From Whole-Brain Data to Functional Circuit Models: The Zebrafish Optomotor Response.

Detailed descriptions of brain-scale sensorimotor circuits underlying vertebrate behavior remain elusive. Recent advances in zebrafish neuroscience offer new opportunities to dissect such circuits via whole-brain imaging, behavioral analysis, functional perturbations, and network modeling. Here, we harness these tools to generate a brain-scale circuit model of the optomotor response, an orienting behavior evoked by visual motion. We show that such motion is processed by diverse neural response types distributed across multiple brain regions. To transform sensory input into action, these regions sequentially integrate eye- and direction-specific sensory streams, refine representations via interhemispheric inhibition, and demix locomotor instructions to independently drive turning and forward swimming. While experiments revealed many neural response types throughout the brain, modeling identified the dimensions of functional connectivity most critical for the behavior. We thus reveal how distributed neurons collaborate to generate behavior and illustrate a paradigm for distilling functional circuit models from whole-brain data.

The efficacy of a transdiagnostic emotion regulation skills training in the treatment of binge-eating disorder-Results from a randomized controlled trial.

OBJECTIVES: Deficits in emotion regulation (ER) have been shown to be associated with binge-eating disorder (BED). To further clarify the causal nature of this association, we tested whether systematically enhancing ER skills would reduce symptoms of BED. METHODS: We randomly allocated N = 101 individuals meeting the criteria for BED to a transdiagnostic ER skills training or to a waitlist control condition (WLC). Primary outcome was the reduction in binges during the treatment-vs.-waiting period as assessed with the Eating Disorder Examination (EDE) interview. RESULTS: Mixed-model ANOVAs indicated that the average pre-to-post decrease in binges assessed with the EDE was significantly greater in the ER skills training condition than in the WLC (d = 0.66). These effects were stable over the 6-month follow-up period (d = 0.72). Remission rates at post/follow-up were 34.4/45.0% in the skills training and 7.5/20.0% in the WLC. Additionally, we found a greater reduction in general eating disorder psychopathology, of food consumption in a bogus taste test and of depression in the ER skills training condition. Moreover, the greater reduction in binge-eating episodes in the training condition was (partially) mediated by a greater increase in ER skills. CONCLUSIONS: The findings provide further support for the assumed importance of deficits in ER as a maintaining factor and, hence, as a target in the treatment of BED. As ER skills trainings have been shown to also reduce other kinds of psychopathology, they might be considered a promising transdiagnostic add-on component to disorder-specific interventions.

Attentional processing of body images in women with overweight and obesity.

PURPOSE: Despite the claim to integrate body image interventions in obesity treatment, little is known about the mechanisms involved in maintaining body dissatisfaction in persons with overweight and obesity. Therefore, the present study sought to investigate attentional processing of body stimuli in women with overweight and obesity (OW). METHODS: Women with OW (n = 82) and normal weight controls (NW; n = 44) conducted two eye-tracking paradigms. In the first paradigm, fixation duration on the subjectively most beautiful and ugliest body part of one's own and a weight-matched control body were analyzed. In the second paradigm, picture pairs including the own and a control body or object were presented and initial fixation orientation was measured. Automatic and intentional processing of the body pictures was manipulated by either indicating on which side which stimuli would appear or not. RESULTS: Women with OW displayed a bias towards the ugliest as opposed to the most beautiful body part, whereas women with NW showed a balanced viewing pattern. Furthermore, both groups showed a preference for bodies relative to the object. However, only women with OW preferred their own relative to the control body during intentional processing. CONCLUSION: Taken together, results point towards a self-focused and deficit-oriented gaze pattern in women with overweight and obesity. Targeting these processes might help to improve obesity treatment outcomes. LEVEL OF EVIDENCE: Level I, experimental study.

Vocal arousal: a physiological correlate of body distress in women with overweight and obesity.

