Greater sustained anxiety but not phasic fear in women compared to men

Startle reflex studies in rodents indicate that female are more reactive than rats in experimental models of sustained anxiety but not in models of phasic fear (Toufexis, 2007). This study examined evidence for a similar effect in humans. Participants were exposed to three conditions, (1) predictable aversive shocks signaled by a cue, (2) unpredictable shocks, and (3) no shocks. Acoustic startle stimuli were delivered regularly across conditions. Phasic startle potential to the threat cue in the predictable condition was not affected by sex. In contrast, and consistent with basic research, the sustained increase in startle in the predictable and unpredictable conditions was greater in women compared to men. Animal studies suggest that such an effect may be mediated by the effects of sexual dimorphism in limbic structures, including the bed nucleus of the stria terminalis. However, psychosocial factors may also contribute to this effect.     

Measuring anxious responses to predictable and unpredictable threat in children and adolescents

Research has highlighted the need for new methods to assess emotions in children on multiple levels to gain better insight into the complex processes of emotional development. The startle reflex is a unique translational tool that has been used to study physiological processes during fear and anxiety in rodents and in human participants. However, it has been challenging to implement developmentally appropriate startle experiments in children. This article describes a procedure that uses predictable and unpredictable aversive events to distinguish between phasic fear and sustained anxiety in children and adolescents. We investigated anxious responses, as measured with the startle reflex, in youths (N = 36, mean age = 12.63 years, range = 7-17) across three conditions: no aversive events (N), predictable aversive events (P), and unpredictable aversive events (U). Short-duration cues were presented several times in each condition. Aversive events were signaled by the cues in the P condition but were presented randomly in the U condition. Participants showed fear-potentiated startle to the threat cue in the P condition. Startle responses were also elevated between cues in the U condition compared with the N condition, suggesting that unpredictable aversive events can evoke a sustained state of anxiety in youths. This latter effect was influenced by sex, being greater in girls than in boys. These findings indicate the feasibility of this experimental induction of the startle reflex in response to predictable and unpredictable events in children and adolescents, enabling future research on interindividual differences in fear and anxiety and their development in youths.     

Contextual fear conditioning predicts subsequent avoidance behaviour in a virtual reality environment

Avoidance behaviour is a crucial component of fear and is importantly involved in the maintenance of anxiety disorders. Presumably, fear conditioning leads to avoidance of the feared object or context. A virtual reality contextual fear conditioning paradigm was used to investigate the association between explicit conditioning effects and subsequent avoidance behaviour. Mild electric shocks were administered in one context (anxiety context), but never in a second context (safety context). Subsequent avoidance behaviour was assessed by asking participants to choose two out of three contexts (a neutral context was added) to visit again. Participants avoided the anxiety context, but did not prefer the safety over the neutral context. Participants with substantial conditioning effects, as reflected in differential valence, arousal and anxiety ratings, avoided the anxiety context but not the safety context. In sum, we demonstrated an association between context conditioning effects on an explicit level and later avoidance behaviour.     

Failure to condition to a cue is associated with sustained contextual fear

The acquisition of a conditioned fear response is adaptive, as it enables the organism to appropriately respond to predictors of aversive events. Consequently, the absence of predictive cues can be used as a signal for safety. We aimed to study whether deficient fear conditioning might lead to maladaptive fear. Following previous work, we predicted that failure to learn the CS-US association would result in higher contextual fear, and that participants who failed to learn would tend to exhibit higher trait anxiety. Conditioning took place in a virtual environment with two contexts. In one of the two contexts, offset of a CS (light) was associated with a shock. Each participant visited two places (a house and an apartment) in each of 12 blocks. In one of these places shocks were administered at the offset of an 8-s period of lights on (CS). The results showed that half of the participants demonstrated differential shock expectancy between situations in the shock context in which the CS was present versus absent. This indicates that these participants learned the contingencies between the shocks and both the context and the light CS. In contrast, the other half of the participants learned only the association with the context. As predicted, learning the CS-US contingency resulted in reduced self-reported fear in the absence of the CS in the danger context compared to the presence of the CS. On the other hand, participants who failed to learn the association displayed a sustained aversive state throughout the duration of the danger context. Skin conductance measures confirmed this pattern of results. Fear-potentiated startle during the threat context compared to the safe context was significant in both groups, while startle was only potentiated during the CS in the threat context in the group that learned the CS association (trend-level significant). Finally, scores on Spielberger's self-report scale of trait anxiety tended to be higher in the group of participants who did not learn the CS-shock association in the danger context compared to participants who did. In conclusion, these results confirm higher contextual fear in participants who did not acquire a conditioned response to the cue in comparison to participants who did. Also, virtual reality contexts provide a useful tool for the study of context conditioning.     

