The electrophysiology of human spatial navigation

描述（由申请人提供）：本研究旨在促进我们对人类空间认知的神经机制的理解。为了做到这一点，我将研究接受长期颅内癫痫监测的患者在执行虚拟导航任务时的记录。这些颅内记录为研究人类认知过程提供了一个独特的机会，与传统的非侵入性脑成像技术相比，它具有更高的时间分辨率。我提出的实验研究了在几个不同版本的黄色出租车（一个虚拟出租车司机的视频游戏）中，神经元峰值活动、脑电波（振荡）和受试者行为之间的关系。我的实验是在最高标准的护理下进行的，除了那些已经在治疗难治性癫痫的患者外，对患者的风险只有最小的风险。这项研究将使我能够将关于导航过程中啮齿动物海马体形成的电生理学的大量文献与人类在空间任务中的行为的心理学研究联系起来。Aim 1的重点是基于不同大脑区域的神经元如何对导航行为的各个方面做出反应来构建人类大脑的功能地图。特别是，在广泛的大脑区域中，我将描述对位置、视图、目标和方向敏感的神经元的普遍性，以及对更复杂的变量（如“按方向定位”细胞和“网格”细胞）做出反应的神经元。目的2探讨这些与导航相关的神经元反应与大脑正在进行的θ波（4-8赫兹）振荡之间的时间关系。在这里，我将测试一个假设，即神经元通过与正在进行的大脑振荡（相位编码）相关的尖峰时间来代表不同的信息，这是最近啮齿动物电生理学研究中提出的。目的3考察了当人们回答有关环境布局的问题时观察到的以观察者为中心的表征的神经基础。这将使我能够检查导航时使用的相同神经模式是否也在人们不积极移动时使用。这项研究与公众健康的相关性：拟议研究的一个目标是创建人类大脑在空间导航过程中的功能地图。这与癫痫的临床治疗直接相关，其中手术过程中的认知映射对于确保成功的术后结果至关重要。此外，提出的研究可能为更有效地治疗空间记忆受损的阿尔茨海默病铺平道路。

DESCRIPTION (provided by applicant): The proposed research seeks to advance our understanding of the neural mechanisms underlying human spatial cognition. To accomplish this, I will study recordings from patients undergoing long-term intracranial epilepsy monitoring while they perform a virtual-navigation task. These intracranial recordings provide a unique opportunity to study human cognitive processes with a higher temporal resolution than can be obtained with conventional, noninvasive brain-imaging techniques. My proposed experiments examine the relation between neuronal spiking activity, brain waves (oscillations), and subjects' behavior during several variants of Yellow Cab, a virtual taxi-driver video game. My experiments are performed with the highest standard of care and pose only minimal risks for the patients beyond those already present to treat refractory epilepsy. This research will allow me to link the extensive literature on the electrophysiology of the rodent hippocampal formation during navigation with psychological research on human behavior in spatial tasks. The focus of Aim 1 is to build a functional map of the human brain based on how neurons across different brain regions respond to various aspects of navigational behavior. In particular, in widespread brain regions, I will characterize the prevalence of neurons with sensitivities for place, view, goal, and heading, as well as neurons responding to more complex variables such as "place-by-direction" cells and "grid" cells. Aim 2 probes the temporal relation between these navigation-related neuronal responses and the brain's ongoing theta (4-8 Hz) oscillations. Here, I will test the hypothesis that neurons represent distinct information by the timing of their spiking in relation to ongoing brain oscillations (phase coding), as suggested in recent studies of rodent electrophysiology. Aim 3 examines the neural basis of the observer-centered representations observed when people answer questions about an environment's layout. This will allow me to examine whether the same neural patterns used during navigation are also in use when people are not actively moving. Relevance of this research to public health: One goal of the proposed research is to create a functional map of the human brain during spatial navigation. This has direct relevance to the clinical treatment of epilepsy, in which cognitive mapping during surgical procedures is crucial for ensuring successful post surgical outcome. Furthermore, the proposed research may pave the way for more effective treatment of Alzheimer's disease in which spatial memory is impaired.