Memory consolidation during sleep studied by direct neuronal recording and stimulation inside human brain

通过人脑内的直接神经元记录和刺激研究睡眠期间的记忆巩固

• 批准号: 9791019
• 负责人: ITZHAK FRIED
• 金额: $ 89.55万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9791019
• 关键词: Acoustic Stimulation; Address; Animal Experimentation; Animals; Auditory; Back; Beds; Behavioral; Brain; Clinical; Cognitive; Coupling; Cues; Deep Brain Stimulation; Development; Discipline; Electric Stimulation; Electrical Stimulation of the Brain; Electrodes; Electroencephalography; Electrophysiology (science); Event; Foundations; Future; General Population; Goals; Hippocampus (Brain); Human; Infrastructure; Learning; Literature; Location; Measures; Medial; Memory; Memory Disorders; Memory impairment; Napping; Neocortex; Neurobiology; Neurology; Neurons; Neurophysiology - biologic function; Noise; Paired-Associate Learning; Patient Monitoring; Patients; Performance; Personal Satisfaction; Phase; Play; Positioning Attribute; Protocols documentation; Psychology; Quality of life; Research; Resolution; Rodent; Role; Sensory; Site; Sleep; Sleep disturbances; Slow-Wave Sleep; Specificity; Stimulus; System; Technology; Temporal Lobe; Testing; Time; Visual; Work; awake; base; cell assembly; clinical application; experience; human subject; improved; innovation; interdisciplinary collaboration; long term memory; memory consolidation; memory recall; multidisciplinary; neocortical; nervous system disorder; neural correlate; neurophysiology; neurosurgery; relating to nervous system; response; sleep behavior; sleep position; sleep spindle; sound

Project Summary/Abstract Memory is critical for cognitive well-being, and sleep is critical for memory consolidation, yet the underlying mechanisms in the human brain are poorly understood. Research on memory and sleep so far has suffered from a substantial gap between non-invasive cognitive research in humans and detailed electrophysiological research in animals. This proposal seeks a breakthrough by capitalizing on a highly unique opportunity to record and modulate activity of single neurons and neuronal assemblies in the human medial temporal lobe and neocortex during memory tasks and sleep. Recording from depth electrodes in neurosurgical patients, the study will investigate the role of information exchange between hippocampus and neocortex in memory consolidation. To bridge the gap between cognitive human research and mechanistic animal research, two essential approaches will be used. (a) Establish the neural correlates of sleep activities that predict successful memory, using paired-associate learning and object-location association tasks. The leading hypothesis is that coordinated coupling between neocortical slow waves, sleep spindles and hippocampal ripples, co-occurring with reactivation of neuronal ensembles that were selectively engaged in the learning task, will be maximally correlated with successful memory performance after sleep. (b) Test the causal role of these sleep events by modulating them via sensory or direct electrical brain stimulation. This causal approach will involve (1) Auditory Targeted Memory Reactivation. We will examine the neural and behavioral effects of repeating, during slow wave sleep, auditory cues that had been paired with selected stimuli during learning. A widely-held but untested hypothesis is that this will cause reactivation of the neuronal assemblies that encoded those memories. Our ability to record single neurons and hippocampal oscillatory activity during learning and sleep positions us uniquely to test this hypothesis. (2) Locking bursts of intracranial electrical brain stimulation or auditory stimulation to endogenous oscillations. We will achieve well-timed stimulation through the development of a closed-loop system that drives stimulation in the neocortex based on real-time sleep activity in the hippocampus. We will examine the effects of stimulation on memory and electrophysio- logical activity, such as slow waves and ripples. It is anticipated that about 25 patients with depth electrodes will be studied during the 2-year project. This exploratory study builds on the unique capabilities of our center at UCLA to stimulate and record in the human brain, not only intracranial EEG but also well-localized field potentials and single neurons whose response-specificity can be followed before, during, and after sleep. Assembling a group of experts from a wide array of disciplines—including neurobiology of sleep and memory in humans and rodents, neuroengineering, psychology, neurology, and neurosurgery—the proposed study will probe the underlying neuronal mechanisms of memory consolidation in sleep using correlative and causal measures, employing a systematic and reliable approach.

项目摘要/摘要 记忆对于认知福祉至关重要，睡眠对于记忆巩固至关重要，但是基础 人脑中的机制知之甚少。到目前为止的记忆和睡眠研究已经遭受 从人类的非侵入性认知研究与详细的电生理学之间的巨大差距 动物的研究。该建议通过利用一个高度独特的机会来寻求突破 记录和调节人媒体中单个神经元和神经元组件的活性 记忆任务和睡眠期间的叶和新皮层。从神经外科的深度电极记录 患者，该研究将研究海马和新皮层之间信息交流的作用 内存合并。为了弥合认知人类研究与机械动物研究之间的差距， 将使用两种基本方法。 （a）建立预测睡眠活动的神经回复 成功的内存，使用配对缔合学习和对象安装关联任务。领导 假设是新皮层慢波，睡眠纺锤体和海马之间的协同耦合 涟漪，与选择性参与学习的神经元集合的重新激活 任务将与睡眠后成功的内存性能最大关系。 （b）测试因果关系 这些睡眠事件是通过感觉或直接的电脑刺激来调节它们的。这个催化 方法将涉及（1）听觉靶向内存重新激活。我们将检查神经和行为 重复的效果，在慢波睡眠期间，在慢波睡眠中，与选定刺激配对的听觉提示 学习。广泛但未检验的假设是，这将导致神经元组件的重新激活 这编码了这些记忆。我们记录单个神经元和海马振荡活动的能力 学习和睡眠使我们独特地定位了这一假设。 （2）颅内电气的锁定爆发 内源振荡的脑刺激或听觉刺激。我们将实现及时的刺激 通过开发基于实时的新皮层刺激的闭环系统 海马中的睡眠活动。我们将检查刺激对记忆和电物体的影响 逻辑活动，例如慢波和波纹。预计大约有25例深度电子的患者 将在为期两年的项目中进行研究。这项探索性研究以我们中心的独特功能为基础 在加州大学洛杉矶分校，刺激和记录人脑，不仅是颅内脑电图，而且还稳定的场 可以在睡眠之前，期间和之后遵循反应特异性的电位和单个神经元。 组装一群来自各种学科的专家 - 包括睡眠和记忆的神经生物学 在人类和啮齿动物中，神经工程，心理学，神经病学和神经外科手术 - 拟议的研究将 探测使用相关和催化的睡眠中记忆巩固的基本神经元机制 采用系统可靠的方法。