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Involvement of the central nucleus and basolateral complex of the amygdala in fear conditioning measured with fear-potentiated startle in rats trained concurrently with auditory and visual conditioned stimuli.

The goal of this work was to test the involvement of the central nucleus and basolateral complex of the amygdala in fear conditioning, using auditory and visual conditioned stimuli (CSs). The acoustic startle reflex in rats was used as the behavioral index of conditioning because startle is reliably enhanced in the presence of a conditioned stimulus (CS) previously paired with a footshock. Initially, differential conditioning procedures indicated reliable discrimination between a noise CS and a visual CS. Subsequently, the effects of amygdala lesions were evaluated when both modalities were paired with shocks in the same rats. Electrolytic or ibotenic acid lesions of the central nucleus of the amygdala blocked fear-potentiated startle to both auditory and visual CSs, consistent with the idea that the central nucleus serves as a response independent, final common relay for fear conditioning. Similarly, pre- or post-training electrolytic or NMDA-induced lesions of the basolateral complex of the amygdala, which damaged the lateral nucleus, and most of the basolateral nucleus, disrupted fear-potentiated startle to both CS modalities. This finding is consistent with the suggestion that, in fear conditioning, the basolateral complex of the amygdala serves as an obligatory relay of sensory information from subcortical and cortical sensory areas to the central nucleus of the amygdala.

Acoustic Stimulation↗

AMPA receptor facilitation accelerates fear learning without altering the level of conditioned fear acquired.

Rats treated with the AMPA receptor-facilitating drug 1-(quinoxolin-6-ylcarbonyl)piperidine (BDP-12) during training acquired fear conditioning to a tone faster than vehicle-treated controls. The effect on acquisition was dependent on the dose given. BDP-12-treated rats and vehicle-treated controls reached the same level of conditioned fear and extinguished at the same rate. The dissociation of learning rate from these other normally covariant measures suggests that the drug had a specific and isolated effect on acquisition. Controls for drug effects on stimulus sensitivity, locomotor activity, generalized fearfulness, and other performance factors support this interpretation. The known action of BDP-12 on receptor dynamics suggests that its effect on acquisition may be attributed to specific modulation of an AMPA and NMDA receptor-dependent plasticity mechanism. The finding that the drug accelerates acquisition but does not affect the level of conditioned fear acquired parallels the effect of the drug on long-term potentiation (LTP) (increasing the rate but not the ceiling of potentiation) and suggests that common mechanisms may underlie fear conditioning and LTP.

Animals↗

Understanding the effects of fear-arousing communications: the role of cognitive factors and amount of fear aroused.

This paper reports an experimental study investigating the role of cognitive factors and fear in mediating the effects of "fear-arousing" health threat communications. Seventy-seven cigarette smokers were shown either a videotape about smoking or a control videotape on a different health topic before completing a questionnaire assessing their intentions to try to quit, the level of fear aroused, and three cognitive factors: (a) probability difference (perceived reduction in risk of health damage that follows from successful cessation), (b) utility of health damage, and (c) confidence. The smoking videotape influenced probability difference, utility, intentions, and follow-up reports of attempts at cessation. As predicted, both probability difference and utility influenced intention, which in turn influenced behavior. Neither confidence nor the amount of fear aroused by the videotape had significant effects on intention.

Adult↗

Willingness to pay for dental fear treatment. Is supplying dental fear treatment socially beneficial?

The aim of this paper is to discuss the social desirability of supplying dental fear treatment in addition to dental treatment using the results from a treatment programme for patients with severe dental fear. The programme consisted of three different dental fear treatments: Cognitive therapy, applied relaxation and nitrous oxide sedation, in addition to dental treatment. To evaluate the effects of uncertainty on the patients' benefits from the programme, we elicited their willingness to pay, both before and after receiving treatment, since we expected patients to be uncertain about the outcome of the dental fear treatment. We found that the social desirability of the treatment was very sensitive to uncertainty. While only 24% of the patients were willing to pay the actual cost of the treatment before attending, 71% were willing to pay afterwards. This implies that many patients who would benefit from the treatment ex post are not willing to pay the cost of the treatment ex ante, and will thus not receive any treatment unless it is subsidized.

