Transferring the approach avoidance task into virtual reality: a study in patients with alcohol use disorder versus healthy controls.

Study aims were to (I) transfer the measurement of the approach bias (Apb) related to alcoholic stimuli via the Approach Avoidance Task (AAT) into Virtual Reality (VR), (II) check whether measuring Apb in VR leads to similar or different results compared to the classical PC-based version, (III) check the validity of VR versus PC-based bias scores in terms of relatedness to clinical variables. Different 'grasping-conditions' were tested and contrasted in VR concerning (Ia) feasibility (performance): (1) never grasp, (2) always grasp, (3) grasp when PULLing stimuli towards oneself. (Ib) Differences in the bias scores between patients with alcohol use disorder (AUD) and healthy controls (HC) were examined for each grasping-condition. (II) PC-based bias scores were computed and contrasted for AUD versus HC. (III) Correlations of the different VR- versus PC-based bias scores with AUD symptom severity and impulsivity were checked to evaluate validity. (Ia) Grasping-condition 1, followed by 3, showed acceptable (> 50%) and good (> 80%) rates of correct performances allowing for robust median estimation. (Ib) Significant differences in the resulting bias scores emerged between AUD and HC only for grasping-condition 1 (p = 0.034) and 3 at trend-level (p = 0.093). For grasping-condition 1 the Apb Median for AUD was different from zero at a non-significant trend-level (p = 0.064). (II) The PC-based bias scores did not discriminate between AUD versus HC groups. (III) Grasping-condition 1 and 3 VR-based bias scores correlated significantly with impulsivity. In sum, transferring the AAT into VR is feasible, valid, and best implemented without an additional grasping-component when using the VR-controller. This way of Apb assessment represents a viable, perhaps even superior, alternative to PC-based assessments. Trial registration The trial was pre-registered at AsPredicted #76854: 'Transferring the approach avoidance task into virtual reality', 10/13/2021; prior to any analyses being undertaken.

Differential Orbitofrontal Cortex Responses to Chocolate Images While Performing an Approach-Avoidance Task in the MRI Environment.

Background: Chocolate is one of the most frequently craved foods, and it often challenges self-regulation. These cravings may be underpinned by a neural facilitation of approach behavior toward chocolate. This preregistered study investigated the behavioral and neural correlates of such a bias using functional magnetic resonance imaging (fMRI) and reaction times (RTs). Methods: A total of n = 30 frequent chocolate eaters performed a relevant-feature approach-avoidance task (AAT) in the MRI scanner using buttons to enlarge (approach) or to shrink (avoid) pictures of chocolate and inedible control objects. We tested (a) whether implicit RT-based approach biases could be measured in a supine position in the scanner, (b) whether those biases were associated with activity in reward-related brain regions such as the insula, amygdala, striatum, and orbitofrontal cortex (OFC), and (c) whether individual RT-based bias-scores correlated with measures of chocolate craving. Results: Behaviorally, we found a highly reliable approach bias toward chocolate, defined by faster RTs in the compatible conditions (approach chocolate, avoid objects) compared to the incompatible conditions (avoid chocolate, approach objects). Neurally, this compatibility effect involved activity in the left medial OFC, a neural response that was positively correlated with individual approach bias scores. Conclusions: This study shows that the relevant feature AAT can be implemented in an fMRI setting in a supine position using buttons. An approach bias toward chocolate seems related to medial OFC activation that might serve to devalue chocolate when it has to be avoided. Our demonstration of neural and behavioral approach biases for chocolate underscores the need for stimulus-specific cognitive trainings to support healthy consumption and successful self-regulation.

Is less more? Dismantling imaginal retraining and examining the effects of psychoeducation and embodied cognition on craving and alcohol consumption in problem drinkers: A randomized controlled trial.