PURPOSE: Numerous studies highlight the relevance of body image in the development and maintenance of overweight and obesity mostly using self-reported data. Given the importance of physiological assessment methods, the present study aimed at investigating vocally encoded emotional arousal as a correlate of body distress in women with overweight and obesity. METHODS: Cognitions of women with overweight and obesity (OW; n = 22) as well as normal weight controls (NW; n = 22) were assessed by means of a thought-sampling procedure during a mirror exposure and a control condition. Fundamental frequency (f0) as a marker of vocally encoded emotional arousal as well as verbalized body-related cognitions were analyzed during this experimental task. RESULTS: A stronger increase in f0 between the control and the mirror exposure condition was found in OW compared to NW. Furthermore, there were significant positive correlations between vocally encoded emotional arousal and various measures of body image. CONCLUSION: The findings support the utility of vocally encoded emotional arousal as an objective physiological correlate of the evaluative dimension of body image in women with overweight and obesity. LEVEL OF EVIDENCE: Level I, experimental study.

Eye-tracking study on the effects of happiness and sadness on body dissatisfaction and selective visual attention during mirror exposure in bulimia nervosa.

OBJECTIVE: Abundant research points to the central role of body image disturbances in the occurrence of eating disorders (ED). While emotional arousal has been identified as a trigger for binge eating in bulimia nervosa (BN), empirical knowledge on the influence of emotions on body image in individuals with BN is scarce. The present study sought to experimentally examine effects of a positive and negative emotion induction on body dissatisfaction and selective attention towards negatively valenced body parts among people with BN. METHOD: In a randomized-controlled cross-over design, happiness and sadness were induced by film clips one-week apart in women with BN (n = 23) and non-ED controls (n = 26). After the emotion induction, participants looked at their body in a full-length mirror, while their attentional allocation was recorded with the help of a mobile eye tracker. Participants repeatedly rated their momentary body dissatisfaction. RESULTS: Induction of happiness led to a significant decrease in self-reported body dissatisfaction. Furthermore, attentional bias (higher gaze duration and frequency) towards the most disliked body part relative to the most liked body part was significantly greater in the sadness than happiness condition in BN. No significant effects of emotion induction on gaze duration and gaze frequency during mirror exposure were found for controls. DISCUSSION: In line with assumptions of current models on ED, findings support the notion that emotional state influences the body image of patients with BN.

Whole-brain activity mapping onto a zebrafish brain atlas.

In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open-source atlas containing molecular labels and definitions of anatomical regions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated extracellular signal­regulated kinase (ERK) as a readout of neural activity, we have developed a system to create and contextualize whole-brain maps of stimulus- and behavior-dependent neural activity. This mitogen-activated protein kinase (MAP)-mapping assay is technically simple, and data analysis is completely automated. Because MAP-mapping is performed on freely swimming fish, it is applicable to studies of nearly any stimulus or behavior. Here we demonstrate our high-throughput approach using pharmacological, visual and noxious stimuli, as well as hunting and feeding. The resultant maps outline hundreds of areas associated with behaviors.

Emotional Awareness in Depressive and Anxiety Symptoms in Youth: A Meta-Analytic Review.

Emotion regulation is assumed to play an important role in depressive and anxiety symptoms in youth. However, the role of core components of emotion regulation, such as emotional awareness, is not well understood so far. Thus this meta-analysis aimed to examine the relationship between depressive and anxiety symptoms with emotional awareness in youth. A systematic literature search (PsycINFO, Medline, Google Scholar) identified 21 studies, from which 34 effect sizes were extracted. Results from random effects models showed that difficulties in emotional awareness were significantly correlated with a medium effect size for each, depressive and anxiety symptoms separately, and for their combined effects (overall outcome). Additionally, further analyses revealed that age was a significant moderator of the relationship between emotional awareness with depressive and anxiety symptoms, with younger samples (mean age ≤ 12 years) showing a stronger association between difficulties in emotional awareness and depressive and anxiety symptoms as compared to older samples (mean age > 12 years). The results suggest that emotional awareness may be of relevance for depressive and anxiety symptoms in youth. Future work is required to examine longitudinal developments, moderators, and mediators in multi-method approaches. Moreover, children and adolescents may benefit from interventions that aim to enhance emotional awareness.

