Papers by Dieuwke Sevenster
Biological Psychology, Sep 1, 2018
Fear learning reflects the adaptive ability to learn to anticipate aversive events and to display... more Fear learning reflects the adaptive ability to learn to anticipate aversive events and to display preparatory fear reactions based on prior experiences. Usually, these learning experiences are modeled in the lab with pairings between neutral conditioned stimuli and aversive unconditioned stimulus (i.e., fear conditioning via CS-US pairings). Nevertheless, for humans, fear learning can also be based on verbal instructions. In this review, we consider the role of verbal instructions in laboratory fear learning. Specifically, we consider both the effects of verbal instructions on fear responses in the absence of CS-US pairings as well as the way in which verbal instructions moderate fear established via CS-US pairings. We first focus on the available empirical findings about both types of effects. More specifically, we consider how these effects are moderated by elements of the fear conditioning procedure (i.e., the stimuli, the outcome measures, the relationship between the stimuli, the participants, and the broader context). Thereafter, we discuss how well different mental-process models of fear learning account for these empirical findings. Finally, we conclude the review with a discussion of open questions and opportunities for future research.
Learning and Motivation
The degree of generalization from a fearful context to other contexts is determined by precision ... more The degree of generalization from a fearful context to other contexts is determined by precision of the original fear memory. Experiences before and after fear learning affect memory precision. Pre-exposure to a similar context before context conditioning results in increased generalization to the similar context. In contrast, exposure to the conditioning context after fear learning reduces fear generalization. In the current study we aimed to investigate whether the events before and after fear learning interact. We hypothesized that pre-exposure-induced enhanced generalization could be reduced by a return to the conditioning context. We found that, in contrast to previous findings, pre-exposure did not affect generalization. However, a reminder of the conditioning context reduced generalization to both a similar and a different context. The results stress the dynamic nature of emotional memory.
Journal of Behavior Therapy and Experimental Psychiatry
BACKGROUND AND OBJECTIVES Pavlovian fear conditioning paradigms are valuable to investigate fear ... more BACKGROUND AND OBJECTIVES Pavlovian fear conditioning paradigms are valuable to investigate fear learning and the return of extinguished fear in the lab. However, their validity is limited, because the aversive stimuli (e.g., electric shocks) typically lack the modalities and complexity of real-world aversive experiences. To overcome this limitation, we examined fear acquisition, extinction and contextual renewal using an audiovisual unconditioned stimulus (US). METHOD On day 1, 50 healthy participants completed an acquisition phase in a specific context (i.e., desk or bookcase, 'context A'). Pictures of colored lamps served as conditioned stimuli and an aversive film clip was used as US. On day 2, extinction took place in the same context ('context A') or in a different context ('context B'). Afterwards, renewal was tested in the acquisition context (AAA vs. ABA design). RESULTS As hypothesized, fear acquisition and extinction, as measured by US expectancy ratings, fear potentiated startle (FPS), and skin conductance responses (SCRs), were successful. Most importantly, conditioned responding was renewed on all measures in the ABA condition, but not in the AAA condition. Differential renewal (i.e., larger renewal for CS + than for CS-) was only observed for US expectancy ratings. LIMITATIONS The return of conditioned responses was non-differential for FPS and SCR. CONCLUSIONS The current set-up enables investigation of fear renewal using an audiovisual US. Future studies can utilize this paradigm to investigate interventions that aim to reduce fear renewal by modifying the US memory, such as Eye Movement Desensitization and Reprocessing and imagery rescripting.