BACKGROUND: Imaginal retraining, a type of approach-bias-modification performed in one's own imagination, is effective in reducing alcohol craving in problem drinkers. This study aims to segregate three main components of the original technique and compare their effectiveness in reducing craving and alcohol consumption. METHODS: The study was conducted online. Interested individuals wishing to reduce their alcohol consumption underwent a baseline assessment (T0), whereby a total of N = 200 included participants were randomly assigned to one of four study arms. There were three active groups receiving different training manuals: psychoeducation + advice only (PE), PE + a simplified motor in-sensu AAT instruction (AAT0), and the 'enriched' original imaginal retraining technique (including the components PE + enhanced movements + an embodied cognition/ emotion induction instruction) (AAT+), vs. a wait-list control (WLC). Participants in the three active arms were instructed to train twice a day (10 mins. each) over the course of four weeks, whereafter a post-test was conducted (T1). A follow-up took place one month later (T2). Repeated measures ANOVAs were computed to test for differential changes of the four groups over time (group*time interaction effects) concerning craving and alcohol consumption. Both per-protocol and intention-to-treat analyses (PPA, ITTA) were conducted. RESULTS: In both PPA and ITTA, significant group*time interaction effects were identified, whereby false-discovery-rate corrected post-hoc tests revealed that AAT0 most consistently reduced craving with stability towards follow-up. Results concerning alcohol consumption (g ethanol) were inconsistent. CONCLUSION: This study demonstrates that a simplified version of the imaginal retraining technique yields consistent results concerning craving reduction. This may hint towards the central importance of the core element of retraining: a movement of pushing (imagined) alcoholic beverages away. Possibly, more complex forms of imaginal retraining need further instruction than a written manual, such as instructive videos.

Personality-Related Factors and Depressive Symptomatology Predict Behavioral Control in Patients With Alcohol Use Disorders.

In the face of increasing social, economic, and health consequences of alcohol use disorders (AUDs) and limited effects of available treatment options, the search for novel prevention and management methods continues to remain a timely and valid endeavor. This, however, requires a better grasp of the theoretical framework underlying addiction mechanisms. With the goal to extend the existing body of evidence on AUDs, we set out to investigate the effect of personality-related factors and depressive symptomatology on (i) impulsivity, (ii) cognitive response inhibition, and (iii) the links between the two measures of behavioral control (different facets of impulsivity and response inhibition) in a treatment-seeking AUD sample. To this end, 53 male (n = 45) and female (n = 8) inpatients at an alcohol rehabilitation center completed three self-report questionnaires: the International Personality Item Pool (IPIP-50), the Beck Depression Inventory Second Edition (BDI-II) and the Barratt Impulsiveness Scale (BIS-11) and performed one behavioral task-an alcohol go/no go task. Regression analyses revealed conscientiousness, intellect, and depression level to be important potential predictors of self-report impulsivity and processing speed in recovering drinkers. No significant links were observed between the two measures of behavioral control, thus complementing evidence that while they both encompass behavioral under-regulation, they may indeed represent distinct psychological constructs.

A dismantling study on imaginal retraining in overweight or obese women.

Imaginal retraining is a variant of approach bias modification and transfers the method into one's own mind. As the technique contains multiple elements, this pilot study aimed to dismantle which of its components is most efficient in reducing craving for high-calorie food. A total of 113 women were randomly allocated to one out of six conditions containing a short intervention to mentally manipulate a picture displaying high-calorie foods. Four of the interventions involved different combinations of elements of the imaginal retraining technique, while the remaining two conditions comprised thought suppression or merely observing a picture. Participants rated their level of craving, as well as three pictures containing healthy and unhealthy foods regarding their pleasantness before and after the interventions took place. Within-group changes were assessed with paired t-tests (in case of non-normal data Wilcoxon paired t-tests) and between-group differences with one-way ANOVAs (non-parametric Kruskal-Wallis tests). A trend level reduction in craving was found in the imaginal retraining condition with and without a movement. A post hoc analysis of both conditions joint together showed a statistically significant reduction in craving. In addition, positive picture appraisal for unhealthy foods was significantly reduced in both imaginal retraining conditions (with and without movement) with medium to large effect sizes. This study demonstrated that imaginal retraining with an arm movement can reduce craving and picture appraisal for high-calorie foods significantly in a one-time application. It is a promising technique to reduce appraisal for unhealthy high-calorie foods. Future studies should repeat the experiment in situations of high craving and allow for a personalized selection of stimuli.

