Deficient safety learning characterizes high trait anxious individuals

Trait anxiety is a well-established risk factor for developing anxiety disorders, but evidence for abnormal associative fear learning in high trait anxious (HTA) individuals is inconclusive. In part, this may due to limitations in the scope and measures used to assess fear learning. The current study therefore assessed fear learning across multiple response domains and multiple test phases in a two-day discriminative fear-conditioning paradigm. We tested whether trait anxiety is associated with deficient safety learning, by comparing HTA individuals (N = 20) and healthy Controls (N = 22). HTA participants showed stronger fear on the startle response and distress ratings to the safety (CS⁻) but not to the threat stimulus (CS⁺) during acquisition, along with impaired extinction and re-extinction. Trait anxiety did not affect skin conductance responses and effects on UCS-expectancy were limited. We conclude that high trait anxiety may be characterized by deficient safety learning which in turn may promote persistent and generalized fear responses.     

Effects of cycling exercise on the soleus H-reflex and state anxiety among men with low or high trait anxiety

The present study examined the effects of low- and high-intensity cycling exercise on the H-reflex and state anxiety among men having low (n=20) or high (n=20) trait anxiety. Participants completed measures of state anxiety and underwent elicitation and recording of the H-reflex in the soleus muscle before and 10 min after three 20-min conditions: (1) quiet rest, (2) cycling at 40% VO2peak, and (3) cycling at 70% VO2peak. We found that (1) exercise, but not quiet rest, resulted in a reduction of the H-reflex; the magnitude of the reduction did not differ between men having low or high trait anxiety; (2) exercise and quiet rest resulted in similar reductions of state anxiety, and the magnitude of the reductions was larger for men having high trait anxiety than low trait anxiety; and (3) reductions of the H-reflex were unrelated to reductions of self-reported state anxiety across all three conditions. Contrary to prior opinion, the postexercise reduction in the H-reflex reported by previous researchers and in the present study appears to be unrelated to self-reported anxiety after exercise.     

Differences between trait fear and trait anxiety: Implications for psychopathology

Fear and anxiety are poorly delineated in much of the clinical and research literatures. Although some theorists and researchers have posited explanations for how trait fear and trait anxiety differ, many others conceptualize the constructs as largely or entirely interchangeable. The primary goals of this review are to examine clinical conceptualizations and neurobiological studies of fear and anxiety, examine the animal and human literatures on the correlates of fear and anxiety, provide clearer definitions of these two constructs, and discuss their implications for psychopathology. A secondary goal is to evaluate content of self-report measures of trait fear and anxiety, and meta-analyze the relations between self-reported trait fear and anxiety. We found that existing measures share significant content overlap across constructs. Despite this overlap, our meta-analysis revealed only a moderate (r = 0.32) relationship between measures of trait fear and anxiety, with an even lower relationship (r = 0.14) when we examined trait fear measures operationalized in terms of harm avoidance. These findings suggest that fear and anxiety are largely distinct emotions, and that psychological disorders of trait fear and trait anxiety warrant classification in separate higher-order categories. Moreover, they suggest that future research should focus on deriving more content valid measures of trait fear and trait anxiety from the neurobiological and diagnostic literatures.     

EEG-correlates of trait anxiety in the stop-signal paradigm

The relationship between trait anxiety and event-related EEG oscillatory reactions in the stop-signal paradigm was studied in 15 non-clinical subjects with average age of 26 years (13 men). In the paradigm, subjects responded to target stimuli by pressing one of the two choice buttons. In 30 out of 130 trials, target presentation was followed by a stop-signal, indicating that subjects had to refrain from a prepared motor response. The subject's level of anxiety was assessed using the State Trait Anxiety Inventory. Wide-band desynchronization (8-25 Hz) was found before button-press. It was sustained after the subjects pressed the button at 7-14 Hz frequency range. Also, synchronization at 15-25 Hz band occurred in 400-1400 ms after the button-press. Synchronization at lower frequencies (1-7 Hz) was also found during 0-700 ms after the stop-signal onset. Also, desynchronization at 8-20 Hz was found in 300-800 ms after stop-signal onset. The group with higher anxiety showed desynchronization at 10-13 Hz in 0-800 ms after the button-press, whereas the group with lower anxiety showed synchronization at the same frequency range. In 0-600 ms after stop-signal onset, desynchronization at 8-13 Hz was observed in the group with higher anxiety, whereas the group with lower anxiety demonstrated synchronization or weak desynchronization. Our findings support the Eysenck et al. [M.W. Eysenck, N. Derakshan, R. Santos, M.G. Calvo, Anxiety and cognitive performance: attentional control theory, Emotion 7(2) (2007) 336-356] theory that subjects with higher anxiety have more attentional control over reaction and increased use of processing resources as compared with lower anxiety subjects.     