Behavioural Brain Research
The generalization of aversive memory can be defined as the phenomenon in which a situation simil... more The generalization of aversive memory can be defined as the phenomenon in which a situation similar to (but distinctive from) a previous aversive event triggers an avoidance response. This phenomenon has been suggested to play a role in several psychological disorders. In this study, we investigate the effects of novelty on the generalization of fear memories, and the involvement of noradrenergic and dopaminergic systems in this process. For this study we used male Wistar rats (3 months old, 300-400 g). The participation of each neurotransmitter system was evaluated separately (two set of experiments). In each experimental set, the animals were divided in groups (8 animals each): (i) control, (ii) novelty, and, (iii) antagonist + novelty group (timolol, a β-adrenergic antagonist, or SCH23390, a D1/D5 dopaminergic antagonist, in the first and in the second set of experiments, respectively). Additionaly, to investigate whether novelty exposure increases the levels of noradrenaline and/or dopamine in the hippocampus fifteen animals were divided in three groups (5 animals each).: (i) naïve, (ii) control; and, (iii) novelty. To examine aversive memory, and generalization of aversive memory, we trained adult male Wistar rats in an inhibitory avoidance (IA) memory task and after in a modified inhibitory avoidance (MIA). Before the MIA training some of the animals were exposed to environmental novelty (open field). Immediately before this novelty exposure, some animals received intrahippocampal infusion of timolol (β-adrenergic antagonist), SCH23390 (D1/D5 antagonist) or vehicle to evaluate the involvement of noradrenergic and dopaminergic systems. Finally, to evaluate aversive memory and generalization of aversive memory respectively, half of the animals in each group were tested on IA and half on MIA. We confirmed that the exposure to novelty blocks the generalization of aversive memory, but moreover, demonstrated that this process involves activation of β-adrenergic and dopaminergic D1/D5 pathways. We additionally observed that exposure to novelty raises hippocampal levels of noradrenaline and dopamine. This suggests that these neurotransmitters not only influence long-term memory (LTM) as such, but also aversive memory generalization.
Neurobiology of Learning and Memory
Fear extinction is the well-known process of fear reduction through repeated re-exposure to a fea... more Fear extinction is the well-known process of fear reduction through repeated re-exposure to a feared stimulus without the aversive outcome. The last two decades have witnessed a surge of interest in extinction learning. First, extinction learning is observed across species, and especially research on rodents has made great strides in characterising the physical substrate underlying extinction learning. Second, extinction learning is considered of great clinical significance since it constitutes a crucial component of exposure treatment. While effective in reducing fear responding in the short term, extinction learning can lose its grip, resulting in a return of fear (i.e., laboratory model for relapse of anxiety symptoms in patients). Optimization of extinction learning is, therefore, the subject of intense investigation. It is thought that the success of extinction learning is, at least partly, determined by the mismatch between what is expected and what actually happens (prediction error). However, while much of our knowledge about the neural circuitry of extinction learning and factors that contribute to successful extinction learning comes from animal models, translating these findings to humans has been challenging for a number of reasons. Here, we present an overview of what is known about the animal circuitry underlying extinction of fear, and the role of prediction error. In addition, we conducted a systematic literature search to evaluate the degree to which state-of-the-art neuroimaging methods have contributed to translating these findings to humans. Results show substantial overlap between networks in animals and humans at a macroscale, but current imaging techniques preclude comparisons at a smaller scale, especially in sub-cortical areas that are functionally heterogeneous. Moreover, human neuroimaging shows the involvement of numerous areas that are not typically studied in animals. Results obtained in research aimed to map the extinction circuit are largely dependent on the methods employed, not only across species, but also across human neuroimaging studies. Directions for future research are discussed.
Scientific reports, Jan 5, 2017
At the core of anxiety disorders lies the tendency to generalize fear from a threatening to a saf... more At the core of anxiety disorders lies the tendency to generalize fear from a threatening to a safe situation. A deeper understanding of the mechanisms that facilitate and restrain generalization in humans is therefore needed. Rodent studies showed that pre-exposure to a context that is similar to the threatening context enhanced generalization to the similar context. In Experiment 1 we replicated these animal findings in humans (US-expectancy). Studies on the underlying mechanisms showed that the pre-exposure representation was recalled during conditioning (due to similarity between the contexts) and the shock also became linked to the recalled representation, resulting in greater generalization. In Experiment 2 we developed a pre-exposure procedure that increased the ability to distinguish between the conditioned and pre-exposure contexts, such that presentation of the former would no longer result in recall of the latter. We then observed that overgeneralization (US-expectancy) wa...
