The development of an attentional bias for angry faces following Pavlovian fear conditioning

Although it is well documented that fear responses develop following aversive Pavlovian conditioning, it is unclear whether fear learning also manifests in the form of attentional biases for fear-related stimuli. Boschen, Parker, and Neumann (Boschen, M. J., Parker, I., & Neumann, D. L. (2007). Changes in implicit associations do not occur simultaneously to Pavlovian conditioning of physiological anxiety responses. Journal of Anxiety Disorders, 21, 788-803.) showed that despite the acquisition of differential skin conductance conditioned responses to angry faces paired (CS+) and unpaired (CS−) with an aversive shock, development of implicit associations was not subsequently observed on the Implicit Association Test. In the present study, participants (N = 76) were assigned either to a Shock or NoShock group and completed a similar aversive Pavlovian conditioning procedure with angry face CS+ and CS− stimuli. Participants next completed a visual probe task in which the angry face CS+ and CS− stimuli were paired with angry face control stimuli and neutral faces. Results confirmed that differential fear conditioning was observed in the Shock group but not in the NoShock group, and that the Shock group subsequently showed a selective attentional bias for the angry face CS+ compared with the CS− and control stimuli during the visual probe task. The findings confirm the interplay between learning-based mechanisms and cognitive processes, such as attentional biases, in models of fear acquisition and have implications for treatment of the anxiety disorders.     

Classical conditioning of autonomic fear responses is independent of contingency awareness

The role of contingency awareness in classical conditioning experiments using human subjects is currently under debate. This study took a novel approach to manipulating contingency awareness in a differential Pavlovian conditioning paradigm. Complex sine wave gratings were used as visual conditional stimuli (CS). By manipulating the fundamental spatial frequency of the displays, we were able to construct pairs of stimuli that varied in discriminability. One group of subjects was given an "easy" discrimination, and another was exposed to a "difficult" CS+ and CS-. A 3rd group was exposed to a stimulus that was paired with the unconditional stimulus (UCS) 50% of the time and served as a control. Skin conductance response (SCR) and continuous UCS expectancy data were measured concurrently throughout the experiment. Differential UCS expectancy was found only in the easy discrimination group. Differential SCRs were found in the easy discrimination group as well as in the difficult discrimination group, but not in the 50% contingency control. The difficult discrimination group did not exhibit differential UCS expectancy but did show clear differential SCR. These observations support a dual process interpretation of classical conditioning whereby conditioning on an implicit level can occur without explicit knowledge about the contingencies. The role of contingency awareness in classical conditioning experiments using human subjects is currently under debate. This study took a novel approach to manipulating contingency awareness in a differential Pavlovian conditioning paradigm. Complex sine wave gratings were used as visual conditional stimuli (CS). By manipulating the fundamental spatial frequency of the displays, we were able to construct pairs of stimuli that varied in discriminability. One group of subjects was given an "easy" discrimination, and another was exposed to a "difficult" CS+ and CS-. A 3rd group was exposed to a stimulus that was paired with the unconditional stimulus (UCS) 50% of the time and served as a control. Skin conductance response (SCR) and continuous UCS expectancy data were measured concurrently throughout the experiment. Differential UCS expectancy was found only in the easy discrimination group. Differential SCRs were found in the easy discrimination group as well as in the difficult discrimination group, but not in the 50% contingency control. The difficult discrimination group did not exhibit differential UCS expectancy but did show clear differential SCR. These observations support a dual process interpretation of classical conditioning whereby conditioning on an implicit level can occur without explicit knowledge about the contingencies.     

Opioid receptors mediate direct predictive fear learning: evidence from one-trial blocking

Pavlovian fear learning depends on predictive error, so that fear learning occurs when the actual outcome of a conditioning trial exceeds the expected outcome. Previous research has shown that opioid receptors, including μ-opioid receptors in the ventrolateral quadrant of the midbrain periaqueductal gray (vlPAG), mediate such predictive fear learning. Four experiments reported here used a within-subject one-trial blocking design to study whether opioid receptors mediate a direct or indirect action of predictive error on Pavlovian association formation. In Stage I, rats were trained to fear conditioned stimulus (CS) A by pairing it with shock. In Stage II, CSA and CSB were co-presented once and co-terminated with shock. Two novel stimuli, CSC and CSD, were also co-presented once and co-terminated with shock in Stage II. The results showed one-trial blocking of fear learning (Experiment 1) as well as one-trial unblocking of fear learning when Stage II training employed a higher intensity footshock than was used in Stage I (Experiment 2). Systemic administrations of the opioid receptor antagonist naloxone (Experiment 3) or intra-vlPAG administrations of the selective μ-opioid receptor antagonist CTAP (Experiment 4) prior to Stage II training prevented one-trial blocking. These results show that opioid receptors mediate the direct actions of predictive error on Pavlovian association formation.     