Effects of pre- or post-training entorhinal cortex AP5 injection on fear conditioning

Fear conditioning is one of the most studied paradigms to assess the neural basis of emotional memory. The circuitry involves NMDA receptor activation in the amygdala and, in the case of contextual conditioning, in the hippocampus. Entorhinal cortex is one of the major input/output structures to the hippocampus and also projects to the amygdala, both through glutamatergic transmission. Other learning tasks involving hippocampus and amygdala, such as inhibitory avoidance, require entorhinal cortex during acquisition and consolidation. However, the involvement of NMDA receptors mediated transmission in entorhinal cortex in fear conditioning acquisition and consolidation is not clear. To investigate that issue, rats were trained in fear conditioning to both contextual and tone conditioned stimulus. Immediately before, immediately, 30 or 90 min after training they received NMDA antagonist AP5 or saline injections bilaterally in the entorhinal cortex (AP-6.8 mm, L +/-5.0 mm DV-6.8 mm). Contextual fear conditioning was measured 24 h after training, and tone fear conditioning 48 h after training. AP5 injections selectively impaired contextual fear conditioning only when injected pre-training. Post-training injections had no effect. These findings suggest that entorhinal cortex NMDA receptors are necessary for acquisition, but not for consolidation, of contextual fear conditioning. On the other hand, both acquisition and consolidation of tone fear conditioning seem to be independent of NMDA receptors in the entorhinal cortex.     

Startle modulation and explicit valence evaluations dissociate during backward fear conditioning

Blink startle magnitude is linearly modulated by affect such that, relative to neutral stimuli, startle magnitude is inhibited during pleasant stimuli and potentiated during unpleasant stimuli. Andreatta, Mühlberger, Yarali, Gerber, and Pauli (2010), however, report a dissociation between startle modulation and explicit valence evaluations during backward conditioning, a procedure in which the unconditional stimulus precedes the conditional stimulus (CS). Relative to controls, startles elicited during the CS were inhibited, suggesting that the CS had acquired positive valence, but participants still evaluated the CS as unpleasant after the experiment. In Experiment 1, we aimed to replicate this dissociation using a trial‐by‐trial measure of CS valence to measure startle modulation and CS valence simultaneously during forward and backward differential fear conditioning. In Experiment 2, we examined whether early and late portions of the CS could acquire differential valence by presenting startle probes at early and late probe positions during the CS. In both experiments, the dissociation between startle modulation and explicit valence evaluations in backward conditioning replicated, with CS+ evaluated as less pleasant than CS‐, but startles elicited during CS+ inhibited relative to CS‐. In Experiment 2, we provide preliminary evidence that this inhibition was present early, but not late, during the CS+. The results replicate the dissociation between implicit and explicit CS valence reported by Andreatta et al. (2010) using a trial‐by‐trial measure of valence. We also provide preliminary evidence that this dissociation may occur because the implicit and explicit measures are recorded at different times during the CS presentation.     

Skin conductance fear conditioning impairments and aggression: A longitudinal study

Autonomic fear conditioning deficits have been linked to child aggression and adult criminal behavior. However, it is unknown if fear conditioning deficits are specific to certain subtypes of aggression, and longitudinal research is rare. In the current study, reactive and proactive aggression were assessed in a sample of males and females when aged 10, 12, 15, and 18 years old. Skin conductance fear conditioning data were collected when they were 18 years old. Individuals who were persistently high on proactive aggression measures had significantly poorer conditioned responses at 18 years old when compared to others. This association was not found for reactive aggression. Consistent with prior literature, findings suggest that persistent antisocial individuals have unique neurobiological characteristics and that poor autonomic fear conditioning is associated with the presence of increased instrumental aggressive behavior.     

