疼痛恐惧的神经机制及其消退

疼痛恐惧是疼痛基础和临床研究中的一个重要课题。个体对疼痛信息产生过度警觉,诱发不恰当的回避行为,扰乱机体的正常功能,加剧疼痛的现象即为疼痛恐惧。疼痛恐惧可影响个体的疼痛感知以及疼痛相关的注意和回避行为,且在慢性疼痛(如慢性肌骨骼疼痛)的发展、维持个体正常生理功能的丧失中起着重要作用。疼痛恐惧的形成与表达涉及杏仁核、海马、背侧前扣带回皮层、和前额叶皮层等脑区的参与。当前的疼痛恐惧消退的心理-行为干预方法可在疼痛恐惧加工的不同阶段(巩固、再巩固和消退)消退个体的疼痛恐惧。然而,由于恐惧记忆形成过程较为复杂并受多种因素影响,疼痛恐惧记忆消退方法效果较不稳定,其基础研究与临床应用之间仍存在较大的鸿沟。将来研究有必要考虑到疼痛恐惧形成环境的差异以及个体人格特质/心理状态的差异,逐步完善相关消退方法并将其引入临床镇痛,以期帮助患者弱化、擦除甚至改写困扰他们的疼痛恐惧,从而缓解甚至消除病患的疼痛。     

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。     

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。     

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。     

恐惧学习的发展认知神经机制研究回顾与展望

恐惧可以帮助个体快速地评估危险情景,并调动生理和行为反应来应对危险刺激。恐惧发展始于婴儿时期,神经回路表现为杏仁核未参与恐惧反应,但杏仁核功能连接可以预测早期恐惧反应;发展到童年期的恐惧学习特点为安全学习不足和过度泛化,其根源是负责辨别刺激的海马还处于发育中;进入青春期恐惧加工主要特征是由于前额叶发育较晚导致的消退能力弱。恐惧虽有益于人类生存,但恐惧异常会引发焦虑障碍,本文从恐惧的习得、消退和泛化三个阶段,对比了焦虑与健康青少年的恐惧学习差异。最后,文章从增加婴儿时期研究、创新青少年恐惧研究范式和开发安全有效的干预手段三个方面对未来研究提出展望,以期进一步推动恐惧研究的发展。     

疼痛恐惧对疼痛的影响及其认知机制

疼痛恐惧是把将要出现的疼痛刺激视为主要威胁而产生的一种恐惧,它会影响与疼痛相关的感知觉、注意、回避行为以及安慰剂止痛的效果.疼痛恐惧的认知模型主要有活动回避模型、恐惧-回避模型以及内感受性恐惧条件模型.未来的研究要进一步探究疼痛恐惧的认知机制,完善疼痛恐惧的认知模型并扩展疼痛恐惧的研究方法.     

疼痛恐惧的形成及其对疼痛知觉的影响

脑岛、杏仁核是疼痛恐惧形成的重要神经网络中心。疼痛恐惧增强了慢性疼痛患者的疼痛知觉体验, 进而加剧抑郁、焦虑情绪和功能损伤程度。脑岛、杏仁核、前额皮层和前扣带回是疼痛恐惧影响疼痛知觉的重要神经基础。通过认知方法干预疼痛恐惧可以改善患者的抑郁、焦虑情绪, 减少功能损伤。未来研究应拓展疼痛恐惧的测量工具, 采用功能磁共振成像技术进一步揭示疼痛恐惧影响慢性疼痛患者疼痛知觉的神经机制。     

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。     

Investigating the effectiveness of brief cognitive reappraisal training to reduce fear in adolescents

As adolescent anxiety is common and costly, identifying effective strategies to reduce symptoms is a priority. This study tested whether adolescents could learn to use cognitive reappraisal strategies to attenuate fear during extinction learning. Fifty-seven participants (12–15 years) viewed images of two neutral faces, one which was paired with a fearful expression and shrieking scream (conditioned threat stimulus) and the other that was never paired with the aversive outcome (conditioned safety stimulus) during fear acquisition. Before extinction, participants either received cognitive appraisal training, which explored alternative, benign meanings associated with the scream or a control activity. Self-reported fear ratings in the cognitive reappraisal group were significantly lower to both the conditioned threat and safety stimuli after extinction than the control group. These findings did not characterise fear-potentiated startle data. Potential reasons for the lack of consistency between measures are considered.     

The Effect of Counterconditioning on Evaluative Responses and Harm Expectancy in a Fear Conditioning Paradigm

In fear conditioning, extinction targets harm expectancy as well as the fear response, but it often fails to eradicate the negative affective value that is associated with the conditioned stimulus. In the present study, we examined whether counterconditioning can serve to reduce evaluative responses within fear conditioning. The sample consisted of 70 nonselected students, 12 of whom were men. All participants received acquisition with human face stimuli as the conditioned stimuli and an unpleasant white noise as the unconditioned stimulus. After acquisition, one third of the sample was allocated to an extinction procedure. The other participants received counterconditioning with either a neutral stimulus (neutral tone) or a positive stimulus (baby laugh). Results showed that counterconditioning (with both neutral and positive stimuli), in contrast to extinction, successfully reduced evaluative responses. This effect was found on an indirect measure (affective priming task), but not on self-report. Counterconditioning with a positive stimulus also tended to enhance the reduction of conditioned skin conductance reactivity. The present data suggest that counterconditioning procedures might be a promising approach in diminishing evaluative learning and even expectancy learning in the context of fear conditioning.     

