Attention Bias Modification for Anxiety: A Randomized Control Trial With Biomarkers

Anxiety disorders are the most common psychiatric diagnosis, affecting as many as 29% of people during their lifetime. In addition to the devastating personal cost of anxiety, the yearly economic cost to society has been estimated to be around $46.6 billion in the U.S. Empirically-based treatments for anxiety have improved in recent years, but barriers to access, side effects, and high remission rates (\~50%) suggest the need for complementary treatments. Computer-based attention bias modification treatment (ABMT), which is brief, cost-effective, and easy to administer, targets a key mechanism in pathological anxiety - the threat bias, or exaggerated attention feared or threatening stimuli. Two decades of research show that reducing threat bias via computerized ABMT also reduces anxiety severity at levels comparable to gold-standard treatments. Despite its promise, no randomized clinical trials (RCTs) have evaluated specific mechanisms underlying ABMT's effects on anxiety, nor identified predictors of treatment response. Therefore, it remains unclear how and for whom ABMT is effective, limiting clinical translation. This study is a randomized clinical trial using a highly sensitive measure of neurocognitive functioning to delineate key mechanisms of an emerging treatment for anxiety. Specifically, the study will use scalp-recorded event-related potentials (ERPs) to elucidate neurocognitive processes implicated in attention bias modification treatment (ABMT) and to predict treatment response. Researchers will recruit 90 anxious patients to engage in the study and pursue the following three specific aims: Aim 1 will examine relations between neural and behavioral responses to threat prior to ABMT. Researchers will test whether greater behavioral threat bias is associated with ERP responses indicating greater attention capture by threat (larger P1 and P2 ERPs), and reduced top-down control of attention to threat (smaller N2, N2pc, P3 ERPs). Aim 2 will examine the effects of ABMT on ERPs to threat, threat bias, and anxiety. Analyses will focus on whether ABMT relative to placebo training will result in greater reductions in automatic attention capture and/or controlled attention to threat measured via ERPs. Aim 3 will examine relations between ERP responses to threat and reductions in threat bias and anxiety. Researchers will test whether post-training neural changes, specified in Aim 2, will be associated with reductions in behavioral threat bias and anxiety severity. These predicted relations,together with those tested in Aim 2a, support the utility of these ERPs as neural markers for the specific cognitive processes underlying ABMT efficacy. Researchers will also explore whether ERP measures of greater attention capture and/or reduced control of attention to threat at baseline predict treatment response, helping identify which patients will benefit most from ABMT. Through the innovative combination of a highly sensitive neurocognitive measure and an RCT design, this proposal aims to delineate core neurocognitive responses to threat as mechanisms in the remediation of anxiety. Confirmation of study hypotheses would, ultimately, accelerate the pace of development of more biologically-informed, accessible, and targeted interventions for anxiety.