Attention Bias Modification Treatment Versus a Selective Serotonin Reuptake Inhibitor Or Waiting List Control for Social Anxiety Disorder: A Randomized Clinical Trial.

OBJECTIVE: Social anxiety disorder is common and impairing. The efficacy of pharmacotherapy is moderate, highlighting the need for alternative therapies. This study compared the efficacy of gaze-contingent music reward therapy (GC-MRT), an eye-tracking-based attention bias modification treatment, with a selective serotonin reuptake inhibitor (SSRI) treatment or a waiting list control condition in reducing social anxiety disorder symptoms. Superior clinical effects of similar magnitude were expected for the active treatments relative to the control condition. METHODS: Participants were 105 treatment-seeking adults with social anxiety disorder, randomly allocated to 12 weeks of GC-MRT, SSRI, or waiting list control. Mean changes in clinician-rated and self-reported social anxiety symptoms from baseline to mid- and posttreatment assessments were compared between groups using generalized estimating equations. Changes in attentional dwell time on threat were also examined. RESULTS: Analysis indicated a significant differential reduction in symptoms between groups. Patients in the GC-MRT and SSRI groups had lower social anxiety scores at the mid- and posttreatment assessments compared with patients in the waiting list group. The efficacy of the active treatments did not differ. Only patients in the GC-MRT group showed reduction in dwell time on threat from baseline to posttreatment assessment. CONCLUSIONS: Eye-tracking-based attention bias modification is an acceptable and effective treatment option for social anxiety disorder.

Resting state connectivity predictors of symptom change during gaze-contingent music reward therapy of social anxiety disorder.

BACKGROUND: Social anxiety disorder (SAD) is common, first-line treatments are often only partially effective, and reliable predictors of treatment response are lacking. Here, we assessed resting state functional connectivity (rsFC) at pre-treatment and during early treatment as a potential predictor of response to a novel attention bias modification procedure, gaze-contingent music reward therapy (GC-MRT). METHODS: Thirty-two adults with SAD were treated with GC-MRT. rsFC was assessed with multi-voxel pattern analysis of fMRI at pre-treatment and after 2-3 weeks. For comparison, 20 healthy control (HC) participants without treatment were assessed twice for rsFC over the same time period. All SAD participants underwent clinical evaluation at pre-treatment, early-treatment (week 2-3), and post-treatment. RESULTS: SAD and depressive symptoms improved significantly from pre-treatment to post-treatment. After 2-3 weeks of treatment, decreased connectivity between the executive control network (ECN) and salience network (SN), and increased connectivity within the ECN predicted improvement in SAD and depressive symptoms at week 8. Increased connectivity between the ECN and default mode network (DMN) predicted greater improvement in SAD but not depressive symptoms at week 8. Connectivity within the DMN decreased significantly after 2-3 weeks of treatment in the SAD group, while no changes were found in HC over the same time interval. CONCLUSION: We identified early changes in rsFC during a course of GC-MRT for SAD that predicted symptom change. Connectivity changes within the ECN, ECN-DMN, and ECN-SN may be related to mechanisms underlying the clinical effects of GC-MRT and warrant further study in controlled trials.

Neurophysiological predictors of gaze-contingent music reward therapy among adults with social anxiety disorder.

Social anxiety disorder (SAD) is associated with fear of negative evaluation and heightened performance monitoring. The best-established treatments help only a subset of patients, and there are no well-established predictors of treatment response. The current study investigated whether individual differences in processing errors might predict response to gaze-contingent music reward therapy (GC-MRT). At baseline, healthy control subjects (HC; n = 20) and adults with SAD (n = 29), ages 19-43 years, completed the Flanker Task while electroencephalography (EEG) data were recorded. SAD participants then received up to 12 sessions over 8 weeks of GC-MRT, designed to train participants' attention away from threatening and toward neutral faces. Clinical assessments were completed 9- (post-treatment) and 20-weeks (follow-up) after initiating the treatment. At baseline, compared to HC, SAD performed the task more accurately and exhibited increased error-related negativity (ERN) and delta power to error commission. After controlling for age and baseline symptoms, more negative ERN and increased frontal midline theta (FMT) predicted reduced self-reported social anxiety symptoms at post-treatment, and FMT also predicted clinician-rated and self-reported symptom reduction at the follow-up assessment. Hypervigilance to error is characteristic of SAD and warrants further research as a predictor of treatment response for GC-MRT.

