Protracted amygdalar response predicts efficacy of a computer-based intervention targeting attentional patterns in transdiagnostic clinical anxiety

Abstract

Individuals with clinical anxiety demonstrate an attention bias toward threatening information, which is thought to be partially driven by heightened amygdala activity to perceived threat. Attention Bias Modification (ABM) is a computer-based treatment that trains attention toward neutral stimuli and away from threatening stimuli. Alterations in initial processing of threat have been linked to ABM responses, but the impact of protracted processing in the aftermath of neutral and threatening information on ABM outcomes has not been well studied. Our study tested whether sustained activity in the amygdala, which occurred after neutral and threatening stimuli had been removed, could predict which individuals would respond well to ABM. Unmedicated anxious individuals underwent a baseline fMRI assessment during performance of a task sensitive to protracted emotional processing. Afterward, they were randomized to complete eight sessions of ABM ( n = 38) or a sham training ( n = 19). ABM patients who displayed greater sustained bilateral amygdalar response in the aftermath of neutral stimuli displayed the least improvement in self-reported (but not clinician-rated) vigilance symptoms. In contrast, amygdalar response did not predict improvement in sham patients. Results suggest that in certain anxious individuals, the amygdala may have a robust protracted response even to subjectively neutral cues, which could make these individuals a poor fit for ABM because of its focus on repeatedly retraining attention toward neutral cues. Findings may help elucidate neural mechanisms of ABM and promote the identification of a subset of anxious patients who would be good candidates for this intervention.

Time course of pupillary response to threat words before and after attention bias modification for transdiagnostic anxiety disorders: A randomized controlled trial

“…Separate models were run for pupillary response for each emotion and epoch condition for several reasons. First, regression‐based analyses that examine valence or epoch effects separately can provide useful information regarding cognitive–affective processing biases relevant to ABM efficacy (Beevers, Clasen, Enock, & Schnyer, 2015; Kret et al., 2013; Price et al., 2018; Woody et al., 2019). Second, this approach reduces the statistical assumptions and complexity required of HLM models and also allows for easier comparisons with a previous publication from the project, which utilized HLM (Price et al., 2019).…”

“…Additionally, some anxious individuals exhibit perseverative attention to threat during sustained stages of processing, which can maintain negative affect and worry (Brosschot, Gerin, & Thayer, 2006; Burkhouse, Woody, Owens, & Gibb, 2015; Price et al., 2013). Although biases at each stage of attentional processing are present simultaneously in many patients, the temporal stages of AB are posited as dissociable dimensions of threat processing that exert unique influences on the development and maintenance of anxious vigilance and possibly require distinct interventions (Price et al., 2018; Woody et al., 2019).…”

“…The current study was a secondary analysis of a previously described study (Price et al., 2018; Price, Woody, Panny, & Siegle, 2019; Woody et al., 2019). Of note, the current study was not designed and optimized to test group‐level effects of ABM (relative to sham).…”

“…To maximize power for these specific aims focused on mechanisms underlying ABM response, the study design included uneven allocation to the ABM versus sham condition; thus, preserving an a priori focus on the ABM group enhances statistical power to characterize the ABM sample consistent with primary study aims. The sham condition was included to probe specificity of results to ABM through effect size comparison, consistent with prior publications from this sample(Price et al, 2018(Price et al, , 2019Woody et al, 2019).…”

Impaired neural habituation to neutral faces in families genetically enriched for social anxiety disorder

“…Several lines of evidence implicate impaired habituation in social anxiety (SA): a prolonged habituation response, for example, in the amygdala, has been linked to inhibited temperament (Blackford, Allen, Cowan, & Avery, ; Blackford, Avery, Cowan, Shelton, & Zald, ; Schwartz, ; Schwartz et al, ), a stable trait which is considered to be a risk factor for SAD (Clauss, Avery, & Blackford, ; Clauss & Blackford, ); furthermore, a study in a community sample of young adults revealed slower neural habituation of neutral faces in individuals with higher levels of social fearfulness (Avery & Blackford, ). These findings are further supported by work in nonhuman primates with an anxious temperament (cf., Fox & Kalin, ), and a recent study demonstrating that a sustained amygdala response to neutral stimuli predicts a worse response to attention bias modification treatment in transdiagnostic clinical anxiety (Woody et al, ). Together, these observations support the link between impaired habituation and the vulnerability for SA.…”