Insular Cortex Modulation by Repetitive Transcranial Magnetic Stimulation with Concurrent Functional Magnetic Resonance Imaging: Preliminary Findings

Background/Objectives: The insula is a deep, functionally heterogeneous region involved in various pathological conditions. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising therapeutic avenue for neuromodulation, yet very few studies have directly investigated its effec...

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Main Authors: Daphné Citherlet, Olivier Boucher, Manon Robert, Catherine Provost, Arielle Alcindor, Ke Peng, Louis De Beaumont, Dang Khoa Nguyen
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Brain Sciences
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Online Access:https://www.mdpi.com/2076-3425/15/7/680
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author Daphné Citherlet
Olivier Boucher
Manon Robert
Catherine Provost
Arielle Alcindor
Ke Peng
Louis De Beaumont
Dang Khoa Nguyen
author_facet Daphné Citherlet
Olivier Boucher
Manon Robert
Catherine Provost
Arielle Alcindor
Ke Peng
Louis De Beaumont
Dang Khoa Nguyen
author_sort Daphné Citherlet
collection DOAJ
description Background/Objectives: The insula is a deep, functionally heterogeneous region involved in various pathological conditions. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising therapeutic avenue for neuromodulation, yet very few studies have directly investigated its effects on insular activity. Moreover, empirical evidence of target engagement of this region remains scarce. This study aimed to stimulate the insula with rTMS and assess blood oxygen level-dependent (BOLD) signal modulation using concurrent functional magnetic resonance imaging (fMRI). Methods: Ten participants were recruited, six of whom underwent a single session of 5 Hz high-frequency rTMS over the right insular cortex inside the MRI scanner. Stimulation was delivered using a compatible MRI-B91 TMS coil. Stimulation consisted of 10 trains of 10 s each, with a 50 s interval between trains. Frameless stereotactic neuronavigation ensured precise targeting. Paired t-tests were used to compare the mean BOLD signal obtained between stimulation trains with resting-state fMRI acquired before the rTMS stimulation session. A significant cluster threshold of q < 0.01 (False Discovery Rate; FDR) with a minimum cluster size of 10 voxels was applied. Results: Concurrent rTMS-fMRI revealed the significant modulation of BOLD activity within insular subregions. Increased activity was observed in the anterior, middle, and middle-inferior insula, while decreased activity was identified in the ventral anterior and posterior insula. Additionally, two participants reported transient dysgeusia following stimulation, which provides further evidence of insular modulation. Conclusions: These findings provide preliminary evidence that rTMS can modulate distinct subregions of the insular cortex. The combination of region-specific BOLD responses and stimulation-induced dysgeusia supports the feasibility of using rTMS to modulate insular activity.
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spelling doaj-art-1daf2efb9e164c5fabe5c51ac78d4d682025-08-20T02:45:45ZengMDPI AGBrain Sciences2076-34252025-06-0115768010.3390/brainsci15070680Insular Cortex Modulation by Repetitive Transcranial Magnetic Stimulation with Concurrent Functional Magnetic Resonance Imaging: Preliminary FindingsDaphné Citherlet0Olivier Boucher1Manon Robert2Catherine Provost3Arielle Alcindor4Ke Peng5Louis De Beaumont6Dang Khoa Nguyen7Neurosciences Axis, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC H2X 0A9, CanadaNeurosciences Axis, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC H2X 0A9, CanadaNeurosciences Axis, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC H2X 0A9, CanadaCentre de Recherche de l’Hôpital du Sacré-Cœur de Montréal, Montreal, QC H4J 1C5, CanadaNeurosciences Axis, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC H2X 0A9, CanadaDepartment of Electrical and Computer Engineering, University of Manitoba, Winnipeg, MB R3T 5V6, CanadaCentre de Recherche de l’Hôpital du Sacré-Cœur de Montréal, Montreal, QC H4J 1C5, CanadaNeurosciences Axis, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC H2X 0A9, CanadaBackground/Objectives: The insula is a deep, functionally heterogeneous region involved in various pathological conditions. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising therapeutic avenue for neuromodulation, yet very few studies have directly investigated its effects on insular activity. Moreover, empirical evidence of target engagement of this region remains scarce. This study aimed to stimulate the insula with rTMS and assess blood oxygen level-dependent (BOLD) signal modulation using concurrent functional magnetic resonance imaging (fMRI). Methods: Ten participants were recruited, six of whom underwent a single session of 5 Hz high-frequency rTMS over the right insular cortex inside the MRI scanner. Stimulation was delivered using a compatible MRI-B91 TMS coil. Stimulation consisted of 10 trains of 10 s each, with a 50 s interval between trains. Frameless stereotactic neuronavigation ensured precise targeting. Paired t-tests were used to compare the mean BOLD signal obtained between stimulation trains with resting-state fMRI acquired before the rTMS stimulation session. A significant cluster threshold of q < 0.01 (False Discovery Rate; FDR) with a minimum cluster size of 10 voxels was applied. Results: Concurrent rTMS-fMRI revealed the significant modulation of BOLD activity within insular subregions. Increased activity was observed in the anterior, middle, and middle-inferior insula, while decreased activity was identified in the ventral anterior and posterior insula. Additionally, two participants reported transient dysgeusia following stimulation, which provides further evidence of insular modulation. Conclusions: These findings provide preliminary evidence that rTMS can modulate distinct subregions of the insular cortex. The combination of region-specific BOLD responses and stimulation-induced dysgeusia supports the feasibility of using rTMS to modulate insular activity.https://www.mdpi.com/2076-3425/15/7/680insular cortexrTMSfMRIneuromodulationneurostimulationhigh-frequency
spellingShingle Daphné Citherlet
Olivier Boucher
Manon Robert
Catherine Provost
Arielle Alcindor
Ke Peng
Louis De Beaumont
Dang Khoa Nguyen
Insular Cortex Modulation by Repetitive Transcranial Magnetic Stimulation with Concurrent Functional Magnetic Resonance Imaging: Preliminary Findings
Brain Sciences
insular cortex
rTMS
fMRI
neuromodulation
neurostimulation
high-frequency
title Insular Cortex Modulation by Repetitive Transcranial Magnetic Stimulation with Concurrent Functional Magnetic Resonance Imaging: Preliminary Findings
title_full Insular Cortex Modulation by Repetitive Transcranial Magnetic Stimulation with Concurrent Functional Magnetic Resonance Imaging: Preliminary Findings
title_fullStr Insular Cortex Modulation by Repetitive Transcranial Magnetic Stimulation with Concurrent Functional Magnetic Resonance Imaging: Preliminary Findings
title_full_unstemmed Insular Cortex Modulation by Repetitive Transcranial Magnetic Stimulation with Concurrent Functional Magnetic Resonance Imaging: Preliminary Findings
title_short Insular Cortex Modulation by Repetitive Transcranial Magnetic Stimulation with Concurrent Functional Magnetic Resonance Imaging: Preliminary Findings
title_sort insular cortex modulation by repetitive transcranial magnetic stimulation with concurrent functional magnetic resonance imaging preliminary findings
topic insular cortex
rTMS
fMRI
neuromodulation
neurostimulation
high-frequency
url https://www.mdpi.com/2076-3425/15/7/680
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