Emotion Regulation Strategies in Depressive and Anxiety Symptoms in Youth: A Meta-Analytic Review.

The role of emotion regulation in subclinical symptoms of mental disorders in adolescence is not yet well understood. This meta-analytic review examines the relationship between the habitual use of prominent adaptive emotion regulation strategies (cognitive reappraisal, problem solving, and acceptance) and maladaptive emotion regulation strategies (avoidance, suppression, and rumination) with depressive and anxiety symptoms in adolescence. Analyzing 68 effect sizes from 35 studies, we calculated overall outcomes across depressive and anxiety symptoms as well as psychopathology-specific outcomes. Age was examined as a continuous moderator via meta-regression models. The results from random effects analyses revealed that the habitual use of all emotion regulation strategies was significantly related to depressive and anxiety symptoms overall, with the adaptive emotion regulation strategies showing negative associations (i.e., less symptoms) with depressive and anxiety symptoms whereas the maladaptive emotion regulation strategies showed positive associations (i.e., more symptoms). A less frequent use of adaptive and a more frequent use of maladaptive emotion regulation strategies were associated with depressive and anxiety symptoms comparably in the respective directions. Regarding the psychopathology-specific outcomes, depressive and anxiety symptoms displayed similar patterns across emotion regulation strategies showing the strongest negative associations with acceptance, and strongest positive associations with avoidance and rumination. The findings underscore the relevance of adaptive and also maladaptive emotion regulation strategies in depressive and anxiety symptoms in youth, and highlight the need to further investigate the patterns of emotion regulation as a potential transdiagnostic factor.

Gating of attention towards food stimuli in binge eating disorder.

Cognitive models of eating disorders propose that attentional biases for disorder-relevant stimuli contribute to eating disorder pathology. Empirical evidence of a contribution of attentional biases for binge eating disorder (BED) is still scarce. The aim of the present study was to assess attention engagement towards, and disengagement from, food stimuli in overweight females with BED (n = 25) and a group of overweight and obese women without BED (OW; n = 30). Participants completed a rapid serial visual presentation (RSVP) paradigm with food and neutral words as target stimuli. This task can be used to decompose an attentional bias for food stimuli into its stimulus engagement and stimulus disengagement components. Findings indicate that facilitated stimulus engagement for food stimuli over neutral stimuli was more pronounced in the BED group compared to the OW group. Conversely, there were no substantial disengagement effects in either group. Thereby, results support the idea that early attentional processes are biased in BED.

Effects of two cognitive regulation strategies on the processing of food cues in high restrained eaters. An event-related potential study.

This study tested the effects of cognitive regulation (CR) on the attentional processing of food cues in restrained eaters (RE) by means of event-related potentials (ERPs). In a within-subject-design, RE (n = 23) were presented pictures of highly palatable food and office items while ERPs were recorded. Prior to the presentation of the food stimuli, participants were either instructed to engage in reappraisal or to attempt to suppress cravings - both cognitive regulation (CR) strategies - or to simply watch the pictures. Prior to the presentation of the neutral stimuli, participants were instructed to simply watch them. Following each picture presentation, momentary craving was assessed. Main results showed that engaging in CR significantly reduced ERP amplitudes compared to the food watch condition. Passively attending to food pictures yielded significantly higher craving scores compared to engaging in CR. In addition, craving was significantly lower in the reappraisal than in the suppression condition. Therefore, reappraisal could potentially increase the ability to inhibit the appetitive motivation to eat.

General and food-specific inhibitory deficits in binge eating disorder.