Adult↗

The human fear-circuitry and fear-induced fainting in healthy individuals--the paleolithic-threat hypothesis.

The Paleolithic-Threat hypothesis reviewed here posits that habitual efferent fainting can be traced back to fear-induced allelic polymorphisms that were selected into some genomes of anatomically, mitochondrially, and neurally modern humans (Homo sapiens sapiens) in the Mid-Paleolithic because of the survival advantage they conferred during periods of inescapable threat. We posit that during Mid-Paleolithic warfare an encounter with "a stranger holding a sharp object" was consistently associated with threat to life. A heritable hardwired or firm-wired (prepotentiated) predisposition to abruptly increase vagal tone and collapse flaccidly rather than freeze or attempt to flee or fight in response to an approaching sharp object, a minor injury, or the sight of blood, may have evolved as an alternative stress-induced fear-circuitry response. Such a stable (balanced) polymorphism for the hemodynamically "paradoxical" flaccid-immobility in response to these stimuli may have increased some non-combatants' chances of survival. This is consistent with the unusual age and sex pattern of fear-induced fainting. The Paleolithic-Threat hypothesis also predicts a link to various hypo-androgenic states (e. g. low dehydroxy-epiandrosterone-sulfate. We offer five predictions testable via epidemiological, clinical, and ethological/ primatological methods. The Paleolithic-Threat hypothesis has implications for research in the aftermath of man-made disasters, such as terrorism against civilians, a traumatic event in which this hypothesis predicts epidemics of fear-induced fainting.

Adult↗

Treatment of claustrophobias and snake/spider phobias: fear of arousal and fear of context.

Forty-nine individuals with fears of snakes or spiders, and 21 individuals with claustrophobic fear were assigned randomly to two sessions of either in vivo exposure plus relaxation or in vivo exposure plus disconfirmation of misappraisals of bodily sensations. Behavioral, subjective and physiological assessments were conducted pre and post treatment, and 4 weeks later. As hypothesized, disconfirmation of misappraisals of bodily sensations benefited claustrophobic fear reduction, but had little effect on fears of snakes or spiders. However, differential treatment effects failed to generalize to nontargetted phobic situations, or generalize over time. In addition, the two treatments affected basic beliefs about arousal sensations equally.

Adolescent↗

5-HT2- and D1-mechanisms of the basolateral nucleus of the amygdala enhance conditioned fear and impair unconditioned fear.

The inferior colliculus (IC) is involved in processing of auditory information, but also integrates acoustic information of aversive nature. In fact, chemical stimulation of the IC with semicarbazide (SMC) - an inhibitor of the GABA synthesizing enzyme glutamic acid decarboxylase - has been found to cause defensive behavior in an open-field test and functions as an unconditioned stimulus in the place conditioned aversion test (PCA). A question has arisen regarding whether the basolateral nucleus of the amygdala (BLA) is involved in the acquisition of the aversive information ascending from the IC and whether dopaminergic and serotoninergic mechanisms of the BLA regulate this process. Recent evidence has shown that inactivation of the BLA with muscimol inhibits the PCA and causes an increase in the aversiveness of the chemical stimulation of the IC. Based on this, we examined the effects of ketanserin and SCH-23390, antagonists of the 5HT(2) and D(1) receptors, respectively, on the conditioned and unconditioned fear elicited by IC stimulation with SMC. The results obtained confirm the crucial role of 5-HT(2)- and D(1)-mechanisms of the BLA on conditioned fear in that ketanserin and SCH-23390 injections into the BLA caused a reduction in the PCA. On the other hand, ketanserin and SCH-23390 injections into the BLA enhanced the aversiveness of the IC injections of SMC. These findings suggest that while 5-HT(2) and DA(1) mechanisms in the BLA appear to facilitate the conditioned fear they inhibit the unconditioned fear triggered by IC activation.

