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Learning theories of depression propose that negative thinking is acquired through subsequent rewarding experiences and is often resistant to change even when it becomes associated with punishment. We examined whether this persistency of negative thinking is related to current and future levels of depressive symptoms among adolescents. Persistency of negative self-referent thinking was assessed by means of a decision-making task, namely the emotional reversal learning task. This task offers participants the choice between thinking about negative and positive self-related aspects. Their choice for negative self-referent thinking is initially rewarded but is later punished. Therefore, participants were expected to efficiently switch between negative and positive self-referent thinking, and to internally update their reward expectancy for these thinking options. Results showed that persistency of negative self-referent thinking was related to concurrent levels of depressive symptoms, replicating earlier findings in adults. However, persistency of negative thinking was unrelated to future levels of depressive symptoms. These findings suggest that adolescents with depressive symptoms tend to hold on to the belief that negative self-referent thinking has beneficial consequences, even when it is no longer being rewarded. This tendency should be seen as a concurrent feature of depression, as the predictive value is still in question.

Experimental Psychopathology (EPP) and the Research Domain Criteria (RDoC) are research approaches that have developed in parallel, providing inter-related yet different scientific frameworks to investigate psychopathology at the intersection of fundamental and applied research. Here we address the overlap and differences between RDoC and EPP, and the challenges that both approaches face. Although overlap between EPP and RDoC can be clearly observed, each approach has its own unique strengths and weaknesses. These aspects will be illustrated by examples with respect to fear conditioning, an experimental procedure that has played a central role in both EPP and RDoC. We see much potential in boosting psychopathology research by combining the strengths of these two approaches ispartof: Current Opinion in Psychology vol:41 pages:118-123 ispartof: location:Netherlands status: published

Excessive avoidance is a key feature of pathological anxiety. However, the precise mechanisms underlying the development of excessive avoidance are still unknown. In the present study, we tested the hypothesis that excessive avoidance, especially in individuals with high Intolerance of Uncertainty (IU) is aimed at distress reduction via the enhancement of subjective perceived control in uncertain-threat environments. In our experiment, participants learned to avoid an uncertain aversive sound through a discriminated free operant procedure. In a later test phase in extinction, we manipulated the amount of avoidance responses available per trial by creating a limited and an unrestricted response condition. Nonetheless, the aversive sound could be effectively avoided in both conditions. We measured response frequency, avoidance confidence ratings and anxiety-predisposing traits such as intolerance of uncertainty, trait anxiety and distress tolerance. The degree of distress suffered during trials was inferred from post-trial relief ratings that were requested after trials in which the aversive sound had been omitted. In the avoidance acquisition phase, we found a positive association between prospective intolerance of uncertainty (P-IU) and the decline rate of distress. This relationship was not significant, however, when inhibitory intolerance of uncertainty (I-IU) was controlled for. At test, we found that the increase in avoidance responses led to distress reduction through the enhancement of avoidance confidence. Finally, we found a significant modulating role of P-IU in the effect of response limit on distress reduction that lends further support to our hypothesis. Specifically, P-IU was positively associated with the effect of response limit on distress. However, such modulating role was not significant when controlling for trait anxiety or I-IU. ispartof: INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY vol:179 pages:89-100 ispartof: location:Netherlands status: published

Research from recent decades has highlighted the distinction between excitatory and inhibitory Pavlovian learning mechanisms. Based on this distinction, state-of-the-art exposure therapy for anxiety disorders emphasizes inhibitory learning and retrieval as its primary mechanism for long-term reduction in fear, anxiety, and avoidance. Seven years ago, we (Craske, et al., 2014) summarized exposure therapy from an inhibitory learning approach, focusing on eight exposure optimization strategies. Here, we update this model based on recent work and describe how to conduct exposure therapy from an inhibitory retrieval approach and encourage further empirical investigation of its basic premises. To this end, we guide the reader in the use of the OptEx Nexus: a clinician's tool for conducting exposure therapy from an inhibitory retrieval approach. We categorize exposure strategies as fundamental (expectancy violation, attention to feared stimulus/situation, removal of safety signals, and mental rehearsal after exposure), advanced (deepened extinction, occasional reinforced extinction), and promoting generalization of learning (retrieval cues, multiple contexts, stimulus variability, positive affect). We additionally discuss extinction learning with distal future feared outcomes, the role of avoidance, and alternative models/approaches to exposure therapy, including counterconditioning, novelty-enhanced extinction, latent cause models, and reconsolidation. Lastly, we illustrate clinical implementation via vignettes of exposure therapy from an inhibitory retrieval approach (see Supplemental materials).

The generalization of learned behavior has been extensively investigated, but accounting for variance in generalized responding remains a challenge. Based on recent advances, we demonstrate that the inclusion of perceptual measures in generalization research may lead to a better understanding of both intra- and interindividual differences in generalization. We explore various ways through which perceptual variability can influence generalized responding. We investigate its impact on the ability to discriminate between stimuli and how similarity between stimuli may be variable, rather than fixed, because of it. Subsequently, we argue that perceptual variations can yield different learning experiences and that interindividual differences in generalized responding may be understood from this perspective. Finally, we point to the role of memory and decision-making within this context. Throughout this paper, we argue that accounting for perception in current generalization protocols will improve the precision of obtained generalization gradients and the ability to infer latent mechanisms. This can inspire future attempts to use generalization gradients as a (clinical) predictor or to relate them to individual traits and neural correlates and, ultimately, may lead to new theoretical and clinical insights. ispartof: Psychonomic Bulletin & Review vol:28 issue:1 pages:1-19 ispartof: location:United States status: Published online

