Effects of varenicline and cognitive bias modification on neural response to smoking-related cues:Study protocol for a randomized controlled study

BACKGROUND: Smoking-related cues can trigger drug-seeking behaviors, and computer-based interventions that reduce cognitive biases towards such cues may be efficacious and cost-effective cessation aids. In order to optimize such interventions, there needs to be better understanding of the mechanisms underlying the effects of cognitive bias modification (CBM). Here we present a protocol for an investigation of the neural effects of CBM and varenicline in non-quitting daily smokers. METHODS/DESIGN: We will recruit 72 daily smokers who report smoking at least 10 manufactured cigarettes or 15 roll-ups per day and who smoke within one hour of waking. Participants will attend two sessions approximately one week apart. At the first session participants will be screened for eligibility and randomized to receive either varenicline or a placebo over a seven-day period. On the final drug-taking day (day seven) participants will attend a second session and be further randomized to one of three CBM conditions (training towards smoking cues, training away from smoking cues, or control training). Participants will then undergo a functional magnetic resonance imaging scan during which they will view smoking-related pictorial cues. Primary outcome measures are changes in cognitive bias as measured by the visual dot-probe task, and neural responses to smoking-related cues. Secondary outcome measures will be cognitive bias as measured by a transfer task (modified Stroop test of smoking-related cognitive bias) and subjective mood and cigarette craving. DISCUSSION: This study will add to the relatively small literature examining the effects of CBM in addictions. It will address novel questions regarding the neural effects of CBM. It will also investigate whether varenicline treatment alters neural response to smoking-related cues. These findings will inform future research that can develop behavioral treatments that target relapse prevention. TRIAL REGISTRATION: Registered with Current Controlled Trials: ISRCTN65690030. Registered on 30 January 2014

Emotional recognition training modifies neural response to emotional faces but does not improve mood in healthy volunteers with high levels of depressive symptoms

Background: There is demand for new, effective and scalable treatments for depression, and development of new forms of cognitive bias modification (CBM) of negative emotional processing biases has been suggested as possible interventions to meet this need. Methods: We report two double blind RCTs, in which volunteers with high levels of depressive symptoms (Beck Depression Inventory ii (BDI-ii) > 14) completed a brief course of emotion recognition training (a novel form of CBM using faces) or sham training. In Study 1 (N = 36), participants completed a post-training emotion recognition task whilst undergoing functional magnetic resonance imaging to investigate neural correlates of CBM. In Study 2 (N = 190), measures of mood were assessed post-training, and at 2-week and 6-week follow-up. Results: In both studies, CBM resulted in an initial change in emotion recognition bias, which (in Study 2) persisted for 6 weeks after the end of training. In Study 1, CBM resulted in increases neural activation to happy faces, with this effect driven by an increase in neural activity in the medial prefrontal cortex and bilateral amygdala. In Study 2, CBM did not lead to a reduction in depressive symptoms on the BDI-ii, or on related measures of mood, motivation and persistence, or depressive interpretation bias at either 2 or 6-week follow-ups. Conclusions: CBM of emotion recognition has effects on neural activity that are similar in some respects to those induced by Selective Serotonin Reuptake Inhibitors (SSRI) administration (Study 1), but we find no evidence that this had any later effect on self-reported mood in an analogue sample of non-clinical volunteers with low mood (Study 2).</br

Mapping dynamic interactions among cognitive biases in depression

Depression is theorized to be caused in part by biased cognitive processing of emotional information. Yet, prior research has adopted a reductionist approach that does not characterize how biases in cognitive processes such as attention and memory work together to confer risk for this complex multifactorial disorder. Grounded in affective and cognitive science, we highlight four mechanisms to understand how attention biases, working memory difficulties, and long-term memory biases interact and contribute to depression. We review evidence for each mechanism and highlight time- and context-dependent dynamics. We outline methodological considerations and recommendations for research in this area. We conclude with directions to advance the understanding of depression risk, cognitive training interventions, and transdiagnostic properties of cognitive biases and their interactions

Understanding vulnerability for depression from a cognitive neuroscience perspective: a reappraisal of attentional factors and a new conceptual framework

We propose a framework to understand increases in vulnerability for depression after recurrent episodes that links attention processes and schema activation to negative mood states, by integrating cognitive and neurobiological findings. Depression is characterized by a mood-congruent attentional bias at later stages of information processing. The basic idea of our framework is that decreased activity in prefrontal areas, mediated by the serotonin metabolism which the HPA axis controls, is associated with an impaired attenuation of subcortical regions, resulting in prolonged activation of the amygdala in response to stressors in the environment. Reduced prefrontal control in interaction with depressogenic schemas leads to impaired ability to exert attentional inhibitory control over negative elaborative processes such as rumination, leading in turn to sustained negative affect. These elaborative processes are triggered by the activation of negative schemas after confrontation with stressors. In our framework, attentional impairments are postulated as a crucial process in explaining the increasing vulnerability after depressive episodes, linking cognitive and biological vulnerability factors. We review the empirical data on the biological factors associated with the attentional impairments and detail how they are associated with rumination and mood regulation. The aim of our framework is to stimulate translational research

Gaze cuing of attention in snake phobic women: the influence of facial expression

Only a few studies investigated whether animal phobics exhibit attentional biases in contexts where no phobic stimuli are present. Among these, recent studies provided evidence for a bias toward facial expressions of fear and disgust in animal phobics. Such findings may be due to the fact that these expressions could signal the presence of a phobic object in the surroundings. To test this hypothesis and further investigate attentional biases for emotional faces in animal phobics, we conducted an experiment using a gaze-cuing paradigm in which participants\u2019 attention was driven by the task-irrelevant gaze of a centrally presented face. We employed dynamic negative facial expressions of disgust, fear and anger and found an enhanced gaze-cuing effect in snake phobics as compared to controls, irrespective of facial expression. These results provide evidence of a general hypervigilance in animal phobics in the absence of phobic stimuli, and indicate that research on specific phobias should not be limited to symptom provocation paradigms