Amygdala↗

Driving fear and driving skills: comparison between fearful and control samples using standardised on-road assessment.

The present study explores driving skills in a group of 50 media-recruited driving-fearful and 50 control drivers, all of whom were women. Participants completed an on-road practical driving assessment with a professional driving instructor. Diagnostic as well as pre-post self-report and instructor driving assessments were conducted. Fearful drivers made more errors on the driving assessment than controls. However, the pattern of errors was identical for both groups, indicating that fear and anxiety may be associated with the number rather than the type of driving errors made. These differences remained when factors such as driving history, current driving frequency, and diagnosis were controlled using case selection. More research is needed to replicate the findings in more diverse samples. Additional work should also aim to clarify the specific role of driving skills in driving fear, which will facilitate treatment planning for exposure-based treatments and help identify cases where driving skills assessment may be appropriate.

Accidents, Traffic↗

Pain and pain-related fear are associated with functional and social disability in an occupational setting: evidence of mediation by pain-related fear.

This study examined the role of work-related, psychosocial and psychological factors in predicting functional and social disability in working employees. In a cross-sectional design, 890 working employees (reporting at least 1 day of back pain during the past year) completed self-report measures of back pain, disability, pain-related fear, negative and positive affectivity, job satisfaction, job stress and physical work load. Regression analyses revealed that pain intensity was a strong predictor of functional (beta = .69, p < .001) and social disability (beta = .67, p < .001). Fear of (re)injury due to movement (beta = .25, p < .001; beta = .28, p < .001) had additional predictive value in both models. Further, (singular) mediation tests indicated that fear for (re)injury partially mediated the relation between pain intensity and disability, and between negative affectivity and disability. Finally, path analyses revealed both fear and pain intensity as mediators between negative affectivity and disability. Overall, our findings point at the relevance of the cognitive-behavioral model of avoidance in occupational settings.

Adult↗

The neuropsychology of fear learning and fear regulation.

In the current review article it is suggested that fear is a central emotional state that can be activated by external threat cues. The subcortical defensive system cannot only be activated by intrinsically aversive events but shows also strong plasticity enabling previously innocuous stimuli to get access to the fear system after they were paired with painful outcomes. On the other hand, aversive conditioning does not only result in the acquisition of a defensive disposition, the organism also learns on a pure cognitive level that one stimulus predicts the occurrence of another stimulus. It is suggested here that potentiation of the acoustic startle reflex is a rather specific measure for fear acquisition, while skin conductance discrimination indexes contingency learning. It is shown that the acquisition of fear-potentiated startle does not require cortical processing of the conditioned stimulus. Moreover, data indicate that conditioned startle potentiation is abolished in patients with unilateral lesions of the amygdala. Finally, conditioned startle potentiation can be obtained without contingency awareness, which on the other hand is necessary for skin conductance conditioning to occur. It is suggested that the learning of stimulus relations is mediated by the hippocampus and that conditioned startle potentiation is also mediated by the hippocampus in trace conditioning.

Animals↗

Fear activation and distraction during the emotional processing of claustrophobic fear.

We tested several hypotheses derived from the emotional processing theory of fear reduction by manipulating claustrophobic participants' focus of attention during in vivo exposure. Sixty participants displaying marked claustrophobic fear were randomized to one of four exposure conditions. Each participant received a total of 30-min of self-guided exposure 2-weeks after pretreatment testing. One group attended to threatening words and images during exposure (TW) and was compared to a control group that attended to neutral words and images (NW). A third group performed a demanding cognitive load task--a modified Seashore Rhythm Test during exposure (SR) and was compared to an exposure only (EO) control group. Contrary to prediction, the threat word manipulation was not associated with lower levels of fear following treatment. Consistent with prediction, the distraction manipulation resulted in less fear reduction at post-treatment. Treatment process analyses revealed that the negative effects of distraction on treatment outcome manifested early as slower between-trial habituation. These results and their relevance to emotional processing theory are discussed.

Adolescent↗

Fears born and bred: toward a more inclusive theory of fear acquisition.