Studies of perceptual generalization have recently demonstrated a close relationship between stimulus perception and conditioned responding, suggesting that incorrect stimulus perception might account for certain characteristics of generalization gradients. In this study, we investigated whether common phenomena, such as the area and peak shift in conditioned responding, relate to perceptual errors. After a differential conditioning procedure, in which one circle was paired with the presentation of an aversive picture whereas a different-sized circle was not, we combined a generalization test with a three-alternative forced-choice perceptual categorization task where participants had to indicate on every trial whether the presented circle was one of the two circles from the conditioning phase or a different one, after which US-expectancy ratings were collected. The typical peak and area shift were observed when conditioned responses were plotted on a physical dimension. However, when stimulus perception was incorporated generalization gradients diverged from the typical gradient. Both the area and peak shift largely disappeared when accounting for perceptual errors. These findings demonstrate the need to incorporate perceptual mechanisms in associative models. ispartof: Psychological Research-Psychologische Forschung vol:85 issue:4 pages:1801-1813 ispartof: location:Germany status: published

Extinction learning is assumed to represent a core mechanism underlying exposure therapy. Empirical evaluations of this assumption, however, are largely lacking. The current study investigated whether neural activations and self-report outcomes during extinction learning and extinction recall could specifically predict exposure therapy response in specific phobia. In this double-blind randomized controlled trial, individuals with spider phobia (N = 45; female/male = 41/4) were on group basis randomly allocated to exposure therapy (n = 25; female/male = 24/1) or progressive muscle relaxation (PMR; n = 20; female/male = 17/3). Intervention effects were measured with the Fears of Spiders questionnaire. Participants also underwent a three-day fear conditioning, extinction learning, and extinction recall paradigm during functional magnetic resonance imaging at baseline. Extinction outcomes were self-reported fear and threat expectancy, and neural responses during conditioned stimulus processing and during extinction-related prediction errors (US omissions) in regions of interest (ventromedial prefrontal cortex (vmPFC) and nucleus accumbens). Results showed that exposure therapy resulted in stronger symptom reductions than PMR (Cohen's d = 0.90). Exposure therapy response was specifically predicted by prediction-error related vmPFC activation during early extinction. There were also indications vmPFC activations during conditioned safety stimulus processing at early extinction predicted therapy outcome. Neural activations during extinction recall and self-report data did however not predict therapy outcome. These findings indicate that exposure therapy may rely on neural extinction learning processes. Prediction errors are thought to drive the extinction learning process, and prediction error-related vmPFC activation specifically predicted therapy outcome. The extent to which vmPFC processes safety signals may additionally be predictive of exposure therapy response, but the specificity is less clear.

Safety learning generates associative links between neutral stimuli and the absence of threat, promoting the inhibition of fear and security-seeking behaviours. Precisely how safety learning is mediated at the level of underlying brain systems, particularly in humans, remains unclear. Here, we integrated a novel Pavlovian conditioned inhibition task with ultra-high field (UHF) fMRI to examine the neural basis of inhibitory safety learning in 49 healthy participants. In our task, participants were conditioned to two safety signals: a conditioned inhibitor that predicted threat-omission when paired with a known threat signal (A+/AX-), and a standard safety signal that generally predicted threat-omission (BC-). Both safety signals evoked equivalent autonomic and subjective learning responses but diverged strongly in terms of underlying brain activation. The conditioned inhibitor was characterized by more prominent activation of the dorsal striatum, anterior insular and dorsolateral prefrontal cortex compared to the standard safety signal, whereas the latter evoked greater activation of the ventromedial prefrontal cortex, posterior cingulate and hippocampus, among other regions. Further analyses of the conditioned inhibitor indicated that its initial learning was characterized by consistent engagement of dorsal striatal, midbrain, thalamic, premotor, and prefrontal subregions. These findings suggest that safety learning via conditioned inhibition involves a distributed cortico-striatal circuitry, separable from broader cortical regions involved with processing standard safety signals (e.g., CS-). This cortico-striatal system could represent a novel neural substrate of safety learning, underlying the initial generation of ‘stimulus-safety’ associations, distinct from wider cortical correlates of safety processing, which facilitate the behavioral outcomes of learning.Significance statementIdentifying safety is critical for maintaining adaptive levels of anxiety, but the neural mechanisms of human safety learning remain unclear. Using ultra-high field fMRI, we compared learning-related brain activity for a conditioned inhibitor, which actively predicted threat-omission, and a standard safety signal (CS-), which was passively unpaired with threat. The inhibitor engaged an extended circuitry primarily featuring the dorsal striatum, along with thalamic, midbrain, and premotor/prefrontal cortex regions. The CS-exclusively involved cortical safety-related regions observed in basic safety conditioning, such as the vmPFC. These findings extend current models to include learning-specific mechanisms for encoding stimulus-safety associations, which might be distinguished from expression-related cortical mechanisms. These insights may suggest novel avenues for targeting dysfunctional safety learning in psychopathology.