Developmental aspects of fear: Comparing the acquisition and generalization of conditioned fear in children and adults

Most research on human fear conditioning and its generalization has focused on adults whereas only little is known about these processes in children. Direct comparisons between child and adult populations are needed to determine developmental risk markers of fear and anxiety. We compared 267 children and 285 adults in a differential fear conditioning paradigm and generalization test. Skin conductance responses (SCR) and ratings of valence and arousal were obtained to indicate fear learning. Both groups displayed robust and similar differential conditioning on subjective and physiological levels. However, children showed heightened fear generalization compared to adults as indexed by higher arousal ratings and SCR to the generalization stimuli. Results indicate overgeneralization of conditioned fear as a developmental correlate of fear learning. The developmental change from a shallow to a steeper generalization gradient is likely related to the maturation of brain structures that modulate efficient discrimination between danger and (ambiguous) safety cues. © 2016 The Authors. Developmental Psychobiology Published by Wiley Periodicals, Inc. Dev Psychobiol 58: 471–481, 2016.     

Threat and trait anxiety affect stability of gaze fixation

Threat accelerates early visual information processing, as shown by shorter P100 latencies of pattern Visual Evoked Potentials in subjects with low trait anxiety, but the opposite is true for high anxious subjects. We sought to determine if, and how, threat and trait anxiety interact to affect stability of gaze fixation. We used video oculography to record gaze position in the presence and in the absence of a fixational stimulus, in a safe and a verbal threat condition in subjects characterised for their trait anxiety. Trait anxiety significantly predicted fixational instability in the threat condition. An extreme tertile analysis revealed that fixation was less stable in the high anxiety group, especially under threat or in the absence of a stimulus. The effects of anxiety extend to perceptual and sensorimotor processes. These results have implications for the understanding of individual differences in occulomotor planning and visually guided behavior.     

Fear but not awareness predicts enhanced sensory processing in fear conditioning

It is not clear whether enhanced cortical processing of reinforced stimuli as reported by neuroimaging studies is due to expectancy of an aversive event alone or to activation of the fear system. The present study investigated cortical and autonomic responses of aware participants using an instructed fear conditioning design. Steady-state visual evoked fields (ssVEF) and heart rate change were recorded to assess sensory processing and activation of the fear system by reinforced (CS+) and nonreinforced stimuli (CS-). Participants who showed heart rate acceleration demonstrated increased ssVEFs in visual and parietal cortex during CS+ in acquisition trials. Heart rate decelerators did not show enhanced cortical activation with respect to the CS+. Participants in both groups reported awareness of CS-US contingencies. Awareness of stimulus contingency in fear conditioning seems not to be sufficient to elicit enhanced visual cortical processing.     

Extinction in fear conditioning: Effects on startle modulation and evaluative self-reports

A basic feature of human evaluative conditioning is that the reported acquired valence of a previously neutral conditioned stimulus (CS) that has been paired with a valenced unconditioned stimulus (US), is resistant to extinction. The present study investigated whether startle modulation, sometimes presented as an index of acquired valence, reflected this basic feature. In a differential fear conditioning paradigm ( n = 38) with an electrocutaneous stimulus as the US, a strong extinction manipulation was conducted by removing the US-electrodes and by extended extinction trials. At the end of extinction, the results corroborated previous findings of evaluative conditioning in that the reported valence for CS+ was still more negative than for CS−, despite disappearance of the differential skin conductance responses. However, startle modulation did not show resistance-to-extinction. Results were discussed in terms of recent conceptualizations of extinction.     

REM sleep deprivation affects extinction of cued but not contextual fear conditioning

Previous research has demonstrated that rapid eye movement (REM), or paradoxical, sleep deprivation can interfere with the retention of certain types of learning tasks, particularly spatial learning. The present study investigated the effects of 6 h of REM sleep deprivation on the retention and extinction of both cued and contextual conditioning tasks in rats. Sleep-deprived animals showed normal retention of both types of conditioning tasks but retarded extinction of the cued task and a trend toward attenuated spontaneous recovery of the contextual task. The results provide further evidence for the involvement of REM sleep in learning and memory processes.     

