The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
A distinct biomarker of continuous transcutaneous vagus nerve stimulation treatment in major depressive disorder
Open accessAbstract
Background Major depression is the fourth leading cause of disability worldwide and poses a socioeconomic burden worldwide. Transcutaneous vagus nerve stimulation (tVNS) is a promising noninvasive clinical device that may reduce the severity of major depression. However, the neural mechanism underlying continuous tVNS has not yet been elucidated.Objective We aimed to explore the effect of hypothalamic subregion functional connectivity (FC) changes during continuous tVNS treatment on major depressive disorder (MDD) patients and to identify the potential biomarkers for treatment outcomes.Methods Forty-one mild to moderate MDD patients were recruited and received either real or sham tVNS treatment for 4 weeks. We used a seed-to-whole brain approach to estimate the FC changes of hypothalamic subregions and their surrounding control areas during continuous tVNS treatment and explored their association with clinical outcome changes after 4 weeks of treatment.Results Of the thirty-six patients that completed the study, those in the tVNS group had significantly lower scores on the 24-item Hamilton Depression (HAM-D) Rating Scale compared to the sham tVNS group after 4 weeks of treatment. The FC between the bilateral medial hypothalamus (MH) and rostral anterior cingulate cortex (rACC) was significantly decreased during tVNS but not during sham tVNS. The strength of this FC was significantly correlated with HAM-D improvements after 4 weeks of tVNS.Conclusion The FC between the bilateral MH and rACC may serve as a potential biomarker for the tVNS state and predict treatment responses. Our results provide insights into the neural modulation mechanisms of continuous tVNS and reveal a potential therapeutic target for MDD patients.
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“The interventions used in the control groups were all sham taVNS.[13–15]”
From Transcutaneous auricular vagus nerve stimulation in treating major depressive disorder: A systematic review and meta-analysis (2018) · cites this paper as [15]
In the citing paper
“In contrast, the confounding bias was not reported in any of these 2 trials.[14,15]”
From Transcutaneous auricular vagus nerve stimulation in treating major depressive disorder: A systematic review and meta-analysis (2018) · cites this paper as [15]
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“One studies recorded the side effects of transcutaneous auricular vagus nerve stimulation in treating major depressive disorder but did not report the adverse outcomes.[15]”
From Transcutaneous auricular vagus nerve stimulation in treating major depressive disorder: A systematic review and meta-analysis (2018) · cites this paper as [15]
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Cites
The Brain's Default Network: Anatomy, Function, and Relevance to Disease
Buckner, R. L., Andrews‐Hanna, J. R., & Schacter, D. L. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1440.011 · Cited by 9,761
Ashburner, J., & Friston, K. J. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.02.018 · Cited by 7,507
Whiteford, H. A., Degenhardt, L., Rehm, J., Baxter, A. J., Ferrari, A. J., Erskine, H. E., Charlson, F. J., Norman, R. E., Flaxman, A. D., Johns, N., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(13)61611-6 · Cited by 6,006
Maldjian, J. A., Laurienti, P. J., Kraft, R., & Burdette, J. H. (2003) · NeuroImage · doi:10.1016/s1053-8119(03)00169-1 · Cited by 5,066 · cited 1×
“The bilateral medial hypothalamus (MH) (MNI coordinates: x1⁄4±4; y1⁄4 2; z1⁄4 12 plus 2mm sphere) and lateral hypothalamus (LH) (MNI coordinates: x1⁄4±6; y1⁄4 9; z1⁄4 10 plus 2mm sphere) [30] were selected as seeds using WFU-Pick Atlas software [31] (Fig.”
Trivedi, M. H., Rush, A. J., Wisniewski, S. R., Nierenberg, A. A., Warden, D., Ritz, L., Norquist, G., Howland, R. H., Lebowitz, B., McGrath, P. J., et al. (2006) · American Journal of Psychiatry · doi:10.1176/appi.ajp.163.1.28 · Cited by 3,879 · cited 1×
“Despite the availability of a variety of treatments, around 30% of patients fail to respond to antidepressant medication [3] or psychological treatment [4].”
Methods to detect, characterize, and remove motion artifact in resting state fMRI
Power, J. D., Mitra, A., Laumann, T. O., Snyder, A. Z., Schlaggar, B. L., & Petersen, S. E. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2013.08.048 · Cited by 3,748 · cited 1×
“In the last step, global signal regression (GSR) was applied to reduce head motion-related signal changes [29].”
