive functions such as imagined navigation. Finally, the project will determine how spatial information is encoded in more complex real-world scenarios, when multiple information sources (e.g., multiple people) are present. To address these questions, intracranial medial temporal lobe activity will be recorded from two rare participant groups: (1) Participants with permanently implanted depth electrodes for the treatment of focal epilepsy through responsive neurostimulation (RNS), who provide a unique opportunity to record deep brain oscillations during free movement and naturalistic behavior; and (2) hospitalized epilepsy patients with temporarily implanted intracranial electrodes in the epilepsy monitoring unit (EMU), from whom joint oscillatory and single-neuron activity can be recorded. In addition, this award will allow me to complete a multifaceted career development plan: Since my current experience with electrophysiological recordings is limited to oscillatory activity from RNS participants, I will learn to record and analyze human single-neuron activity from EMU patients in a clinical setting. My training will be guided by pioneers in this research area, and will take place at UCLA, one of the world’s leading institutions in the clinical and research work with these patient populations. I will further attend seminars, coursework, and conferences, to develop not only as an experimentalist, but also as an independent leader and science communicator. Together, this will provide me with the necessary set of skills for my transition to independence.