Prolonged fasting influences threat and reward processing, two fundamental systems underpinning adaptive behaviors. In animals, overnight fasting sensitizes the mesolimbic-dopaminergic activity governing avoidance, reward, and fear-extinction learning. Despite evidence that overnight fasting may also affect reward and fear learning in humans, effects on human avoidance learning have not been studied yet. Here, we examined the effects of 16h-overnight fasting on instrumental avoidance and relief from threat omission. To this end, 50 healthy women were randomly assigned to a fasting (N=25) or a re-feeding group (N=25) and performed an Avoidance-Relief Task. We found that fasting decreases unnecessary avoidance during signaled safety; this effect was mediated via a reduction in relief pleasantness during signaled absence of threat. A fasting-induced reduction in relief was also found during fear extinction learning. We conclude that fasting optimizes avoidance and safety learning. Future studies should test whether these effects also hold for anxious individuals.

In anxiety-related disorders, excessive avoidance often coexists with an impaired sense of control over external threats. In contrast, lab studies have shown that avoidance responding increase with higher objective controllability over threat, accompanied with more confidence in the effectiveness of the avoidance response. One reason for this divergence could be that those lab studies are overly simplistic with a single, avoidable threat.We conducted an experiment that additionally included a completely uncontrollable threat, and we manipulated the reinforcement rate of the avoidance response to the (semi-)controllable threat (75% versus 100%).The 100% group showed increased avoidance to the controllable threat and decreased avoidance to the unavoidable threat over learning. Interestingly, compared to the 100% group, the 75% group displayed less confidence in their avoidance to the controllable threat and they avoided the uncontrollable threat more often.Only two reinforcement rates of effective avoidance were included, which may limit the generalizability of the current findings. Perceived control was not directly measured.Lower reinforcement rates create ambiguity between effective and ineffective situations of avoidance, which engenders generalization of unpredictability from effective to ineffective situation, thereby driving up ineffective avoidance rates. Partially reinforced effective avoidance responses and elevated ineffective avoidance responses together lead to more exposure to uncontrollable threat, weakening the sense of control over the threat, which could further increase avoidance behaviors. Controllability is often overlooked in avoidance research but can be key to understanding the development of maladaptive avoidance behaviors.

Fear of weight gain is a cardinal feature of eating disorders, including Anorexia Nervosa (AN). This fear motivates behaviors aimed at avoiding weight gain, such as restricting food intake. Of note, avoidance in AN is not confined to food-related items but extends to intense emotional states. Despite the presence of several forms of excessive avoidance in AN, little is known about the mechanisms underpinning avoidance behavior in AN. In the present exploratory study, we investigated whether university students with an elevated desire to avoid weight gain (as measured through self-reported Drive for Thinness, DT) show deficits in generic avoidance learning. Two-hundred and seventy-five female students filled in the Eating Disorder Inventory-II (EDI-II) and performed a food-unrelated avoidance task. Generalized and linear mixed models (GLMM) revealed that students scoring higher on the DT scale of the EDI-II showed more ineffective avoidance, suggesting a tendency for excessive avoidance in at-risk individuals for AN. Similar results might extend to other eating disorders. ispartof: Behaviour Research And Therapy vol:142 pages:1-7 ispartof: location:England status: published

Short-chain fatty acids (SCFAs), the main metabolites produced by bacterial fermentation of dietary fibre in the gastrointestinal tract, are speculated to have a key role in microbiota-gut-brain crosstalk. However, the pathways through which SCFAs might influence psychological functioning, including affective and cognitive processes and their neural basis, have not been fully elucidated. Furthermore, research directly exploring the role of SCFAs as potential mediators of the effects of microbiota-targeted interventions on affective and cognitive functioning is sparse, especially in humans. This Review summarizes existing knowledge on the potential of SCFAs to directly or indirectly mediate microbiota-gut-brain interactions. The effects of SCFAs on cellular systems and their interaction with gut-brain signalling pathways including immune, endocrine, neural and humoral routes are described. The effects of microbiota-targeted interventions such as prebiotics, probiotics and diet on psychological functioning and the putative mediating role of SCFA signalling will also be discussed, as well as the relationship between SCFAs and psychobiological processes. Finally, future directions to facilitate direct investigation of the effect of SCFAs on psychological functioning are outlined.

Abstract. People apply what they learn from experience not only to the experienced stimuli, but also to novel stimuli. But what determines how widely people generalize what they have learned? Using a predictive learning paradigm, we examined the hypothesis that a low (vs. high) probability of an outcome following a predicting stimulus would widen generalization. In three experiments, participants learned which stimulus predicted an outcome (S+) and which stimulus did not (S−) and then indicated how much they expected the outcome after each of eight novel stimuli ranging in perceptual similarity to S+ and S−. The stimuli were rings of different sizes and the outcome was a picture of a lightning bolt. As hypothesized, a lower probability of the outcome widened generalization. That is, novel stimuli that were similar to S+ (but not to S−) produced expectations for the outcome that were as high as those associated with S+.

Psychological stress triggers the release of cortisol following the activation of the hypothalamic-pituitary-adrenal (HPA) axis and elicits concomitant subjective responses. Coherence among the stress response systems is theoretically expected, presumably to optimize the organism's response to environmental challenges, but has received little empirical support possibly due to the assumption of linear associations. The present study examined the associations between cortisol responses to the Maastricht Acute Stress Test (MAST) and concomitant subjective stress responses as well as mood states over the past weeks in 133 healthy men. Latent class growth analysis (LCGA) was applied on individual cortisol and subjective stress responses to identify homogeneous response trajectories within the larger heterogeneous population and enable testing non-linear relationships while retaining the temporal resolution of the stress responses. LCGA revealed four latent cortisol response classes, labeled as mild responders (n = 15), moderately-low responders (n = 46), moderately-high responders (n = 48), and hyper responders (n = 24). These latent classes were not associated with concomitant subjective stress responses. Similarly, the three distinct latent classes capturing the variability in subjective stress responses were also not associated with concomitant cortisol responses. Experiencing higher levels of stress over the previous weeks, however, increased the likelihood of exhibiting a hyper cortisol stress response profile. Positive and negative affective states, and anxious and depressive symptomology over the previous weeks were not associated with cortisol response trajectories. Contrary to previous findings supporting a quadratic association in healthy females, our results do not support the response coherence hypothesis in healthy males subjected to the MAST, but suggest that recent levels of perceived stress may influence the cortisol response to acute stress.