Amygdala and hippocampal activity during acquisition and extinction of human fear conditioning

Previous functional magnetic resonance imaging (fMRI) studies have characterized brain systems involved in conditional response acquisition during Pavlovian fear conditioning. However, the functional neuroanatomy underlying the extinction of human conditional fear remains largely undetermined. The present study used fMRI to examine brain activity during acquisition and extinction of fear conditioning. During the acquisition phase, participants were either exposed to light (CS) presentations that signaled a brief electrical stimulation (paired group) or received light presentations that did not serve as a warning signal (control group). During the extinction phase, half of the paired group subjects continued to receive the same treatment, whereas the remainder received light alone. Control subjects also received light alone during the extinction phase. Changes in metabolic activity within the amygdala and hippocampus support the involvement of these regions in each of the procedural phases of fear conditioning. Hippocampal activity developed during acquisition of the fear response. Amygdala activity increased whenever experimental contingencies were altered, suggesting that this region is involved in processing changes in environmental relationships. The present data show learning-related amygdala and hippocampal activity during human Pavlovian fear conditioning and suggest that the amygdala is particularly important for forming new associations as relationships between stimuli change.     

Associative regulation of Pavlovian fear conditioning: unconditional stimulus intensity, incentive shifts, and latent inhibition.

Conditional stimuli (CS) associated with painful unconditional stimuli (US) produce a naloxone-reversible analgesia. The analgesia serves as a negative-feedback regulation of fear conditioning that can account for the impact of US intensity and CS predictiveness on Pavlovian fear conditioning. In Experiment 1 training under naloxone produced learning curves that approached the same high asymptote despite US intensity. Shifting drug treatment during acquisition had effects that paralleled US intensity shifts. In Experiment 3 naloxone reversed Hall-Pearce (1979) negative transfer using a contextual CS, indicating that conditional analgesia acquired during the CS-weak-footshock phase retards acquisition in the CS-strong-footshock phase. Experiment 5 used a tone CS in both a latent-inhibition and a negative-transfer procedure. Only negative transfer was blocked by naloxone. Therefore, negative transfer but not latent inhibition is mediated by a reduction of US processing.     

Instructed fear learning,extinction, and recall: additive effects of cognitive information on emotional learning of fear

The effects of instruction on learning of fear and safety are rarely studied. We aimed to examine the effects of cognitive information and experience on fear learning. Fourty healthy participants, randomly assigned to three groups, went through fear conditioning, extinction learning, and extinction recall with two conditioned stimuli (CS+). Information was presented about the presence or absence of conditioned stimulus–unconditioned stimulus (CS–US) contingency at different stages of the experiment. Information about the CS–US contingency prior to fear conditioning enhanced fear response and reduced extinction recall. Information about the absence of CS–US contingency promoted extinction learning and recall, while omission of this information prior to recall resulted in fear renewal. These findings indicate that contingency information can facilitate fear expression during fear learning, and can facilitate extinction learning and recall. Information seems to function as an element of the larger context in which conditioning occurs.     

Using pavlovian higher-order conditioning paradigms to investigate the neural substrates of emotional learning and memory

In first-order Pavlovian conditioning, learning is acquired by pairing a conditioned stimulus (CS) with an intrinsically motivating unconditioned stimulus (US; e.g., food or shock). In higher-order Pavlovian conditioning (sensory preconditioning and second-order conditioning), the CS is paired with a stimulus that has motivational value that is acquired rather than intrinsic. This review describes some of the ways higher-order conditioning paradigms can be used to elucidate substrates of learning and memory, primarily focusing on fear conditioning. First-order conditioning, second-order conditioning, and sensory preconditioning allow for the controlled demonstration of three distinct forms of memory, the neural substrates of which can thus be analyzed. Higher-order conditioning phenomena allow one to distinguish more precisely between processes involved in transmission of sensory or motor information and processes involved in the plasticity underlying learning. Finally, higher-order conditioning paradigms may also allow one to distinguish between processes involved in behavioral expression of memory retrieval versus processes involved in memory retrieval itself.     

Emotional conditioning to masked stimuli and modulation of visuospatial attention

Two studies investigated the effects of conditioning to masked stimuli on visuospatial attention. During the conditioning phase, masked snakes and spiders were paired with a burst of white noise, or paired with an innocuous tone, in the conditioned stimulus (CS)+ and CS- conditions, respectively. Attentional allocation to the CSs was then assessed with a visual probe task, in which the CSs were presented unmasked (Experiment 1) or both unmasked and masked (Experiment 2), together with fear-irrelevant control stimuli (flowers and mushrooms). In Experiment 1, participants preferentially allocated attention to CS+ relative to control stimuli. Experiment 2 suggested that this attentional bias depended on the perceived aversiveness of the unconditioned stimulus and did not require conscious recognition of the CSs during both acquisition and expression.     

