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.

项目总结/摘要 丧失形成新记忆和恢复旧记忆的能力是人类最可怕的痛苦之一 条件它存在于各种神经系统疾病中，包括颞叶癫痫，创伤性脑 损伤，并且是影响美国数百万人的阿尔茨海默病（AD）的首要特征之一， 更多的世界各地。几十年的研究已经证实，陈述性记忆， 最近经历的事实和事件，取决于海马和相关的结构，在内侧 颞叶（MTL），包括内嗅皮层。我们的实验室在单神经元研究方面处于领先地位 在过去的二十年里，他一直致力于人类MTL的生理学研究，并且是第一个发表使用深部脑的研究结果的小组。 刺激（DBS）人的内鼻-海马电路以调节人的记忆。我们的方法 基于记录单个神经元、神经元集合和局部场的活动的独特机会 电位（LFP），以及在神经外科患者中应用神经回路的深部脑刺激。这些 难治性癫痫患者植入颅内深部电极，以确定其 可能手术治愈癫痫病灶。我们最初的发现显示，当我们的大脑中有一个 DBS在学习期间应用于内嗅区[1]。在这个项目的最初资助期间，我们建立在 这一成功是通过测试DBS在各种各样的大脑活动相关的记忆任务，并证明 刺激是否会改善记忆的关键预测因素是精确的空间靶向。 刺激电极到内嗅区的白色物质（角束）。在新的补助金中，我们将 通过使用微刺激进一步完善我们对内鼻-海马电路的调制， 精确地识别导致增强记忆的应用DBS的空间和时间特征。通过 同时微刺激和记录，该项目将阐明单 神经元反应、LFP振荡和作为记忆增强基础的DBS。一个主要目标 将DBS的研究从编码扩展到巩固的关键记忆阶段， 检索，在三个记忆任务。重要的是，我们将探讨DBS对整合的影响， 睡眠为潜在的临床干预提供了一个有趣和可行的时间窗口。一个关键 我们调制的一个组成部分将涉及使用新的闭环技术来提供刺激 在时间上与已被证明对编码至关重要的内源性振荡协调， 在睡眠中进行巩固。该项目旨在对这些机制提出重要见解， 人类记忆及其通过人类闭环DBS的增强，因此可能有助于 这对开发人类记忆障碍的新治疗方法具有重要意义。