Alleged differences between associative and non-associative perspectives are sometimes more apparent than real. The non-associative model describes a pathway to fear that is complementary to associative pathways. It does not seek to usurp conditioning models as applied to evolutionary-neutral fear. We discuss vexing definitional issues surrounding what qualifies as a conditioning event and what characterises the non-associative pathway. Genetic findings are shown to be consistent with the non-associative model of fear. Following discussion of the relation between stress-diathesis models and the non-associative position we conclude by urging a developmental, life-course approach to the understanding of fear acquisition.

Conditioning, Psychological↗

Infusion of quinpirole and muscimol into the ventral tegmental area inhibits fear-potentiated startle: implications for the role of dopamine in fear expression.

Dopamine (DA) D2 and gamma-aminobutyric acid (GABA)A somatodendritic receptors tonically inhibit mesolimbic projection neurons in the A10 DA cell grouping of the ventral tegmentum. In the present study we determined the contribution of the ventral tegmental area (VTA) to the expression of a classically conditioned fear-induced increase in the acoustic startle reflex. Saline applied to VTA neurons did not modify the capacity of a light previously associated with footshock to potentiate acoustic startle amplitudes; conversely, bilateral administration of the DA D2/3 agonist quinpirole or the GABAA receptor agonist muscimol into the ventral tegmentum blocked fear-potentiated startle without altering baseline acoustic startle responding. It was suggested that DA VTA neurons regulate the excitatory aspects of fear expression by gating levels of aversive emotional arousal within the amygdala-based fear system.

Analysis of Variance↗

Insulin-treated diabetes patients with fear of self-injecting or fear of self-testing: psychological comorbidity and general well-being.

OBJECTIVE: To examine psychological functioning and self-management behaviours of Dutch adult patients with insulin-requiring diabetes mellitus suffering from extreme fear of self-injecting (FSI) and/or fear of self-testing (FST). METHODS: A cross-sectional survey was performed in a sample of insulin-treated diabetes patients (n=1275; 51.1% male; age 49.7+/-15.8 years; 58.0% Type 1 diabetes), assessing FSI and FST. Patients completed the questionnaires concerning trait/state anxiety, depression, fear of hypoglycemia, diabetes-related distress, diabetes self-care activities, and general well-being. Comparisons were made on these measures between patients with extremely high scores on FSI and/or FST (> or = 95th percentile) and the other patients. Patients with extreme scores on FSI and/or FST were invited to take part in a second survey to assess the prevalence of major depression, common fears/phobias, and psychoneuroticism. RESULTS: People with extreme FSI/ FST scores, as compared to the other patients, reported higher levels of trait/state anxiety and depression. This group also reported more fear of hypoglycaemia and diabetes-related distress, had lower levels of general well-being, and reported less frequent self-monitoring of blood glucose. The second survey showed 11.1% of patients with extreme FSI/FST reporting scores indicating major depression. Prevalence of scores greater than or equal to the high scores on phobias (38.0-63.3%) and psychoneuroticism (27.8%) were consistently higher than norm group prevalences. DISCUSSION: Extreme levels of FSI and/or FST are associated with high diabetes-related distress, poor general well-being, and psychological comorbidity, as well as poorer adherence to the diabetes treatment regimen. It is concluded that patients with extreme FSI/FST are often burdened with more than this specific phobia.

Adult↗

Increased social fear and decreased fear of objects in monkeys with neonatal amygdala lesions.

