A double-blind trial of decoded neurofeedback intervention for specific phobias.

Aim: A new closed-loop fMRI method called multi-voxel neuro-reinforcement has the potential to alleviate the subjective aversiveness of exposure-based interventions by directly inducing phobic representations in the brain, outside of conscious awareness. The current study seeks to test this method as an intervention for specific phobia. Methods: In a randomized, double-blind, controlled single-university trial, individuals diagnosed with at least two (1 target, 1 control) animal subtype specific phobias were randomly assigned (1:1:1) to receive 1, 3, or 5 sessions of multi-voxel neuro-reinforcement in which they were rewarded for implicit activation of a target animal representation. Amygdala response to phobic stimuli was assessed by study staff blind to target and control animal assignments. Pre-treatment to post-treatment differences were analyzed with a 2-way repeated-measures ANOVA. Results: A total of 23 participants (69.6% female) were randomized to receive 1 (n=8), 3 (n=7), or 5 (n=7) sessions of multi-voxel neuro-reinforcement. Eighteen (n=6 each group) participants were analyzed for our primary outcome. After neuro-reinforcement, we observed an interaction indicating a significant decrease in amygdala response for the target phobia but not the control phobia. No adverse events or dropouts were reported as a result of the intervention. Conclusion: Results suggest multi-voxel neuro-reinforcement can specifically reduce threat signatures in specific phobia. Consequently, this intervention may complement conventional psychotherapy approaches with a non-distressing experience for patients seeking treatment. This trial sets the stage for a larger randomized clinical trial to replicate these results and examine the effects on real-life exposure. Clinical Trial Registration: The now-closed trial was prospectively registered at ClinicalTrials.gov with ID NCT03655262.