Experimental research has shown that generalization of fear extinction from a generalization stimulus (GS) is minimal compared to generalization of fear extinction from the conditional stimulus itself (CS+). This poses a challenge to extinction-based treatments of anxiety because the exact CS is often not known or unavailable. However, experimental studies failed to disentangle differences in stimulus identity (CS + or GS) from differences in the level of fear (GS typically elicits less fear than CS+). Here, we test the hypothesis that a high level of fear is key to extinction learning and generalization, rather than the identity of the stimulus under extinction (CS + or GS). For that purpose, we took advantage of the peak-shift phenomenon that describes the conditions under which a GS can elicit equal or higher levels of responding, compared to the CS+. Hence, we compared the generalizability of fear extinction following exposure to the CS + itself, to a 'weak' GS that elicits less fear, and to a 'peak' GS that elicits as much fear as the CS+. First, the results replicated, with a new set of stimuli, the observation that extinction of a skin conductance response and US-expectancy generalizes only weakly from a weak GS to CS+. Second, extinction generalized strongly from a peak GS towards CS+, as hypothesized. Third, extinction with the peak GS even outperformed extinction with the CS+, as it generalized more strongly across the generalization gradient. Together, these results support exposure treatment strategies that focus on the fear-eliciting potential of stimuli (often described as a fear hierarchy), rather than their learning history. We propose that stimulus typicality and/or intensity may explain the enhanced effects of a 'peak' GS over the CS+ in enhancing the generalization of fear extinction. ispartof: BEHAVIOUR RESEARCH AND THERAPY vol:111 pages:1-8 ispartof: location:England status: published

Return of fear poses a problem for extinction-based therapies of clinical anxiety. Experimental research has discovered several pathways to return of fear, one of which is known as reinstatement. Here, we evaluated in rats the potential of scopolamine, a non-selective muscarinic receptor antagonist that is also safe for use in humans, to prevent the reinstatement of extinguished fear. We conducted three experiments with a total sample of 96 female rats. All rats went through a fear acquisition session (tone-shock pairings, CS-US), followed by two extinction sessions (CS only) and a post-extinction fear memory test. Twenty-four hours later, rats were placed in the same or a different context from extinction and received two unsignaled foot shock (US) presentations. On the following day, CS-evoked freezing returned when the reinstating USs had occurred in the same context compared to a different context (context-dependent reinstatement, Experiment 1). Systemic administration of scopolamine before or after the reinstating USs blocked the return of CS-evoked freezing on the following day (Experiments 2 and 3). Our findings suggest that administering scopolamine around the time of an aversive experience could prevent relapse of extinguished fears in humans.

Fear renewal occurs when the context changes after fear extinction; however, whether avoidance is also influenced by context changes following fear extinction is untested. Forty-two participants performed an avoidance task within a typical fear renewal procedure. During Pavlovian conditioning, two stimuli (CS+) were associated with an aversive electrical stimulus (US), while a third stimulus was not (CS-). During subsequent avoidance learning, clicking a button canceled the delivery of the US during one but not the other CS+. Fear-related levels were then reduced by removing the US and the button in a new context (fear extinction with response prevention [Ext-RP]). Next, persistence of avoidance was tested in the extinction context B (group ABB) or the original conditioning context A (group ABA). We also tested whether ratings of relief pleasantness (based on both the CS- and the avoided CS+) during avoidance and Ext-RP predicted individual levels of persistent avoidance. Results showed that persistent avoidance was higher in conditioning context A than in extinction context B, and was predicted by higher relief pleasantness during avoidance conditioning. We conclude that persistent avoidance poses a threat to the long-term success of Ext-RP, and we propose that interventions aimed at mitigating the influence of context and relief levels might prove beneficial in this regard. ispartof: BEHAVIOUR RESEARCH AND THERAPY vol:138 ispartof: location:England status: published

Perceptual sensitivity for dyspnea (i.e. breathlessness) is often quantified using the slope of magnitude estimations plotted against the physical stimulus intensities of respiratory loads. This study investigated whether this slope and its stability varies as a function of (1) affective versus sensory aspects of dyspnea, and (2) interindividual differences in Fear of Suffocation. Eighty-three healthy women performed a load magnitude estimation task twice one week apart. Resistive loads of increasing magnitude (0-2.4-5-7.4-12.4-20 cmH20/l/s) were repeatedly presented for a single flow-targeted inspiration. One group rated the intensity of loads, another their unpleasantness. Neither slopes nor intercepts differed between sensory versus affective aspects of dyspnea. Intercepts were lower in the second compared to the first session. Fear of Suffocation was associated with flatter slopes. Test-retest reliabilities were low to moderate suggesting that perceptual sensitivity to dyspnea is less stable than commonly assumed. ispartof: BIOLOGICAL PSYCHOLOGY vol:169 ispartof: location:Netherlands status: published