International journal of psychophysiology : official journal of the International Organization of Psychophysiology, Jan 21, 2015
Cardiac activity provides possible markers for the identification of those at risk for the develo... more Cardiac activity provides possible markers for the identification of those at risk for the development of anxiety disorders. Cardiac deceleration has been linked to impaired fear conditioning while low heart rate variability (HRV) has been associated with elevated contextual anxiety and enhanced startle potentiation to affective stimuli. In the current study we examined individual differences in conditioned responses as a function of cardiac activity. In addition to classifying participants as decelerators and accelerators, we examined baseline fear responding and conditioned responses in participants with low and high resting state heart rate variability. We complemented well-established physiological measures (startle response and skin conductance) and online distress and retrospective expectancy ratings of fear conditioning with measures of heart rate (HR). In contrast to accelerators, decelerators did not show any sign of startle fear conditioning, but demonstrated increased differential conditioning of online distress. Only marginal differences in contextual anxiety and conditioned fear responding were observed for low and high HRV individuals. These results may contribute to the identification of individuals who are at risk for the development of anxiety disorders.
Journal of visualized experiments : JoVE, 2014
The basic design used in our human fear-conditioning studies on disrupting reconsolidation includ... more The basic design used in our human fear-conditioning studies on disrupting reconsolidation includes testing over different phases across three consecutive days. On day 1 - the fear acquisition phase, healthy participants are exposed to a series of picture presentations. One picture stimulus (CS1+) is repeatedly paired with an aversive electric stimulus (US), resulting in the acquisition of a fear association, whereas another picture stimulus (CS2-) is never followed by an US. On day 2 - the memory reactivation phase, the participants are re-exposed to the conditioned stimulus without the US (CS1-), which typically triggers a conditioned fear response. After the memory reactivation we administer an oral dose of 40 mg of propranolol HCl, a β-adrenergic receptor antagonist that indirectly targets the protein synthesis required for reconsolidation by inhibiting the noradrenaline-stimulated CREB phosphorylation. On day 3 - the test phase, the participants are again exposed to the unreinf...
Psychophysiology
Instructed extinction after fear conditioning is relatively effective in attenuating electroderma... more Instructed extinction after fear conditioning is relatively effective in attenuating electrodermal responding. Testing the single-process account of fear learning, we examined whether this manipulation similarly affects the startle response. Skin conductance responses (SCRs), startle responses, and online unconditioned stimulus (US) expectancy ratings were measured during fear acquisition (Day 1), extinction, and reinstatement (Day 2). Before extinction onset, half of the subjects were instructed that the conditioned stimulus would not be followed by the US (Instructed Extinction) whereas the other subjects were not instructed (Normal Extinction). This simple instruction completely abolished both differential SCR and US expectancy ratings, but not the startle fear response. Although the manipulation facilitated extinction learning, it did not prevent the recovery of the startle response. The present findings are better explained by a dual- rather than a single-process account of fea...
Frontiers in Behavioral Neuroscience
There is conflicting evidence as to whether awareness is required for conditioning of the skin co... more There is conflicting evidence as to whether awareness is required for conditioning of the skin conductance response (SCR). Recently, Schultz and Helmstetter (2010) reported SCR conditioning in contingency unaware participants by using difficult to discriminate stimuli. These findings are in stark contrast with other observations in human fear conditioning research, showing that SCR predominantly reflects contingency learning. Therefore, we repeated the study by Schultz and Helmstetter and additionally measured conditioning of the startle response, which seems to be less sensitive to declarative knowledge than SCR. While we solely observed SCR conditioning in participants who reported awareness of the contingencies (n = 16) and not in the unaware participants (n = 18), we observed startle conditioning irrespective of awareness. We conclude that SCR but not startle conditioning depends on conscious discriminative fear learning.