The amygdala has been implicated in the mediation of emotional and species-specific social behavior (Kling et al., 1970; Kling and Brothers, 1992; Kluver and Bucy, 1939; Rosvold et al., 1954). Humans with bilateral amygdala damage are impaired in judging negative emotion in facial expressions and making accurate judgements of trustworthiness (Adolphs et al., 1998, 1994). Amygdala dysfunction has also been implicated in human disorders ranging from social anxiety (Birbaumer et al., 1998) to depression (Drevets, 2000) to autism (Bachevalier, 1994; Baron-Cohen et al., 2000; Bauman and Kemper, 1993). We produced selective amygdala lesions in 2-week-old macaque monkeys who were returned to their mothers for rearing. At 6-8 months of age, the lesioned animals demonstrated less fear of novel objects such as rubber snakes than age-matched controls. However, they displayed substantially more fear behavior than controls during dyadic social interactions. These results suggest that neonatal amygdala lesions dissociate a system that mediates social fear from one that mediates fear of inanimate objects. Furthermore, much of the age-appropriate repertoire of social behavior was present in amygdala-lesioned infants indicating that these lesions do not produce autistic-like behavior in monkeys. Finally, amygdala lesions early in development have different effects on social behavior than lesions produced in adulthood.

Aging↗

Learned fear, emotional reactivity and fear of heights: a factor analytic map from a large F(2) intercross of Roman rat strains.

Anxiety-related behaviours were evaluated across various tests in a 800 F(2)-intercross of the Roman high- and low-avoidance inbred rats. These tests either evoke unlearned (open field [OF]; plus-maze [PM]; hole-board [HB]; spontaneous activity [A]; and acoustic startle reflex [ASR]) or learned (classical fear conditioning [CFC]; and shuttlebox avoidance conditioning [SAC]), anxious/fearful responses. Using factor analysis (oblique rotation), we obtained a six-fold solution with 14 variables derived from all tests. These six factors represented SAC, CFC, PM anxiety, PM and OF activity, ASR anxiety, plus a mixed whole of anxious and activity variables (from OF and A), respectively. In searching for a smaller number of meaningful factors, we applied a three-factor solution that coherently corresponded with differentiated facets of fearfulness, rather than with the tests. Results showed that (1) measures of SAC and CFC strongly loaded onto Factor 1, labelled as "Learned Fear"; (2) a blend of almost all variables loaded onto Factor 2, called "Emotional Reactivity"; and (3) open arm behaviour in the PM loaded onto Factor 3, called "Fear of Heights." After discussing limitations of this apparently consistent behavioural map of anxiety, we advance some connections between those factors with quantitative trait loci candidates (genetic markers) as detected in the same sample.

Animals↗

Factors related to fear in patients undergoing cataract surgery: a qualitative study focusing on factors associated with fear and reassurance among patients who need to undergo cataract surgery.

The aim was to identify factors that are related to fear among patients who need to undergo cataract surgery. The data were collected by focus group interviews (n=27). The doctor-patient relationship, patient education, the wait, hospital organization, social support, sensations, previous experience, outcome of surgery, and coping strategies were identified as the main factors that contribute to feelings of fear related to cataract surgery. Five stages of fear were identified: at home after diagnosis, during preparation for surgery at the hospital, the day of surgery, the post-operative visits, and the period after these follow-up visits at home. A model regarding the factors related to fear in patients awaiting cataract surgery was developed, which emphasizes the importance of a good doctor-patient relationship, and the need for patient education that is tailored to the individual patients.

Aged↗

Modeling processes in the acquisition of fears: vicarious electrodermal conditioning to fear-relevant stimuli.

Fear-relevant (snakes, spiders, and rats) and fear-irrelevant (flowers, mushrooms, and berries) pictures were compared as conditioned and instigating stimuli in a vicarious classical conditioning paradigm with skin conductance responses as the dependent variable. A female confederate model and subject watched the pictures side by side. A female stimulus presentations, the experimenter interrupted to investigate alleged overreactions of the model to one of the stimulus classes. The model then vividly described a phobia for this object, which was to serve as a vicarious instigating stimulus. The experiment continued for a few conditioning trials, and then the experimenter announced that the disturbing stimulus would be omitted before the second part of the experiment. There was no effect of stimulus content on vicariously instigated responses, although significant overall instigation was observed. However, the responses to the stimulus that was paired with the model's phobic stimulus, that is, the vicariously conditioned responses, failed to extinguish during the second part of the experiment when it was fear-relevant but extinguished immediately when it was fear-irrelevant.

Adult↗