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。     

积极情绪对条件性恐惧泛化的抑制作用

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安全刺激也产生恐惧反应。本研究采用经典条件恐惧范式,以US主观预期、回溯性恐惧评定、回溯性效价评定和皮电反应作为恐惧反应的指标,通过"最好自我"训练来诱发被试的积极情绪,考察了恐惧习得后的积极情绪对于恐惧泛化的影响。本研究发现,积极情绪能有效地抑制条件性恐惧的泛化,增强被试对安全信号的学习,并对消退后的恐惧重建现象起到预防作用。研究同时显示,恐惧泛化在主观评定指标和生理指标间出现了分离,这表明积极情绪对恐惧泛化的抑制作用是一个综合的过程,可能涉及到不同的作用机制。本研究结果提示可以通过诱发积极情绪,抑制条件性恐惧的泛化,对临床干预有一定的启发意义。     

疼痛恐惧的形成、泛化与消退

疼痛恐惧源于把疼痛等同于伤害的灾难化信念及对疼痛的负性解释, 它在慢性疼痛和能力丧失的发生和发展过程中起着重要作用。疼痛恐惧可以通过联合学习和观察学习等方式获得, 并且在具有相似特征的刺激中存在泛化现象。通过教育干预和等级暴露疗法等可以成功消退疼痛恐惧, 在消退过程中要控制安全信息等因素的不良影响。在疼痛恐惧的获得与消退中, 主要有杏仁核, 脑岛和前扣带皮层等脑区参与。未来的研究可以集中在深入探讨疼痛恐惧形成中的泛化及消退后的恢复、再巩固等现象, 加强其临床上的应用, 并综合心理、生物和认知神经科学, 研究疼痛恐惧的获得、泛化与消退的深层机制。     

基于知觉的恐惧泛化的认知神经机制

恐惧泛化是条件性恐惧反应转移到另一个相似但安全的刺激的现象。适当的恐惧泛化对人类有积极意义, 而过度的恐惧泛化则不利于个体有效地适应环境。基于知觉的恐惧泛化研究揭示了恐惧泛化的规律, 因而被广泛应用。本文首先梳理了对知觉恐惧泛化的相关研究, 介绍恐惧泛化的经典理论基础—巴普洛夫条件反射以及恐惧泛化梯度; 其次简要回顾基于多个感觉通道(即视觉、听觉、情景)的知觉恐惧泛化研究现状; 再次, 分别对海马、杏仁核、脑岛和前额叶等脑区在恐惧泛化中的作用进行回顾, 进一步总结出恐惧泛化的神经环路结构模型。最后, 简要区分了基于知觉的恐惧泛化和正在兴起的基于概念的恐惧泛化, 进而指出未来研究需要结合基于概念的恐惧泛化、区分被试对刺激的辨别力、增加恐惧刺激材料的准确性及多样化、结合激素等个体差异和多模态脑成像数据来展开。     

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。     

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。     

催产素影响恐惧习得和消退的认知神经机制

恐惧是一种基本的情绪, 在人类的生存和适应中发挥着重要作用。先前的研究表明, 杏仁核、背侧前扣带回、脑岛等脑区是条件化恐惧习得的认知神经基础, 杏仁核、海马和腹内侧前额叶等脑区在恐惧消退过程中发挥重要作用。研究发现, 催产素与恐惧习得和恐惧消退过程密切相关。恐惧习得过程中, 催产素影响杏仁核、背侧前扣带回的活动, 影响杏仁核与背侧前扣带回和脑干间的功能连接, 促进或抑制恐惧习得过程; 恐惧消退过程中, 催产素影响了杏仁核和腹内侧前额叶的活动, 并且影响杏仁核与内侧前额叶和海马间的功能连接, 促进或抑制恐惧消退过程。未来研究应从性别差异、神经网络模型、身心发育和病理研究等角度展开, 力图深入理解催产素影响恐惧情绪加工的认知神经机制。     

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。     

情景变换诱发已消退恐惧记忆重现的神经环路

暴露疗法是治疗创伤后应激障碍的主要行为疗法。当被试反复暴露于可引起恐惧反应的条件刺激(如白噪音), 但却不伴有非条件刺激(如足底电击)时, 恐惧记忆将被消退, 形成消退记忆。但恐惧记忆并未从根本上被擦除, 当被试在消退训练以外的情景暴露于条件刺激时, 已消退的恐惧记忆将会重现。海马、内侧前额叶皮层、杏仁核等脑区及其相互连接的神经环路是情景诱发恐惧记忆重现的生理基础。情景变化诱发恐惧记忆重现过程中, 海马可能是通过直接投射至杏仁核基底核、杏仁核外侧核或通过边缘前皮质间接调控杏仁核基底核、杏仁核外侧核的功能, 产生恐惧反应。     

