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

• 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

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毁灭性的痛苦之一。 睡眠对于学习和记忆很重要，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，并整合到预先存在的长期记忆中。对于事实和事件的记忆（陈述性记忆）尤其如此，这取决于人类海马体内部和周围的大脑区域。有证据表明，海马体依赖的陈述性记忆在称为慢波睡眠的睡眠阶段得到巩固，其中大的慢波主导大脑活动。这种巩固被认为是由海马体和额叶皮层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进行临床监测的癫痫患者学习和记忆的影响。这种设置为从人脑内部（包括单个神经元水平）直接记录提供了难得的机会。该项目还提供了在睡眠期间刺激大脑的独特机会，这对于建立睡眠和巩固之间的因果关系是必要的。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，并通过在这个综合领域培训学生和开发新方法来造福社会。该结果可能对患有影响记忆的神经系统疾病的个体产生影响。结果将通过参加会议和研讨会以及媒体渠道和互联网广泛传播。拟议的研究研究了睡眠在记忆巩固中所起的因果作用，并基于直接记录和刺激从人脑到单个神经元水平的神经元活动的机会。经知情同意后，加州大学洛杉矶分校植入颅内深度电极的癫痫患者将在睡眠期间参与结合录音和颅内电刺激的学习/记忆范例。研究人员打算通过让参与者在睡前执行学习任务、记录和操纵睡眠期间的大脑活动以及评估睡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针对癫痫患者（PI：Itzhak Fried）进行，同时与以色列 Yuval Nir ​​博士的实验室（与健康志愿者）合作进行。该研究将开发和验证可靠且敏感的范式，这些范式对睡眠（特别是短睡）对记忆表现可变的个体的陈述性记忆的有益影响敏感。该研究的重点是涉及物体位置关联以及物体和人物图像之间的配对关联的学习任务。其次，研究小组将确定与不睡眠条件相比，哪些睡眠活动与学习和记忆的改善最相关。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会促进记忆巩固。一个关键的预测是，睡眠与这种实时闭环刺激相结合将比不受干扰的睡眠更大程度地提高记忆能力。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力优点和能力进行评估，被认为值得支持。更广泛的影响审查标准。

项目成果

Modulation of Human Memory by Deep Brain Stimulation of the Entorhinal-Hippocampal Circuitry

内嗅-海马回路的深部脑刺激对人类记忆的调节

• DOI: 10.1016/j.neuron.2020.02.024
• 发表时间: 2020-04
• 期刊: Neuron
• 影响因子: 16.2
• 作者: Mankin, Emily A.;Fried, Itzhak
• 通讯作者: Fried, Itzhak

Local Sleep Oscillations: Implications for Memory Consolidation

局部睡眠振荡：对记忆巩固的影响

• DOI: 10.3389/fnins.2019.00813
• 发表时间: 2019-08
• 期刊: Frontiers in Neuroscience
• 影响因子: 4.3
• 作者: Geva;Nir, Yuval
• 通讯作者: Nir, Yuval

Reduced neural feedback signaling despite robust neuron and gamma auditory responses during human sleep

尽管人类睡眠期间神经元和伽玛听觉反应强劲，但神经反馈信号减少

• DOI: 10.1038/s41593-022-01107-4
• 发表时间: 2022-07
• 期刊: Nature Neuroscience
• 影响因子: 25
• 作者: Hayat, Hanna;Marmelshtein, Amit;Krom, Aaron J.;Sela, Yaniv;Tankus, Ariel;Strauss, Ido;Fahoum, Firas;Fried, Itzhak;Nir, Yuval
• 通讯作者: Nir, Yuval

Stimulation of the right entorhinal white matter enhances visual memory encoding in humans

刺激右侧内嗅白质增强人类视觉记忆编码

• DOI: 10.1016/j.brs.2020.11.015
• 发表时间: 2021-01
• 期刊: Brain Stimulation
• 影响因子: 7.7
• 作者: Mankin EA;Aghajan ZM;Schuette P;Tran ME;Tchemodanov N;Titiz A;Kalender G;Eliashiv D;Stern J;Weiss SA;Kirsch D;Knowlton B;Fried I;Suthana N
• 通讯作者: Suthana N