Neural substrates of individual differences in human fear learning: Evidence from concurrent fMRI, fear-potentiated startle, and US-expectancy data

To provide insight into individual differences in fear learning, we examined the emotional and cognitive expressions of discriminative fear conditioning in direct relation to its neural substrates. Contrary to previous behavioral-neural (fMRI) research on fear learning--in which the emotional expression of fear was generally indexed by skin conductance--we used fear-potentiated startle, a more reliable and specific index of fear. While we obtained concurrent fear-potentiated startle, neuroimaging (fMRI), and US-expectancy data, healthy participants underwent a fear-conditioning paradigm in which one of two conditioned stimuli (CS(+) but not CS(-)) was paired with a shock (unconditioned stimulus [US]). Fear learning was evident from the differential expressions of fear (CS(+) > CS(-)) at both the behavioral level (startle potentiation and US expectancy) and the neural level (in amygdala, anterior cingulate cortex, hippocampus, and insula). We examined individual differences in discriminative fear conditioning by classifying participants (as conditionable vs. unconditionable) according to whether they showed successful differential startle potentiation. This revealed that the individual differences in the emotional expression of discriminative fear learning (startle potentiation) were reflected in differential amygdala activation, regardless of the cognitive expression of fear learning (CS-US contingency or hippocampal activation). Our study provides the first evidence for the potential of examining startle potentiation in concurrent fMRI research on fear learning.     

Computer-assisted behavioral assessment of Pavlovian fear conditioning in mice

In Pavlovian fear conditioning, a conditional stimulus (CS, usually a tone) is paired with an aversive unconditional stimulus (US, usually a foot shock) in a novel context. After even a single pairing, the animal comes to exhibit a long-lasting fear to the CS and the conditioning context, which can be measured as freezing, an adaptive defense reaction in mice. Both context and tone conditioning depend on the integrity of the amygdala, and context conditioning further depends on the hippocampus. The reliability and efficiency of the fear conditioning assay makes it an excellent candidate for the screening of learning and memory deficits in mutant mice. One obstacle is that freezing in mice has been accurately quantified only by human observers, using a tedious method that can be subject to bias. In the present study we generated a simple, high-speed, and highly accurate algorithm that scores freezing of four mice simultaneously using NIH Image on an ordinary Macintosh computer. The algorithm yielded a high correlation and excellent linear fit between computer and human scores across a broad range of conditions. This included the ability to score low pretraining baseline scores and accurately mimic the effects of two independent variables (shock intensity and test modality) on fear. Because we used a computer and digital video, we were able to acquire a secondary index of fear, activity suppression, as well as baseline activity scores. Moreover, we measured the unconditional response to shock. These additional measures can enhance the sensitivity of the assay to detect interesting memory phenotypes and control for possible confounds. Thus, this computer-assisted system for measuring behavior during fear conditioning allows for the standardized and carefully controlled assessment of multiple aspects of the fear conditioning experience.     

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.     

Automated assessment of conditioning parameters for context and cued fear in mice

A behavioral technique often used to evaluate the cognitive performance of rats and mice is the fear conditioning paradigm. During conditioned fear experiments, freezing responses shown by rodents after exposure to environmental stimuli previously paired to an aversive experience provide a behavioral index of the animal's associative abilities. The present study examined the ability of a computer-controlled automated Freeze Monitor system for recording immobility behavior in mice. The sensitivity of the automated procedure to detect group differences caused by the application of various training protocols was also evaluated. Statistical analyses revealed significant positive correlations between immobility scores obtained with the automated apparatus and hand-scored data collected by a continuous or a time-sampling method. Behavioral patterns recorded by the computerized system were very similar to those obtained by the hand-scoring methods adopted. In particular, during context testing, exposure to environmental stimuli previously paired with a mild foot shock (unconditioned stimulus [US]) evoked increased immobility behavior in mice conditioned with the US compared with levels of immobility displayed by mice previously confined to the same contextual stimuli without receiving the US. Moreover, although during conditioned stimulus (CS) testing, mice previously exposed to the US displayed high levels of immobility when confined to environmental cues much different from those paired with the US (contextual fear generalization), both hand-scored and automated results revealed the effect of CS–US pairing (increased immobility) only in mice trained to associate the two stimuli (paired group) but not in mice exposed to both CS and US separated by a 40-sec time interval (unpaired group) or in mice receiving only the US (US group) during conditioning sessions. Overall, the results show associative conditioning measured in an automated apparatus and highlight the utility of obtaining both latency as well as beam interruption parameters.     