Equine-Assisted Therapy for Posttraumatic Stress Disorder Among Military Veterans: An Open Trial.

Objective: As veterans have high rates of posttraumatic stress disorder (PTSD) and historically poor treatment outcomes and high attrition, alternative treatments have gained much popularity despite lack of rigorous research. In this study, a recently developed and manualized 8-session group Equine-Assisted Therapy for PTSD (EAT-PTSD) was tested in an open trial to assess its preliminary feasibility, acceptability, and outcomes for military veterans.Methods: The study was conducted from July 2016 to July 2019. Sixty-three treatment-seeking veterans with PTSD enrolled. PTSD diagnosis was ascertained using the Structured Clinical Interview for DSM-5, Research Version (SCID-5-RV) and confirmed using the Clinician-Administered PTSD Scale (CAPS-5). Mean age was 50 years, and 23 patients (37%) were women. Clinician and self-report measures of PTSD and depression were assessed at pretreatment, midtreatment, and posttreatment and at a 3-month follow-up. An intent-to-treat analysis and a secondary analysis of those who completed all 4 clinical assessments were utilized.Results: Only 5 patients (8%) withdrew from treatment, 4 before midtreatment and 1 afterward. Posttreatment assessment revealed marked reductions in both clinician-rated and self-reported PTSD and depression symptoms, which persisted at 3-month follow-up. Specifically, mean (SD) CAPS-5 scores fell from 38.6 (8.1) to 26.9 (12.4) at termination. Thirty-two patients (50.8%) showed clinically significant change (≥ 30% decrease in CAPS-5 score) at posttreatment and 34 (54.0%) at follow-up.Conclusions: Manualized EAT-PTSD shows promise as a potential new intervention for veterans with PTSD. It appears safe, feasible, and clinically viable. These preliminary results encourage examination of EAT-PTSD in larger, randomized controlled trials.Trial Registration: ClinicalTrials.gov identifier: NCT03068325.

Neural changes following equine-assisted therapy for posttraumatic stress disorder: A longitudinal multimodal imaging study.

BACKGROUND: While effective treatments for posttraumatic stress disorder (PTSD) exist, many individuals, including military personnel and veterans fail to respond to them. Equine-assisted therapy (EAT), a novel PTSD treatment, may complement existing PTSD interventions. This study employs longitudinal neuro-imaging, including structural magnetic resonance imaging (sMRI), resting state-fMRI (rs-fMRI), and diffusion tensor imaging (DTI), to determine mechanisms and predictors of EAT outcomes for PTSD. METHOD: Nineteen veterans with PTSD completed eight weekly group sessions of EAT undergoing multimodal MRI assessments before and after treatment. Clinical assessments were conducted at baseline, post-treatment and at 3-month follow-up. RESULTS: At post-treatment patients showed a significant increase in caudate functional connectivity (FC) and reduction in the gray matter density of the thalamus and the caudate. The increase of caudate FC was positively associated with clinical improvement seen immediately at post-treatment and at 3-month follow-up. In addition, higher baseline caudate FC was associated with greater PTSD symptom reduction post-treatment. CONCLUSIONS: This exploratory study is the first to demonstrate that EAT can affect functional and structural changes in the brains of patients with PTSD. The findings suggest that EAT may target reward circuitry responsiveness and produce a caudate pruning effect from pre- to post-treatment.

A randomized controlled trial of gaze-contingent music reward therapy for major depressive disorder.