Sensation seeking and the aversive motivational system

Sensation seeking (SS) has traditionally been viewed as a phenomenon of the appetitive motivational system. The limited SS research exploring contributions from the aversive motivational system reveals greater anxious reactivity to dangerous activities among low sensation seekers. The present study extends this line of work by comparing levels of fear and anxiety during anticipation of predictable and unpredictable aversive stimuli across high- and low-SS groups. Low sensation seekers displayed greater fear-potentiated startle (FPS) to predictable aversive stimuli, and only those low on SS showed FPS and skin conductance response effects during experimental contexts in which aversive stimuli were delivered unpredictably. Findings implicate enhanced apprehensive anticipation among those low on SS as a potential deterrent for their participation in intense and threatening stimulus events.     

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.     

Contextual fear conditioning predicts subsequent avoidance behaviour in a virtual reality environment

Avoidance behaviour is a crucial component of fear and is importantly involved in the maintenance of anxiety disorders. Presumably, fear conditioning leads to avoidance of the feared object or context. A virtual reality contextual fear conditioning paradigm was used to investigate the association between explicit conditioning effects and subsequent avoidance behaviour. Mild electric shocks were administered in one context (anxiety context), but never in a second context (safety context). Subsequent avoidance behaviour was assessed by asking participants to choose two out of three contexts (a neutral context was added) to visit again. Participants avoided the anxiety context, but did not prefer the safety over the neutral context. Participants with substantial conditioning effects, as reflected in differential valence, arousal and anxiety ratings, avoided the anxiety context but not the safety context. In sum, we demonstrated an association between context conditioning effects on an explicit level and later avoidance behaviour.     

Exposure to a stressor produces a long lasting enhancement of fear learning in rats

In contextual fear conditioning, footshock is given in a context, and re-exposure to this context elicits the conditional defensive response of freezing, a reliable behavioral index of conditional fear. Normally, the amount of contextual freezing is directly proportional to the number of shocks an animal receives in the context. However, pre-exposure to a stressor can produce an enhancement in conditional freezing. Pre-exposure to repeated footshock in one context produces an enhancement of conditional freezing to cues associated with a single shock in a second distinct context. This model of stress-enhanced fear learning (SEFL) can be utilized to study how stress affects learning of future aversive events. The experiments in this paper characterize the magnitude and longevity of SEFL. In the first experiment, the number of footshocks given during the pre-exposure session was varied and conditional fear to the single shock was assessed. Pre-exposure to 1 shock did not produce an enhancement in fear learning in the second context, but pre-exposure to 4 or 15 shocks did. The time-course of the enhancement was examined in the next two experiments. These experiments show that SEFL persists for at least 3 months.     

Determinants of early- vs late-onset dental fear in a longitudinal-epidemiological study.

A longitudinal investigation of risk factors for early- and late-onset dental fear was conducted. Early-onset dental fear was related to conditioning experiences (indexed via caries level and tooth loss), service use patterns, stress reactive personality and specific beliefs about health professionals. Late-onset dental fear was related to aversive conditioning experiences, irregular service use and an external locus of control. In contrast to recent findings for dental anxiety, personality factors were not strongly related to the onset of dental fear in young adulthood. The key role played by conditioning events in the development of both early- and late-onset dental fear was confirmed. Conditioning events appear to play a different role in the development of dental fear vs dental anxiety. This may reflect important, but largely ignored differences between these two closely-related constructs. Interventions for early-onset dental fear should aim to modify both the dental fear and the personality vulnerabilities that may contribute to the development of dental fear early in the life-course.     