The development of fear learning and generalization in 8-13 year-olds

The current study examined developmental changes in fear learning and generalization in 40 healthy 8–13 year‐olds using an aversive conditioning paradigm adapted from Lau et al. [Lau et al. [2008] Journal of the American Academy of Child and Adolescent Psychiatry 47:94–102]. In this task, the conditioned stimuli (CS+/CS?) are two neutral female faces, and the unconditioned stimulus is a fearful, screaming face. The second phase of the study also included a generalization stimulus (GS): a 50% blend of the CS± faces. The eye‐blink startle reflex was utilized to measure defensive responding. Patterns of fear learning and generalization were qualified by child age. Older children demonstrated greater fear learning (i.e., larger startle during CS+ than CS?) than younger children. In addition, older children exhibited the typical pattern of generalization observed in adults, whereas younger children did not. Finally, fear learning also related to contingency awareness; only children who correctly identified the CS+ demonstrated fear‐potentiated startle to the CS+. Clinical implications and future directions are discussed. © 2011 Wiley Periodicals,Inc. Dev Psychobiol 54: 675–684, 2012.     

Amygdala-dependent and amygdala-independent pathways for contextual fear conditioning

The basolateral amygdala (BLA), consisting of the lateral and basal nuclei, is considered to be essential for fear learning. Using a temporary inactivation technique, we found that rats could acquire a context-specific long-term fear memory without the BLA but only if intensive overtraining was used. BLA-inactivated rats' learning curves were characterized by slow learning that eventually achieved the same asymptotic performance as rats with the BLA functional. BLA inactivation abolished expression of overtrained fear when rats were overtrained with a functional BLA. However, BLA-inactivation had no effect on the expression of fear in rats that learned while the BLA was inactivated. These data suggest that there are primary and alternate pathways capable of mediating fear. Normally, learning is dominated by the more efficient primary pathway, which prevents learning in the alternate pathway. However, alternate pathways compensate when the dominant pathway is compromised.     

Males show stronger contextual fear conditioning than females after context pre-exposure

Estradiol affects the structure and function of the hippocampus. We have found that repeated estradiol affects neurogenesis and cell death in the hippocampus of adult female, but not male rats. In the present study we sought to determine whether using the same regimen of estradiol would influence hippocampus-dependent behaviour. Adult male and female rats were given estradiol or sesame oil for 15 days, and then tested using a contextual pre-exposure paradigm in which performance depends on the hippocampus. The time spent freezing displayed by rats was scored on subsequent days in (1) the training context, (2) a novel context in which rats had never been shocked, and (3) the training context a second time. Irrespective of treatment, males showed stronger memory for the context by exhibiting greater freezing in both the training context exposures and the novel context. Previous estradiol treatment, in either sex, did not affect the ability to learn and retain information about the training context. However, female rats treated with estradiol and exposed to a novel context after fear conditioning exhibited less freezing behaviour than controls. Taken together, our results demonstrate that gonadectomized male rats outperform females, regardless of previous treatment with estradiol, on a hippocampus-contextual fear conditioning test, and that previous estradiol treatment has a subtle effect on performance in female but not male rats.     

Evaluative conditioning affects the subsequent acquisition of differential fear conditioning as indexed by electrodermal responding and stimulus evaluations

It is currently unclear whether the acquisition of negative stimulus valence in evaluative and fear conditioning paradigms is interrelated or independent. The present study used a transfer paradigm to address this question. Three groups of participants were trained in a picture-picture evaluative conditioning paradigm before completing acquisition of differential fear conditioning using graphical shapes as conditional stimuli (CSs). In group congruent, the shape used as CS+ (paired with the US during fear conditioning) was paired with negative pictures, whereas the shape used as CS− (presented alone during fear conditioning) was paired with positive pictures. In group incongruent, the shape used as CS+ was paired with positive pictures, whereas the shape used as CS− was paired with negative pictures. In group different, different shapes were employed in evaluative and fear conditioning. Acquisition of differential electrodermal responses emerged within fewer acquisition trials in groups congruent and different than in group incongruent. Transfer of evaluative learning across paradigms was evident only after removal of participants who failed to display evaluative conditioning. The current research indicates that stimulus valence acquired during evaluative conditioning transfers to fear conditioning and will differentially affect the acquisition of fear learning as indexed by subjective evaluations and electrodermal responses. The findings suggest that evaluative and fear conditioning are not independent.     

