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。     

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。     

认知重评对负性效价的抑制促进条件性恐惧消退

认知重评能有效降低个体对情感刺激的负性情绪体验, 但指导性认知重评在恐惧记忆治疗中效果存在争议。本文将认知重评范式与辨别式条件恐惧反应范式结合, 以效价和US预期值为指标, 探讨指导性认知重评训练对恐惧情绪习得和消退的影响效果。以低认知重评能力个体为被试, 在实验前24 h进行指导性认知重评训练。条件性恐惧任务为期2天, 第一天完成条件性恐惧的习得和消退任务, 第二天完成条件性恐惧的再消退任务。结果显示, 经过重评训练后个体在条件性恐惧任务中的恐惧情绪效价显著较低, 说明认知重评有效降低低认知重评能力个体在急性应激状态下的负性情绪体验。所有被试均成功完成辨别式条件性恐惧的习得和消退任务, 因此重评训练并不削弱个体对危险或者安全信息的辨别能力。但在条件性恐惧的消退过程中, 认知重评指导训练加快了恐惧消退, 且24 h后测得的条件性恐惧程度显著较低, 说明指导性重评提高了条件性恐惧记忆的消退效率, 并减弱了条件性恐惧的消退返回。     

非条件刺激降低再评估对条件性恐惧消退的影响

诸多情绪障碍治疗的关键在于促进条件性恐惧反应的消退, 研究证明非条件刺激再评估能够引起恐惧反应的变化。本研究将非条件刺激降低再评估范式应用于消退训练, 以主观预期值、皮电反应作为恐惧反应指标, 考察恐惧习得后非条件刺激强度降低对条件性恐惧消退的影响, 并运用评价性条件作用探讨非条件刺激再评估的作用机制。结果表明：在消退阶段, 降低组对条件刺激的皮电反应显著低于控制组。同时评价性条件作用结果显示：经过非条件刺激再评估, 降低组较控制组对条件刺激的评价更为正性。说明非条件刺激降低再评估有效改变条件刺激的负性效价, 降低个体的恐惧反应、促进恐惧消退。     

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。     

提取-消退范式中复合刺激对恐惧消退的影响

情绪障碍治疗的关键在于消退条件性恐惧记忆,研究证明基于记忆再巩固的提取-消退范式能有效消除或改写原有的恐惧记忆。本研究将提取-消退范式应用到更复杂的恐惧记忆中,采用多感官复合刺激(声音+图片)作为条件刺激,以皮电反应作为恐惧反应指标,考察采用单个线索(声音或图片)、复合线索(声音+图片)进行提取-消退对条件性恐惧记忆的消退效果有何差异。结果表明:声音线索提取-消退组出现了自发恢复和重建效应,图片提取-消退组只出现了重建效应,复合刺激提取-消退组未出现自发恢复和重建效应。说明由复合刺激线索引发的条件性恐惧,采用复合刺激中的单个较强线索或原有完整线索进行提取-消退,对恐惧记忆的消退效果最好。     

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。     

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。     

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。     

刺激性质和预测情境对负性情绪习得的影响:ERP研究

探讨刺激性质和预测情境对负性情绪习得的影响及负性情绪产生的神经机制。采用事件相关电位(ERP)技术和条件性恐惧模型,18名被试在不同预测情境中做情绪判断任务,记录与负性非条件刺激(US)匹配和与中性US匹配的条件刺激(CS)诱发的ERP,考察负性情绪的产生机制。脑电结果显示:在可预测情境下,与中性US相比,负性US联结的CS诱发的P3波幅显著降低,i CNV波幅显著升高;在不可预测情境下,负性US和中性US联结的CS诱发的P3和i CNV波幅没有显著差异。此研究结果表明,刺激性质和预测情境交互影响负性情绪反应:在可预测情境下,负性情绪的产生由US性质决定;而在不可预测情境下,负性情绪的产生由刺激出现的预测情境决定。     

Different mechanisms of fear extinction dependent on length of time since fear acquisition

Fear extinction is defined as a decline in conditioned fear responses (CRs) following nonreinforced exposure to a feared conditioned stimulus (CS). Behavioral evidence indicates that extinction is a form of inhibitory learning: Extinguished fear responses reappear with the passage of time (spontaneous recovery), a shift of context (renewal), and unsignaled presentations of the unconditioned stimulus (reinstatement). However, there also is evidence to suggest that extinction is an "unlearning" process corresponding to depotentiation of potentiated synapses within the amygdala. Because depotentiation is induced more readily at short intervals following LTP induction and is not inducible at all at a sufficient delay, it may be that extinction initiated shortly following fear acquisition preferentially engages depotentiation/"unlearning," whereas extinction initiated at longer delays recruits a different mechanism. We investigated this possibility through a series of behavioral experiments examining the recoverability of conditioned fear following extinction. Consistent with an inhibitory learning mechanism of extinction, rats extinguished 24-72 h following acquisition exhibited moderate to strong reinstatement, renewal, and spontaneous recovery. In contrast, and consistent with an erasure mechanism, rats extinguished 10 min to 1 h after acquisition exhibited little or no reinstatement, renewal, or spontaneous recovery. These data support a model in which different neural mechanisms are recruited depending on the temporal delay of fear extinction.     