自悯写作对恐惧消退的促进作用

先前研究表明,自悯干预能够改善焦虑相关精神疾病的心理症状,然而自悯改善焦虑的作用机制尚不清楚。以恐惧消退为基础的暴露疗法是治疗焦虑症的关键疗法,研究自悯干预如何促进恐惧消退从而增强暴露疗法的效果有助于阐释暴露疗法的作用机制。本研究共56名有效健康被试,在恐惧习得之后,将匹配自悯水平和焦虑水平的被试随机分配进行自悯写作或非自悯日常写作,最后进行恐惧消退测试,并通过检测写作前后的正负性情绪变化以及恐惧消退早期、晚期的电击预期反应和皮肤电反应来探究自悯写作对恐惧消退的影响及其作用机制。结果显示,两种写作任务均降低了被试的负性情绪;相比于非自悯日常写作,自悯写作显著降低了被试在恐惧消退早期和晚期的对威胁和安全线索的电击预期反应。相比于消退晚期,自悯组消退早期的皮肤电反应更弱。这一结果表明,自悯写作能够调节对威胁和安全线索的反应来促进恐惧消退。本研究首次运用实验室恐惧消退模型探讨自我怜悯调节威胁刺激的加工机制,有助于解释自悯改善焦虑症状的心理和生理机制,并强调了在基于恐惧消退范式的暴露疗法中增加认知干预的必要性。     

Discrimination between safe and unsafe stimuli mediates the relationship between trait anxiety and return of fear

Individuals with anxiety disorders show deficits in the discrimination between a cue that predicts an aversive outcome and a safe stimulus that predicts the absence of that outcome. This impairment has been linked to increased spontaneous recovery of fear following extinction, however it is unknown if there is a link between discrimination and return of fear in a novel context (i.e. context renewal). It is also unknown if impaired discrimination mediates the relationship between trait anxiety and either spontaneous recovery or context renewal. The present study used a differential fear conditioning paradigm to examine the relationships between trait anxiety, discrimination learning, spontaneous recovery and context renewal in healthy volunteers. Fear learning was assessed using continuous ratings of US expectancy and subjective ratings of fear. Discrimination mediated the relationships between trait anxiety and both spontaneous recovery and context renewal such that elevated trait anxiety was associated with poorer discrimination, which in turn was associated with increased fear at test phases. Results are discussed in terms of the genesis and maintenance of anxiety disorders.     

Recalling safety: cooperative functions of the ventromedial prefrontal cortex and the hippocampus in extinction

Anxiety disorders are commonly treated with exposure-based therapies that rely on extinction of conditioned fear. Persistent fear and anxiety following exposure therapy could reflect a deficit in the recall of extinction learning. Animal models of fear learning have elucidated a neural circuit for extinction learning and recall that includes the amygdala, ventromedial prefrontal cortex (vmPFC), and hippocampus. Whereas the amygdala is important for extinction learning, the vmPFC is a site of neural plasticity that allows for the inhibition of fear during extinction recall. We suggest that the vmPFC receives convergent information from other brain regions, such as contextual information from the hippocampus, to determine the circumstances under which extinction or fear will be recalled. Imaging studies of human fear conditioning and extinction lend credence to this extinction network. Understanding the neural circuitry underlying extinction recall will lead to more effective therapies for disorders of fear and anxiety.     

Classical fear conditioning in the anxiety disorders: a meta-analysis

Fear conditioning represents the process by which a neutral stimulus comes to evoke fear following its repeated pairing with an aversive stimulus. Although fear conditioning has long been considered a central pathogenic mechanism in anxiety disorders, studies employing lab-based conditioning paradigms provide inconsistent support for this idea. A quantitative review of 20 such studies, representing fear-learning scores for 453 anxiety patients and 455 healthy controls, was conducted to verify the aggregated result of this literature and to assess the moderating influences of study characteristics. Results point to modest increases in both acquisition of fear learning and conditioned responding during extinction among anxiety patients. Importantly, these patient-control differences are not apparent when looking at discrimination studies alone and primarily emerge from studies employing simple, single-cue paradigms where only danger cues are presented and no inhibition of fear to safety cues is required.     

