条件性恐惧记忆消退返回的性别差异

采用预期判断任务考察男女性对已消退的条件性恐惧记忆是否会出现消退返回的现象。结果表明: (1)在对已习得的条件性恐惧记忆消退后4个小时进行测试, 被试整体会出现明显的消退返回现象; (2)对消退返回现象的性别差异进行比较, 女性比男性的消退返回现象更突出, 并且差异显著; (3)与男性相比, 女性对条件性恐惧记忆具有易习得难消退的趋势, 但是性别差异不显著。研究结果验证了消退返回现象存在的普遍性, 并且有着显著的性别差异, 为以后对创伤后应激障碍患者的治疗应考虑性别因素提供了心理学依据。     

条件性恐惧泛化的性别差异

恐惧的过度泛化是焦虑障碍的核心症状之一, 表现为患者对与原危险刺激极不相似的中性刺激也有着较高强度的恐惧反应。临床上, 女性比男性更有可能患焦虑障碍, 因而对恐惧泛化进行性别差异研究可以为解释女性有着更高焦虑障碍发病率提供新的角度, 同时为临床治疗提供参考。本研究采用辨别性条件恐惧范式, 以主观预期值和皮电反应值作为测量指标, 从行为和生理两个层面对条件性恐惧泛化程度和恐惧泛化消退的性别差异进行研究。结果发现, 在恐惧泛化程度上, 未出现显著性别差异。在恐惧泛化消退上, 在主观预期值和皮电反应值两个层面均有着显著性别差异, 具体表现为相较于男性, 女性恐惧泛化的消退更慢, 持续时间更长。研究结果表明, 女性焦虑障碍高发病率的潜在影响因素之一可能在于女性对于恐惧泛化刺激的难以消除。     

厌恶与恐惧情绪习得的性别差异研究:一项ERP研究

采用事件相关电位技术（ERPs）,用条件性习得范式探讨厌恶与恐惧情绪习得的性别差异。行为结果表明,在成功习得厌恶、恐惧和中性情绪之后,男女性在唤醒度维度上,性别差异显著;脑电结果表明,在早期N1和P2成分,厌恶情绪与恐惧情绪的习得无显著性别差异;但男女不同性别在N2成分上差异显著,主要表现为女性在厌恶、恐惧、中性这三类CS的N2成分均差异显著,但男性仅厌恶与中性情绪的CS差异显著。结果表明在负性情绪的习得中,女性比男性更敏感。     

睡眠对恐惧学习的影响及其认知神经机制

睡眠问题可能会诱发恐惧相关情绪障碍(焦虑、创伤性应激障碍、恐怖症等),研究睡眠影响恐惧学习的认知神经机制,有助于增强对恐惧相关情绪障碍的预测、诊断和治疗。以往研究表明睡眠剥夺影响恐惧习得和消退主要是通过抑制vmPFC活动,阻碍其与杏仁核的功能连接,从而导致恐惧习得增强或是消退学习受损。进一步研究发现睡眠不同阶段对恐惧学习相关脑区有独特的影响:剥夺(缺乏)快速眼动睡眠会抑制vmPFC活动、增强杏仁核、海马激活,导致恐惧习得增强,消退学习受损,此外边缘皮层的功能连接减少破坏了记忆巩固(恐惧记忆和消退记忆);而慢波睡眠主要与海马变化有关,慢波睡眠期间进行目标记忆重激活可促进恐惧消退学习。未来研究需要增加睡眠影响恐惧泛化的神经机制研究、及昼夜节律中断对恐惧消退的影响,以及关注动物睡眠研究向人类睡眠研究转化中存在的问题。     

分类和概念对恐惧泛化的影响机制

恐惧泛化与多种焦虑障碍的病理基础密切相关。例如创伤后应激障碍个体往往持续地逃避与创伤事件有关的刺激,遭受着创伤痛苦折磨。本文在厘清知觉辨别与恐惧泛化关系的基础上,着力于高级认知过程(分类与概念相似性、典型性和人工概念)对恐惧泛化的影响,回顾了恐惧泛化的相关神经机制,并揭示恐惧泛化对焦虑障碍患者的临床治疗启示。未来研究应将知觉和高级认知维度的恐惧泛化进行整合研究,同时扩充恐惧习得和泛化的神经回路,以促进人类恐惧泛化更深入的研究。     

干预条件性恐惧记忆表达的相关影响因素分析

创伤后应激障碍是个体经历严重应激后形成的一种焦虑障碍, 对其治疗的关键是熄灭由创伤应激导致的条件性恐惧记忆。条件性恐惧的动物模型研究发现恐惧记忆一旦获得后就难以熄灭, 容易复发, 而这一点也是PTSD的关键临床症状表现之一。因此, 如何更好更持久地熄灭恐惧记忆, 是一个具有重要理论和临床意义的研究热点。本文围绕促进恐惧记忆的长久消退和破坏恐惧记忆的再巩固两方面的行为或药理干预及机制进行综述。针对本文所述的几种基础实验处理, 临床上可以研究治疗创伤后应激障碍的相应疗法。     

