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: 9790983
• 负责人: ITZHAK FRIED
• 金额: $ 60.2万
• 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/9790983
• 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 丧失形成新记忆和找回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 它是影响美国数百万人的阿尔茨海默病(AD)的首批特征之一， 全球范围内还有更多。几十年的研究已经确立了陈述性记忆，即记忆的能力 最近经历的事实和事件，取决于内侧的海马体和相关结构 颞叶(MTL)，包括内嗅皮层。我们的实验室在单个神经元方面一直处于领先地位 人类MTL的生理学研究已有二十年，并且是第一个利用深部大脑发表研究结果的研究小组 刺激(DBS)人类内嗅觉-海马体回路以调节人类记忆。我们的方法 基于记录单个神经元、神经元组件和局部场活动的独特机会 在神经外科患者中应用神经回路的脑深部刺激。这些 顽固性癫痫患者是否植入了颅内深部电极，以确定他们的 癫痫的焦点是可能的手术治疗。我们的初步发现显示，当空间记忆显著增强时 在学习过程中，DBS被应用于内嗅区[1]。在这个项目的最初资助期，我们建立在 这一成功是通过在广泛的海马体依赖记忆任务中测试DBS并展示 预测刺激是否会改善记忆的关键因素是大脑中 刺激电极至内嗅区白质(角束)。在续期拨款中，我们将 通过使用微刺激来进一步完善我们对内嗅觉-海马体回路的调制 准确识别应用的DBS的空间和时间特征，从而增强记忆。穿过 同时进行微刺激和录音，该项目将阐明单个 神经元反应，LFP振荡，以及作为记忆增强基础的DBS。首要目标 将把对星展银行的调查从编码扩展到整合的关键记忆阶段和 提取，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，这为潜在的临床干预提供了一个耐人寻味和可行的时间窗口。一位批评者 我们调制的组成部分将涉及使用新的闭环技术来提供刺激 与已被证明对编码至关重要的内生振荡在时间上协调， 恢复，并在睡眠期间进行巩固。该项目旨在发展对这些机制的批判性见解 在人类中通过闭环式DBS增强人类记忆，因此可能有助于 对人类记忆障碍的新治疗方法的开发具有重要意义。