OBJECTIVE: To investigate behavioral inhibition in individuals with binge eating disorder (BED) compared with overweight and obese individuals without BED (No-BED). METHOD: Participants with BED (n = 31) and the weight-matched No-BED group (n = 29) completed an inhibitory control task (stop-signal task, SST) with food and neutral stimuli. RESULTS: The BED group needed more time to stop an ongoing response, as indicated by increased stop signal reaction time (SSRT) relative to the No-BED group. Additionally, compared with the No-BED group, the BED group displayed more difficulty inhibiting responses elicited by food stimuli. The deficits in behavioral response inhibition were also found to be related to the severity of reported symptoms. DISCUSSION: There is a general deficit in late stage behavioral inhibition in BED, and this may be particularly pronounced in the context of food stimuli.

Attentional bias for food cues in binge eating disorder.

The aim of the present study was to investigate an attentional bias toward food stimuli in binge eating disorder (BED). To this end, a BED and a weight-matched control group (CG) completed a clarification task and a spatial cueing paradigm. The clarification task revealed that food stimuli were faster detected than neutral stimuli, and that this difference was more pronounced in BED than in the CG. The spatial cueing paradigm indicated a stimulus engagement effect in the BED group but not in the CG, suggesting that an early locus in stimulus processing contributes to differences between BED patients and obese controls. Both groups experienced difficulty disengaging attention from food stimuli, and this effect was only descriptively larger in the BED group. The effects obtained in both paradigms were found to be correlated with reported severity of BED symptoms. Of note, this relationship was partially mediated by the arousal associated with food stimuli relative to neutral stimuli, as predicted by an account on incentive sensitization.

Cognitive interference and a food-related memory bias in binge eating disorder.

The present study was concerned with cognitive interference and a specific memory bias for eating-related stimuli in binge eating disorder (BED). Further objectives were to find out under which circumstances such effects would occur, and whether they are related with each other and with reported severity of BED symptoms. A group of women diagnosed with BED and a matched sample of overweight controls completed two paradigms, an n-back task with lures and a recent-probes task. The BED group generally experienced more interference in the n-back task. Additionally, they revealed selectively increased interference for food items in the recent-probes task. Findings can be reconciled with the view that control functions are generally impaired in BED, and that there is an additional bias for eating-related stimuli, both of which were related with reported severity of BED symptoms.

Effects of rumination and acceptance on body dissatisfaction in binge eating disorder.

Overvaluation of shape and weight and the corresponding body dissatisfaction are a maintenance factor for the psychopathology of binge eating disorder (BED). Evidence suggests potential benefits of various emotion regulation (ER) strategies in the modification of body dissatisfaction. Therefore, in the present study body dissatisfaction was experimentally induced in women with BED (n=30) using model pictures. Then, participants were instructed to either ruminate on present emotions and thoughts or accept whatever thoughts and feelings come up. Body dissatisfaction and mood were assessed prior to, immediately after and 4 minutes after the induction. Main results reveal that ER strategies had no differential impact on body dissatisfaction. However, in the rumination condition mood significantly worsened over time. Overall, the results suggest that ER strategies have a limited impact on the experience of body dissatisfaction in BED. However, having an impact on mood, they may be important with regard to the maintenance of pathological eating behaviour in BED. Association.

Effects of exposure to plus-size fashion models on weight-related attitudes in bulimia nervosa: Findings from an exploratory study.

BACKGROUND AND OBJECTIVES: Eating disorders are often linked to the internalization of the thin-ideal and weight stigma. The present exploratory study investigates the effects of plus-sized fashion media on weight-related attitudes in bulimia nervosa (BN). METHODS: Women with BN (n=27) and without an eating disorder (n=28) were exposed to 17 pictures of plus-size fashion models. Participants rated the attractiveness of the models. Before and after the exposure task, participants completed questionnaires on their attitudes towards people with higher weight as well as thin-ideal media. RESULTS: The BN group rated the bodies of the plus-size fashion models as less attractive than controls, whereas no group differences were found in attractiveness ratings for the models' faces or full images. In both groups, negative attitudes about people with higher weight significantly decreased after viewing plus-size model pictures. Attitudes toward thin-ideal media remained unchanged, with scores higher for BN than controls. LIMITATIONS: This exploratory study has several limitations, such as the lack of a control condition, small sample size, and reliance on only self-report data. CONCLUSIONS: These exploratory results imply that the positive effects of plus-sized model images on reducing negative assumptions about people with high weight may not be limited to healthy individuals but also seem to extend to women with BN. Further controlled studies with larger samples and long-term assessments are needed to confirm these findings.