A dismantling study on imaginal retraining in smokers.

Imaginal retraining is a noncomputerized variant of cognitive bias modification, an intervention aimed at reducing craving in substance use disorders and behavioral addictions. We conducted a dismantling study to elucidate which of its multiple components are effective and hence essential ingredients of the training and which are ineffective (and hence perhaps dispensable) in reducing craving. We randomized 187 smokers to one out of six conditions that instructed participants to perform a brief intervention. In four of these, participants were instructed to perform isolated components of the imaginal retraining protocol, and in the two other conditions participants either suppressed or simply observed (control condition) the image of a cigarette. Before and after the intervention, participants were asked to rate their level of craving and how pleasant they found three smoking-related images. We examined within-group changes by means of paired t-tests separately across conditions (trial registration: DRKS00021044). Mental distancing from cigarettes (without a corresponding actual physical movement; non-motor retraining) led to a significant decline in craving (paired t-test), which remained significant when compared to the control condition. The effects of other components of the retraining were less consistent. The present study shows that a single therapeutic "dose" of distinct components involved in imaginal retraining can reduce craving for cigarettes. Future trials should investigate the effectiveness of components of imaginal retraining not yet tested (e.g., mood induction) and whether combinations and repetition of single components strengthen or dilute efficacy.

Brain functional connectivity differs when viewing pictures from natural and built environments using fMRI resting state analysis.

Human beings evolved in "natural" environments. Many intervention studies have shown that exposure to natural environments (compared to built/urban environments) reduces stress and increases cognitive functioning. We set out to test differences in fMRI functional connectivity while showing participants photographs from natural versus built environments (matched in terms of scenicness ratings). No differences in self-reported perceived stress, rumination, valence, arousal or dominance were observed. However, functional connectivity was significantly higher when participants saw natural rather than built environmental photographs in circuits consisting of dorsal attention network (DAN) and ventral attention network (VAN), DAN and default mode network (DMN) and DMN and Somatomotor connections. In addition, we observed lower functional connectivity during the natural environment condition correlated with more years that individuals spent in major cities during upbringing. Future studies, linking changes in cognitive functioning due to nature exposure and alterations in functional connectivity, are warranted.

A randomized controlled trial of a virtual reality based, approach-avoidance training program for alcohol use disorder: a study protocol.

BACKGROUND: The approach-avoidance training program (AATP) has shown preliminary promise as an add-on to standard treatment for alcohol dependence. However, knowledge is lacking as to whether the effectiveness of AATP can be enhanced further when performed in a typical drinking situation. The main aim of this study is to investigate whether approach-avoidance training implemented in a virtual reality bar environment is superior to the classical joystick PC-version of the AATP. METHODS: The study will be implemented as a randomized controlled trial. A total of 204consecutively enrolled alcohol use disorder (AUD) patients, recruited from alcohol inpatient clinics in Germany, Poland and Denmark, will be randomized into one of three groups at the start of standard alcohol treatment: group A) stimuli-relevant AATP + treatment as usual (TAU); group B) stimuli-relevant AATP in virtual reality + TAU, and group C) TAU only (control group). Treatment outcomes will be assessed at pre-treatment, post-treatment and 3-month follow-up. Repeated-measures ANOVA will be applied to compare the trajectories of the groups over time on drinking, craving and impulsiveness outcomes. It is hypothesized that the two experimental groups will achieve better treatment outcomes compared to group C and that group B will achieve better outcomes than group A. DISCUSSION: This study is the first trial examining the effectiveness of stimuli-relevant AATP delivered in a VR environment. The use of VR has shown promise in enhancing the effectiveness of other psychological treatments and since AATP has already been shown effective as add-on treatment, it is of interest to investigate whether these effects can be further enhanced by implementing the program in more ecologically valid environments. If proven effective, the AATP-VR can, like the AATP, be implemented easily and cheaply as add-on treatment or continued care to enhance the effectiveness of current evidence-based treatment. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04283305 Registration date: 24.02.20.

