Evidence map›Paper›PMID 34365067›Full record

Trial reportJournal of psychiatric research2021

Respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) modulates brain response to stress in major depression.

Ronald G Garcia, Justine E Cohen, Arielle D Stanford, Aileen Gabriel, Jessica Stowell, Harlyn Aizley, Riccardo Barbieri, David Gitlin, Vitaly Napadow, Jill M Goldstein

Registry-linked trialOpen access · greenAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of psychiatric research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07498881 (LasaiOn), which is not on this map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07498881 nanot yet recruitingnot on this mapstarted 2026, after this paper: background citation

LasaiOn: An Intervention Program to Reduce Emotional Distress

TypeinterventionalSponsorUniversity of the Basque Country (UPV/EHU)Ran2026 to 2028Enrolled200ConditionsAdultArmsLasaiON
3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

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  11. A narrative review of vagus nerve stimulation in stroke.Journal of central nervous system disease · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Ronald G GarciaDepartment of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Innovation Center on Sex Differences in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Justine E CohenDepartment of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Innovation Center on Sex Differences in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Arielle D StanfordTranslational Medicine, Alkermes Inc, Waltham, MA, USA.
Aileen GabrielInnovation Center on Sex Differences in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Jessica StowellDepartment of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Harlyn AizleyDepartment of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Innovation Center on Sex Differences in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Riccardo BarbieriDepartment of Electronics, Information and Bioengineering, Politecnico di Milano, Milano, Italy; Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
David GitlinDepartment of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Vitaly NapadowAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Innovation Center on Sex Differences in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Logan University, Chesterfield, MO, USA.
Jill M GoldsteinDepartment of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Innovation Center on Sex Differences in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: jill_goldstein@hms.harvard.edu.
Harvard University · USAlkermes (United States) · USBrigham and Women's Hospital · USLogan University · US

Funding

Boston Biomedical Innovation CenterU54HL119145 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GOLAN, DAVID E., LOSCALZO, JOSEPH · 2013 to 2021
$18.8M
Sex Differences in Major Depression, Part II: Impact of Prenatal Immune, Autonomic and Neurovascular FunctionU54MH118919 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI Gabriela Apiou · 2020 to 2026
$12.7M
Mapping the linkage between auricular vagus nerve receptors and cardiovagal modulationOT2OD023867 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI NAPADOW, VITALY · 2016 to 2021
$3.4M
Neural-Physiology Biosignature Shared across Negative Valence and Arousal DomainsR21MH103468 · NIMH · BRIGHAM AND WOMEN'S HOSPITAL · PI GOLDSTEIN, JILL M, NAPADOW, VITALY · 2014 to 2015
$482k
NHLBI NIH HHS U54 HL119145NIH HHS OT2 OD023867NIMH NIH HHS R21 MH103468NIMH NIH HHS U54 MH118919
6 · The paper itself

Abstract

backgroundNegative stress significantly impacts major depressive disorder (MDD), given the shared brain circuitry between the stress response and mood. Thus, interventions that target this circuitry will have an important impact on MDD. The aim of this study was to evaluate the acute effects of a novel respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) technique in the modulation of brain activity and connectivity in women with MDD in response to negative stressful stimuli.

methodsTwenty premenopausal women with recurrent MDD in an active episode were included in a cross-over experimental study that included two functional MRI visits within one week, randomized to receive exhalatory- (e-RAVANS) or inhalatory-gated (i-RAVANS) at each visit. Subjects were exposed to a visual stress challenge that preceded and followed RAVANS. A Factorial analysis was used to evaluate the effects of RAVANS on brain activity and connectivity and changes in depressive and anxiety symptomatology post-stress.

resultsCompared with i-RAVANS, e-RAVANS was significantly associated with increased activation of subgenual anterior cingulate, orbitofrontal and ventromedial prefrontal cortices and increased connectivity between hypothalamus and dorsolateral prefrontal cortex, and from nucleus tractus solitarii to locus coeruleus and ventromedial prefrontal cortex. Changes in brain activity and connectivity after e-RAVANS were significantly associated with a reduction in depressive and anxiety symptoms.

conclusionsOur study suggests exhalatory-gated RAVANS effectively modulates brain circuitries regulating response to negative stress and is associated with significant acute reduction of depressive and anxiety symptomatology in women with recurrent MDD. Findings suggest a potential non-pharmacologic intervention for acute relief of depressive symptomatology in MDD.

Indexed as

Major Depressive DisorderVagus Nerve StimulationBrainDepressionFemaleHumansMagnetic Resonance ImagingfMRIMajor depressionRespirationStress responseTranscutaneous auricular vagus nerve stimulationVagus nerve

Identifiers

PMID34365067
PMCPMC8429271
OpenAlexW3192466867

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.