状态焦虑对条件性恐惧泛化的影响

恐惧的过度泛化是焦虑障碍患者重要的潜在病因,探索焦虑对恐惧泛化的影响具有重要意义。本研究在恐惧习得后,通过恐惧创伤电影范式诱发状态焦虑组被试的焦虑水平,采用主观预期值和皮电反应值作为指标,考察状态焦虑对条件性恐惧泛化的影响。结果表明,恐惧创伤电影范式显著提高了状态焦虑组被试的焦虑水平。在泛化阶段,状态焦虑组被试表现出更强的恐惧泛化,对与条件刺激相似的泛化刺激表现出更强烈的恐惧以及更高的预期。状态焦虑使得被试恐惧泛化的消退更慢,持续时间更长。研究同时发现,在状态焦虑下,被试对条件刺激的辨识出现增强趋势。研究结果提示在对经历负性事件个体进行临床干预时,可通过降低其焦虑水平来减少过度泛化。     

阻碍条件性恐惧记忆消退的原因分析

创伤后应激障碍是个体经历严重应激后形成的一种焦虑障碍,对其治疗的关键是消退由创伤应激导致的条件性恐惧记忆,但目前最有效的暴露疗法并不能真正有效地抑制患者恐惧记忆的表达.对条件性恐惧的动物模型研究发现情绪性增强效应、恐惧记忆二级条件化与再巩固、内侧前额叶皮层功能不足等均能够阻碍条件性恐惧记忆的消退.针对这几个方面可以探索治疗创伤后应激障碍的相应方法.     

认知重评阻断条件化恐惧记忆的习得与表达——对恐惧反应的长程抑制作用

情绪调节是人类特有的、并能有效控制个体情绪反应的行为方式,认知重评是其中最有效的调节策略之一。恐惧记忆是参与情绪障碍形成的重要病理机制,且已习得的恐惧反应难消退、易复发。为了考察认知重评能否起到长久抑制恐惧反应的效应,本研究利用条件化恐惧范式,第一天进行条件化恐惧习得训练,并在习得后间隔24 h及31天进行恐惧记忆的表达及自发恢复测试。实验1中,随机将被试分为两组,要求其在恐惧习得过程中进行认知重评或自然感受;在实验2,同样随机将被试分为两组,但要求其在恐惧记忆表达过程中进行认知重评或自然感受。结果发现,习得阶段进行认知重评显著降低了恐惧记忆的习得、表达及自发恢复过程中的SCR水平。同样,表达阶段进行认知重评也降低了此阶段的恐惧水平,且显著抑制了恐惧记忆的自发恢复。结果提示,在面对应激时,个体如果能够成功地利用想象进行认知重评,就有可能避免应激事件对个体的心理或精神造成伤害。     

自我关注与社交焦虑：负面评价恐惧的中介与关系型自我构念的调节

为明确自我关注对社交焦虑的影响机制,建构了一个有调节的中介模型,考察负面评价恐惧、关系型自我构念的作用以及性别差异。选取446名大学生进行问卷调查。结果表明：（1）自我关注部分通过负面评价恐惧的中介作用间接预测社交焦虑;（2）关系型自我构念调节中介模型的前半路径：在高关系型自我构念下,自我关注可以显著预测负面评价恐惧;在低关系型自我构念下,该预测作用不显著;（3）有调节的中介模型存在性别差异：在女生群体中,负面评价恐惧的中介效应大于男生群体,且关系型自我构念的调节作用显著;而在男生群体中,该调节效应不显著。     

Amygdala upregulation of NCAM polysialylation induced by auditory fear conditioning is not required for memory formation, but plays a role in fear extinction

There is much interest to understand the mechanisms leading to the establishment, maintenance, and extinction of fear memories. The amygdala has been critically involved in the processing of fear memories and a number of molecular changes have been implicated in this brain region in relation to fear learning. Although neural cell adhesion molecules (NCAMs) have been hypothesized to play a role, information available about their contribution to fear memories is scarce. We investigate here whether polysialylated NCAM (PSA-NCAM) contributes to auditory fear conditioning in the amygdala. First, PSA-NCAM expression was evaluated in different amygdala nuclei after auditory fear conditioning at two different shock intensities. Results showed that PSA-NCAM expression was increased 24 h post-training only in animals subjected to the highest shock intensity (1mA). Second, PSA-NCAM was cleaved in the basolateral amygdaloid complex through micro-infusions of the enzyme endoneuraminidase N, and the consequences of such treatment were investigated on the acquisition, consolidation, remote memory expression, and extinction of conditioned fear memories. Intra-amygdaloid cleavage of PSA-NCAM did not affect acquisition, consolidation or expression of remote fear memories. However, intra-amygdaloid PSA-NCAM cleavage enhanced fear extinction processes. These results suggest that upregulation of PSA-NCAM is a correlate of fear conditioning that is not necessary for the establishment of fear memory in the amygdala, but participates in mechanisms precluding fear extinction. These findings point out PSA-NCAM as a potential target for the treatment of psychopathologies that involve impairment in fear extinction.     

