Fear expression and return of fear following threat instruction with or without direct contingency experience

Prior research showed that mere instructions about the contingency between a conditioned stimulus (CS) and an unconditioned stimulus (US) can generate fear reactions to the CS. Little is known, however, about the extent to which actual CS US contingency experience adds anything beyond the effect of contingency instructions. Our results extend previous studies on this topic in that it included fear potentiated startle as an additional dependent variable and examined return of fear (ROF) following reinstatement. We observed that CS US pairings can enhance fear reactions beyond the effect of contingency instructions. Moreover, for all measures of fear, instructions elicited immediate fear reactions that could not be completely overridden by subsequent situational safety information. Finally, ROF following reinstatement for instructed CS+s was unaffected by actual experience. In summary, our results demonstrate the power of contingency instructions and reveal the additional impact of actual experience of CS US pairings

Examining Extinction in Evaluative Conditioning

Evaluative conditioning involves the learning of attitudes and preferences. These attitudes and preferences can be unlearnt via extinction; however, recent research has shown that attitudes and preferences can relapse. The investigation examined whether presenting positive and negative stimuli alone during extinction would reduce relapse in evaluative conditioning. Across three experiment presenting additional stimuli did not reduce relapse

Is conditioning a useful framework for understanding the development and treatment of phobias?

Despite the prevalence of therapeutic interventions based on conditioning models of fear acquisition, conditioning has been seen by many as a poor explanation of how fears develop: partly because research on conditioning has become less mainstream and models of teaming have become increasingly more complex. This article reviews some of what is now known about conditioning/associative teaming and describes how these findings account for some early criticisms of conditioning models of fear acquisition. It also describes how pathways to fear such as vicarious teaming and fear information can be conceptualised as forms of associative teaming that obey the same teaming rules. Some popular models of conditioning are then described with a view to highlighting the important components in teaming. Finally, suggestions are made about how what we know about conditioning can be applied to improve therapeutic interventions and prevention programs for child anxiety. (c) 2006 Elsevier Ltd. All rights reserved

Theta activity during REM and NREM sleep and predicting fear learning outcomes

Fear conditioning, extinction, extinction-recall, and renewal are all components of a well-established paradigm used for studying fear learning and response in the laboratory setting, and are used to model anxiety disorders in animals and humans. Studies have recently begun to investigate the role of the brain electrical activity during sleep in emotional learning and memory. Emotionally relevant learning and memory has been associated with a particular activity band, theta rhythm, which can be measured during sleep. Previous studies have suggested theta activity during sleep may be an indicator of maladaptive stress responses. Despite this, there has not been a thorough investigation of theta activity during a full night of sleep and its relationship to subsequent fear responses. The goal of the present study was to assess the relationship between theta activity and fear learning and memory, as well as, theta activity and extinction learning and memory using well-validataed paradigms to study fear responses in humans. Participants (16 females; 15 males; mean age = 23.6; SD = 3.80) underwent two consecutive nights of polysomnographic (PSG) recording in the Sleep and Chronobiology Laboratory at Western Psychiatric Institute and Clinic, before and after fear learning and extinction. Quantitative electroencephalographic spectral analysis was used to measure theta activity during sleep on both nights. Our objective was to evaluate the extent to which theta power during sleep predicts outcomes of fear learning and extinction memory the following day. Results showed higher theta power during the second night of the experiment predicted greater retention of the extinction memory during the fear renewal task completed the following morning. Understanding the relationship between theta power during sleep and fear and extinction learning and memory may identify markers of risk or resilience to anxiety disorders in trauma exposed individuals

PRELIMINARY STUDY OF THE EFFECTS OF POST-RETRIEVAL EXTINCTION ON THE RETURN OF CONDITIONED RESPONSES IN HUMANS

We conducted a preliminary study to replicate the experiment by Schiller et al. (2010), who found that conditional responses (CR) may be permanently inhibited through post-retrieval extinction, a procedure in which subjects are exposed to a stimulus that was present during conditioning (retrieval cue), such as the presentation of the CS without the US or a single presentation of the US alone, followed by extinction. Eleven adult participants underwent Pavlovian conditioning with three colored squares (CS), two of which (CSa+ and CSb+) were paired with a mild electrical stimulation (US), whereas a third stimulus was never paired with a US (CS-). Twenty-four hours later, the participants were divided into two groups (experimental and control) and underwent extinction, which consisted of presenting all CSs without the US. For the experimental group only, a retrieval cue consisting of a single presentation of the CSa+ and CS- without the US was administered 10 min before extinction. In the test phase, the US was administered four times and then followed by a ten-minute interval and a new extinction procedure. Skin conductance responses to the stimuli were measured. Groups did not differ from each other. They presented equivalent levels of conditioning and extinction as well as an increase in CR amplitudes following the presentation of all stimuli in the test phase. These data do not replicate findings from the original study, suggesting that further analyses are needed to identify variables that control Pavlovian conditioning and extinction in humans. Key words: Pavlovian conditioning, post-retrieval extinction, reconsolidation, skin conductance, humans

