Objective Clinical anxiety is prevalent, highly comorbid with other conditions, and associated with significant medical morbidity, disability, and public health burden. Excessive attentional deployment towards threat is a transdiagnostic dimension of anxiety seen at both initial and sustained stages of threat processing. However, group-level observations of these phenomena mask considerable within-group heterogeneity that has been linked to treatment outcomes, suggesting that a transdiagnostic, individual differences approach may capture critical, clinically relevant information. Methods 70 clinically anxious individuals were randomized to receive 8 sessions of Attention Bias Modification (ABM; n=41 included in analysis), a computer-based mechanistic intervention that specifically targets initial stages of threat processing, or a sham control (n=21). Participants completed a mixed block/event-related fMRI task optimized to discriminate transient from sustained neural responses to threat. Results Larger transient responses across a wide range of cognitive-affective regions (e.g., ventrolateral prefrontal cortex, anterior cingulate cortex, amygdala) predicted better clinical outcomes following ABM, in both a priori anatomical regions and whole-brain analyses; sustained responses did not. A spatial pattern recognition algorithm using transient threat responses successfully discriminated the top quartile of ABM responders with 68% accuracy. Conclusions Neural alterations occurring on the relatively transient timescale that is specifically targeted by ABM predict favorable clinical outcomes. Results inform how to expand on the initial promise of neurocognitive treatments like ABM by fine-tuning their clinical indications (e.g., through personalized mechanistic intervention relevant across diagnoses) and by increasing the range of mechanisms that can be targeted (e.g., through synergistic treatment combinations and/or novel neurocognitive training protocols designed to tackle identified predictors of nonresponse).

Anxious youth may experience altered positive affect (PA) relative to healthy youth, perhaps because of greater sensitivity to social experiences. Altered PA may be especially evident during the transition to adolescence, a period in which positive social events increase in salience and value. The current study evaluated whether anxious youth show differences in baseline PA, rate of return to baseline, and variability around baseline PA and tested whether these differences would depend on social context and anxiety subtype. Participants were 176 9- to 14-year-old youth, including 130 clinically anxious (with Social Anxiety Disorder, Generalized Anxiety Disorder, and/or Separation Anxiety Disorder) and 46 healthy youth. Youth reported their current PA, peak PA in the past hour, and social context in natural settings using ecological momentary assessment. Hierarchical linear models showed that both socially anxious and other anxious youth showed greater variability of PA relative to healthy youth. Youth with other anxiety disorders showed higher peak PA to a positive event relative to healthy youth. Feeling close to a friend was associated with higher peak PA, especially for socially anxious youth. Socially anxious youth showed significantly lower peak PA relative to both healthy and other anxious youth when interacting with a less close peer, but similar levels to these youth when interacting with a close friend. These findings suggest that clinically anxious youth may more sensitive to positive events and social interactions than healthy youth. Findings provide potential treatment targets for anxious youth, including applying regulatory strategies to positive events.

On average, anxious patients show altered attention to threat—including early vigilance toward threat and later avoidance of threat—accompanied by altered functional connectivity across brain regions. However, substantial heterogeneity within clinical, neural, and attentional features of anxiety is overlooked in typical group-level comparisons. We used a well-validated method for data-driven parsing of neural connectivity to reveal connectivity-based subgroups among 60 adults with transdiagnostic anxiety. Subgroups were externally compared on attentional patterns derived from independent behavioral measures. Two subgroups emerged. Subgroup A (68% of patients) showed stronger executive network influences on sensory processing regions and a paradigmatic “vigilance–avoidance” pattern on external behavioral measures. Subgroup B was defined by a larger number of limbic influences on sensory regions and exhibited a more atypical and inconsistent attentional profile. Neural connectivity-based categorization revealed an atypical, limbic-driven pattern of connectivity in a subset of anxious patients that generalized to atypical patterns of selective attention.

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.