Converging Evidence for Frontopolar Cortex as a Target for Neuromodulation in Addiction Treatment
Publication: American Journal of Psychiatry
Abstract
Noninvasive brain stimulation technologies such as transcranial electrical and magnetic stimulation (tES and TMS) are emerging neuromodulation therapies that are being used to target the neural substrates of substance use disorders. By the end of 2022, 205 trials of tES or TMS in the treatment of substance use disorders had been published, with heterogeneous results, and there is still no consensus on the optimal target brain region. Recent work may help clarify where and how to apply stimulation, owing to expanding databases of neuroimaging studies, new systematic reviews, and improved methods for causal brain mapping. Whereas most previous clinical trials targeted the dorsolateral prefrontal cortex, accumulating data highlight the frontopolar cortex as a promising therapeutic target for transcranial brain stimulation in substance use disorders. This approach is supported by converging multimodal evidence, including lesion-based maps, functional MRI-based maps, tES studies, TMS studies, and dose-response relationships. This review highlights the importance of targeting the frontopolar area and tailoring the treatment according to interindividual variations in brain state and trait and electric field distribution patterns. This converging evidence supports the potential for treatment optimization through context, target, dose, and timing dimensions to improve clinical outcomes of transcranial brain stimulation in people with substance use disorders in future clinical trials.
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History
Received: 13 December 2022
Revision received: 7 May 2023
Revision received: 26 June 2023
Accepted: 14 July 2023
Published online: 29 November 2023
Published in print: February 01, 2024
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Competing Interests
Dr. Joutsa has received grants from the Finnish Foundation for Alcohol Studies, the Finnish Medical Foundation, the Instrumentarium Research Foundation, the Sigrid Juselius Foundation, Turku University Hospital (VTR funds), and University of Turku, congress travel support from Abbott and AbbVie, and lecturer honoraria from Lundbeck and Novartis, and he has served as consultant for Adamant Health and Summaryx. Dr. Siddiqi has served as a scientific consultant for Magnus Medical and as a clinical consultant for Acacia Mental Health, Boston Precision Neurotherapeutics, and Kaizen Brain Center; he has received investigator-initiated research funding from BrainsWay and Neuronetics; he has served as a speaker for BrainsWay and for PsychU.org (sponsored by Otsuka); he owns intellectual property involving the use of functional connectivity to target TMS; and he owns stock in BrainsWay and Magnus Medical. Dr. Bikson has served as a consultant for, received grants from, served on scientific advisory boards, or has invention assignment agreements with Allergan (AbbVie), Apple, Biovisics, Boston Scientific, Ceragem, GlaxoSmithKline, Google X, Halo Neuroscience, Humm, i-Lumen, Lumenis, Mecta, SafeToddles, and Ybrain; he is an inventor on a patent on brain stimulation held by City University of New York; and he has equity in Soterix Medical. Dr. Paulus has served as an adviser for Hoffmann–La Roche and Spring Care, and he has received royalties from UpToDate. Dr. Fox holds intellectual property on the use of brain connectivity imaging to analyze lesions and guide brain stimulation; he has served as a consultant for Abbott, Boston Scientific, Magnus Medical, and Soterix; and he has received investigator-initiated research funding from Neuronetics. Dr. Hanlon is employed by and has financial interests in BrainsWay. Dr. Ekhtiari has received honoraria from Indivior for speaking at educational events. The other authors report no financial relationships with commercial interests.
Funding Information
Supported in part by the William K. Warren Foundation, by grant 1P20GM121312 from the National Institute of General Medical Sciences Center, by NIDA grant U01DA050989, by funds from the Laureate Institute for Brain Research and the Medical Discovery Team on Addiction at University of Minnesota, and by a Brain and Behavior Foundation (NARSAD) Young Investigator Award to Dr. Ekhtiari. Dr. Moussawi is funded by NIDA grant DA048085 and NIAAA grant AA030505. Dr. Fox is funded by the Nancy Lurie Marks Foundation, the Kaye Family Research Endowment, the Baszucki Brain Research Fund, and NIH grants R01MH113929, R21MH126271, R56AG069086, R01MH115949, and R01AG060987.
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