Functional and neural mechanisms of human fear conditioning: studies in healthy and brain-damaged individuals

Fear conditioning represents the learning process by which a stimulus, after repeated pairing with an aversive event, comes to evoke fear and becomes intrinsically aversive. This learning is essential to organisms throughout the animal kingdom and represents one the most successful laboratory paradigm to reveal the psychological processes that govern the expression of emotional memory and explore its neurobiological underpinnings. Although a large amount of research has been conducted on the behavioural or neural correlates of fear conditioning, some key questions remain unanswered. Accordingly, this thesis aims to respond to some unsolved theoretic and methodological issues, thus furthering our understanding of the neurofunctional basis of human fear conditioning both in healthy and brain-damaged individuals. Specifically, in this thesis, behavioural, psychophysiological, lesion and non-invasive brain stimulation studies were reported. Study 1 examined the influence of normal aging on context-dependent recall of extinction of fear conditioned stimulus. Study 2 aimed to determine the causal role of the ventromedial PFC (vmPFC) in the acquisition of fear conditioning by systematically test the effect of bilateral vmPFC brain-lesion. Study 3 aimed to interfere with the reconsolidation process of fear memory by the means of non-invasive brain stimulation (i.e. TMS) disrupting PFC neural activity. Finally, Study 4 aimed to investigate whether the parasympathetic – vagal – modulation of heart rate might reflect the anticipation of fearful, as compared to neutral, events during classical fear conditioning paradigm. Evidence reported in this PhD thesis might therefore provide key insights and deeper understanding of critical issues concerning the neurofunctional mechanisms underlying the acquisition, the extinction and the reconsolidation of fear memories in humans

Electrophysiological Signatures of Fear Conditioning: From Methodological Considerations to Catecholaminergic Mechanisms and Translational Perspectives

Fear conditioning describes a learning mechanism during which a specific stimulus gets associated with an aversive event (i.e., an unconditioned stimulus; US). Thereby, this initially neutral or arbitrary stimulus becomes a so-called “conditioned” stimulus (CS), which elicits a conditioned threat response. Fear extinction refers to the decrease in conditioned threat responses as soon as the CS is repeatedly presented in the absence of the US. While fear conditioning is an important learning model for understanding the etiology and maintenance of anxiety and fear-related disorders, extinction learning is considered to reflect the most important learning process of exposure therapy. Neurophysiological signatures of fear conditioning have been widely studied in rodents, leading to the development of groundbreaking neurobiological models, including brain regions such as the amygdala, insula, and prefrontal areas. These models aim to explain neural mechanisms of threat processing, with the ultimate goal to improve treatment strategies for pathological fear. Recording intracranial electrical activity of single units in animals offers the opportunity to uncover neural processes involved in threat processing with excellent spatial and temporal resolution. A large body of functional magnetic resonance imaging (fMRI) studies have helped to translate this knowledge about the anatomy of fear conditioning into the human realm. fMRI is an imaging technique with a high spatial resolution that is well suited to study slower brain processes. However, the temporal resolution of fMRI is relatively poor. By contrast, electroencephalography (EEG) is a neuroscientific method to capture fast and transient cortical processes. While EEG offers promising opportunities to unravel the speed of neural threat processing, it also provides the possibility to study oscillatory brain activity (e.g., prefrontal theta oscillations). The present thesis contains six research manuscripts, describing fear conditioning studies that mainly applied EEG methods in combination with other central (fMRI) and peripheral (skin conductance, heart rate, and fear-potentiated startle) measures. A special focus of this thesis lies in methodological considerations for EEG fear conditioning research. In addition, catecholaminergic mechanisms are studied, with the ultimate goal of opening up new translational perspectives. Taken together, the present thesis addresses several methodological challenges for neuroscientific (in particular, EEG) fear conditioning research (e.g., appropriate US types and experimental designs, signal-to-noise ratio, simultaneous EEG-fMRI). Furthermore, this thesis gives critical insight into catecholaminergic (noradrenaline and dopamine) mechanisms. A variety of neuroscientific methods (e.g., EEG, fMRI, peripheral physiology, pharmacological manipulation, genetic associations) have been combined, an approach that allowed us (a) to translate knowledge from animal studies to human research, and (b) to stimulate novel clinical directions