The role of hippocampal processing and slow-wave activity in memory consolidation

 描述(申请人提供)：睡眠在长期记忆巩固中起着关键作用，也就是随着时间的推移最近记忆的稳定性。在人类中，非快速眼动(NREM)睡眠与清醒时间相比，与增强记忆保持和稳定跨海马区-皮质网络的记忆表征有关。编码后睡眠中的特定生理机制被认为支持这种记忆稳定：在NREM睡眠期间协调和同步大规模神经活动的慢波活动或慢振荡，以及在广泛的海马-皮质网络相互作用期间代表先前经验的海马体活动模式的重新激活(重新激活)。慢波在人类记忆保持中的作用已经被证明，在啮齿类动物的NREM睡眠中，与记忆相关的海马体重新激活和相关的海马网相互作用也被证明是强有力的证据。然而，从先前的工作中尚不清楚1)：哪些大脑区域对于产生支持成功的NREM记忆巩固的慢波是至关重要的，先前的工作表明慢波密度和起源优于内侧前额叶皮质(MPFC)；2)：海马重新激活和大规模网络相互作用的机制是否支持人类NREM记忆巩固，因为以前的工作几乎没有测试证据表明海马重新激活和相关的人类大脑网络相互作用。通过将TMS与对NREM大脑活动的高密度EEG和EEG-fMRI测量相结合，这项建议试图通过以下方式弥补这些差距：1)测试mPFC完整性对慢波活动生成和相关的NREM睡眠记忆巩固的因果贡献；2)测试海马区依赖学习是否能为随后的NREM睡眠期间海马区重新激活和大规模网络互动提供强有力的证据，以及NREM海马区活动测量是否从功能上预测记忆巩固成功(跨海马区-皮质网络的记忆保持和神经稳定)。总而言之，这项工作旨在研究对人类睡眠期间长期记忆保持起关键作用的潜在大脑区域和神经机制。这一建议将提高我们对基本记忆机制的理解，这些机制可能是精神和神经疾病状态下记忆缺陷的基础，精神和神经疾病状态通常表现为记忆和睡眠异常的共病损害。此外，这项工作将阐明与几种神经疾病相关的睡眠不足的功能意义，并将有助于成功开发治疗方法，通过针对睡眠生理学的可修改方面来改善记忆缺陷。

 DESCRIPTION (provided by applicant): Sleep plays a critical role in long-term memory consolidation, or the stabilization of recent memories over time. In humans, non-rapid-eye-movement (NREM) sleep, compared to time spent awake, is associated with enhanced memory retention and the stabilization of memory representations across hippocampal-cortical networks. Specific physiological mechanisms during post-encoding sleep are thought to support such memory stabilization: slow wave activity or slow oscillations, which coordinate and synchronize large-scale neural activity during NREM sleep, and the reactivation of hippocampal activity patterns representative of prior experience (`reactivation') during wide-spread hippocampal-cortical network interactions. A functional role of slow waves for the retention of recent memories has been shown in humans, and robust evidence for memory- related hippocampal reactivation and associated hippocampal network interactions has been shown during NREM sleep in rodents. However, it is unclear from prior work 1): which brain regions are critically necessary for the generation of slow waves that support successful NREM memory consolidation, with prior work indicating a predominance of slow wave density and origin over medial prefrontal cortex (mPFC), and 2): whether mechanisms of hippocampal reactivation and large-scale network interactions support human NREM memory consolidation, as little prior work has tested evidence for hippocampal reactivation and associated network interactions in the human brain. By combining TMS with high-density EEG and EEG-fMRI measurements of NREM brain activity, this proposal seeks to remedy these gaps by 1): testing the causal contribution of mPFC integrity to slow wave activity generation and associated NREM sleep memory consolidation, and by 2): testing whether hippocampal-dependent learning results in robust evidence for hippocampal reactivation and large-scale network interactions during subsequent NREM sleep, and whether NREM hippocampal activity measures are functionally predictive of memory consolidation success (memory retention and neural stabilization across hippocampal-cortical networks). In sum, this work aims to study the underlying brain regions and neural mechanisms that critically contribute to long-term memory retention during sleep in humans. This proposal will improve our understanding of basic memory mechanisms that may underlie memory deficits in psychiatric and neurological disease states, which often express co-morbid impairments in memory and sleep abnormalities. Moreover, this work will elucidate the functional significance of sleep loss associated with several neurological disorders and will aid in the successful development of therapeutics to ameliorate memory deficits by targeting modifiable aspects of sleep physiology.