The development of cued versus contextual conditioning in a predictable and an unpredictable human fear conditioning preparation

In this human fear conditioning study, the online development of conditioned US-expectancy to discrete cues and background contexts was measured in two groups. In the paired group (n=30), the CS was systematically followed by an aversive shock (US). In the unpaired group (n=30), CS and US were presented explicitly unpaired. Using US-expectancy ratings, we replicated the basic finding already illustrated in humans with startle modulation. In the paired group, the CS elicited more US-expectancy than the context, whereas in the unpaired group, the context elicited more US-expectancy than the CS. Interestingly, we also observed a trial-by-trial development of conditioning to the context in the unpaired group as indicated by a significant linear trend. This gradual development and the evidence for the role of US-expectancy in contextual fear add to the idea that cued and contextual fear rely on the same basic associative processes.     

Fearing shades of grey: individual differences in fear responding towards generalisation stimuli

Individual differences in fear generalisation have been proposed to play a role in the aetiology and/or maintenance of anxiety disorders, but few data are available to directly support that claim. The research that is available has focused mostly on generalisation of peripheral and central physiological fear responses. Far less is known about the generalisation of avoidance, the behavioural component of fear. In two experiments, we evaluated how neuroticism, a known vulnerability factor for anxiety, modulates an array of fear responses, including avoidance tendencies, towards generalisation stimuli (GS). Participants underwent differential fear conditioning, in which one conditioned stimulus (CS+) was repeatedly paired with an aversive outcome (shock; unconditioned stimulus, US), whereas another was not (CS?). Fear generalisation was observed across measures in Experiment 1 (US expectancy and evaluative ratings) and Experiment 2 (US expectancy, evaluative ratings, skin conductance, startle responses, safety behaviours), with overall highest responding to the CS+, lowest to the CS? and intermediate responding to the GSs. Neuroticism had very little impact on fear generalisation (but did affect GS recognition rates in Experiment 1), in line with the idea that fear generalisation is largely an adaptive process.     

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。     

Differential pavlovian fear conditioning as a function of the qualitative nature of the UCS: Constant versus pulsating shock

Dogs were trained in a shuttlebox to perform an instrumental avoidance response to a visual signal. Then, while pharmacologically immobilized in a hammock, they received differential Pavlovian fear conditioning with two tones: one paired with a constant shock and one with a pulsating shock. During Pavlovian conditioning EKG’s were recorded. Later, in the shuttlebox, Ss received tests for the transfer of control of avoidance responding. Although no significant heart rate differences were found,Ss hurdled the barrier significantly more quickly in response to the tone previously paired with the pulsating shock than to the tone paired with the constant shock, indicating that pulsating shock results in better fear conditioning.     

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。     

Contextual and auditory fear conditioning are mediated by the lateral, basal, and central amygdaloid nuclei in rats

A large body of literature implicates the amygdala in Pavlovian fear conditioning. In this study, we examined the contribution of individual amygdaloid nuclei to contextual and auditory fear conditioning in rats. Prior to fear conditioning, rats received a large electrolytic lesion of the amygdala in one hemisphere, and a nucleus-specific neurotoxic lesion in the contralateral hemisphere. Neurotoxic lesions targeted either the lateral nucleus (LA), basolateral and basomedial nuclei (basal nuclei), or central nucleus (CE) of the amygdala. LA and CE lesions attenuated freezing to both contextual and auditory conditional stimuli (CSs). Lesions of the basal nuclei produced deficits in contextual and auditory fear conditioning only when the damage extended into the anterior divisions of the basal nuclei; damage limited to the posterior divisions of the basal nuclei did not significantly impair conditioning to either auditory or contextual CS. These effects were typically not lateralized, although neurotoxic lesions of the posterior divisions of the basal nuclei had greater effects on contextual fear conditioning when the contralateral electrolytic lesion was placed in the right hemisphere. These results indicate that there is significant overlap within the amygdala in the neural pathways mediating fear conditioning to contextual and acoustic CS, and that these forms of learning are not anatomically dissociable at the level of amygdaloid nuclei.     

Generalisation of fear and avoidance along a semantic continuum

Directly conditioned fear and avoidance readily generalises to dissimilar but conceptually related stimuli. Here, for the first time, we examined the conceptual/semantic generalisation of both fear and avoidance using real words (synonyms). Participants were first exposed to a differential fear conditioning procedure in which one word (e.g., “broth”; CS+) was followed with brief electric shock [unconditioned stimulus (US)] and another was not (e.g., “assist”; CS–). Next, an instrumental conditioning phase taught avoidance in the presence the CS+ but not the CS–. During generalisation testing, synonyms of the CS+ (e.g., “soup”; GCS+) and CS– (e.g., “help”; GCS–) were presented in the absence of shock. Conditioned fear and avoidance, measured via skin conductance responses, behavioural avoidance and US expectancy ratings, generalised to the semantically related, but not to the semantically unrelated, synonyms. Findings have implications for how natural language categories and concepts mediate the expansion of fear and avoidance repertoires in clinical contexts.     

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。