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，经历了长期的发育成熟和年龄相关的衰退， 并且在许多神经和神经精神障碍中被破坏。尽管记忆的核心作用， 健康和疾病，对支持人类记忆的神经机制知之甚少。在 在这个K99/R 00项目中，我建议将来自神经外科患者的联合收割机罕见颅内记录与先进的 电生理学数据分析，以真实的时间跟踪记忆的形成和维持，并预测行为 儿童、青少年和成人。有了这些时空上精确的记忆形成测量， 维持，这项研究将解决有关这一核心神经认知功能的知识的关键差距。 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EEG指标。 内侧颞叶、前额叶皮层和记忆之间的因果关系已经得到了很好的证实。然而，在这方面， 关于内侧颞叶和前额叶相互作用的机制， 人类的记忆这项研究将确定动态的、多层次的神经回路机制 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，基本上未探索的方向。目标1（K99阶段）将映射记忆形成的预测因子， 使用同步记录从单个神经元水平到大规模神经回路水平的维护 从成年人的内侧颞叶和前额叶区域获得。目标2（R 00阶段）将定义 使用获得的颅内记录， 从儿童、青少年和成人的内侧颞叶和前额叶区域。总体假设是 内侧颞叶、前额叶和内侧颞叶-前额叶回路中的亚秒级相互作用将预测 个人记忆的形成这些目标的实现将产生新的机制解释人类 从童年到成年的记忆形成。这项研究与第六和第七项优先事项直接相关。 大脑2025报告，并将准备一个成功的独立研究生涯的主要研究者。 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，以提高她成为独立调查员的轨迹：（1） 单单位神经元数据的分析;（2）多元统计在时间序列数据中的应用;（2）伦理 在临床患者中进行科学研究的各个方面;（4）研究、指导和管理 成功运营实验室所必需的技能。培训将通过以下方式完成： 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， 负责任的研究行为，并为未来的教师职位做准备。

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.