Measuring Electrical Activity from the Human Brain to Predict Memory Formation and Behavior Across the Lifespan

项目概要/摘要 记忆是人类认知的核心，经历长期的发育成熟和与年龄相关的衰退， 并在许多神经系统和神经精神疾病中受到干扰。尽管记忆在其中起着核心作用 健康和疾病方面，人们对支持人类记忆的神经机制知之甚少。在 在这个 K99/R00 项目中，我建议将神经外科患者的罕见颅内记录与先进的记录结合起来 电生理数据分析，实时跟踪记忆形成和维持，并预测行为 儿童、青少年和成人。通过这些时空精确测量记忆形成和 维护，这项研究将解决有关这一核心神经认知功能的知识中的关键差距。 颅内记录和头皮脑电图 (EEG) 测量之间的比较分析将 进一步确定适用于发育、寿命和疾病相关研究的非侵入性脑电图指标。 内侧颞叶、前额叶皮层和记忆之间的因果关系是明确的。然而， 关于内侧颞叶和前额叶区域相互作用以支持的机制的数据很少 人类的记忆。拟议的研究将确定动态、多级神经回路机制 预测人类一生中记忆的形成。该研究计划将遵循两个 互补的、很大程度上尚未探索的方向。目标 1（K99 阶段）将映射记忆形成的预测因素和 使用同步记录进行从单个神经元水平到大规模神经回路水平的维护 从成人内侧颞叶和前额叶区域获得。目标 2（R00 阶段）将定义 使用获得的颅内记录对整个生命周期记忆成功的电生理学预测 来自儿童、青少年和成人的颞内侧和前额叶区域。总体假设是 内侧颞叶、前额叶和内侧颞前额叶回路中的亚秒级相互作用将预测 个体记忆的形成。完成这些目标将为人类产生新颖的机械解释 从童年到成年的记忆形成。这项研究与优先事项 6 和 7 直接相关 BRAIN 2025 报告并将帮助首席研究员为成功的独立研究生涯做好准备。 为了实现这些目标，拟议的职业发展计划将建立在首席研究员的 之前的培训有四个目标，以增强她成为独立调查员的轨迹：(1) 单单元神经元数据分析； (2)多元统计在时间序列数据中的应用； (2)道德 对临床患者进行科学研究的方面； (4) 研究、指导和行政 成功运营实验室所需的技能。培训将通过直接的平衡来完成 来自动物和人类神经生理学家的指导以及神经生理学、统计学、 负责任地进行研究，并为未来的教职做好准备。

PROJECT SUMMARY/ABSTRACT Memory is core to human cognition, undergoes protracted developmental maturation and age-related decline, and is disrupted in numerous neurological and neuropsychiatric disorders. Despite the central role of memory in health and disease, remarkably little is known about the neural mechanisms supporting memory in humans. In this K99/R00 project, I propose to combine rare intracranial recordings from neurosurgical patients and advanced electrophysiological data analysis to track memory formation and maintenance in real time, and predict behavior in children, adolescents, and adults. With these spatiotemporally precise measures of memory formation and maintenance, this research will address critical gaps in knowledge about this core neurocognitive function. Comparative analysis between intracranial recordings and scalp electroencephalography (EEG) measures will further identify non-invasive EEG metrics applicable to developmental, lifespan, and disease-related research. Causal links between the medial temporal lobe, prefrontal cortex, and memory are well-established. However, there is a paucity of data on the mechanisms by which medial temporal and prefrontal regions interact to support memory in humans. The proposed research will determine the dynamic, multi-level neural circuit mechanisms that predict memory formation in humans across the lifespan. This research program will follow two complementary, largely unexplored directions. Aim 1 (K99 phase) will map predictors of memory formation and maintenance from the level of single neurons to that of large-scale neural circuits using simultaneous recordings obtained from medial temporal and prefrontal regions in adults. Aim 2 (R00 phase) will define electrophysiological predictors of memory success across the lifespan using intracranial recordings obtained from medial temporal and prefrontal regions in children, adolescents, and adults. The overarching hypothesis is that sub-second interactions in medial temporal, prefrontal, and medial temporal-prefrontal circuits will predict individual memory formation. Completion of these Aims will generate novel mechanistic explanations of human memory formation from childhood into adulthood. This research is directly relevant to Priorities #6 and #7 of the BRAIN 2025 Report and will prepare the Principal Investigator for a successful independent research career. To achieve these Aims, the proposed career development plan will build upon the Principal Investigator’s previous training with four goals to enhance her trajectory toward becoming an independent investigator: (1) analysis of single-unit neuronal data; (2) application of multivariate statistics to time-series data; (2) ethical aspects of conducting scientific research in clinical patients; and (4) research, mentoring, and administrative skills requisite to run a successful laboratory. Training will be accomplished through a balance of direct mentorship from animal and human neurophysiologists and coursework in neurophysiology, statistics, responsible conduct of research, and preparing for a future faculty position.