Associative learning versus fear habituation as predictors of long-term extinction retention

Violation of unconditioned stimulus (US) expectancy during extinction training may enhance associative learning and result in improved long-term extinction retention compared to within-session habituation. This experiment examines variation in US expectancy (i.e., expectancy violation) as a predictor of long-term extinction retention. It also examines within-session habituation of fear-potentiated startle (electromyography, EMG) and fear of conditioned stimuli (CS) throughout extinction training as predictors of extinction retention. Participants (n?=?63) underwent fear conditioning, extinction and retention and provided continuous ratings of US expectancy and EMG, as well as CS fear ratings before and after each phase. Variation in US expectancy throughout extinction and habituation of EMG and fear was entered into a regression as predictors of retention and reinstatement of levels of expectancy and fear. Greater variation in US expectancy throughout extinction training was significantly predictive of enhanced extinction performance measured at retention test, although not after reinstatement test. Slope of EMG and CS fear during extinction did not predict retention of extinction. Within-session habituation of EMG and self-reported fear is not sufficient for long-term retention of extinction learning, and models emphasizing expectation violation may result in enhanced outcomes.     

Safety Behavior After Extinction Triggers a Return of Threat Expectancy

Safety behavior is involved in the maintenance of anxiety disorders, presumably because it prevents the violation of negative expectancies. Recent research showed that safety behavior is resistant to fear extinction. This fear conditioning study investigated whether safety behavior after fear extinction triggers a return of fear in healthy participants. Participants learned that two stimuli (A and C) were followed by an aversive loud noise (“threat”), and one stimulus (B) was not. Participants then learned to use safety behavior that prevented the loud noise. Next, A and C were no longer followed by the loud noise, which typically led to extinction of threat expectancy. Safety behavior then became available again for C, but not for A and B. All participants used safety behavior on these C trials. In a final test phase, A, B, and C were presented once without the availability to use safety behavior. At each stimulus presentation, participants rated threat expectancy by indicating to what extent they expected that the loud noise would follow. Compared with the last extinction trial, threat expectancy increased for C in the test phase, whereas it did not increase for A and B. Hence, safety behavior after the extinction of classically conditioned fear caused a partial return of fear. The findings suggest that safety behavior may be involved in relapse after exposure-based therapy for anxiety disorders.     

Contribution of Ventrolateral Prefrontal Cortex to the Acquisition and Extinction of Conditioned Fear in Rats

The ventrolateral, agranular insular portion of prefrontal cortex (PFC) in rats is involved in visceral functions and has been shown to be involved in emotional processes. However, its contribution to aversive learning has not been well defined. Classical fear conditioning has been a powerful tool for illuminating some of the primary neural structures involved in aversive emotional learning. We measured both the acquisition and the extinction of conditioned fear following lesions of the ventrolateral PFC of rats. Lesions reduced fear reactivity to contextual stimuli associated with conditioning without affecting CS acquisition, and had no effect on response extinction. Ventrolateral PFC may normally be involved in the processing of contextual information while not being directly involved in extinction processes within the aversive domain.     

Strategic and Automatic Threat Processing in Chronic Musculoskeletal Pain: A Startle Probe Investigation

Attentional bias research with chronic pain samples has yielded conflicting results. In the present investigation the startle paradigm was used to test the postulate that fear‐based mechanisms play an important role in attentional biases for pain‐related threat in chronic pain. Participants, including 31 individuals with chronic musculoskeletal pain and 20 healthy controls, completed a startle task designed to measure attention to different types of words (neutral vs sensory pain vs affective pain vs health catastrophe) presented at different levels of cognitive processing (strategic vs automatic). Measures of fear‐based individual difference variables, including anxiety sensitivity and fear of pain, were also completed. Startle amplitudes and latencies to acoustic startle probes that followed word presentations were recorded. Data were analyzed with repeated measures ANOVAs and correlational analysis. Significant between‐group differences were found indicating that, relative to chronic pain participants, healthy controls had higher startle amplitude index scores for health catastrophe words. There was also a trend among patients with chronic pain for greater startle amplitude index scores for strategic presentations of sensory pain words. In the automatic condition, all participants demonstrated a lower startle latency index for sensory words relative to both affect and health catastrophe words, suggesting participants had more difficulty disengaging from affect and health catastrophe words or were more avoidant of sensory words. Correlational analyses indicated that startle response indices for words related to health catastrophe became more pronounced for chronic pain patients as anxiety sensitivity and fear of pain increased. Implications and directions for future research are discussed.