Ample evidence suggests that consolidated memories, upon their retrieval, enter a labile state, i... more Ample evidence suggests that consolidated memories, upon their retrieval, enter a labile state, in which they might be susceptible to change. It has been proposed that memory labilization allows for the integration of relevant information in the established memory trace (memory updating). Memory labilization and reconsolidation do not necessarily occur when a memory is being reactivated, but only when there is something to be learned during memory retrieval (prediction error). Thus, updating of a fear memory trace should not occur under retrieval conditions in which the outcome is fully predictable (no prediction error). Here, we addressed this issue, using a human differential fear conditioning procedure, by eliminating the very possibility of reinforcement of the reminder cue. A previously established fear memory (picture-shock pairings) was reactivated with shock-electrodes attached (Propranolol group, n = 18) or unattached (Propranolol No-Shock Expectation group, n = 19). We additionally tested a placebo-control group with the shock-electrodes attached (Placebo group, n = 18). Reconsolidation was not triggered when nothing could be learned during the reminder trial, as noradrenergic blockade did not affect expression of the fear memory 24 h later in the Propranolol No-Shock Expectation group. Only when the outcome of the retrieval cue was not fully predictable, propranolol, contrary to placebo, reduced the startle fear response and prevented the return of fear (reinstatement) the following day. In line with previous studies, skin conductance response and shock expectancies were not affected by propranolol. Remarkably, a double dissociation emerged between the emotional (startle response) and more cognitive expression (expectancies, SCR) of the fear memory. Our findings have important implications for reconsolidation blockade as treatment strategy for emotional disorders. First, fear reducing procedures that target the emotional component of fear memory do not necessarily affect the cognitive component and vice versa. Second, mere retrieval of the fear memory is not sufficient to induce its labilization and reconsolidation.
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Research into mental processes has generally focused on the average response and treated individu... more Research into mental processes has generally focused on the average response and treated individual variability as noise (cf. Plomin & Kosslyn, 2001). The application of this method to fear learning has yielded general principles that indicate fear conditioning in most people when a stimulus is followed by an aversive event as well as fear extinction over time when this threat ceases (e.g., Mineka & Oehlberg, 2008). However, researchers have recognized that such a mean learning pattern can reflect an artifact of group averaging and is unlikely to represent the response pattern of any given individual (e.g., Kristjansson, Kircher, & Webb, 2007; Pamir et al., 2011). Individual differences may be especially pertinent to understanding pathological fear learning, given that psychopathology, by definition, reflects a deviation from the mean. Researchers have advocated that to understand mechanisms of abnormal (fear) learning, it is necessary to relate naturally occurring variation in individual dispositions (e.g., traits) to variation in learning (e.g., Kosslyn et al., 2002). Accordingly, our aim in the present study was to examine how selected individual differences in personality are related to variability in fear learning. Cronbach's (1957) classic article on the two disciplines of scientific psychology invited researchers to purposefully seek Aptitude (i.e., personality characteristics) × Treatment (i.e., fear-learning phase) interactions. In line with this call, most notably Eysenck (1965) and several 535914C PXXXX10.
Although disrupting reconsolidation is promising in targeting emotional memories, the conditions ... more Although disrupting reconsolidation is promising in targeting emotional memories, the conditions under which memory becomes labile are still unclear. The current study showed that post-retrieval changes in expectancy as an index for prediction error may serve as a read-out for the underlying processes engaged by memory reactivation. Minor environmental changes define whether retrieval induces memory reconsolidation or the initiation of a new memory trace even before fear extinction can be observed.
The degree of generalization from a fearful context to other contexts is determined by precision ... more The degree of generalization from a fearful context to other contexts is determined by precision of the original fear memory. Experiences before and after fear learning affect memory precision. Pre-exposure to a similar context before context conditioning results in increased generalization to the similar context. In contrast, exposure to the conditioning context after fear learning reduces fear generalization. In the current study we aimed to investigate whether the events before and after fear learning interact. We hypothesized that pre-exposure-induced enhanced generalization could be reduced by a return to the conditioning context. We found that, in contrast to previous findings, pre-exposure did not affect generalization. However, a reminder of the conditioning context reduced generalization to both a similar and a different context. The results stress the dynamic nature of emotional memory.
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Papers by Dieuwke Sevenster