Membrane anchoring γ-secretase modulators with terpene-derived moieties.

Modulation of γ-secretase activity is a promising therapeutic strategy for the treatment of Alzheimer's disease. Herein we report on the synthesis of carprofen- and tocopherol-derived small-molecule modulators carrying terpene moieties as lipophilic membrane anchors. Additionally, these modulators are equipped with an acidic moiety, which contributes to the desired modulatory effect on the γ-secretase with decreased formation of Aß42 and increased Aß38 production.

Increased salivation to mirror exposure in women with binge eating disorder.

Although body image disturbances are not a diagnostic criterion of the binge eating disorder (BED), intervention studies yield evidence of its importance in the maintenance of the disorder. Therefore, the aim of the present study was to experimentally test the influence of body-related schemata in the occurrence of appetite in individuals with BED. After collecting baseline saliva, women with BED and weight matched controls (CG) were either given a food exposure (FE) or mirror exposure (ME), while participants' salivary reaction was assessed once more. In addition, participants repeatedly rated their actual desire to binge (DTB) and emotions. Main results reveal a significant salivation and DTB increase in the FE compared to the baseline condition in both groups. However, only in BED participants salivation and DTB increase were significantly higher in the ME compared to the baseline condition. The results support the importance of body image for the maintenance of BED.

The effects of emotion regulation on the desire to overeat in restrained eaters.

The aim of the present study was to test whether emotion regulation (ER) strategies are underlying processes in the link between negative emotions and the desire to overeat (DTE) in high restrained eaters (HR). Forty-eight female HR and 46 female low restrained eaters (LR) watched three sadness inducing film clips. Thereby, participants were randomly assigned to and trained in one of three conditions while watching the first two clips: to suppress upcoming emotions, to accept upcoming emotions or to reappraise the situation. After that, they participated in an experiment in which the learned ER strategy was implemented while watching the third sadness inducing film clip. DTE and sadness were assessed prior to and at the end of each clip. Additionally, physiological measures of the sympathetic and parasympathetic branch were obtained. In the HR group emotion acceptance and suppression lead to a significant increase of the DTE from baseline to post-film, while there was no change in DTE in the reappraisal condition. However, psychophysiological measures were not moderated by ER strategies. The results are discussed in terms of the limited resource model.

Taking a closer look at body processing in binge eating disorder - Influence of BMI and eating pathology.

Individuals with binge eating disorder (BED) show preferred attention allocation towards their own (vs. another) body, and towards self-disliked (vs. self-liked) body parts. It remains unclear whether these gaze patterns are a consequence of underlying eating pathology or increased weight. In this study, women with BED (N = 73), overweight (N = 38) and healthy weight (N = 42) female control groups (CG) performed two eye-tracking paradigms using pictures of their own and a control-body. In task 1 (processing their own vs. a control-body), the BED group displayed a stronger preference for the own body during more automatic processing relative to the overweight CG, whereas the healthy weight CG showed a balanced attention distribution between both bodies. In task 2, all groups showed a bias towards the most unattractive relative to the most attractive part of their own body. This was strongest in the BED and overweight groups, but only the BED group showed a negative bias towards the control-body. Results indicate a stronger self-focused and deficit-oriented bias in the BED group but also some abnormalities in overweight individuals. Future studies should test whether these biases are modifiable, and whether their modification improves body image.