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.

项目摘要/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感情之一 健康）状况。它存在于各种神经系统疾病中，包括临时叶癫痫，创伤性大脑 受伤，是影响美国数百万人的阿尔茨海默氏病（AD）的第一个特征之一 全球更多。数十年的研究已经确定了声明性记忆，记住的能力 最近经历了事实和事件，取决于海马和相关结构 临时叶（MTL），包括内嗅皮层。我们的实验室一直是单个神经元的领导者 过去二十年的人类MTL的生理学，是第一个使用深脑发布发现的组 人类内部海马电路的刺激（DB）调节人类记忆。我们的方法 基于记录单个神经元，神经元组件和局部领域活动的独特机会 电位（LFP），以及在神经外科患者中对神经元电路的深度刺激。这些 患有顽固性癫痫的患者植入了颅内深度电极以识别其 癫痫发作的焦点以进行手术治疗。我们的初始发现显示了戏剧性的空间内存增强 在学习过程中，将DBS应用于内嗅区域[1]。在这个项目的最初资助期间，我们建立了 通过在海马依赖性内存任务中测试DBS的成功，并证明 刺激是否会改善记忆的关键预测指标是确切的空间靶向 刺激到内嗅区域的白色物质（角束）的电极。在更新的赠款中，我们将 通过使用微刺激到更多的更多 精确地识别应用DBS的空间和临时特征，从而导致增强的内存。通过 该项目同时进行了微刺激和记录，将阐明单一的复杂关系 基于记忆增强的基础的神经元反应，LFP振荡和DB。主要目标 将是将DB的投资从编码扩展到合并和 检索，跨三个内存任务。重要的是，我们将探测DBS对合并的影响 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。批判 调制的组成部分将涉及使用新型闭环技术提供模拟 与内源性振荡及时协调，这对编码至关重要 检索，并在睡眠期间进行巩固。该项目旨在发展对机制的关键见解 人类记忆及其通过人类的闭环DB的增强，因此可能有助于 重要的是开发新的治疗方法来解决人类记忆障碍。