BACKGROUND: Heightened attention allocation toward negative-valanced information and reduced attention allocation toward positive-valanced information represent viable targets for attention bias modification in major depressive disorder. Accordingly, we conducted a randomized controlled trial testing the efficacy of a novel gaze-contingent attention bias modification procedure for major depressive disorder. METHOD: Sixty patients with major depressive disorder were randomly assigned to either eight training sessions of feedback-based gaze-contingent music reward therapy designed to divert patients' gaze toward positive over sad stimuli, or to a control condition which entailed eight sessions of gaze-noncontingent music. Clinician-rated and self-reported measures of depression, and proportion of dwell-time on sad faces, were assessed pretreatment, posttreatment, and at a 3-month follow-up. RESULTS: Gaze-contingent music reward therapy produced a greater reduction in dwell-time on sad faces compared with the control condition, but it failed to generalize to novel faces. Both groups manifested similarly significant reductions in depression symptoms from pre- to posttreatment that were maintained at follow-up. Exploratory analyses suggest that first-episode patients may benefit more from this therapy than patients with a history of multiple episodes. CONCLUSIONS: Gaze-contingent music reward therapy can modify attention biases in depression, but clear differential clinical effects did not emerge. Theoretical and practical implications are discussed.

Anterior hippocampal volume predicts affect-focused psychotherapy outcome.

BACKGROUND: The hippocampus plays an important role in psychopathology and treatment outcome. While posterior hippocampus (PH) may be crucial for the learning process that exposure-based treatments require, affect-focused treatments might preferentially engage anterior hippocampus (AH). Previous studies have distinguished the different functions of these hippocampal sub-regions in memory, learning, and emotional processes, but not in treatment outcome. Examining two independent clinical trials, we hypothesized that anterior hippocampal volume would predict outcome of affect-focused treatment outcome [Interpersonal Psychotherapy (IPT); Panic-Focused Psychodynamic Psychotherapy (PFPP)], whereas posterior hippocampal volume would predict exposure-based treatment outcome [Prolonged Exposure (PE); Cognitive Behavioral Therapy (CBT); Applied Relaxation Training (ART)]. METHODS: Thirty-five patients with posttraumatic stress disorder (PTSD) and 24 with panic disorder (PD) underwent structural magnetic resonance imaging (MRI) before randomization to affect-focused (IPT for PTSD; PFPP for PD) or exposure-based treatments (PE for PTSD; CBT or ART for PD). AH and PH volume were regressed with clinical outcome changes. RESULTS: Baseline whole hippocampal volume did not predict post-treatment clinical severity scores in any treatment. For affect-focused treatments, but not exposure-based treatments, anterior hippocampal volume predicted clinical improvement. Smaller AH correlated with greater affect-focused treatment improvement. Posterior hippocampal volume did not predict treatment outcome. CONCLUSIONS: This is the first study to explore associations between hippocampal volume sub-regions and treatment outcome in PTSD and PD. Convergent results suggest that affect-focused treatment may influence the clinical outcome through the 'limbic' AH, whereas exposure-based treatments do not. These preliminary, theory-congruent, therapeutic findings require replication in a larger clinical trial.

Gaze-Contingent Music Reward Therapy for Clinically Anxious 7- to 10-Year-Olds: An Open Multiple Baseline Feasibility Study.

This multiple-baseline open pilot trial examined feasibility, compliance, acceptability, and preliminary indices of efficacy of Gaze-Contingent Music Reward Therapy (GC-MRT) for anxious 7- to 10-year-old children. GC-MRT is a novel therapy for anxiety disorders that relies on eye-tracking technology and operant conditioning principles to divert attention toward neutral over threat stimuli, with music serving as a reward. Using a multiple-baseline design, 12 children (M age = 8.3 years, SD = .72, range = 7-10; 4 girls) with social anxiety disorder, generalized anxiety disorder, or separation anxiety disorder received 8 therapy sessions. Clinical status was determined via semistructured interviews and questionnaires. Patients were randomized to wait 1, 3, or 5 weeks between initial assessment and beginning of therapy. Self-reported anxiety was recorded weekly, and comprehensive clinical assessments were obtained pre- and posttreatment. All 12 patients completed the full course of GC-MRT within the allocated therapy period. Therapy credibility rates were moderate to high as reported by both children and parents. Clinician-rated anxiety levels remained consistent during baseline measurement and decreased significantly following treatment. Parent-reports also yielded significant reductions in child anxiety symptoms from pre- to posttreatment. However, child-reported anxiety did not change significantly. The results provide preliminary evidence for feasibility, acceptability, and efficacy of GC-MRT for young children with anxiety disorders. Efficacy should now be tested in randomized controlled trials.

