Sequential Prefrontal and Temporoparietal Repetitive Transcranial Magnetic Stimulation (rTMS) for Treatment of Tinnitus With and Without Comorbid Depression: A Case Series and Systematic Review

Creators: Marder, Katharine G.; Cho, Janice; Chincanchan, Ruth; Wilson, Andrew C.; Corlier, Juliana; Krantz, David E.; Ginder, Nathaniel D.; Lee, Jonathan C.; Wilke, Scott A.; Tadayonnejad, Reza; Levitt, Jennifer; Ishiyama, Akira; Leuchter, Michael K.; Leuchter, Andrew F.

Abstract

Background. Tinnitus distress is related to both the loudness and intrusiveness of the tinnitus percept. Treatment approaches targeting both attentional/limbic and auditory systems may better alleviate tinnitus distress than approaches targeting the auditory system alone. Materials and Methods. Ten subjects with chronic tinnitus received sequential rTMS treatment involving: 1) excitatory stimulation administered to the left dorsolateral prefrontal cortex (DLPFC) or inhibitory stimulation administered to the right DLPFC, followed by 2) inhibitory stimulation administered to primary auditory cortex (Heschel's gyrus or HG). A systematic literature review was performed to evaluate the existing literature on sequential repetitive Transcranial Magnetic Stimulation (rTMS) treatment approaches for tinnitus. Results of the case series are interpreted in the context of tinnitus neurobiology and the extant literature. Results. Subjects experienced a significant decrease (average 21.7%) in symptoms on the Tinnitus Functional Index (TFI). Those with tinnitus alone experienced a greater mean symptom reduction than those with comorbid MDD (27.7 vs. 17.0%, respectively). Adverse effects were transient and minor. Literature review confirmed that sequential approaches had some advantages compared to single site rTMS; in general, the addition of 1 Hz treatment at DLPFC was superior to single site rTMS in the short term (1–12 weeks), while the addition of 20 Hz treatment at DLPFC appeared superior in the long term (90–180 days). Conclusions. Sequential rTMS approaches for the treatment of tinnitus—particularly those administering low-frequency treatment at left DLPFC—merit further investigation.

Additional Information

© 2022 Marder, Cho, Chincanchan, Wilson, Corlier, Krantz, Ginder, Lee, Wilke, Tadayonnejad, Levitt, Ishiyama, Leuchter and Leuchter. 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: 10 December 2021; Accepted: 21 March 2022; Published: 19 May 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. KM, DK, NG, JCL, SW, RT, JL, and AL designed treatment and study protocol and performed TMS treatments for the study. RC, AW, JCo, and ML gathered and analyzed case series data with additional input from AL. All authors contributed to data interpretation. JCh and KM primarily performed the literature review with additional input from AL, AI, and ML. KM, JCh, RC, and ML primarily drafted the paper, with additional input from AI and AL. All authors assisted in manuscript editing and approved the final manuscript. Data Availability Statement. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Ethics Statement. The studies involving human participants were reviewed and approved by the Medical Institutional Review Board (IRB) of the University of California, Los Angeles (UCLA) Office of the Human Research Protection Program. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the patients/participants for the publication of any potentially identifiable images or data included in this article. Conflict of Interest. AW has served as a consultant to HeartCloud, Inc. within the past 36 months. JCL has received equipment in-kind support from Magventure Inc. AL discloses that within the past 36 months he has received research support from the National Institutes of Health, Department of Defense, and NeuroSigma, Inc. He has served as a consultant to NeoSync, Inc., and ElMindA. He is Chief Scientific Officer of Brain Biomarker Analytics LLC (BBA). ML has equity interest in BBA. ML discloses he has served as a consultant to Neuroelectrics, Inc. within the past 36 months. 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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