Metacognitive Training for Obsessive-Compulsive Disorder: a study protocol for a randomized controlled trial.

BACKGROUND: A high number of patients with obsessive-compulsive disorder (OCD) do not receive cognitive-behavioral therapy with exposure and response prevention, which is the most effective treatment for OCD. Therefore, Metacognitive Training for OCD (MCT-OCD) was developed, which is a structured group therapy aiming at the modification of dysfunctional (meta-)cognitive biases, beliefs and coping styles. It can be administered by less trained personnel, thus may reach a higher number of patients. An uncontrolled pilot study (MCT-OCD pilot version) provided first evidence that the training is highly accepted by patients; OC symptoms decreased with a high effect size (η2partial = 0.50). The aim of the present study is to address the shortcomings of the pilot study (e.g., no control group) and to assess the efficacy of the revised version of the MCT-OCD in the framework of a randomized controlled trial. METHODS: Eighty patients with OCD will be recruited. After a blinded assessment at baseline (-t1), patients will be randomly assigned either to the intervention group (MCT-OCD; n = 40) or to a care as usual control group (n = 40). The MCT-OCD aims to enhance patients' metacognitive competence in eight modules by addressing dysfunctional (meta-)cognitive biases and beliefs associated with OCD (e.g., intolerance of uncertainty). After 8 weeks, patients will be invited to a post assessment (t1), and then they will receive a follow-up online questionnaire 3 months following t1 (t2). The primary outcome is the Y-BOCS total score, and the secondary outcomes include the HDRS, OCI-R, OBQ-44, MCQ-30, WHOQOL-BREF, BDI-II, and subjective appraisal ratings of the MCT-OCD. We expect that OC symptoms will decrease more in the intervention group compared with the care as usual control group from -t1 to t1 and that treatment gains will be maintained until t2. DISCUSSION: The planned study is the first to investigate the MCT-OCD, a promising new treatment, in a randomized controlled trial. The MCT-OCD may help to overcome existing treatment barriers for patients with OCD. TRIAL REGISTRATION: German Registry for Clinical Studies ( DRKS00013539 ), 22.02.2018.

Reduction of the tumorigenic potential of human retinoblastoma cell lines by TFF1 overexpression involves p53/caspase signaling and miR-18a regulation.

Trefoil factor family (TFF) peptides have been shown to play a pivotal role in oncogenic transformation, tumorigenesis and metastasis by changing cell proliferation, apoptosis, migration and invasion behavior of various cancer cell lines. In the study presented, we investigated the effect of TFF1 overexpression on cell growth, viability, migration and tumorigenicity of different retinoblastoma (RB) cell lines. Transient TFF1 overexpression significantly increases RB cell apoptosis levels. Stable, lentiviral TFF1 overexpression likewise decreases RB cell viability, proliferation and growth and significantly increases apoptosis as revealed by WST-1 assays, BrdU and DAPI cell counts. TFF1-induced apoptosis is executed via cleaved caspase-3 activation as revealed by caspase blockage experiments and caspase-3 immunocytochemistry. Results from pG13-luciferase reporter assays and Western blot analyses indicate that TFF1-induced apoptosis is mediated through transcriptional activity of p53 with concurrently downregulated miR-18a expression. In ovo chicken chorioallantoic membrane (CAM) assays revealed that TFF1 overexpression significantly decreases the size of tumors forming from Y79 and RB355 cells and reduces the migration potential of RB355 cells. Differentially expressed genes and pathways involved in cancer progression were identified after TFF1 overexpression in Y79 cells by gene expression array analysis, underlining the effects on reduced tumorigenicity. TFF1 knockdown in RBL30 cells revealed caspase-3/7-independent apoptosis induction, but no changes on cell proliferation level. In summary, the in vitro and in vivo data demonstrate for the first time a tumor suppressor function of TFF1 in RB cells which is at least partly mediated by p53 activation and miR-18a downregulation.