Deficits in trace cued fear conditioning in galanin-treated rats and galanin-overexpressing transgenic mice

Galanin inhibits the release of several neurotransmitters and produces performance deficits in a variety of spatial and aversive learning and memory tasks. The experiments in this study investigated the role galanin has in emotional learning and memory using a standard delay cued and contextual fear conditioning task. Rats were administered galanin into the lateral ventricles before training, and scored for freezing behavior in the same context and in a novel context with and without an auditory cue (CS) that had been paired previously with an aversive stimulus (US). Galanin-overexpressing transgenic mice were tested in an identical behavioral protocol. The galanin-administered rats and the transgenic mice were not significantly different from their respective controls on this task. A more challenging trace cued and contextual fear conditioning procedure was administered to separate groups of galanin-treated rats and galanin-overexpressing transgenic mice. Subjects were trained with the same CS and US, however, a 2.5-sec delay was inserted between CS offset and US onset. Following the trace conditioning, rats administered galanin and mice overexpressing galanin both exhibited significantly less freezing to the CS in the novel context as compared with their control groups. These results indicate that the observed disruption of cued fear conditioning was specific to the more difficult trace conditioning task. These findings are the first demonstration that galanin impairs performance on an emotional memory task and support the hypothesis that galanin-induced deficits are specific to more difficult cognitive tasks.     

The Effects of Uncontrollable, Unpredictable Aversive and Appetitive Events: Similar Effects Warrant Similar, but not Identical, Explanations?

Exposure to uncontrollable, unpredictable appetitive events produces a variety of cognitive debilitations and vegetative changes, as does exposure to uncontrollable, unpredictable aversive events. Similarities include impaired escape from aversive events, impaired discrimination, finicky consumption, analgesia, and body weight loss. However, in stark contrast, uncontrollable aversive stress causes reduced motor activity where as similar appetitive treatment does not; aversively induced debilitation is causally related to energy regulation, whereas the appetitively induced effects are not. Parallel mechanisms are suggested to explain these effects in terms of a revised anxiety account of the aversive effects, and a frustration account of the appetitive effects. Finally, factors likely to limit important research to resolve the many remaining issues are identified: negative presentation of animal research, political decision making, and ignorance and fear in committees which review the ethics of research.     

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。     

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。     

All we need is a cue to remember: the effect of an extinction cue on renewal

In the present study, it was investigated by employing a human fear conditioning paradigm whether an extinction retrieval cue can attenuate renewal of conditioned responding after an extinction treatment procedure, and if so, what the precise role of such an extinction cue comprises. It was hypothesized that such a cue can attenuate renewal and would function as a safety signal capable of directly inhibiting the expectancy of an aversive outcome and conditioned skin conductance responding to a conditioned stimulus. The results demonstrated that the extinguished expectancy of an aversive outcome was renewed when the CS was presented outside the extinction context and that an extinction cue attenuated this effect. This extinction cue, however, only transferred its inhibitory properties to other, non-extinguished stimuli when there was no contextual switch. This safety signal function was not observed after a switch in context. Possible functions of the extinction cue and its application in extinction-based exposure treatments are discussed.     

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。     

Heart rate reactivity in HAD and LAD rats during Pavlovian fear conditioning

Recently, we reported that High-Alcohol-Drinking (HAD) rats exhibited selective deficits in active avoidance learning under alcohol-naive conditions, and that administration of moderate doses of alcohol (0.5 and 1.0 g/kg) facilitated learning in these rats (Blankenship et al., 2000; Rorick et al., 2003b). We hypothesized that the deficits resulted from excessive fear in the aversive learning context and that the anxiolytic properties of alcohol may have contributed to the improved learning that was observed after alcohol administration. This hypothesis was supported by a recent study in which prolonged freezing in HAD rats was seen after a classical fear conditioning procedure (Rorick et al., 2003a). To provide additional evidence that HAD rats indeed exhibit behaviors consistent with the expression of increased fear in aversive learning contexts, we employed a Pavlovian fear conditioning task to measure heart rate in HAD and Low-Alcohol-Drinking (LAD) rats. In this study, HAD (HAD-1 and HAD-2) and LAD (LAD-1 and LAD-2) rats were assigned to one of three pre-exposure conditions: Context Only, Context/Tone, or Sequential (Context Only followed by Context/Tone) Pre-Exposure. Following pre-exposure, fear conditioning acquisition and extinction procedures were identical for all groups. Results indicated that although no baseline differences were observed between HAD and LAD rats, HAD rats receiving Context-Only pre-exposure exhibited excessive heart rate reactivity to the tone conditional stimulus during fear conditioning acquisition, compared to LAD rats receiving the same pre-exposure conditions. These findings support the hypothesis that HAD rats exhibit behaviors consistent with increased fear in aversive learning contexts, as measured by autonomic conditioning.     

