Lerner Itamar, Lupkin Shira M, Sinha Neha, Tsai Alan, Gluck Mark A
Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, New Jersey 07102
Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, New Jersey 07102.
J Neurosci. 2017 Nov 15;37(46):11233-11244. doi: 10.1523/JNEUROSCI.0578-17.2017. Epub 2017 Oct 23.
Sleep, and particularly rapid eye movement sleep (REM), has been implicated in the modulation of neural activity following fear conditioning and extinction in both human and animal studies. It has long been presumed that such effects play a role in the formation and persistence of posttraumatic stress disorder, of which sleep impairments are a core feature. However, to date, few studies have thoroughly examined the potential effects of sleep prior to conditioning on subsequent acquisition of fear learning in humans. Furthermore, these studies have been restricted to analyzing the effects of a single night of sleep-thus assuming a state-like relationship between the two. In the current study, we used long-term mobile sleep monitoring and functional neuroimaging (fMRI) to explore whether trait-like variations in sleep patterns, measured in advance in both male and female participants, predict subsequent patterns of neural activity during fear learning. Our results indicate that higher baseline levels of REM sleep predict reduced fear-related activity in, and connectivity between, the hippocampus, amygdala and ventromedial PFC during conditioning. Additionally, skin conductance responses (SCRs) were weakly correlated to the activity in the amygdala. Conversely, there was no direct correlation between REM sleep and SCRs, indicating that REM may only modulate fear acquisition indirectly. In a follow-up experiment, we show that these results are replicable, though to a lesser extent, when measuring sleep over a single night just before conditioning. As such, baseline sleep parameters may be able to serve as biomarkers for resilience, or lack thereof, to trauma. Numerous studies over the past two decades have established a clear role of sleep in fear-learning processes. However, previous work has focused on the effects of sleep following fear acquisition, thus neglecting the potential effects of baseline sleep levels on the acquisition itself. The current study provides the first evidence in humans of such an effect. Specifically, the results of this study suggest that baseline rapid eye movement (REM) sleep may serve a protective function against enhanced fear encoding through the modulation of connectivity between the hippocampus, amygdala, and the ventromedial PFC. Building on this finding, baseline REM measurements may serve as a noninvasive biomarker for resilience to trauma or, conversely, to the potential development of posttraumatic stress disorder following trauma.
在人类和动物研究中，睡眠，尤其是快速眼动睡眠（REM），与恐惧条件反射和消退后的神经活动调节有关。长期以来，人们一直认为这种作用在创伤后应激障碍的形成和持续中发挥作用，而睡眠障碍是创伤后应激障碍的一个核心特征。然而，迄今为止，很少有研究彻底考察条件反射前睡眠对人类后续恐惧学习获得的潜在影响。此外，这些研究仅限于分析一晚睡眠的影响——因此假定两者之间存在类似状态的关系。在本研究中，我们使用长期移动睡眠监测和功能神经成像（fMRI）来探究在男性和女性参与者中预先测量的睡眠模式的特质样变化是否能预测恐惧学习过程中随后的神经活动模式。我们的结果表明，较高的基线快速眼动睡眠水平预示着在条件反射过程中海马体、杏仁核和腹内侧前额叶皮质之间与恐惧相关的活动及连接性会降低。此外，皮肤电反应（SCR）与杏仁核的活动呈弱相关。相反，快速眼动睡眠与皮肤电反应之间没有直接关联，这表明快速眼动可能仅间接调节恐惧获得。在后续实验中，我们表明，在条件反射前仅测量一晚睡眠时，这些结果虽然程度较轻但仍可重复。因此，基线睡眠参数可能能够作为对创伤恢复力或缺乏恢复力的生物标志物。过去二十年的众多研究已经明确了睡眠在恐惧学习过程中的作用。然而之前的研究集中在恐惧获得后的睡眠影响上，从而忽略了基线睡眠水平对获得过程本身的潜在影响。本研究提供了人类中这种影响的首个证据。具体而言，本研究结果表明，基线快速眼动睡眠可能通过调节海马体、杏仁核和腹内侧前额叶皮质之间的连接性，对增强的恐惧编码起到保护作用。基于这一发现，基线快速眼动测量可能作为一种非侵入性生物标志物，用于衡量对创伤的恢复力，或者相反，用于衡量创伤后创伤后应激障碍的潜在发展。