Unhealthy yet Avoidable-How Cognitive Bias Modification Alters Behavioral and Brain Responses to Food Cues in Individuals with Obesity

Obesity is associated with automatically approaching problematic stimuli, such as unhealthy food. Cognitive bias modification (CBM) could beneficially impact problematic approach behavior. However, it is unclear which mechanisms are targeted by CBM in obesity. Candidate mechanisms include: (1) altering reward value of food stimuli; and (2) strengthening inhibitory abilities. Thirty-three obese adults completed either CBM or sham training during functional magnetic resonance imaging (fMRI) scanning. CBM consisted of implicit training to approach healthy and avoid unhealthy foods. At baseline, approach tendencies towards food were present in all participants. Avoiding vs. approaching food was associated with higher activity in the right angular gyrus (rAG). CBM resulted in a diminished approach bias towards unhealthy food, decreased activation in the rAG, and increased activation in the anterior cingulate cortex. Relatedly, functional connectivity between the rAG and right superior frontal gyrus increased. Analysis of brain connectivity during rest revealed training-related connectivity changes of the inferior frontal gyrus and bilateral middle frontal gyri. Taken together, CBM strengthens avoidance tendencies when faced with unhealthy foods and alters activity in brain regions underpinning behavioral inhibition.Peer reviewe

Protocol for a randomized controlled trial examining multilevel prediction of response to behavioral activation and exposure-based therapy for generalized anxiety disorder.

BACKGROUND:Only 40-60% of patients with generalized anxiety disorder experience long-lasting improvement with gold standard psychosocial interventions. Identifying neurobehavioral factors that predict treatment success might provide specific targets for more individualized interventions, fostering more optimal outcomes and bringing us closer to the goal of "personalized medicine." Research suggests that reward and threat processing (approach/avoidance behavior) and cognitive control may be important for understanding anxiety and comorbid depressive disorders and may have relevance to treatment outcomes. This study was designed to determine whether approach-avoidance behaviors and associated neural responses moderate treatment response to exposure-based versus behavioral activation therapy for generalized anxiety disorder. METHODS/DESIGN:We are conducting a randomized controlled trial involving two 10-week group-based interventions: exposure-based therapy or behavioral activation therapy. These interventions focus on specific and unique aspects of threat and reward processing, respectively. Prior to and after treatment, participants are interviewed and undergo behavioral, biomarker, and neuroimaging assessments, with a focus on approach and avoidance processing and decision-making. Primary analyses will use mixed models to examine whether hypothesized approach, avoidance, and conflict arbitration behaviors and associated neural responses at baseline moderate symptom change with treatment, as assessed using the Generalized Anxiety Disorder-7 item scale. Exploratory analyses will examine additional potential treatment moderators and use data reduction and machine learning methods. DISCUSSION:This protocol provides a framework for how studies may be designed to move the field toward neuroscience-informed and personalized psychosocial treatments. The results of this trial will have implications for approach-avoidance processing in generalized anxiety disorder, relationships between levels of analysis (i.e., behavioral, neural), and predictors of behavioral therapy outcome. TRIAL REGISTRATION:The study was retrospectively registered within 21 days of first participant enrollment in accordance with FDAAA 801 with ClinicalTrials.gov, NCT02807480. Registered on June 21, 2016, before results

Attention retraining in social anxiety disorder: an fMRI study

Research suggests that patients with social anxiety disorder (SAD) have an attentional bias toward socially threatening stimuli, and recent studies have shown that computerized interventions designed to train attention away from such stimuli decrease attentional bias and SAD symptomatology. The current study sought to replicate findings from previous attention retraining studies and to examine neural mechanisms underlying attentional biases in SAD using functional magnetic resonance imaging (fMRI). Thirty-two SAD patients were randomized to complete either eight 15-minute sessions of a probe detection task designed to train attention away from disgust faces (n=16), or a placebo control task (n=16). Before and after these sessions, patients completed an fMRI probe detection task. Sixteen matched healthy controls also completed this fMRI task on one occasion. Study hypotheses were as follows: (a) post-intervention, SAD patients in the retraining condition would show greater reductions in attentional bias and SAD symptomatology compared to patients in the placebo condition; (b) SAD patients would show greater amygdala activation, and less prefrontal cortex (PFC) activation, when viewing negative faces than healthy controls; and (c) post-intervention, SAD patients in the retraining condition would show less amygdala activation, and greater PFC activation, when viewing negative faces than patients in the placebo condition. Results showed no between-group differences in attentional bias or SAD symptomatology post-intervention, with both groups showing significant symptom reduction. However, attentional bias change was significantly correlated with symptom change across the entire SAD sample (N=32) and was predictive of Liebowitz Social Anxiety Scale scores at post-intervention. Neuroimaging results showed hypo-activation in the orbitofrontal cortex and anterior cingulate cortex at pre-treatment for the SAD group compared to healthy controls. At post-treatment, this difference was no longer significant across the entire SAD group (N=32). Finally, results indicated that activation at pre-treatment in the posterior cingulate cortex/precuneus was significantly correlated with symptom change across the entire SAD sample. These results suggest that SAD patients may not be engaging higher-level cortical regions as readily as healthy controls and add to the recent growing body of research suggesting that attention retraining may not be an effective treatment for patients with SAD