Return of fear in a human differential conditioning paradigm caused by a return to the original acquistion context

In a differential human fear conditioning paradigm evidence for ABA-renewal was obtained manipulating the lighting in the experimental room. During acquisition in either a dark or illuminated room, one neutral slide was sometimes paired with a loud aversive noise whereas another slide was not. Subsequently, extinction took place in the opposite lighting context. When afterwards the participants were tested again in the original acquisition context, measurements revealed a recovery of the conditioned electrodermal response and an increase in the retrospective verbal US-expectancy ratings. No response recovery was obtained in an AAA-group that received acquisition, extinction and test trials in one and the same context. Several theoretical explanations for this type of return of fear as well as implications for clinical practice are discussed.     

The effects of uncontrollable, unpredictable aversive and appetitive events: Similar effects warrant similar, but not identical, explanations?

Exposure to uncontrollable, unpredictable appetitive events produces a variety of cognitive debilitations and vegetative changes as does exposure to uncontrollable, unpredictable aversive events. Similarities include impaired escape from aversive events, impaired discrimination, finicky consumption, analgesia, and body weight loss. However, in stark contrast, uncontrollable aversive stress causes reduced motor activity where as similar appetitive treatment does not; aversively induced debilitation is causally related to energy regulation, whereas the appetitively induced effects are not. Parallel mechanisms are suggested to explain these effects in terms of a revised anxiety account of the aversive effects, and a frustration account of the appetitive effects. Finally, factors likely to limit important research to resolve the many remaining issues are identified: negative presentation of animal research, political decision making, and ignorance and fear in committees which review the ethics of research. The research reported here was supported by a Sydney University Special Project Grant and Australian Research Council Grants to R.F.S. Job. The paper was completed while the author was supported by a Special Study Leave Grant from the University of Sydney.     

Stronger renewal in human fear conditioning when tested with an acquisition retrieval cue than with an extinction retrieval cue

It was previously demonstrated in our laboratory that conditioned fear in humans can renew after extinction, when this procedure took place in a different context (ABA-renewal [Vansteenwegen et al. (2005). Return of fear in a human differential conditioning paradigm caused by a return to the original acquisition context. Behaviour Research and Therapy, 43(3), 323–336]). Using the same experimental design, we now tested the power of retrieval cues to interact with this contextual renewal phenomenon. Two groups went through acquisition and extinction (in a different context). They were then tested in the original acquisition context and in the presence of a retrieval cue. In the acquisition-cue group, this cue previously featured during the acquisition procedure; in the extinction-cue group, the cue previously featured during the extinction procedure. As expected, renewal of conditioned electro-dermal responding and retrospective expectancy ratings was strongest in the acquisition-cue group. Theoretical and clinical implications of this finding are discussed.     

The Malicious Serpent: Snakes as a prototypical stimulus for an evolved module of fear

As reptiles, snakes may have signified deadly threats in the environment of early mammals. We review findings suggesting that snakes remain special stimuli for humans. Intense snake fear is prevalent in both humans and other primates. Humans and monkeys learn snake fear more easily than fear of most other stimuli through direct or vicarious conditioning. Neither the elicitation nor the conditioning of snake fear in humans requires that snakes be consciously perceived; rather, both processes can occur with masked stimuli. Humans tend to perceive illusory correlations between snakes and aversive stimuli, and their attention is automatically captured by snakes in complex visual displays. Together, these and other findings delineate an evolved fear module in the brain. This module is selectively and automatically activated by once-threatening stimuli, is relatively encapsulated from cognition, and derives from specialized neural circuitry.