Dopamine, one of the main neurotransmitters in the mammalian brain, has been implicated in the coding of prediction errors that govern reward learning as well as fear extinction learning. Psychotherapy too can be viewed as a form of error-based learning, because it challenges erroneous beliefs and behavioral patterns in order to induce long-term changes in emotions, cognitions and behaviors. Exposure therapy, for example, relies in part on fear extinction principles to violate erroneous expectancies of danger and induce novel safety learning that inhibits and therefore reduces fear in the long term. As most forms of psychotherapy, however, exposure therapy suffers from non-response, dropout and relapse. This narrative review focuses on the role of midbrain and prefrontal dopamine in novel safety learning and investigates possible pathways through which dopamine-based interventions could be used as an adjunct to improve both the response and the long term effects of the therapy. Convincing evidence exists for an involvement of the midbrain dopamine system in the acquisition of new, safe memories. Additionally, prefrontal dopamine is emerging as a key ingredient for the consolidation of fear extinction. We propose that applying a dopamine Prediction Error perspective to psychotherapy can inspire both pharmacological and non-pharmacological studies aimed at discovering innovative ways to enhance the acquisition of safety memories. Additionally, we call for further empirical investigations on dopamine-oriented drugs that might be able to maximize consolidation of successful fear extinction and its long-term retention after therapy, and we propose to also include investigations on non-pharmacological interventions with putative prefrontal dopaminergic effects, like working memory training. ispartof: Translational Psychiatry vol:10 issue:1 pages:1-13 ispartof: location:United States status: published

ispartof: BIOLOGICAL PSYCHIATRY vol:87 issue:10 pages:870-871 ispartof: location:United States status: published

Generalised avoidance behaviours are a common diagnostic feature of anxiety-related disorders and a barrier to affecting changes in anxiety during therapy. However, strategies to mitigate generalised avoidance are under-investigated. Even less attention is given to reducing the category-based generalisation of avoidance. We therefore investigated the potential of an operant-based approach. Specifically, it was examined whether reinforcing competing (non-avoidance) behaviours to threat-predictive cues would interfere with the expression of generalised avoidance. Using a matching-to-sample task, artificial stimulus categories were established using physically dissimilar nonsense shapes. A member of one category (conditioned stimulus; CS1) was then associated with an aversive outcome in an Acquisition context, unless an avoidance response was made. Next, competing behaviours were reinforced in response to the CS1 in new contexts. Finally, we tested for the generalisation of avoidance to another member of the stimulus category (generalisation stimulus; GS1) in both a Novel context and the Acquisition context. The selective generalisation of avoidance to GS1 was observed, but only in the Acquisition context. In the Novel context, the generalisation of avoidance to GSs was significantly reduced. A comparison group (Experiment 2), which did not learn any competing behaviours, avoided GS1 in both contexts. These findings suggest that reinforcing competing behavioural responses to threat-predictive cues can lead to reductions in generalised avoidance. This study is among the first study to demonstrate sustained reductions in generalised avoidance resulting from operant-based protocols, and the clinical and research implications are discussed. ispartof: QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY vol:73 issue:12 pages:2119-2131 ispartof: location:England status: published

Attachment is an inborn behavioral system that is biologically driven and essential for survival. During child development, individual differences in (in)secure attachment emerge. The development of different attachment behaviors has been traditionally explained as a process during which experiences with (lack of) responsive and supportive care are internalized into working models of attachment. However, this idea has been criticized for being vague and even untestable. With the aim of unraveling this black box, we propose to integrate evidence from conditioning research with attachment theory to formulate a Learning Theory of Attachment. In this review, we explain how the development of individual differences in attachment security at least partly follows the principles of classical and operant conditioning. We combine observed associations between attachment and neurocognitive and endocrinological (cortisol, oxytocin, and dopamine) processes with insights in conditioning dynamics to explain the development of attachment. This may contribute to the explanation of empirical observations in attachment research that are insufficiently accounted for by traditional attachment theory. ispartof: Neuroscience And Biobehavioral Reviews vol:113 pages:287-298 ispartof: location:United States status: published

Aunque aprender a evitar ciertas situaciones puede resultarnos adaptativo y ventajoso, ya que con ello reducimos el contacto con amenazas, en ocasiones estas conductas pueden alterar nuestra vida llegando a ser difíciles de controlar o eliminar. De hecho, la evitación excesiva e inflexible es un síntoma frecuente en gran variedad de trastornos psicológicos relacionados con ansiedad. En nuestro laboratorio nos preguntamos si ciertas variables de personalidad podrían predisponer a la adquisición de este tipo de conductas. Nuestro estudio sugiere que el rasgo de intolerancia a la incertidumbre, presente en numerosos trastornos de ansiedad, está relacionado con una evitación poco adaptativa.