Gaze-Contingent Music Reward Therapy for Social Anxiety Disorder: A Randomized Controlled Trial.

OBJECTIVE: Patients with social anxiety disorder exhibit increased attentional dwelling on social threats, providing a viable target for therapeutics. This randomized controlled trial examined the efficacy of a novel gaze-contingent music reward therapy for social anxiety disorder designed to reduce attention dwelling on threats. METHOD: Forty patients with social anxiety disorder were randomly assigned to eight sessions of either gaze-contingent music reward therapy, designed to divert patients' gaze toward neutral stimuli rather than threat stimuli, or to a control condition. Clinician and self-report measures of social anxiety were acquired pretreatment, posttreatment, and at 3-month follow-up. Dwell time on socially threatening faces was assessed during the training sessions and at pre- and posttreatment. RESULTS: Gaze-contingent music reward therapy yielded greater reductions of symptoms of social anxiety disorder than the control condition on both clinician-rated and self-reported measures. Therapeutic effects were maintained at follow-up. Gaze-contingent music reward therapy, but not the control condition, also reduced dwell time on threat, which partially mediated clinical effects. Finally, gaze-contingent music reward therapy, but not the control condition, also altered dwell time on socially threatening faces not used in training, reflecting near-transfer training generalization. CONCLUSIONS: This is the first randomized controlled trial to examine a gaze-contingent intervention in social anxiety disorder. The results demonstrate target engagement and clinical effects. This study sets the stage for larger randomized controlled trials and testing in other emotional disorders.

Can doubt attenuate access to internal states? Implications for obsessive-compulsive disorder.

BACKGROUND AND OBJECTIVES: We have previously reported that obsessive-compulsive individuals perform more poorly on tasks that require accurate perception of internal states. As these individuals are also characterized by elevated levels of doubt regarding internal states, the causal relationship between doubt and accurate perception remained unclear. The presented study examines whether undermining participants' confidence in their ability to accurately produce a specific internal state would affect their performance on a task that requires accurate perception of this state. METHODS: Participants were trained to produce specific levels of forearm muscle tension and then required to produce various tension levels in four experimental phases. The first three alternated in terms of whether the participants viewed a biofeedback monitor while the fourth offered participants several times the choice to view the monitor. Prior to the task, half of the participants received instructions that undermined their confidence in their ability to accurately assess their own muscle tension. We measured participants' accuracy in producing the required muscle tension levels and the number of times they requested to view the monitor in the final phase. RESULTS: Undermined confidence participants were less accurate in producing the required muscle tension levels in the absence of biofeedback, and were also more likely to request the monitor in the final phase. CONCLUSIONS: Doubt can affect performance on tasks that require perceiving and experiencing internal states. This finding supports the possibility that access to internal states in OCD is attenuated due to elevated levels of doubt regarding these states.

Seeking proxies for internal states in obsessive-compulsive disorder.

Pervasive doubts are a central feature of obsessive-compulsive disorder (OCD). We have theorized that obsessive doubts can arise in relation to any internal state and lead to compensatory reliance on more discernible substitutes (proxies), including rules and rituals. Previous findings corroborated this hypothesis, but were based on students with high and low OCD tendencies and did not control for anxiety. The present study tested our hypothesis in OCD participants using both anxiety disorders and nonclinical controls. Twenty OCD participants, 20 anxiety disorders participants, and 20 nonclinical participants underwent 2 experimental procedures. In the first, participants had to produce specific levels of muscle tension with and without the aid of biofeedback. In the second, participants were asked to subjectively assess their own muscle tension after viewing preprogrammed false feedback showing either increasing or decreasing levels of muscle tension. As predicted, OCD participants were less accurate than anxiety disorder and nonclinical participants in producing designated levels of muscle tension when biofeedback was not available and more likely to request the biofeedback when given the opportunity to do so. In the false feedback procedure, OCD participants were more influenced by the false biofeedback when judging their own level of muscle tension compared with the 2 controls groups. In both procedures, anxiety disorder participants did not differ from the nonclinical controls. These results support the hypothesis that individuals with OCD have attenuated access to and reduced confidence in their internal states, and that this deficit is specific to OCD and not attributable to anxiety.

