Cited by 142Transcranial Magnetic Stimulation StudiesVagus Nerve Stimulation ResearchTreatment of Major Depression

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A frontal-vagal network theory for Major Depressive Disorder: Implications for optimizing neuromodulation techniques

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Iseger, Tabitha A., van Bueren, Nienke E.R., Kenemans, J. Leon, Gevirtz, Richard, Arns, Martijn·2020·Brain Stimulation

DOI 10.1016/j.brs.2019.10.006

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Abstract

Major Depressive Disorder (MDD) is a psychiatric disorder characterized by high comorbidity with cardiovascular disease. Furthermore, a combination of high heart rate (HR) and low heart rate variability (HRV) has been frequently reported in depressed patients. The present review proposes a frontal-vagal (brain-heart) network that overlaps with functional nodes of the depression network. Moreover, we summarize neuromodulation studies that have targeted key nodes in this depression network, with subsequent impact on heart rate (HR) or heart-rate-variability (HRV), such as the dorsolateral prefrontal cortex (DLPFC), subgenual anterior cingulate cortex (sgACC), and the vagus nerve (VN). Based on the interplay of this frontal-vagal network, we emphasize the importance of including HR and HRV measurements in human depression studies, in particular those that conduct neuromodulation, in order to obtain a better understanding of the pathways that are affected, and we explore the possibilities of using this frontal-vagal interplay as a method for target engagement in neuromodulation treatments. This frontal-vagal network theory opens-up the possibility for individualizing neuromodulation treatments such as rTMS. A recent development called Neuro-Cardiac-Guided TMS (NCG-TMS), was developed based on this theory, and an individual-participant meta-analysis is presented. Four studies provide consistent and replicable support for NCG-TMS as a target engagement method, with consistent HR deceleration during frontal TMS and HR acceleration during motor strip TMS.

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Fig. 1 Visual overview of sympathetic and parasympathetic brain-heart connections. Anatomical and functional connections between the brain, spinal cord and the heart for the sympathetic pathway (accelerator nerve, indicated in green) and the parasympathetic pathway (vagus nerve, indicated in blue).CC-BY · From the PDF

Fig. 2 Example of the NCG-TMS method.CC-BY · From the PDF

Fig. 3 Results from the individual participant meta-analysis, pooling the results from 4 studies.CC-BY · From the PDF

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Research works printed but not linked: 1

T.A. Iseger, F. Padberg, J.L. Kenemans, H. van Dijk & M. Arns. Neuro-cardiac-guided TMS: a validation study (under review at NeuroImage).

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See all 142

Authors: Iseger, T. A., van Bueren, N. E. R., Kenemans, J. L., Gevirtz, R., & Arns, M.
Affiliations: Utrecht University (NL)
Alliant University (US)
Corresponding author: Arns, Martijn
ORCID: Iseger, Tabitha A.
Kenemans, J. Leon
Gevirtz, Richard
Arns, Martijn
Venue: Brain Stimulation
Publisher: Elsevier BV
Published: 2020-01
Volume: 13
Issue: 1
Pages: 1-9
ISSN: 1876-4754 (ISSN-L)
1935-861X
DOI: 10.1016/j.brs.2019.10.006
OpenAlex: W2979927084
Cited by: 142
References: 98
Citations by year: 2026: 17 · 2025: 26 · 2024: 17 · 2023: 18 · 2022: 18 · 2021: 31 · 2020: 15
FWCI: 1.67
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Brain stimulation (publishedVersion, cc-by)
PubMed (publishedVersion)
Research Publications (Maastricht University) (publishedVersion, cc-by)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
Radboud Repository (Radboud University) (submittedVersion)
Radboud Repository (Radboud University) (submittedVersion, other-oa)
Research Publications (Maastricht University) (submittedVersion, cc-by)
Topics: Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords: major depressive disorder, heart rate variability, heart rate, vagus nerve, neuromodulation, repetitive transcranial magnetic stimulation, dorsolateral prefrontal cortex, subgenual anterior cingulate cortex, heart-brain interaction, cardiovascular comorbidity
MeSH terms: Depressive Disorder, Major, Major Depressive Disorder, Gyrus Cinguli, Heart Rate, Humans, Motor Cortex, Vagus Nerve, Prefrontal Cortex, Transcranial Magnetic Stimulation

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A frontal-vagal network theory for Major Depressive Disorder: Implications for optimizing neuromodulation techniques

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