The Neuroendocrinology of Stress: A Never Ending Story
Lightman, S. L. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01711.x · Cited by 3,588
Nestler, E. J., Barrot, M., DiLeone, R. J., Eisch, A. J., Gold, S. J., & Monteggia, L. M. (2002) · Neuron · doi:10.1016/s0896-6273(02)00653-0 · Cited by 3,217 · cited 3×
“Some of these brain regions are also believed to be involved in the pathogenesis and remission of MDD, particularly the hypothalamus [18,22].”
Self-referential processing in our brain—A meta-analysis of imaging studies on the self
Northoff, G., Heinzel, A., de Greck, M., Bermpohl, F., Dobrowolny, H., & Panksepp, J. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2005.12.002 · Cited by 2,792
From motivation to action: Functional interface between the limbic system and the motor system
MOGENSON, G., JONES, D., & YIM, C. (1980) · Progress in Neurobiology · doi:10.1016/0301-0082(80)90018-0 · Cited by 2,331
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Autonomic and neural responses to varying transcutaneous cervical electrical stimulation parameters
Debnath, S., Fylaktou, F., Gurfein, B. T., & Zanos, T. P. (2026) · Bioelectronic Medicine · doi:10.1186/s42234-026-00210-2
“…durations up to 9 months (Vonck et al. 1999; Busch et al. 2013; Hein et al. 2013; Clancy et al. 2014; Kreuzer et al. 2014; Capone et al. 2015; Frangos et al. 2015; Hasan et al. 2015; Straube et al. 2015; Bauer et al. 2016; Fang et al. 2016; Rong et al. 2016; Yakunina et al. 2017; Tu et al. 2018).”
The EASE framework: A scalable auricular self-care approach for mental health promotion
Li, K., Zhang, Z., Wu, J., & Kong, J. (2026) · Brain Behavior and Immunity Integrative · doi:10.1016/j.bbii.2026.100188
Tong, Y., Ye, Z., Jiang, Q., Li, C., Xiao, J., Zeng, R., Wang, H., & Li, C. (2026) · Frontiers in Physiology · doi:10.3389/fphys.2026.1881568
Staffel, S., & Richlan, F. (2026) · Applied Sciences · doi:10.3390/app16188978
Su, Y., Liu, Y., Chen, J., Li, X., Liu, T., & Fu, W. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1972200
“Tu et al. (2018) (31) (C1; voxel p <.001, cluster FDR), using hypothalamic seeds during on/off blocks, found medial-hypothal-amus connectivity with left rACC and right MFG to be lower, and with cerebellum higher, in real than sham during stimulation; the medial-hypothalamus – rACC on-vs-off change…”
Influential
Metadata
- Authors
- Tu, Y., Fang, J., Cao, J., Wang, Z., Park, J., Jorgenson, K., Lang, C., Liu, J., Zhang, G., Zhao, Y., Zhu, B., Rong, P., & Kong, J.
- Affiliations
- Harvard University (US)
- China Academy of Chinese Medical Sciences (CN)
- Corresponding author
- Rong, Peijing
- Kong, Jian
- ORCID
- Venue
- Brain stimulation
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 11
- Issue
- 3
- Pages
- 501-508
- ISSN
- 1876-4754 (ISSN-L)
- 1935-861X
- PMC
- PMC5930128
- OpenAlex
- W2792997548
- Cited by
- 104
- References
- 66
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 15 · 2023: 12 · 2022: 13 · 2021: 21 · 2020: 10 · 2019: 4 · 2018: 3
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain stimulation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Beijing Municipal Science & Technology Commission (Z161100002616003)
- National Natural Science Foundation of China (81471389, 81473780, 81303056, 81674072, 81774433)
- NIH/NCCIH (R01AT006364, R01AT008563, R21AT008707, R61AT009310, P01AT006663)
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- transcutaneous vagus nerve stimulation, major depressive disorder, functional connectivity, medial hypothalamus, rostral anterior cingulate cortex, treatment response biomarkers, Hamilton Depression Rating Scale
- MeSH terms
- Adolescent, Adult, Aged, Brain, Major Depressive Disorder, Transcutaneous Electric Nerve Stimulation, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Vagus Nerve, Biomarkers, Treatment Outcome, Vagus Nerve Stimulation, Young Adult
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