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

项目摘要/摘要 记忆对认知健康至关重要，睡眠对记忆巩固至关重要，但潜在的 人们对人脑的机制知之甚少。到目前为止，关于记忆和睡眠的研究受到了影响 从人类非侵入性认知研究和详细的电生理之间的巨大差距 在动物身上进行研究。这项提议寻求突破，利用一个非常独特的机会 记录和调节人内侧颞叶单个神经元和神经元组件的活动 在记忆任务和睡眠过程中的脑叶和新皮质。神经外科中的深度电极记录 患者，这项研究将调查海马体和新皮质之间的信息交换在 记忆巩固。为了弥合认知人类研究和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关联 成功记忆，使用配对联想学习和物体位置关联任务。领先者 假说是新皮质慢波、睡眠纺锤体和海马区之间的协调耦合 涟漪，与选择性地参与学习的神经元集合的重新激活共同出现 任务，将最大限度地与睡眠后的成功记忆性能相关。(B)检验下列因素的因果作用 这些睡眠事件通过感觉或直接电刺激大脑来调节它们。这个因果关系 该方法将涉及(1)听觉靶向记忆重新激活。我们将检查神经和行为 在慢波睡眠期间，重复与所选刺激配对的听觉提示的效果 学习。一个被广泛接受但未经检验的假说是，这将导致神经元组件重新激活。 对这些记忆进行了编码。我们记录单个神经元和海马区振荡活动的能力 学习和睡眠为我们检验这一假设提供了独特的条件。(2)颅内电信号的闭锁爆发 脑刺激或听觉刺激对内源性振荡的影响。我们将实现适时的刺激 通过开发一个闭环系统来驱动基于实时的大脑皮层刺激 海马体的睡眠活动。我们将研究刺激对记忆和电生理的影响。 有逻辑的活动，如慢波和涟漪。预计约有25名患者使用深度电极 将在为期两年的项目中进行研究。这项探索性研究建立在我们中心独特的能力基础上 在加州大学洛杉矶分校刺激和记录在人脑中，不仅是颅内脑电，而且是良好的局域场 电位和单个神经元，其反应特异性可在睡眠前、睡眠中和睡眠后追踪。 汇集了一组来自多个学科的专家--包括睡眠和记忆的神经生物学 在人类和啮齿动物中，神经工程学、心理学、神经学和神经外科--拟议的研究将 用相关性和因果关系探讨睡眠中记忆巩固的潜在神经机制 措施，采用系统和可靠的方法。

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.