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NSF/SBE-BSF: The role of sleep in memory consolidation: intracranial human electrophysiology and electrical stimulation

NSF/SBE-BSF：睡眠在记忆巩固中的作用：颅内人体电生理学和电刺激

基本信息

批准号：
1756473
负责人：
Itzhak Fried
金额：
$ 55万
依托单位：
University of California-Los Angeles
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-15 至 2022-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1756473&HistoricalAwards=false
关键词：
NSF SBE BSF role sleep

项目摘要

Memory loss is one of the most devastating afflictions of the human condition. Sleep is important for learning and memory because it improves memory consolidation - the transformation of new memories that are formed during wakefulness into stable memories that are integrated into pre-existing long-term memories. This is particularly true for memory for facts and events (declarative memory), which depends on brain regions in and around the human hippocampus. There is evidence that declarative hippocampus-dependent memories are consolidated during a sleep-stage called slow-wave-sleep, where large slow waves dominate brain activity. This consolidation is thought to be mediated by interactions between the hippocampus and brain areas in the frontal cortex. In this project, the researchers aim to study the effects of sleep on learning and memory in epilepsy patients implanted with depth electrodes for clinical monitoring. This setting provides a rare opportunity for direct recordings from inside the human brain, including at the level of individual neurons. The project also affords a unique opportunity to stimulate the brain during sleep, which is necessary for establishing a causal relationship between sleep and consolidation. This research will advance scientific knowledge on how specific sleep processes aid memory consolidation, and benefit society by training students in this integrative field, and developing new methods. The results may have implications for individuals suffering from neurological disorders affecting memory. Results will be disseminated broadly through participation in conferences and workshops, as well as media channels and the internet. The proposed research studies the causal role that sleep plays in memory consolidation, and is based on a an opportunity to record and stimulate neuronal activity directly from the human brain down to the level of single neurons. Upon informed consent, epilepsy patients at UCLA implanted with intracranial depth electrodes will participate in learning/memory paradigms combined with recordings and intracranial electrical stimulation during sleep. The researchers intend to advance beyond the state-of-the-art by having participants perform a learning task before sleep, record and manipulate brain activity during sleep, and evaluate subsequent memory after sleep. First, they will validate the behavioral benefits of sleep on memory consolidation. This study will be performed at UCLA with epilepsy patients (PI: Itzhak Fried), and in parallel in collaboration with Dr. Yuval Nir's lab in Israel (with healthy volunteers). The study will develop and validate paradigms that are reliable and sensitive to the beneficial effects of sleep, and short naps in particular, on declarative memory among individuals with variable memory performance. The study focuses on a learning task involving object-position associations, as well as paired associations between object and person images. Second, the research team will determine which sleep activities correlate best with learning and memory improvements as compared to no-sleep conditions. Finally, the team will evaluate causal mechanisms through intracranial stimulation to determine whether stimulation locked to endogenous slow oscillations promotes memory consolidation. A key prediction is that sleep in conjunction with such real-time closed-loop stimulation will benefit memory performance to a greater extent than undisturbed sleep.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

记忆丧失是人类最具破坏性的痛苦之一。睡眠对学习和记忆很重要，因为它可以改善记忆巩固--将清醒时形成的新记忆转化为稳定的记忆，并整合到先前存在的长期记忆中。对于事实和事件的记忆（陈述性记忆）来说尤其如此，这取决于人类海马体及其周围的大脑区域。有证据表明，陈述性的校园依赖记忆是在一个被称为慢波睡眠的睡眠阶段巩固的，在这个阶段，大的慢波主导着大脑活动。这种巩固被认为是由海马体和额叶皮质中的大脑区域之间的相互作用介导的。在这个项目中，研究人员旨在研究睡眠对植入深度电极用于临床监测的癫痫患者学习和记忆的影响。这种设置提供了一个难得的机会，从人脑内部直接记录，包括在单个神经元的水平。该项目还提供了一个独特的机会，在睡眠期间刺激大脑，这是建立睡眠和巩固之间的因果关系所必需的。这项研究将推进关于特定睡眠过程如何帮助记忆巩固的科学知识，并通过在这一综合领域培训学生和开发新方法来造福社会。这些结果可能对患有影响记忆的神经系统疾病的人有影响。将通过参加会议和讲习班以及媒体渠道和互联网广泛传播成果。这项拟议中的研究研究了睡眠在记忆巩固中的因果作用，并基于直接从人脑记录和刺激神经元活动到单个神经元水平的机会。获得知情同意后，在UCLA植入颅内深部电极的癫痫患者将参与学习/记忆模式，并在睡眠期间进行记录和颅内电刺激。研究人员打算通过让参与者在睡眠前执行学习任务，记录和操纵睡眠期间的大脑活动，并评估睡眠后的后续记忆来超越最先进的水平。首先，他们将验证睡眠对记忆巩固的行为益处。这项研究将在加州大学洛杉矶分校的癫痫患者（PI：Itzhak Fried）中进行，并与以色列Yuval Nir博士的实验室（健康志愿者）合作进行。这项研究将开发和验证范式，这些范式对睡眠的有益影响是可靠和敏感的，特别是短暂的小睡，对具有可变记忆表现的个体的陈述性记忆的影响。本研究的重点是一个学习任务，涉及对象的位置协会，以及配对的对象和人的形象之间的关联。其次，研究小组将确定与无睡眠条件相比，哪些睡眠活动与学习和记忆改善最相关。最后，研究小组将通过颅内刺激评估因果机制，以确定锁定内源性慢振荡的刺激是否促进记忆巩固。一个关键的预测是，与这种实时闭环刺激相结合的睡眠将比不受干扰的睡眠更有利于记忆性能。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。