Pavlovian Disgust Conditioning and Generalization: Specificity and Associations With Individual Differences

Although studies have identified differences between fear and disgust conditioning, much less is known about the generalization of conditioned disgust. This is an important gap in the literature given that overgeneralization of conditioned disgust to neutral stimuli may have clinical implications. To address this knowledge gap, female participants (n = 80) completed a Pavlovian conditioning procedure in which one neutral food item (conditioned stimulus; CS+) was followed by disgusting videos of individuals vomiting (unconditioned stimulus; US) and another neutral food item (CS–) was not reinforced with the disgusting video. Following this acquisition phase, there was an extinction phase in which both CSs were presented unreinforced. Importantly, participants also evaluated generalization stimuli (GS+, GS?) that resembled, but were distinct from, the CS after each conditioning phase. As predicted, the CS+ was rated as significantly more disgusting and fear inducing than the CS? after acquisition and this pattern persisted after extinction. However, disgust ratings of the CS+ after acquisition were significantly larger than fear ratings. Participants also rated the GS+ as significantly more disgusting, but not fear inducing, than the GS? after acquisition. However, this effect was not observed after extinction. Disgust proneness did predict a greater increase in disgust and fear ratings of the CS+ relative to the CS? after acquisition and extinction. In contrast, trait anxiety predicted only higher fear ratings to the CS+ relative to the CS? after acquisition and extinction. Disgust proneness nor trait anxiety predicted the greater increase in disgust to the GS+ relative to the GS? after acquisition. These findings suggest that while conditioned disgust can generalize, individual difference variables that predict generalization remain unclear. The implications of these findings for disorders of disgust are discussed.     

Microstimulation reveals opposing influences of prelimbic and infralimbic cortex on the expression of conditioned fear

Recent studies using lesion, infusion, and unit-recording techniques suggest that the infralimbic (IL) subregion of medial prefrontal cortex (mPFC) is necessary for the inhibition of conditioned fear following extinction. Brief microstimulation of IL paired with conditioned tones, designed to mimic neuronal tone responses, reduces the expression of conditioned fear to the tone. In the present study we used microstimulation to investigate the role of additional mPFC subregions: the prelimbic (PL), dorsal anterior cingulate (ACd), and medial precentral (PrCm) cortices in the expression and extinction of conditioned fear. These are tone-responsive areas that have been implicated in both acquisition and extinction of conditioned fear. In contrast to IL, microstimulation of PL increased the expression of conditioned fear and prevented extinction. Microstimulation of ACd and PrCm had no effect. Under low-footshock conditions (to avoid ceiling levels of freezing), microstimulation of PL and IL had opposite effects, respectively increasing and decreasing freezing to the conditioned tone. We suggest that PL excites amygdala output and IL inhibits amygdala output, providing a mechanism for bidirectional modulation of fear expression.     

Selective and protracted effect of nifedipine on fear memory extinction correlates with induced stress response

Memory extinction, defined as a decrease of a conditioned response as a function of a non-reinforced conditioned stimulus presentation, has high biological and clinical relevance. Extinction is not a passive reversing or erasing of the plasticity associated with acquisition, but a novel, active learning process. Nifedipine blocks L-type voltage gated calcium channels (LVGCC) and has been shown previously to selectively interfere with the extinction, but not the acquisition, of fear memory. We studied here the effect of retrograde and anterograde shifts of nifedipine application, with respect to an extinction training, on the extinction of fear conditioning. Subcutaneous injection of 30 mg/kg nifedipine, at least up to 4 h before the extinction session, significantly impaired extinction, as did intraperitoneal injection of 15 mg/kg nifedipine, at least up to 2 h before extinction training. However, the injection of nifedipine also induced a strong and protracted stress response. The pharmacokinetics of nifedipine suggest that it was mainly this stress response that triggered the specific inhibition of extinction, not the blockade of LVGCC in the brain. Our results support recent findings that stress selectively interferes with the extinction, but not the acquisition, of fear memory. They also indicate that a pharmacological approach is not sufficient to study the role of brain LVGCC in learning and memory. Further research using specific genetically modified animals is necessary to delineate the role of LVGCC in fear memory extinction.     

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.     

Genetic Gating of Human Fear Learning and Extinction: Possible Implications for Gene-Environment Interaction in Anxiety Disorder

ABSTRACT— Pavlovian fear conditioning is a widely used model of the acquisition and extinction of fear. Neural findings suggest that the amygdala is the core structure for fear acquisition, whereas prefrontal cortical areas are given pivotal roles in fear extinction. Forty-eight volunteers participated in a fear-conditioning experiment, which used fear potentiation of the startle reflex as the primary measure to investigate the effect of two genetic polymorphisms (5-HTTLPR and COMTval158met) on conditioning and extinction of fear. The 5-HTTLPR polymorphism, located in the serotonin transporter gene, is associated with amygdala reactivity and neuroticism, whereas the COMTval158met polymorphism, which is located in the gene coding for catechol-O-methyltransferase (COMT), a dopamine-degrading enzyme, affects prefrontal executive functions. Our results show that only carriers of the 5-HTTLPR s allele exhibited conditioned startle potentiation, whereas carriers of the COMT met/met genotype failed to extinguish conditioned fear. These results may have interesting implications for understanding gene-environment interactions in the development and treatment of 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.     

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.