This manuscript is part of a special issue to commemorate professor Paul Eelen, who passed away on August 21, 2016. Paul was a clinically oriented scientist, for whom learning principles (Pavlovian or operant) were more than salivary responses and lever presses. His expertise in learning psychology and his enthusiasm to translate this knowledge to clinical practice inspired many inside and outside academia. Several of his original writings were in the Dutch language. Instead of editing a special issue with contributions of colleagues and friends, we decided to translate a selection of his manuscripts to English to allow wide access to his original insights and opinions. Even though the manuscripts were written more than two decades ago, their content is surprisingly contemporary. This introductory article presents a reflection on Paul’s career and legacy and introduces the selected manuscripts that are part of this special issue. ispartof: Psychologica Belgica vol:58 issue:1 pages:212-221 ispartof: location:England status: published

Recent studies have shown that avoidance behavior may become excessive and inflexible (i.e., detached from its incentive value and resistant to extinction). On the other hand, prospective intolerance of uncertainty (P-IU) has been defined as a factor leading to excessive responding in uncertain situations. Thus, uncertain avoidance situations may be taken as a relevant scenario to examine the role of intolerance of uncertainty as a factor that facilitates excessive and inflexible avoidance behavior. In our experiment, we tested the hypothesis that P-IU is associated with excessive and inflexible avoidance in an outcome devaluation paradigm. Specifically, healthy participants learned in a free-operant discriminative task to avoid an aversive sound, and were tested in extinction to measure the sensitivity of avoidance responses to the devaluation of the sound aversiveness. The results showed that an increase in P-IU was positively associated to an increase in insensitivity to the devaluation. Moreover, P-IU was also related to an increase in the frequency of avoidance responses during the instrumental learning phase, and to resistance to extinction. Interestingly, these associations involving P-IU were still significant when trait anxiety was controlled for. The pattern of results suggests that P-IU may be a vulnerability factor for excessive and inflexible avoidance, which, in turn, has been found to be associated with several mental disorders.

This study examined developmental differences in contextual and perceptual generalization of fear and avoidance learning. Adults (N = 39) and adolescents (N = 44) completed differential fear acquisition wherein each conditional stimulus (CS) appeared in a background context. In the dangerous context, one stimulus (CS+) predicted an aversive sound, and the other stimulus (CS-) did not. In the safe context, the aversive sound was never administered with either CS. During fear generalization, participants were presented with three generalization stimuli (GSs), ranging on a perceptual continuum from threat to safety stimuli, in both contexts. Participants then completed avoidance conditioning and avoidance generalization phases, allowing them to actively avoid the upcoming aversive sound by pressing an avoidance button. Developmental differences emerged in threat perception, physiological arousal, avoidance behavior, and eye movements during contextual fear learning and generalization. Adolescents showed less discrimination between stimuli and contexts than adults, resulting primarily from their elevated fear responses to safety and generalized stimuli. Developmental differences in fear learning should be further explored in future research, as they could explain why adolescence is a sensitive developmental period for anxiety.

Fear extinction models have a key role in our understanding of anxiety disorders and their treatment with exposure therapy. Here, we tested whether individual differences in fear extinction learning and fear extinction recall in the laboratory were associated with the outcomes of an exposure therapy analog (ETA). Fifty adults with fear of spiders participated in a two-day fear-learning paradigm assessing fear extinction learning and fear extinction recall, and then underwent a brief ETA. Correlational analyses indicated that enhanced extinction learning was associated with better ETA outcome. Our results partially support the idea that individual differences in fear extinction learning may be associated with exposure therapy outcome, but suggest that further research in this area is needed. This work was supported by an ANPIR grant to E. F. (grant numberBA-3/2016); a KU Leuven program funding grant (grant number PF/10/005) and FP7 Marie Curie International Outgoing Fellowship (grantnumber 627743) to B. V.; PROMOSAM Investigación en procesos, me-canismos y tratamientos psicológicos para la promoción de la saludmental grant to M. T-F. (grant number PSI2014-56303-RED); Carlos IIIHealth Institute/FEDER grant to M. A. F. (grant number PI16/00144).

Human functional magnetic resonance imaging (fMRI) studies suggest that the ventromedial prefrontal cortex (vmPFC) contributes to the learned discrimination of threat and safety signals, although its precise contribution to these processes remains unclear. One hypothesis is that the vmPFC supports the positive affective processing of safety signals linked to their implicit stress-relieving properties. We set out to test this hypothesis and to examine the specificity of vmPFC responses to safety signal processing versus its high level of 'default mode' activity. Sixty participants completed an fMRI conditioning task that involved the generation of a conditioned threat (CS+) and safety (CS-) signal following the completion of a pre-conditioning baseline. Confirming past findings, activation of the vmPFC and other midline cortical and parietal areas - broadly resembling the default mode network - robustly discriminated between the CS- and CS+. However, when adjusting for this network's characteristic 'baseline' activity, only a subset of regions, including the vmPFC, was activated by the CS-. Regional selectivity for safety signal processing was confirmed by demonstrating a significant correlation between the magnitude of vmPFC responses and self-rated positive affect evoked by the CS-. Taken together, our current findings confirm a link between human vmPFC activity and the positive affective processing of safety signals. We discuss these findings with regards a broader model of human vmPFC function and its suggested higher-order contribution to emotionally adaptive behavior.

