A pre-registered decoded neurofeedback intervention for specific phobias

Background Treatment attrition rates can be high for specific phobia, partly due to the subjectively aversive nature of exposure therapy that involves direct exposure to fear- and panic-inducing stimuli. A new closed-loop fMRI method called multi-voxel neuro-reinforcement has the potential to alleviate the subjective aversiveness of 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 pre-registered clinical trial, individuals (N=18) with at least two animal subtype specific phobias underwent double-blind multi-voxel neuro-reinforcement for one of the two feared animals, with the untargeted one serving as control. Unaware of the target of neuro-reinforcement (i.e., the target animal), participants were guided with visual feedback and rewarded for implicit activation of the target representation. Amygdala response to phobic stimuli was assessed pre-treatment and post-treatment using photographic image presentations. Attentional capture to phobic stimuli was assessed using an affective Stroop task. Results Confirming our pre-registered hypothesis, a significant interaction between phobia type (target/control) and time (pre-treatment/post-treatment) was found for amygdala response. There was also a nonsignificant trend ( p= 0.055) for the hypothesized attentional capture during the affective Stroop. In both measures, responding to the phobia targeted with neuro-reinforcement was selectively reduced compared to the placebo control. Conclusions Results suggest multi-voxel neuro-reinforcement has the potential to be a successful intervention for specific phobia. Multi-voxel neuro-reinforcement decreased physiological and behavioral responses to specific phobia through reduced amygdala activation and attentional capture by phobic stimuli. Consequently, multi-voxel neuro-reinforcement may complement current conventional psychotherapy approaches while providing a non-distressing experience for patients seeking treatment. ### Competing Interest Statement Author Mitsuo Kawato is an inventor of patents owned by the Advanced Telecommunications Research Institute International related to the present work (PCT/JP2012/078136 [WO2013/06 871 9517] and PCT/JP2014/61543 [WO2014/178322]). ### Clinical Trial NCT03655262 ### Funding Statement HL received financial support from the US National Institute of Mental Health (R61MH113772) and The Templeton World Charity Foundation (RA537-01). MK was supported by AMED under grant number JP18dm0307008. MGC received financial support from the US National Institute of Mental Health (R61MH113772). VT-D received financial support from the Fonds de Recherche du Quebec - Sante (FRQS). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of University of California, Los Angeles gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.