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

Abstract

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.

Keywords: decoding; fMRI; neurofeedback; phobia; reinforcement.

Figure 1.

Functional alignment of brain data into phobic participant brain using hyperalignment. (A) All participants complete a near-identical task in the fMRI scanner where 3600 images are rapidly viewed during 0.98 second presentations. Phobic patients view happy human faces instead of their own phobic categories. Healthy controls view images from all categories. (B) Transformation parameters into the functionally aligned common model space are determined with phobic image trials withheld. Data from all participants for all categories (including phobic categories) are transformed into the common model space and then reverse transformed into the native space of the current phobic participant. A machine-learning classifier can then be trained on phobic images in the phobic participant’s native brain space despite the participant never having personally viewed the images.

Figure 2.

Study design and activation of Target and Control representations. (A) Timeline detailing patient activities during each day’s fMRI session with sample stimuli from each day. Before beginning the treatment program patients undergo a decoder construction session where they view non-phobic images to enable hyperalignment with healthy control subjects. On day 1 of treatment, patients complete a pre-test in which phobic (and non-phobic) images are rated for fearfulness. Over the next 5 days, patients complete their assigned number of multi-voxel neuro-reinforcement sessions (1, 3, or 5 days). On day 7, patients complete the same task as a post-test to assess changes in amygdala and SCR response to treated and untreated phobias. (B) Representation pattern activation (measured by feedback score) for Target phobia compared to Control phobia. Target phobia pattern was activated significantly more than Control during neuro-reinforcement. *** p<0.001

Figure 3.

CONSORT diagram of recruitment flow.

Figure 4.

Changes in fear test amygdala responses and affective Stroop reaction times following neuro-reinforcement. (A) Amygdala response in the fear test showed a greater decrease in the Target than Control phobias following neuro-reinforcement. (B) Response times in the affective Stroop task showed a greater decrease in the Target than Control phobias following neuro-reinforcement. * p<0.05 indicate significant Time (pre/post) effect in the Target condition when controlling for days of neuro-reinforcement and number of phobias.