Onno Kruse

Don’t fear ‘fear conditioning’: Methodological considerations for the design and analysis of studies on human fear acquisition, extinction, and return of fear

HighlightsOriginates from discussions on replicability and researchers degrees of freedom.Aims at stimulating discussions on methods applied in fear conditioning research.Addresses critical issues on terminology, design, methods, analysis.Serves as comprehensive compendium and critical evaluation of read‐out measures.Highlights methodological considerations when studying individual differences. ABSTRACT The so‐called ‘replicability crisis’ has sparked methodological discussions in many areas of science in general, and in psychology in particular. This has led to recent endeavours to promote the transparency, rigour, and ultimately, replicability of research. Originating from this zeitgeist, the challenge to discuss critical issues on terminology, design, methods, and analysis considerations in fear conditioning research is taken up by this work, which involved representatives from fourteen of the major human fear conditioning laboratories in Europe. This compendium is intended to provide a basis for the development of a common procedural and terminology framework for the field of human fear conditioning. Whenever possible, we give general recommendations. When this is not feasible, we provide evidence‐based guidance for methodological decisions on study design, outcome measures, and analyses. Importantly, this work is also intended to raise awareness and initiate discussions on crucial questions with respect to data collection, processing, statistical analyses, the impact of subtle procedural changes, and data reporting specifically tailored to the research on fear conditioning.

Altered Appetitive Conditioning and Neural Connectivity in Subjects With Compulsive Sexual Behavior

INTRODUCTION There has been growing interest in a better understanding of the etiology of compulsive sexual behavior (CSB). It is assumed that facilitated appetitive conditioning might be an important mechanism for the development and maintenance of CSB, but no study thus far has investigated these processes. AIM To explore group differences in neural activity associated with appetitive conditioning and connectivity in subjects with CSB and a healthy control group. METHODS Two groups (20 subjects with CSB and 20 controls) were exposed to an appetitive conditioning paradigm during a functional magnetic resonance imaging experiment, in which a neutral stimulus (CS+) predicted visual sexual stimuli and a second stimulus (CS-) did not. MAIN OUTCOME MEASURES Blood oxygen level-dependent responses and psychophysiologic interaction. RESULTS As a main result, we found increased amygdala activity during appetitive conditioning for the CS+ vs the CS- and decreased coupling between the ventral striatum and prefrontal cortex in the CSB vs control group. CONCLUSION The findings show that neural correlates of appetitive conditioning and neural connectivity are altered in patients with CSB. The increased amygdala activation might reflect facilitated conditioning processes in patients with CSB. In addition, the observed decreased coupling could be interpreted as a marker for impaired emotion regulation success in this group.

Impact of COMT Val158Met‐polymorphism on appetitive conditioning and amygdala/prefrontal effective connectivity

Appetitive conditioning is an important mechanism for the development, maintenance, and treatment of psychiatric disorders like substance abuse. Therefore, it is important to identify genetic variations, which impact appetitive conditioning. It has been suggested that the Val158Met‐polymorphism in the Catechol‐O‐Methyl‐Transferase (COMT) is associated with the alteration of neural processes of appetitive conditioning due to the central role of the dopaminergic system in reward processing. However, no study has so far investigated the relationship between variations in the COMT Val158Met‐polymorphism and appetitive conditioning. In this fMRI study, an appetitive conditioning paradigm was applied, in which one neutral stimulus (CS+) predicted appetitive stimuli (UCS) while a second neutral stimulus (CS−) was never paired with the UCS. As a main result, we observed a significant association between the COMT Val158Met‐genotype and appetitive conditioning: skin conductance responses (SCRs) revealed a significant difference between CS+ and CS− in Val/Val‐allele carriers but not in the other genotype groups. Val/Val‐allele carriers showed increased hemodynamic responses in the amygdala compared with the Met/Met‐allele group in the contrast CS+ > CS−. In addition, psychophysiological‐interaction analysis revealed increased effective amygdala/ventromedial prefrontal cortex connectivity in Met/Met‐allele carriers. The increased amygdala activity points to facilitated appetitive conditioning in Val/Val‐allele carriers while the amygdala/prefrontal connectivity results could be regarded as a marker for altered emotion regulation during conditioning, which potentially impacts appetitive learning sensitivity. The SCRs finding indicates a stronger conditioned response in the Val/Val‐allele group and dovetails with the neural differences between the groups. These findings contribute to the current research on COMT in emotional processing. Hum Brain Mapp 36:1093–1101, 2015.

