Modulating salience network connectivity through olfactory nerve stimulation

Abstract Depression is associated with reduced functional connectivity within the brain’s salience network and its strengthened interactions with the default mode network (DMN). Modification of this clinical pattern is challenging. Leveraging the direct neural pathways from olfactory processing regi...

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Main Authors: Carina Heller, Maria Geisler, Nicolas L. Mayer, Annabelle Thierfelder, Martin Walter, Thomas Hummel, Ilona Croy
Format: Article
Language:English
Published: Nature Publishing Group 2025-08-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-025-03500-6
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author Carina Heller
Maria Geisler
Nicolas L. Mayer
Annabelle Thierfelder
Martin Walter
Thomas Hummel
Ilona Croy
author_facet Carina Heller
Maria Geisler
Nicolas L. Mayer
Annabelle Thierfelder
Martin Walter
Thomas Hummel
Ilona Croy
author_sort Carina Heller
collection DOAJ
description Abstract Depression is associated with reduced functional connectivity within the brain’s salience network and its strengthened interactions with the default mode network (DMN). Modification of this clinical pattern is challenging. Leveraging the direct neural pathways from olfactory processing regions to the salience network, we explored the effects of electrical stimulation of the olfactory mucosa on brain connectivity. In a randomized, blinded within-subject design, 45 healthy individuals received olfactory or trigeminal nerve stimulation followed by resting-state fMRI. Olfactory stimulation resulted in a significant increase in functional connectivity between the salience network and the piriform cortex – a primary olfactory structure. Importantly, this stimulation increased functional connectivity within the salience network and weakened connectivity between the salience network and the DMN. These findings suggest that olfactory stimulation may modulate connectivity patterns implicated in depression, offering a novel potential minimal invasive therapeutic strategy. However, as these results were obtained from a healthy cohort, further studies are required to evaluate the efficacy in individuals with depression.
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spelling doaj-art-21aa45fe24f549d6b943e52f3fce5ace2025-08-24T11:51:43ZengNature Publishing GroupTranslational Psychiatry2158-31882025-08-0115111010.1038/s41398-025-03500-6Modulating salience network connectivity through olfactory nerve stimulationCarina Heller0Maria Geisler1Nicolas L. Mayer2Annabelle Thierfelder3Martin Walter4Thomas Hummel5Ilona Croy6Department of Psychiatry and Psychotherapy, Jena University HospitalLab for Autonomic Neuroscience, Imaging and Cognition (LANIC), Department of Psychosomatic Medicine and Psychotherapy, Jena University HospitalSmell & Taste Clinic, Department of Otorhinolaryngology, University Hospital Carl Gustav Carus, Technische Universität DresdenDepartment of Clinical Psychology, Friedrich Schiller University JenaDepartment of Psychiatry and Psychotherapy, Jena University HospitalSmell & Taste Clinic, Department of Otorhinolaryngology, University Hospital Carl Gustav Carus, Technische Universität DresdenGerman Center for Mental Health (DZPG), Partner Site Jena-Magdeburg-HalleAbstract Depression is associated with reduced functional connectivity within the brain’s salience network and its strengthened interactions with the default mode network (DMN). Modification of this clinical pattern is challenging. Leveraging the direct neural pathways from olfactory processing regions to the salience network, we explored the effects of electrical stimulation of the olfactory mucosa on brain connectivity. In a randomized, blinded within-subject design, 45 healthy individuals received olfactory or trigeminal nerve stimulation followed by resting-state fMRI. Olfactory stimulation resulted in a significant increase in functional connectivity between the salience network and the piriform cortex – a primary olfactory structure. Importantly, this stimulation increased functional connectivity within the salience network and weakened connectivity between the salience network and the DMN. These findings suggest that olfactory stimulation may modulate connectivity patterns implicated in depression, offering a novel potential minimal invasive therapeutic strategy. However, as these results were obtained from a healthy cohort, further studies are required to evaluate the efficacy in individuals with depression.https://doi.org/10.1038/s41398-025-03500-6
spellingShingle Carina Heller
Maria Geisler
Nicolas L. Mayer
Annabelle Thierfelder
Martin Walter
Thomas Hummel
Ilona Croy
Modulating salience network connectivity through olfactory nerve stimulation
Translational Psychiatry
title Modulating salience network connectivity through olfactory nerve stimulation
title_full Modulating salience network connectivity through olfactory nerve stimulation
title_fullStr Modulating salience network connectivity through olfactory nerve stimulation
title_full_unstemmed Modulating salience network connectivity through olfactory nerve stimulation
title_short Modulating salience network connectivity through olfactory nerve stimulation
title_sort modulating salience network connectivity through olfactory nerve stimulation
url https://doi.org/10.1038/s41398-025-03500-6
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