Obsessive-compulsive tendencies may be associated with attenuated access to internal states: evidence from a biofeedback-aided muscle tensing task.

The present study was motivated by the hypothesis that inputs from internal states in obsessive-compulsive (OC) individuals are attenuated, which could be one source of the pervasive doubting and checking in OCD. Participants who were high or low in OC tendencies were asked to produce specific levels of muscle tension with and without biofeedback, and their accuracy in producing the required muscle tension levels was assessed. As predicted, high OC participants performed more poorly than low OC participants on this task when biofeedback was not available. When biofeedback was provided, the difference between the groups was eliminated, and withdrawing the monitor again reversed this effect. Finally, when given the opportunity, high OC participants were more likely than low OC participants to request biofeedback. These results suggest that doubt in OCD may be grounded in a real and general deficiency in accessing internal states.

Obsessive-compulsive tendencies and undermined confidence are related to reliance on proxies for internal states in a false feedback paradigm.

BACKGROUND AND OBJECTIVES: We have previously hypothesized that obsessive-compulsive (OC) tendencies are associated with a general lack of subjective conviction regarding internal states, which leads to compensatory seeking of and reliance on more discernible substitutes (proxies) for these states (Lazarov, A., Dar, R., Oded, Y., & Liberman, N. (2010). Behaviour Research and Therapy, 48, 516-523). This article presents two studies designed to provide further support to this hypothesis by using false biofeedback as a proxy for internal states. METHODS: In Study 1 we presented high and low OC participants with pre-programmed false feedback showing either increasing or decreasing levels of muscle tension. In Study 2 we presented similar false feedback on level of relaxation to non-selected participants, half of which received instructions that undermined their confidence in their ability to assess their own level of relaxation. RESULTS: In Study 1, high OC participants were more affected by false biofeedback when judging their own level of muscle tension than were low OC participants. In Study 2, undermined confidence participants were more affected by false biofeedback when judging their own level of relaxation as compared to control participants. LIMITATIONS: Our findings are based on a non-clinical, highly functioning, largely female student sample and their generalization to OCD requires replication with a sample of OCD patients. CONCLUSIONS: These results provide converging evidence for our hypothesis by replicating and extending our previous findings. We discuss the implication of our hypothesis for the understanding and treatment of OCD and outline directions for future research.

Are obsessive-compulsive tendencies related to reliance on external proxies for internal states? Evidence from biofeedback-aided relaxation studies.

This article presents two studies that examine the hypothesis that obsessive-compulsive (OC) tendencies are associated with a general deficiency in subjective conviction, which leads to seeking and reliance on external proxies to compensate for that deficiency. We examined this hypothesis using a biofeedback-aided relaxation procedure. In Study 1 low OC participants performed better on a relaxation task than high OC participants. More importantly, viewing the biofeedback monitor (an external proxy for the internal state of relaxation) had a different effect on the two groups: Whereas high OC participants performed better, low OC participants did not. In addition, when given the opportunity, high OC participants requested the biofeedback monitor more than did the low OC participants. In Study 2 high OC participants were more affected by false biofeedback when judging their level of relaxation compared to low OC participants. Real relaxation level differences between the two false biofeedback phases among the two groups were not found. These results provide preliminary support for the hypothesis that obsessive-compulsive disorder is associated with deficient subjective conviction in internal states and increased reliance on external proxies. Implications for the understanding of OCD-related rules and rituals as well as for cognitive therapy for OCD are discussed.