Neural correlates of appetitive extinction in humans

Abstract Appetitive extinction receives attention as an important model for the treatment of psychiatric disorders. However, in humans, its underlying neural correlates remain unknown. To close this gap, we investigated appetitive acquisition and extinction with fMRI in a 2-day monetary incentive delay paradigm. During appetitive conditioning, one stimulus (CS+) was paired with monetary reward, while another stimulus (CS−) was never rewarded. Twenty-four hours later, subjects underwent extinction, in which neither CS was reinforced. Appetitive conditioning elicited stronger skin conductance responses to the CS+ as compared with the CS−. Regarding subjective ratings, the CS+ was rated more pleasant and arousing than the CS− after conditioning. Furthermore, fMRI-results (CS+ − CS−) showed activation of the reward circuitry including amygdala, midbrain and striatal areas. During extinction, conditioned responses were successfully extinguished. In the early phase of extinction, we found a significant activation of the caudate, the hippocampus, the dorsal and ventral anterior cingulate cortex (dACC and vACC). In the late phase, we found significant activation of the nucleus accumbens (NAcc) and the amygdala. Correlational analyses with subjective ratings linked extinction success to the vACC and the NAcc, while associating the dACC with reduced extinction. The results reveal neural correlates of appetitive extinction in humans and extend assumptions from models for human extinction learning.

Altered reward learning and hippocampal connectivity following psychosocial stress

&NA; Acute stress has a profound influence on learning, as has been demonstrated in verbal learning or fear conditioning. However, its effect on appetitive conditioning is still unclear. Fear conditioning research suggests the possibility of overgeneralization of conditioning to the CS‐ under acute stress due to its effect on prefrontal and hippocampal processing. In this study, participants (N = 56 males) were subjected to the Trier Social Stress Test or a placebo version. After that, all participants underwent an appetitive conditioning paradigm in the fMRI, in which one neutral cue (CS+) was repeatedly paired with reward, while another (CS‐) was not. Importantly, the stress‐group revealed overgeneralization of conditioning to the CS‐ on the behavioral level. On the neural level, stressed participants showed increased connectivity between the hippocampus and amygdala, vACC, and OFC, which maintain specificity of conditioning and also showed reduced differential activation. The results indicate overgeneralization of appetitive conditioning promoted by maladaptive balancing of pattern separation and pattern completion in the hippocampus under acute stress and are discussed with respect to clinical implications. HighlightsAppetitive conditioning is overgeneralized from CS + to CS‐ under acute stress.Reduced differential activation in vACC, OFC, hippocampus, amygdala under stress.Increased hippocampal connectivity to vACC, dACC, OFC, amygdala under stress.

Predictors for (Problematic) Use of Internet Sexually Explicit Material: Role of Trait Sexual Motivation and Implicit Approach Tendencies Towards Sexually Explicit Material

ABSTRACT Problematic use of Internet sexually explicit material (SEM) is thought to be a possible precursor of a clinically relevant disorder labeled as hypersexuality, sexual compulsion, sexual impulse control disorder, or sexual addiction. Knowledge about possible risk factors for developing a problematic Internet SEM use is scarce. The present study investigated whether trait sexual motivation and implicit approach tendencies towards sexual material are predictors of problematic SEM use and of the daily time spent watching SEM. Trait sexual motivation describes the general individual motivation to be sexually active in a long-lasting, trait-like perspective and can be measured by the Trait Sexual Motivation Questionnaire. In a behavioral experiment, we used the Approach-Avoidance Task (AAT) for measuring implicit approach tendencies towards sexual material. Symptoms of problematic Internet SEM use were assessed by the short Internet Addiction Test, modified for cybersex. Trait sexual motivation explained more variance of problematic Internet SEM use than implicit approach tendencies measured by the AAT. This was true for men as well as for women. Implicit approach tendencies towards SEM were correlated with trait sexual motivation, which could point to a common biological basis.

Increased skin conductance responses and neural activity during fear conditioning are associated with a repressive coping style

