Treatment of Spider Phobia Using Repeated Exposures and Adjunctive Repetitive Transcranial Magnetic Stimulation: A Proof-of-Concept Study

Creators: Leuchter, Michael K.; Rosenberg, Benjamin M.; Schapira, Giuditta; Wong, Nicole R.; Leuchter, Andrew F.; McGlade, Anastasia L.; Krantz, David E.; Ginder, Nathaniel D.; Lee, Jonathan C.; Wilke, Scott A.; Tadayonnejad, Reza; Levitt, Jennifer; Marder, Katharine G.; Craske, Michelle G.; Iacoboni, Marco

Abstract

Background. Specific phobias represent the largest category of anxiety disorders. Previous work demonstrated that stimulating the ventromedial prefrontal cortex (vmPFC) with repetitive Transcranial Magnetic Stimulation (rTMS) may improve response to exposure therapy for acrophobia. Objective. To examine feasibility of accelerating extinction learning in subjects with spider phobia using intermittent Theta Burst Stimulation (iTBS) rTMS of vmPFC. Methods. In total, 17 subjects with spider phobia determined by spider phobia questionnaires [Spider Phobia Questionnaire (SPQ) and Fear of Spiders questionnaire (FSQ)] underwent ratings of fear of spiders as well as behavioral and skin conductance data during a behavioral avoidance test (BAT). Subjects then received a sequential protocol of in vivo spider exposure followed by iTBS for three sessions administered to either active or control treatment sites (vmPFC [n = 8] or vertex [n = 9], respectively), followed 1 week later by repetition of questionnaires and BAT.ResultsAll subjects improved significantly regardless of group across both questionnaires (FSQ η2 = 0.43, p = 0.004; SPQ η2 = 0.39, p = 0.008) and skin conductance levels during BAT (Wald χ2 = 30.9, p 0.5). Conclusion. This proof-of-concept study provides preliminary evidence that a sequential exposure and iTBS over vmPFC is feasible and may have rTMS intensity-dependent effects on treatment outcomes, providing evidence for future areas of study in the use of rTMS for phobias.

Additional Information

© 2022 Leuchter, Rosenberg, Schapira, Wong, Leuchter, McGlade, Krantz, Ginder, Lee, Wilke, Tadayonnejad, Levitt, Marder, Craske and Iacoboni. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Received: 26 November 2021; Accepted: 10 February 2022; Published: 15 March 2022. We thank the Ryan Family for their generous support of innovative approaches to depression treatment and of groundbreaking TMS technology. This project was made possible by the Ryan Family Fund for TMS Research. Author Contributions. ML, BR, AL, AM, MC, and MI designed the study with input from DK, NG, JCL, SW, RT, JL, and KM. ML, BR, and GS recruited the subjects for the study. BR, GS, and NW performed the behavioral testing and exposure trials and gathered the corresponding data. AL, DK, NG, JCL, SW, RT, JL, and KM performed the TMS treatments. ML and BR analyzed the study data with input and statistical support from AM, AL, MC, and MI. ML and BR primarily drafted the manuscript. All authors contributed to the data interpretation, assisted in manuscript editing, and approved the final manuscript. Data Availability Statement. The datasets presented in this article are not readily available due to privacy or ethical restrictions. Requests to access the datasets should be directed to ML, mkleuchter@mednet.ucla.edu. Ethics Statement. The studies involving human participants were reviewed and approved by the UCLA Medical IRB #3. The patients/participants provided their written informed consent to participate in this study. Conflict of Interest. ML discloses that he has served as a consultant to Neuroelectrics, Inc., within the past 36 months. AL has served as a consultant to NeoSync, Inc., Ionis Pharmaceuticals, Inc., and ElMindA. AL is Chief Scientific Officer of Brain Biomarker Analytics LLC (BBA), and has equity interest in BBA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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