人类记忆再巩固研究现状及临床应用

巩固的记忆被提取后,进入不稳定状态,再重新稳定下来,这个过程称为记忆再巩固。本文首先阐述人类记忆再巩固主要研究方法和经典范式,梳理记忆再巩固在人类恐惧记忆和情景记忆两个方面的相关研究,并从认知神经科学角度整理记忆再巩固的加工机制。然后总结记忆再巩固应用于创伤性应激障碍和药物成瘾等心理障碍临床治疗的相关文献。最后本文提出未来研究的方向和建议,希冀对人类记忆再巩固的理论研究和临床应用提供新思路。     

应激激素对恐惧消退作用的神经生理机制

恐惧消退是指反复呈现条件刺激（conditioned stimulus, CS）而不匹配无条件刺激（unconditioned stimulus, US）,从而消除个体已有的恐惧反应。应激激素,如去甲肾上腺素（Norepinephrine,NE）和糖皮质激素（Glucocorticoids,GCs）,可通过影响腹内侧前额叶、杏仁核和海马等与消退学习有关的神经回路的活动,调节恐惧消退学习效果。NE和GCs对恐惧消退学习的调节作用受激素水平与激素用药时间的影响,且其调节效果存在性别差异。未来研究需进一步探索应激激素如何影响恐惧消退学习效果,并思考如何利用其影响效果促进暴露疗法疗效。     

Preextinction Stress Prevents Context-Related Renewal of Fear

Extinction learning, which creates new safety associations, is thought to be the mechanism underlying exposure therapy, commonly used for the treatment of anxiety disorders and posttraumatic stress disorder. The relative strength and availability for retrieval of both the fear and safety memories determine the response in a given situation. While the fear memory is often context-independent and may easily generalize, extinction memory is highly context-specific. “Renewal” of the extinguished fear memory might thus occur following a shift in context. The aim of the current work was to create an enhanced and generalized extinction memory to a discrete stimulus using stress exposure before extinction learning, thereby preventing renewal. In our contextual fear conditioning paradigm, 40 healthy men acquired (Day 1), retrieved and extinguished (Day 2) the fear memories, with no differences between the stress and the control group. A significant difference between the groups emerged in the renewal test (Day 3). A renewal effect was seen in the control group (N = 20), confirming the context-dependency of the extinction memory. In contrast, the stress group (N = 20) showed no renewal effect. Fear reduction was generalized to the acquisition context as well, suggesting that stress rendered the extinction memory more context-independent. These results are in line with previous studies that showed contextualization disruption as a result of pre-learning stress, mediated by the rapid effects of glucocorticoids on the hippocampus. Our findings support research investigating the use of glucocorticoids or stress induction in exposure therapy and suggest the right timing of administration in order to optimize their effects.     

Single prolonged stress disrupts retention of extinguished fear in rats

Clinical research has linked post-traumatic stress disorder (PTSD) with deficits in fear extinction. However, it is not clear whether these deficits result from stress-related changes in the acquisition or retention of extinction or in the regulation of extinction memories by context, for example. In this study, we used the single prolonged stress (SPS) animal model of PTSD and fear conditioning procedures to examine the effects of prior traumatic stress on the acquisition, retention, and context-specificity of extinction. SPS administered one week prior to fear conditioning had no effect on the acquisition of fear conditioning or extinction but disrupted the retention of extinction memories for both contextual and cued fear. This SPS effect required a post-stress incubation period to manifest. The results demonstrate that SPS disrupts extinction retention, leading to enhanced fear renewal; further research is needed to identify the neurobiological processes through which SPS induces these effects.     

状态焦虑对条件恐惧习得和消退的影响

采用44名正常女性大学生作为被试, 通过心理社会压力暴露的方法诱发焦虑组被试的状态焦虑, 采用主观预期值作为指标, 考察焦虑对条件恐惧习得和消退的直接影响, 并探讨这种影响是否也表现在评价性条件作用上。结果表明：心理社会压力暴露显著提高了焦虑组被试的状态焦虑。在习得阶段, 状态焦虑降低了被试对条件刺激的辨别条件恐惧反应, 具体而言, 状态焦虑降低了被试对CS+的主观预期值, 但是却提高了对CS?的主观预期值; 在消退阶段, 状态焦虑抑制了被试对条件刺激的消退。状态焦虑的影响也表现在评价性条件作用上, 和控制组相比, 焦虑组在习惯化和消退阶段对条件刺激表现出了更为负性的效价评定。