In two experiments, using an online conditioned suppression task, we investigated the possibility of reinstatement of extinguished feature-target compound presentations after sequential feature-positive discrimination training in humans. Furthermore, given a hierarchical account of Pavlovian modulation (e.g., Bonardi, 1998; Bonardi and Jennings, 2009), we predicted A-US reinstatement to be stronger than US-only reinstatement. In Experiment 1, participants learned a sequential feature-positive discrimination (X→A+|A-), which was subsequently extinguished (X→A-). During the following reinstatement phase, group US-only received US-only presentations (not signalled), group A-US received A-US presentations, and the Control group received exposure to the context, but no CSs or USs, for an equal amount of time. Reinstatement of differential X→A/A responding was observed in the US-only group but not in the Control or A-US groups. Although differential X→A/A responding was not significant in group A-US, responding to the X→A compound was significantly stronger compared to that in group US-only. Hence, it could be the case the group A-US showed stronger reinstatement, but that differential responding was abolished due to excitation gained by A. Experiment 2 was set up to circumvent the acquired excitation of A by testing transfer of the feature after A-US reinstatement to a different target, B. Participants acquired two discriminations, X→A/A and Y→B/B, of which X→A was then extinguished. Subsequently, group A-US received reinforced presentations of A during a reinstatement phase while group Control received exposure to the context. Final testing of the novel X→B compound was hypothesized to show higher responding in group A-US than in group Control, but findings of this approach were limited due to acquired equivalence and/or perceptual factors causing a secondary extinction effect. We conclude to have obtained clear evidence in favour of reinstatement of differential responding after human Feature-Positive discrimination training and subsequent compound extinction, but no evidence in favour of A-US presentations being a stronger trigger for reinstatement than are US-only presentations.

Studies of perceptual generalization have recently demonstrated a close relationship between stimulus perception and conditioned responding, suggesting that incorrect stimulus perception might account for certain characteristics of generalization gradients. In this study, we investigated whether common phenomena, such as the area and peak shift in conditioned responding, relate to perceptual errors. After a differential conditioning procedure, in which one circle was paired with the presentation of an aversive picture whereas a different-sized circle was not, we combined a generalization test with a three-alternative forced-choice perceptual categorization task where participants had to indicate on every trial whether the presented circle was one of the two circles from the conditioning phase or a different one, after which US-expectancy ratings were collected. The typical peak and area shift were observed when conditioned responses were plotted on a physical dimension. However, when stimulus perception was incorporated generalization gradients diverged from the typical gradient. Both the area and peak shift largely disappeared when accounting for perceptual errors. These findings demonstrate the need to incorporate perceptual mechanisms in associative models.

In exposure therapy, the client can either be confronted with the fear-eliciting situations in a hierarchical way or in a random way. In the current study we developed a procedure to investigate the effects of hierarchical versus random exposure on long-term fear responding in the laboratory. Using a fear conditioning procedure, one stimulus (CS+) was paired with an electric shock (US), whereas another stimulus was not paired with the shock (CS-). The next day, participants underwent extinction training including presentations of the CS-, CS+ and a series of morphed stimuli between the CS- and CS+. In the hierarchical extinction condition (HE; N = 32), participants were first presented with the CS-, subsequently with the morph most similar to the CS-, then with the morph most similar to that one, and so forth, until reaching the CS+. In the random extinction condition (RE; N = 32), the same stimuli were presented but in a random order. Fear responding to the CS+, CS- and a new generalization stimulus (GS) was measured on the third day. Higher expectancy violation (t(62) = -2.67, p = .01), physiological arousal (t(62) = -2.08, p = .04) and variability in US-expectancy ratings (t(62) = -2.25, p = .03) were observed in the RE condition compared to the HE condition, suggesting the validity of this novel procedure. However, no differences between the RE and HE condition were found in fear responding as tested one day later, F(1, 62) < 1. In conclusion, we did not find evidence for differential long-term fear responding in modeling hierarchical versus random exposure in Pavlovian fear extinction. ispartof: Behavior Therapy vol:50 issue:5 pages:967-977 ispartof: location:England status: published

Behavior in novel situations is guided by similarities to previous experiences, a phenomenon known as generalization. Despite the widespread influence of generalization on healthy and pathological behavior, insight into the underlying mechanisms is lacking. It remains unclear whether a failure to notice situational changes contributes to the generalization of learned behavior. We combined a fear conditioning and generalization procedure with a perceptual decision task in humans and found that a failure to perceive a novel stimulus as different from the initial fear-evoking stimulus was associated with increased conditioned responding. These findings demonstrate the potential of a perception-centered approach to better understand (pathological) behavior and its underlying mechanism and are a promising avenue for the development of refined generalization protocols. ispartof: Scientific Reports vol:9 issue:1 pages:1-8 ispartof: location:England status: published

Avoidance behaviors are central to the anxiety disorders and implicated in many other forms of psychopathology, but the reinforcing mechanism of avoidance remains largely elusive. It has been suggested that subjective relief during successful omission of threat may serve as a reinforcer and contribute to the development of excessive avoidance. Also, relatively little is known about how avoidance behaviors generalize and what the role is of relief in generalization. The purpose of this experiment was three-fold: (1) to investigate the influence of anxiety-traits on the dynamics of relief during avoidance learning, (2) to characterize the dynamics of relief during avoidance generalization, and (3) to investigate the generalization of avoidance behavior over a dimension of avoidability. In a large sample of 101 participants, two lamp colors (CS+) were first associated with an aversive electrical stimulation (US), while a third color was not (CS-). Next, clicking a button during one CS + could effectively avoid the US (CS + av), but not during the other (CS + unav). Finally, avoidance generalization was tested via button clicks during morphed colors between CS + av and CS + unav (avoidability dimension), and to morphed colors between CS + av and CS- (safety dimension). Throughout the experiment, a relief rating scale appeared whenever a lamp color was not followed by the US. Results revealed that anxiety traits (distress tolerance and intolerance of uncertainty) were associated with higher levels of avoidance and subjective relief. In addition, gradients of avoidance generalization and relief were observed over dimensions of avoidability (CS + av → CS + unav) and safety (CS + av → CS-). Together, these results suggest a role for excessive relief in the development and generalization of maladaptive avoidance.

