. 2025 Jun 23:S1094-7159(25)00190-4.

doi: 10.1016/j.neurom.2025.04.012. Online ahead of print.

Transcutaneous Cervical Vagus Nerve Stimulation Modulates Prefrontal Cortex Activity During Opioid Withdrawal in Individuals With Opioid Use Disorder

Farhan N Rahman¹, Afra Nawar², Jonathon A Nye³, Jaiyoun Choi⁴, Tamara P Lambert⁵, Madeline Robinson², Asim H Gazi⁶, Vikram Abbaraju², Nikolina Tomic², Anna B Harrison², Nora Jaquemet⁴, Kellen Mermin-Bunnell⁴, Hewitt Mesfin⁴, Trinity A Gray⁴, Justine W Welsh⁴, Kelly E Dunn⁷, Marom Bikson⁸, Viola Vaccarino⁹, Amit J Shah¹⁰, Omer T Inan¹¹, James Douglas Bremner¹²

Affiliations

¹ School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA. Electronic address: farhan.rahman@gatech.edu.
² School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
³ Department of Radiology, Medical University of South Carolina, Charleston, SC, USA.
⁴ Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
⁵ Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
⁶ School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA; School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
⁷ Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁸ Department of Biomedical Engineering, The City College of New York, City University of New York, New York, NY, USA.
⁹ Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA; Department of Internal Medicine (Cardiology), Emory University School of Medicine, Atlanta, GA, USA.
¹⁰ Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA; Department of Internal Medicine (Cardiology), Emory University School of Medicine, Atlanta, GA, USA; Joseph Maxwell Cleland Atlanta VA Medical Center, Decatur, GA, USA.
¹¹ School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
¹² Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA; Joseph Maxwell Cleland Atlanta VA Medical Center, Decatur, GA, USA; Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA.

PMID: 40548916
PMCID: PMC12400781 (available on 2026-06-23)
DOI: 10.1016/j.neurom.2025.04.012

Transcutaneous Cervical Vagus Nerve Stimulation Modulates Prefrontal Cortex Activity During Opioid Withdrawal in Individuals With Opioid Use Disorder

Farhan N Rahman et al. Neuromodulation. 2025.

. 2025 Jun 23:S1094-7159(25)00190-4.

doi: 10.1016/j.neurom.2025.04.012. Online ahead of print.

Authors

Affiliations

¹ School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA. Electronic address: farhan.rahman@gatech.edu.
² School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
³ Department of Radiology, Medical University of South Carolina, Charleston, SC, USA.
⁴ Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
⁵ Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
⁶ School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA; School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
⁷ Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁸ Department of Biomedical Engineering, The City College of New York, City University of New York, New York, NY, USA.
⁹ Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA; Department of Internal Medicine (Cardiology), Emory University School of Medicine, Atlanta, GA, USA.
¹⁰ Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA; Department of Internal Medicine (Cardiology), Emory University School of Medicine, Atlanta, GA, USA; Joseph Maxwell Cleland Atlanta VA Medical Center, Decatur, GA, USA.
¹¹ School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
¹² Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA; Joseph Maxwell Cleland Atlanta VA Medical Center, Decatur, GA, USA; Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA.

PMID: 40548916
PMCID: PMC12400781 (available on 2026-06-23)
DOI: 10.1016/j.neurom.2025.04.012

Abstract

Background: Opioid use disorder (OUD) is associated with considerable morbidity and mortality with limited treatment approaches. Understanding brain mechanisms in response to treatment could be useful in guiding future developments in treatment approaches.

Objective: The purpose of this study was to assess the effects of transcutaneous cervical vagus nerve stimulation (tcVNS) on brain response to opioid use cues in patients with OUD in opioid withdrawal.

Materials and methods: Patients with OUD who were in the early stage of recovery and/or on medication underwent brain imaging with positron emission tomography and radiolabeled water in conjunction with stimulation with active tcVNS or sham devices and exposure to opioid-use-related cues.

Results: tcVNS caused a relative increase in function in the anterior cingulate, dorsal anterior cingulate, and left inferior frontal gyrus during exposure to opioid cues. There also was a pattern of increased activation in the ventral striatum and orbitofrontal cortex.

Conclusion: tcVNS modulates brain areas implicated in opioid addiction, suggesting a useful role as an adjunctive therapy for OUD.

Clinical trial registration: The Clinicaltrials.gov registration number for the study is NCT04556552.

Keywords: Noninvasive; opioid use disorder; prefrontal cortex; vagus nerve stimulation.

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Conflict of interest statement

Conflict of Interest James Douglas Bremner reports equipment, drugs, or supplies were provided by electroCore LLC (tcVNS and sham devices). The remaining authors reported no conflict of interest.

References

1. Buchanich JM, Balmert LC, Williams KE, Burke DS. The effect of incomplete death certificates on estimates of unintentional opioid-related overdose deaths in the United States, 1999–2015. Public Health Rep. 2018;133:423–431. - PMC - PubMed
1. U.S. overdose deaths decrease in 2023, first time since 2018. Centers for Disease Control and Prevention. https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2024/20240515.htm; 2024. Accessed July 22, 2024.
1. Spencer MR, Garnett M, Miniño AM. Drug overdose deaths in the United States, 2002–2022. US Department of Health and Human Services, Centers for Disease Control and Prevention. https://www.cdc.gov/nchs/products/databriefs/db491.htm. Accessed July 22, 2024.
1. FastStats. Centers for Disease Control and Prevention. https://web.archive.org/web/20240719122325/. Accessed July 22, 2024.
1. Korf J, Bunney BS, Aghajanian GK. Noradrenergic neurons: morphine inhibition of spontaneous activity. Eur J Pharmacol. 1974;25:165–169. - PubMed

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Transcutaneous Cervical Vagus Nerve Stimulation Modulates Prefrontal Cortex Activity During Opioid Withdrawal in Individuals With Opioid Use Disorder

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Transcutaneous Cervical Vagus Nerve Stimulation Modulates Prefrontal Cortex Activity During Opioid Withdrawal in Individuals With Opioid Use Disorder

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