Sleep and neuroplasticity in complex training

该研究计划的主要目标是更深入地了解睡眠中的声音如何增强学习和记忆。2013年，Ngo at al.研究表明，睡眠期间慢振荡(SOS)的强度和纺锤波的密度可以通过精确计时的声音爆发来提高，这种技术被称为闭环式听觉刺激(CLAS)。增强与第二天的记忆性能改善有关。因此，CLAS提供了一种探索睡眠记忆功能的方法，但声音影响大脑活动的机制尚不清楚，它对现实生活任务(远比迄今研究的简单范例复杂得多)的影响也是未知的。我已经开发出一套非常适合理解这些过程的技能：复杂训练任务的经验，课堂，以及使用脑磁图对清醒和睡眠中的任务引起的振荡进行全脑源建模；这项工作将构成我新实验室研究方向的基础。我提出了三个不同的目标： 目的I：闭环式听觉刺激(CLAS)如何增强慢振荡(SOS)？我们将在MEG的NREM睡眠期间将噪声突发传递到SOS的目标阶段，以检验以下假设：i)信号从初级听觉皮质到次级区域的传播取决于正在进行的SOS阶段；以及，使用来源定位的连接性分析，ii)诱发反应和内源性皮质SOS之间的关键相互作用发生在皮层，而不是脑干，通过唤醒过程。 目的II：NREM睡眠中复杂任务巩固的神经关联是什么？我们将在我们之前开发的基于钢琴的学习范式中建立睡眠依赖记忆巩固的效应(即序列、定时精度)，并使用脑电来表征觉醒任务表现和睡眠巩固的时空特征。我们预测SO和纺锤活动会增加，这与第二天的任务改善成正比。 目标三：我们能通过课堂加强复杂的学习吗？有了在I和II中获得的知识，我们将使用MEG更高的空间分辨率来测试CLAS以依赖于使用的方式增强巩固的假设。我们假设，与无刺激相比，类刺激会增加任务相关脑区的波幅和纺锤密度。 由于Clas具有相当大的健康应用潜力，因此有必要对声音影响内源性大脑活动和记忆的机制有更深入的了解。我们的结果将与许多试图利用睡眠依赖巩固的群体直接相关，并最终可能导致开发出更好的治疗方法，以改善睡眠的认知益处，而睡眠可能会因疾病和衰老而退化。我们的研究结果也将进一步加深我们对睡眠记忆功能的理解。

The principal goal of the research program is to gain a deeper understanding of how learning and memory can be enhanced by sound presented during sleep. In 2013, Ngo at al. demonstrated that the strength of slow oscillations (SOs) and the density of spindles during sleep could be boosted by precisely timed sound bursts, a technique known as closed-loop auditory stimulation (CLAS). Enhancement was related to memory performance improvements the following day. CLAS thus provides a means of probing the memory function of sleep, but the mechanism through which sound affects brain activity is not understood, and its effects on real-life tasks (which are far more complex than the simple paradigms studied to date) are unknown. I have developed a skill set that is uniquely suited to understanding these processes: experience with complex training tasks, CLAS, and whole-brain source modeling of oscillations induced by tasks during wakefulness and those during sleep, using MEG; this work will form the basis of my new lab's research direction. I propose three distinct aims: Aim I: How does closed-loop auditory stimulation (CLAS) enhance slow oscillations (SOs)? We will deliver noise bursts during NREM sleep in the MEG to target phases of SOs, in order to test the hypotheses: i) that signal propagation from the primary auditory cortex to secondary regions depends on the phase of ongoing SOs; and, using source-localized connectivity analysis, ii) that the critical interaction between evoked responses and endogenous cortical SOs takes place in the cortex vs. in the brainstem via processes of arousal. Aim II: What are the neural correlates of complex task consolidation in NREM sleep? We will establish an effect of sleep-dependent memory consolidation in a piano-based learning paradigm that we previously developed (i.e. on sequence, timing accuracy), and characterize spatiotemporal signatures of wake task performance and sleep consolidation using EEG. We predict an increase in SO and spindle activity which is proportional to next-day task improvement. Aim III: Can we enhance complex learning with CLAS? Armed with the knowledge gained in I and II, we will use MEG's higher spatial resolution to test the hypothesis that CLAS enhances consolidation in a use-dependent fashion. We hypothesize that CLAS as compared with no stimulation will increase SO amplitude and spindle density within task-related brain regions. Because CLAS has considerable potential for health applications, a deeper understanding of the mechanisms through which sound can influence endogenous brain activity and memory is necessary. Our results will be directly relevant to the many groups who are trying to harness sleep-dependent consolidation, and may eventually lead to the development of better therapies to the cognitive benefits of sleep that can be degraded by disease and aging. Our results will also further our understanding of the memory function of sleep.