Background and objectives Excessive maladaptive avoidance has been claimed to be one of the mechanisms through which intolerance of uncertainty (IU) may play its causal role in the development and maintenance of several anxiety and compulsive disorders. Consistently, Flores et al. (2018) found that individuals with higher Prospective IU (P-IU), a specific IU subfactor, display excessive avoidance response repetitions in a free-operant discriminative task to avoid an aversive noise. In the present study we tested the hypothesis that P-IU not only predicts the amount of avoidance responses but also how well the temporal distribution of such responses fits the temporal distribution of threats. Methods Further correlation and hierarchical regression analysis of Flores et al.‘s (2018) data served to test this hypothesis. We evaluated two aspects of the temporal distribution of responses: a) for how long participants were performing the responses; b) the behavioral discrimination between threatening and safe time periods. Results The results showed that scoring high in P-IU was positively associated with longer periods of time dedicated to avoiding and with worse behavioral discrimination between threatening and safe time periods. Hierarchical regression analyses indicated that later addition of inhibitory intolerance of uncertainty and trait anxiety did not significantly improved the explained variance. Limitations Our results are exclusively based on the use of a low-cost avoidance response, and the present study does not clarify the precise mechanisms that lead high P-IU people to engage in non-optimal avoidance response distribution through time. Conclusions These results suggest that excessive avoidance is also driven by uncertainty of threat timing and highlight the relevance of P-IU as a vulnerability factor for excessive and outspread avoidance behaviors.

BACKGROUND AND OBJECTIVES: Excessive avoidance of potential threat is a hallmark of anxiety and is thought to maintain fear by preserving the perceived high-threat value of avoided situations. Previous research has shown that the availability of avoidance maintains low-level threat. Here, we investigated whether an opportunity to engage in avoidance in the presence of a low-threat value safety cue would maintain its perceived threat value when avoidance was unavailable. METHODS: In a threat conditioning procedure, one conditional danger stimulus (CS+; A+) was followed by an aversive unconditioned stimulus (US; electric shock), and two safety stimuli (CS-; B- and C-) were never followed by the US. Next, clicking a button present during A+ avoided the scheduled US. Avoidance was then made available during C- for participants in the Experimental group but not in the Control group. In the test, all stimuli were presented without the opportunity to avoid. Threat expectancy, eyeblink startle electromyography (EMG), and skin conductance responses (SCRs) were measured. RESULTS: Findings showed an increase in threat expectancy for only C- in the Experimental group during the test phase following avoidance learning to similar levels as during threat conditioning. Compared to the Control group, threat expectancy for both B- and C- remained higher in Experimental group. SCR and startle EMG data did not corroborate these findings. LIMITATIONS: Further research is needed to test the commonly held clinical assumption that avoidance can increase threat value. CONCLUSIONS: Low-cost avoidance maintains low-threat value of safety cues. ispartof: Journal Of Behavior Therapy And Experimental Psychiatry vol:62 pages:57-64 ispartof: location:Netherlands status: published

Cognitive reappraisal and fear extinction learning represent two different approaches to emotion regulation. While their respective neural correlates have been widely studied with functional magnetic resonance imaging (fMRI), few direct comparisons between these processes have been conducted. We conducted a meta-analysis of fMRI studies of reappraisal and fear extinction, with the aim of examining both commonalities and differences in their neural correlates. We also conducted independent analyses that focused on specific reappraisal strategies (reinterpretation, distancing). Overall, we observed that the dorsal anterior cingulate cortex (dACC) and the bilateral anterior insular cortex (AIC) were similarly consistently engaged by reappraisal and extinction. Extinction was more consistently linked to activation of sensory and emotion processing regions, whereas reappraisal was more consistently associated with activation of a dorsal fronto-parietal network. Interestingly, the amygdala was preferentially deactivated by distancing. These results suggest that the dACC and the AIC are involved in domain-general regulatory networks. Differences between extinction and reappraisal could be explained by their relative processing demands on visual perceptual versus higher cognitive neural systems., Funding for this study was provided by Instituto de Salud Carlos III (ISCIII) (PI16/00889, PI16/00144 and PI14/00292), FEDER funds/ European Regional Development Fund (ERDF) - a way to build Europe-, a PERIS award from the Ministry of Health of the Generalitat de Catalunya (SLT006/17/249), and AGAUR (2017 SGR 1247). CIBERSAM is an initiative of the Carlos III Health Institute. MP-P and MA-N are supported by a FI Grant from AGAUR-Generalitat de Catalunya (2015 FI_B 00839 and 2017 FI_B 00327, respectively), grants co-funded by the European Social Fund (ESF) “ESF, Investing in your future”. JR and CS-M are supported by a ‘Miguel Servet’ contract from the ISCIII (CP14/00041 and CPII16/00048, respectively). AA-E is supported by a PFIS Predoctoral Contract (FI16/00311). BV is supported by a KU Leuven start-up grant STG/17/035. BJH is supported by a National Health and Medical Research Council of Australia (NHMRC) Clinical Career Development Award (1124472).

Dietary fiber and prebiotics consistently modulate microbiota composition and function and hence may constitute a powerful tool in microbiota-gut-brain axis research. However, this is largely ignored in Hooks et al.’s analysis, which highlights the limitations of probiotics in establishing microbiome-mediated effects on neurobehavioural functioning and neglects discussing the potential of prebiotics in warranting the microbiota’s role in such effects. ispartof: Behavioral and Brain Sciences vol:42 status: Published online