Resting cerebral metabolism correlates with skin conductance and functional brain activation during fear conditioning

We investigated whether resting brain metabolism can be used to predict autonomic and neuronal responses during fear conditioning in 20 healthy humans. Regional cerebral metabolic rate for glucose was measured via positron emission tomography at rest. During conditioning, autonomic responses were measured via skin conductance, and blood oxygen level dependent signal was measured via functional magnetic resonance imaging. Resting dorsal anterior cingulate metabolism positively predicted differentially conditioned skin conductance responses. Midbrain and insula resting metabolism negatively predicted midbrain and insula functional reactivity, while dorsal anterior cingulate resting metabolism positively predicted midbrain functional reactivity. We conclude that resting metabolism in limbic areas can predict some aspects of psychophysiological and neuronal reactivity during fear learning.     

Interoception,conditioning, and fear: The panic threesome

The present article aims to illustrate and review evidence on how associative learning involving interoceptive stimuli (interoceptive conditioning) can lead to changes in physiological, emotional, and perceptual outcomes. We first outline a functional perspective on Pavlovian conditioning and provide a general introduction and historical background on interoceptive conditioning as a special instance of Pavlovian conditioning. Next, biological and learning accounts of panic disorder are discussed, followed by an analysis of which stimuli and responses may be most promising to model learning that is relevant to panic disorder. Finally, studies on interoceptive fear conditioning with respiratory stimuli are reviewed and discussed, and future directions are outlined.     

A pragmatic comparison of noise burst and electric shock unconditioned stimuli for fear conditioning research with many trials

Several methods that are promising for studying the neurophysiology of fear conditioning (e.g., EEG, MEG) require a high number of trials to achieve an adequate signal‐to‐noise ratio. While electric shock and white noise burst are among the most commonly used unconditioned stimuli (US) in conventional fear conditioning studies with few trials, it is unknown whether these stimuli are equally well suited for paradigms with many trials. Here, N = 32 participants underwent a 260‐trial differential fear conditioning and extinction paradigm with a 240‐trial recall test 24 h later and neutral faces as conditioned stimuli. In a between‐subjects design, either white noise bursts (n = 16) or electric shocks (n = 16) served as US, and intensities were determined using the most common procedure for each US (i.e., a fixed 95 dB noise burst and a work‐up procedure for electric shocks, respectively). In addition to differing US types, groups also differed in closely linked US‐associated characteristics (e.g., calibration methods, stimulus intensities, timing). Subjective ratings (arousal/valence), skin conductance, and evoked heart period changes (i.e., fear bradycardia) indicated more reliable, extinction‐resistant, and stable conditioning in the white noise burst versus electric shock group. In fear conditioning experiments where many trials are presented, white noise burst should serve as US.     

Reprint of: Resting cerebral metabolism correlates with skin conductance and functional brain activation during fear conditioning

We investigated whether resting brain metabolism can be used to predict autonomic and neuronal responses during fear conditioning in 20 healthy humans. Regional cerebral metabolic rate for glucose was measured via positron emission tomography at rest. During conditioning, autonomic responses were measured via skin conductance, and blood oxygen level dependent signal was measured via functional magnetic resonance imaging. Resting dorsal anterior cingulate metabolism positively predicted differentially conditioned skin conductance responses. Midbrain and insula resting metabolism negatively predicted midbrain and insula functional reactivity, while dorsal anterior cingulate resting metabolism positively predicted midbrain functional reactivity. We conclude that resting metabolism in limbic areas can predict some aspects of psychophysiological and neuronal reactivity during fear learning.