Mechanisms of Memory Enhancement by Deep Brain Stimulation in Humans

深部脑刺激增强人类记忆的机制

• 批准号: 10242009
• 负责人: ITZHAK FRIED
• 金额: $ 58.93万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10242009
• 关键词: Affect; Alzheimer' s Disease; Brain; Characteristics; Clinical; Cognitive; Complex; Conflict (Psychology); Coupled; Deep Brain Stimulation; Development; Electric Stimulation; Electrodes; Epilepsy; Episodic memory; Event; Face; Funding; Grant; Hippocampus (Brain); Human; Image; Imaging technology; Implant; Implanted Electrodes; Intervention; Intractable Epilepsy; Investigation; Laboratories; Lead; Learning; Measures; Medial; Memory; Memory Disorders; Memory Loss; Microelectrodes; Neurons; Operative Surgical Procedures; Organ; Paired-Associate Learning; Patients; Perforant Pathway; Performance; Persons; Pharmaceutical Preparations; Pharmacology; Phase; Physiological; Physiology; Process; Protocols documentation; Publishing; Reporting; Research; Resolution; Retrieval; Seizures; Sleep; Slow-Wave Sleep; Specificity; Stroke; Structure; System; Technology; Temporal Lobe; Temporal Lobe Epilepsy; Testing; Therapeutic; Theta Rhythm; Time; Traumatic Brain Injury; Work; aging population; awake; base; entorhinal cortex; experience; improved; insight; long term memory; memory consolidation; memory encoding; memory process; microstimulation; nervous system disorder; neural circuit; neuromechanism; non rapid eye movement; novel; novel therapeutic intervention; relating to nervous system; response; spatial memory; spatiotemporal; success; therapy development; white matter

Project Summary/Abstract Loss of the ability to form new memories and retrieve old ones is one of the most dreaded afflictions of the human condition. It is present in various neurological disorders, including temporal lobe epilepsy, traumatic brain injury and is one of the first features of Alzheimer’s Disease (AD) affecting millions of people in the US and many more worldwide. Decades of research have established that declarative memory, the ability to remember recently experienced facts and events, depends on the hippocampus and associated structures in the medial temporal lobe (MTL), including the entorhinal cortex. Our laboratory has been a leader in single neuron physiology of the human MTL for last two decades and was the first group to publish findings using deep brain stimulation (DBS) of the entorhinal-hippocampal circuitry in humans to modulate human memory. Our approach is based on the unique opportunity to record activity of single neurons, neuronal assemblies and local field potentials (LFPs), as well as to apply deep brain stimulation of neural circuits in neurosurgical patients. These are patients with intractable epilepsy who have intracranial depth electrodes implanted in order to identify their seizure focus for possible surgical cure. Our initial findings showed dramatic spatial memory enhancement when DBS was applied to the entorhinal area during learning [1]. In the initial funding period of this project, we built on this success by testing DBS across a wide variety of hippocampal-dependent memory tasks and demonstrating that the critical predictor of whether stimulation would improve memory was the precise spatial targeting of the stimulating electrode to the white matter of the entorhinal area (angular bundle). In the renewed grant, we will further refine our modulation of the entorhinal–hippocampal circuitry by using microstimulation to more precisely identify the spatial and temporal features of applied DBS that lead to enhanced memory. Through simultaneous microstimulation and recording, the project will elucidate the complex relationship between single neuronal responses, LFP oscillations, and DBS that underlies memory enhancement. A primary objective will be to expand the investigation of DBS from encoding to the critical memory phases of consolidation and retrieval, across three memory tasks. Importantly, we will probe the effects of DBS on consolidation during sleep which provides an intriguing and feasible time window for potential clinical intervention. A critical component of our modulation will involve the use of novel closed-loop technology to provide stimulation coordinated in time with endogenous oscillations that have been shown to be critically important for encoding, retrieval, and for consolidation during sleep. The project aims at developing critical insights into the mechanisms of human memory and its enhancement through closed-loop DBS in humans, and thus may contribute significantly to the development of novel therapeutic approaches to human memory disorders.

项目概要/摘要 失去形成新记忆和检索旧记忆的能力是人类最可怕的痛苦之一 健康）状况。它存在于各种神经系统疾病中，包括颞叶癫痫、脑外伤 损伤，是影响美国数百万人的阿尔茨海默病 (AD) 的首要特征之一 全球还有更多。数十年的研究已经证实陈述性记忆，即记忆的能力 最近经历的事实和事件，取决于海马体和内侧的相关结构 颞叶（MTL），包括内嗅皮层。我们实验室在单神经元研究方面一直处于领先地位 过去二十年来对人类 MTL 生理学的研究，是第一个利用深部大脑发表研究结果的小组 刺激人类内嗅海马回路以调节人类记忆。我们的方法 基于记录单个神经元、神经元集合和局部场活动的独特机会 电位（LFP），以及对神经外科患者的神经回路进行深部脑刺激。这些 是患有顽固性癫痫的患者，为了识别他们的情况而植入了颅内深度电极 癫痫焦点以进行可能的手术治愈。我们的初步发现表明，当 DBS 在学习期间应用于内嗅区域 [1]。在该项目的初始资助期间，我们建立在 通过在各种海马依赖性记忆任务中测试 DBS 并展示这一成功 刺激是否会改善记忆的关键预测因素是刺激的精确空间定位 刺激内嗅区白质（角束）的电极。在更新的赠款中，我们将 通过使用微刺激来进一步完善我们对内嗅-海马回路的调节 精确识别应用 DBS 的空间和时间特征，从而增强记忆力。通过 同时进行微刺激和记录，该项目将阐明单个个体之间的复杂关系 神经元反应、LFP 振荡和 DBS 是记忆增强的基础。主要目标 将把 DBS 的研究范围从编码扩展到整合的关键记忆阶段 检索，跨越三个记忆任务。重要的是，我们将探讨星展银行对整合的影响 睡眠为潜在的临床干预提供了一个有趣且可行的时间窗口。一个批评的 我们的调制部分将涉及使用新颖的闭环技术来提供刺激 与内源性振荡及时协调，这已被证明对编码至关重要， 检索，并在睡眠期间进行巩固。该项目旨在发展对机制的批判性见解 人类记忆及其通过人类闭环 DBS 的增强，因此可能有助于 对人类记忆障碍新治疗方法的开发具有重要意义。