CAREER: Characterizing mechanisms of navigation and memory using direct human brain recording and stimulation

这个项目的目标是解释人脑是如何支持空间导航和记忆的。为了研究这个问题，我们将直接记录受试者在执行空间导航和记忆任务时的大脑活动。我们将通过让人们在笔记本电脑上使用虚拟现实执行几种不同类型的导航范式来测量大脑如何支持空间记忆的不同方面。我们的参与者是神经外科患者，他们通过手术植入电极作为治疗癫痫的一部分。这些患者自愿参与我们的实验，从而为行为的神经基础提供了罕见的直接人脑数据。我们将分析大脑活动的模式，以了解空间和记忆信息是如何在整个大脑中表现出来的，包括个体区域的局部神经信号以及大脑结构之间的相互作用。此外，除了记录大脑活动外，我们还将在这些任务的某些部分对大脑应用有针对性（和安全）的电刺激模式，使我们能够测试当选定的大脑区域受到刺激时，行为是如何变化的。我们的研究结果将帮助我们了解支持空间导航的基本大脑信号类型，并比较这些信号在大脑结构中的差异。该项目也有一个实质性的教育组成部分，发展教育和推广计划，以推进K-12和大学水平的神经科学教育和研究。我们将在纽约市的学校开设有关导航和记忆神经科学的新课程。为了支持这种拓展，我们将开发新颖而引人入胜的增强现实空间导航协议，使学生能够在日常生活中学习空间记忆。本项目旨在描述人类大脑空间导航和记忆的不同神经机制，重点研究内侧颞叶（MTL）。我们通过四个关键要素来实现这一目标：来自神经外科患者的直接大脑记录，使用虚拟现实定制设计的空间记忆任务，用于分析与空间行为相关的局部和分布式神经信号的新型计算方法，以及用于测试这些信号因果关系的直接脑刺激。我们的研究对象是神经外科患者，他们将执行定制的空间记忆任务，旨在区分不同尺度的空间记忆和非空间记忆对应的神经信号。我们的数据分析将识别出MTL中特定记忆过程的大脑活动模式，以及使用单个神经元峰值和网络振荡的各种大脑区域。所有的实验设计都基于我们的初步数据，在这些数据中，我们表明，不同半球对空间和非空间记忆任务的神经反应本质上是不同的，右MTL支持导航，左MTL支持记忆。此外，为了确定信息是如何在这个网络中传播的，我们将描述我们最近发现的一种新现象——皮层行波的功能作用，在这种现象中，振荡在大脑中传播，以协调区域间的交流。最后，我们将使用电刺激来验证我们的发现。通过结合这些方法的数据，我们将全面了解空间记忆如何在不同的大脑区域中表现出来，并区分信息传播以支持空间记忆和导航的大规模大脑网络。这些实验的结果有可能评估一个关键的理论问题，即内侧颞叶中的单个电生理过程是否支持空间记忆和情景记忆，或者，MTL中单独的神经过程和子区域是否支持多尺度导航和记忆行为的不同方面。这种涉及直接人脑记录和刺激的方法有资格解决这个问题，因为我们将获得的数据克服了动物电生理学和无创神经成像的局限性。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The goal of this project is to explain how the human brain supports spatial navigation and memory. To examine this issue, we will directly record brain activity from subjects performing spatial navigation and memory tasks. We will measure how the brain supports different aspects of spatial memory by having people perform several different types of navigation paradigms using virtual reality on a laptop computer. Our participants are neurosurgical patients who have electrodes surgically implanted as part of treatment for their epilepsy. These patients volunteer to participate in our experiments, thus providing rare direct human brain data on the neural basis of behavior. We will analyze the patterns of brain activity to understand how spatial and memory information is represented across the brain, including both local neural signals in individual regions as well as interactions between brain structures. Further, in addition to recording brain activity, we will also apply targeted (and safe) patterns of electrical stimulation to brains during certain parts of these tasks, allowing us to test how behavior varies when selected brain regions are stimulated. The findings from our research will help us to understand fundamental types of brain signals that support spatial navigation and to compare how these signals differ across brain structures. This project also has a substantial educational component with the development of educational and outreach programs to advance neuroscience education and research at both the K-12 and University levels. We will deploy new curricula on the neuroscience of navigation and memory at New York City schools. To support this outreach, we will develop novel and engaging augmented reality spatial navigation protocols, enabling the students to study spatial memory in their everyday life.This project aims to characterize the distinct neural mechanisms underlying spatial navigation and memory in the human brain, with emphasis on the medial temporal lobe (MTL). We approach this goal with four key elements: direct brain recordings from neurosurgical patients, custom-designed spatial memory tasks using virtual reality, novel computational methods for analyzing local and distributed neural signals related to spatial behavior, and direct brain stimulation for testing the causality of these signals. The subjects in our study are neurosurgical patients who will perform customized spatial memory tasks that are designed to distinguish neural signals corresponding to spatial and non-spatial memory at different scales. Our data analyses will identify patterns of brain activity underlying specific memory processes in the MTL as well as various brain regions using both single-neuron spiking and network oscillations. All experimental designs are grounded in our preliminary data, in which we show that the nature of neural responses to spatial vs. non-spatial memory tasks varies fundamentally across hemisphere, with the right MTL supporting navigation and left MTL supporting memory. Furthermore, to identify how information propagates across this network, we will characterize the functional role of a new phenomenon we recently identified, cortical traveling waves, in which oscillations propagate across the brain to coordinate inter-region communication. Finally, we will use electrical stimulation to causally validate our findings. By combining data across these methods, we will obtain a comprehensive view of how spatial memories are represented in various brain areas and distinguish the large-scale brain networks where information propagates to support spatial memory and navigation. The results of these experiments have the potential for evaluating the key theoretical question of whether a single electrophysiological process in the medial temporal lobe supports both spatial and episodic memory or, alternatively, whether separate neural processes and sub-regions in the MTL support distinct aspects of multi-scale navigation and memory behaviors. THis approach involving direct human brain recordings and stimulation is qualified to address this question because the data we will acquire overcomes limitations of both animal electrophysiology and noninvasive neuroimaging.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.