The investigation of individual differences in coping styles in response to fear conditioning is an important issue for a better understanding of the etiology and treatment of psychiatric disorders. It has been assumed that an avoidant (repressive) coping style is characterized by increased emotion regulation efforts in context of fear stimuli as compared to a more vigilant coping style. However, no study so far has investigated the neural correlates of fear conditioning of repressors and sensitizers. In the present fMRI study, 76 participants were classified as repressors or as sensitizers and were exposed to a fear conditioning paradigm, in which the CS+ predicted electrical stimulation, while another neutral stimulus (CS−) did not. In addition, skin conductance responses (SCRs) were measured continuously. As the main findings, we found increased neural activity in repressors as compared to sensitizers in the ventromedial prefrontal cortex and the anterior cingulate cortex (ACC) during fear conditioning. In addition, elevated activity to the CS+ in amygdala, insula, occipital, and orbitofrontal cortex (OFC) as well as elevated conditioned SCRs were found in repressors. The present results demonstrate increased neural activations in structures linked to emotion down-regulation mechanisms like the ventromedial prefrontal cortex, which may reflect the increased coping effort in repressors. At the same time, repressors showed increased activations in arousal and evaluation-associated structures like the amygdala, the occipital cortex (OCC), and the OFC, which was mirrored in increased SCRs. The present results support recent assumptions about a two-process model of repression postulating a fast vigilant response to fear stimuli, and a second process associated with the down-regulation of emotional responses.

Neural correlates of subjective CS/UCS association in appetitive conditioning

Explicit knowledge of conditioned stimulus (CS)/unconditioned stimulus (UCS) associations is proposed as important factor in classical conditioning. However, while previous studies have focused on its roles in fear conditioning, it has been neglected in the context of appetitive conditioning. The present functional magnetic resonance study aimed to investigate neural activation and functional connectivity linked to subjective CS/UCS association in appetitive conditioning. In total, 85 subjects participated in an appetitive acquisition procedure in which a neutral stimulus (CS+) was paired with a monetary reward, while another neutral stimulus (CS‐) was never paired with the reward. Directly afterwards, subjective CS/UCS association was assessed by measuring the extent to which the CS+ was thought to be associated with the UCS compared to the CS‐. Close relationships were established between subjective CS/UCS association and activations in the primary visual cortex (V1) during the early phase of conditioning and in the striatum during the late conditioning phase. In addition, we observed inverse relationships between subjective CS/UCS association and both V1/ventromedial prefrontal cortex (vmPFC) and striatal/vmPFC connectivity. The results suggest the involvement of decoupling vmPFC connectivity in reward learning in general and the roles of attentional processes in the formation of the subjective CS/UCS association during the early phase and reward prediction during the late phase of appetitive conditioning.

Weights in Visuo-Haptic Softness Perception are not Sticky

The contribution of vision to visuo-haptic softness judgments has been observed to be non-optimal and it has been speculated that the visual weights are “sticky”, i.e., do not account for the senses’ reliabilities [1, 2]. The present study tested the hypothesis of sticky weights by varying the quality of the visual information. Participants discriminated between the softness of two objects with deformable surfaces using only visual, only haptic, or bisensory information. Visually, we displayed the finger’s positions and stimulus deformations in a noisy or precise quality or in a precise quality enhanced by visual force information from color changes of the finger nail. We assessed the reliabilities of the judgments using the method of constant stimuli. In bisensory conditions, discrepancies between the two senses’ information were used to measure each sense’s weight. The reliability of visual judgments was lower with noisy as compared to precise position information, visual force information did not affect reliability. The reliability of bisensory judgments was suboptimal and visual weights were higher than optimal. Not as expected, the visual weights shifted with the visual reliability. The results confirm that visuo-haptic integration of softness information is suboptimal and biased towards vision, but with weights that are “lazy” rather than sticky.

Failure to Replicate the Association Between Fractional Anisotropy and the Serotonin Transporter Gene (5-HTTLPR, rs25531)

Recent work underlines the importance of alterations in white matter (e.g., measured by fractional anisotropy (FA)) as a neural vulnerability marker for psychiatric disorders. In this context, the uncinate fasciculus (UF), which connects the limbic system with prefrontal areas, has repeatedly been linked to psychiatric disorders, fear processing, and anxiety-related traits. Individual differences in FA may partly be genetically determined. Variation in the promoter region of the serotonin transporter gene (serotonin transporter-linked polymorphic region [5-HTTLPR]) is a particularly promising candidate in this context, which has been linked to psychiatric disorders as well as to limbic and prefrontal reactivity. However, findings on the association between the 5-HTTLPR and FA within the UF-tract have been heterogeneous. The present study investigated this relationship and extended previous work by considering different genetic classification approaches as well as sex effects in a human sample (n = 114). All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. As a main result, we did not find any significant relationship between the 5-HTTLPR and FA in the UF-tract although power analyses showed an adequate power. In addition, genotype effects were neither found when different classification approaches were used nor when analyses were carried out in males or females only. The present findings suggest that the association of the 5-HTTLPR and FA seems to be a more labile phenomenon than previously assumed. Possible explanations and limitations are discussed.