Enhancing exposure-based therapy from a translational research perspective

Combining an effective psychological treatment with conventional anxiolytic medication is typically not more effective than unimodal therapy for treating anxiety disorders. However, recent advances in the neuroscience of fear reduction have led to novel approaches for combining psychological therapy and pharmacological agents. Exposure-based treatments in humans partly rely on extinction to reduce the fear response in anxiety disorders. Animal studies have shown that D-cycloserine (DCS), a partial agonist at the glycine recognition site of the glutamatergic N-methyl-D-aspartate receptor facilitates extinction learning. Similarly, recent human trials have shown that DCS enhances fear reduction during exposure therapy of some anxiety disorders. This article discusses the biological and psychological mechanisms of extinction learning and the therapeutic value of DCS as an augmentation strategy for exposure therapy. Areas of future research will be identified.     

Optimizing inhibitory learning during exposure therapy

Prevailing models of exposure therapy for phobias and anxiety disorders construe level of fear throughout exposure trials as an index of corrective learning. However, the evidence, reviewed herein, indicates that neither the degree by which fear reduces nor the ending fear level predict therapeutic outcome. Developments in the theory and science of fear extinction, and learning and memory, indicate that 'performance during training' is not commensurate with learning at the process level. Inhibitory learning is recognized as being central to extinction and access to secondary inhibitory associations is subject to influences such as context and time, rather than fear during extinction training. Strategies for enhancing inhibitory learning, and its retrieval over time and context, are reviewed along with their clinical implications for exposure therapy and directions for future research.     

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.     

Verbal instruction abolishes fear conditioned to racial out-group faces

Previous research has shown resistance to extinction of fear conditioned to racial out-group faces, suggesting that these stimuli may be subject to prepared fear learning. The current study replicated and extended previous research by using a different racial out-group, and testing the prediction that prepared fear learning is unaffected by verbal instructions. Four groups of Caucasian participants were trained with male in-group (Caucasian) or out-group (Chinese) faces as conditional stimuli; one paired with an electro-tactile shock (CS+) and one presented alone (CS−). Before extinction, half the participants were instructed that no more shocks would be presented. Fear conditioning, indexed by larger electrodermal responses to, and blink startle modulation during the CS+, occurred during acquisition in all groups. Resistance to extinction of fear learning was found only in the racial out-group, no instruction condition. Fear conditioned to a racial out-group face was reduced following verbal instructions, contrary to predictions for the nature of prepared fear learning.     

Positive affect predicts less reacquisition of fear: relevance for long-term outcomes of exposure therapy

Much emphasis in fear conditioning research is placed on understanding extinction learning, partly because of its application in treating anxiety disorders. Return of fear after extinction is a problem affecting long-term maintenance of treatment gains. The present study evaluated whether positive affect (PA) is associated with lower rates of reacquisition, or, an increase in fear following re-pairings of the conditional stimulus (CS+) and unconditional stimulus (US; e.g. electric shock) after extinction. Results showed that higher PA before and after extinction was associated with less CS+ fear during reacquisition as measured by skin conductance arousal and US expectancy. Conversely, negative affect was not associated with reacquisition of fear using any measure. These results provide implications for reducing reacquisition with exposure therapy for anxiety disorders.     

Learning to fear outgroups: An associative learning explanation for the development and reduction of intergroup anxiety

Pavlovian conditioning is a form of associative learning shown to contribute to the development and reduction of clinical anxiety and fear, and more recently, intergroup anxiety and fear. The current review provides a synthesis of the literature on associative learning of fear toward outgroups. Findings are reviewed that outline how fear toward the outgroup, relative to the ingroup, can be preferentially learnt and is resistant to extinction‐based techniques. Novel future research directions for intergroup anxiety are then identified based upon previous research on clinical anxiety. It is proposed that processes known to enhance the extinction of specific phobia should be investigated with social stimuli. Specifically, it is argued that exploring cognitive factors during extinction and conducting extinction in multiple contexts may provide new avenues to pursue intergroup harmony through reduced intergroup anxiety. The review concludes by suggesting innovative research designs are needed to validate an associative learning account of fear toward outgroups outside of experimental settings.