Towards personalized, brain-based behavioral intervention for transdiagnostic anxiety: Transient neural responses to negative images predict outcomes following a targeted computer-based intervention.

Abstract

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).

Computational Modeling Applied to the Dot-Probe Task Yields Improved Reliability and Mechanistic Insights

“…Specifically, in exploratory analyses we found no evidence that shifts in extradecisional bias over time mediated acute improvements in clinical symptoms (following either ABM or sham training). These analyses were limited by the relatively small sample sizes in the two arms, the (still suboptimal) test-retest reliability of the DDM indices, and by the fact that robust betweengroup differences in clinical outcomes were not observed in the current study (23). Larger or more clinically homogeneous samples may be required to adequately test for such linkages.…”

“…Full methods and primary clinical findings from the randomized controlled trial (clinicaltrials.gov: NCT02303691) have been reported previously (23). In brief, seventy unmedicated patients reporting clinically elevated levels of trait anxiety and associated clinician-rated disability were randomized to receive active ABM (n=49) or a sham control variant (n=21).…”

“…The ABM and sham conditions were modeled after prior studies(e.g., 24) and have been described in a previous report which focused on fMRI indices, collected during a distinct task, predicting clinical outcomes (see (23) and Supplement for details). Briefly, participants in both groups completed 8 twice-weekly sessions in the laboratory, using an abbreviated version of the dot-probe task as described above, with a few modifications.…”

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

“…This study was approved by the local Institutional Review Board and informed consent was obtained from all patients. Please note, this sample has also been used in analyses from a prior published study 15 .…”

“…Thus, an individual differences approach that examines the timing of threat processing may capture critical, clinically relevant information. For example, prior research has shown that patients who exhibit larger baseline transient neural responses to threatening stimuli across a range of cognitive-affective brain regions display the greatest reductions in clinician-rated vigilance following ABM treatment 15 . This work suggests that patients who display an initial preferential response toward threat in AB-related brain regions are best suited for ABM treatment, which is consistent with prior behavioral work that has shown that initial processing of threat is linked to ABM treatment responses 13,14,16 .…”