Contralateral prefrontal and network engagement during left DLPFC 10 Hz rTMS: an interleaved TMS-fMRI study in healthy adults

Background: High-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) serves as an effective treatment for major depression and other psychiatric disorders. Despite its growing clinical application, the neural mechanisms by which prefront...

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Main Authors: Timo van Hattem, Kai-Yen Chang, Martin Tik, Paul Taylor, Jonas Björklund, Lucia Bulubas, Frank Padberg, Daniel Keeser, Mattia Campana
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:NeuroImage: Clinical
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213158225001329
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author Timo van Hattem
Kai-Yen Chang
Martin Tik
Paul Taylor
Jonas Björklund
Lucia Bulubas
Frank Padberg
Daniel Keeser
Mattia Campana
author_facet Timo van Hattem
Kai-Yen Chang
Martin Tik
Paul Taylor
Jonas Björklund
Lucia Bulubas
Frank Padberg
Daniel Keeser
Mattia Campana
author_sort Timo van Hattem
collection DOAJ
description Background: High-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) serves as an effective treatment for major depression and other psychiatric disorders. Despite its growing clinical application, the neural mechanisms by which prefrontal rTMS exerts its therapeutic effects remain incompletely understood. To address this gap, we investigated the immediate blood-oxygen-level-dependent (BOLD) activity during 600 stimuli of left DLPFC 10 Hz rTMS in healthy individuals using interleaved TMS-fMRI. Methods: In a crossover design, 17 healthy subjects received 10 Hz rTMS (60 trains with 9-second intertrain intervals) over the left DLPFC at 40 % and 80 % of their resting motor threshold (rMT) inside the MR scanner. Results: 10 Hz rTMS over the left DLPFC elicited BOLD responses in prefrontal regions, cingulate cortex, insula, striatum, thalamus, as well as auditory and somatosensory areas. Notably, our findings revealed that 10 Hz rTMS effects were lateralized towards the contralateral (right) DLPFC. Dose-response effects between 40 % vs. 80 % rMT were exclusively observed in the hippocampus. Conclusions: The 10 Hz rTMS protocol used in this study induced distinct target engagement and propagation patterns in the prefrontal cortex. These patterns differ from our previous interleaved TMS-fMRI findings using 600 stimuli of left DLPFC intermittent theta burst stimulation (iTBS) at the same intensities. Thus, interleaved TMS-fMRI emerges as a valuable method for comparing clinical prefrontal rTMS protocols regarding their immediate effect on brain circuits in order to differentiate their action mechanisms and to potentially inform clinical applications.
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spelling doaj-art-31d15b58b68b42909d1d7f0c0bc84c172025-08-20T03:36:44ZengElsevierNeuroImage: Clinical2213-15822025-01-014810386210.1016/j.nicl.2025.103862Contralateral prefrontal and network engagement during left DLPFC 10 Hz rTMS: an interleaved TMS-fMRI study in healthy adultsTimo van Hattem0Kai-Yen Chang1Martin Tik2Paul Taylor3Jonas Björklund4Lucia Bulubas5Frank Padberg6Daniel Keeser7Mattia Campana8Department of Psychiatry and Psychotherapy, University Hospital LMU, LMU Munich, Germany; Neuroimaging Core Unit Munich – NICUM, University Hospital LMU, LMU Munich, Germany; Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany; Department of Neurology & Stroke, University of Tübingen, GermanyDepartment of Psychiatry and Psychotherapy, University Hospital LMU, LMU Munich, Germany; Neuroimaging Core Unit Munich – NICUM, University Hospital LMU, LMU Munich, GermanyHigh Field MR Center, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria; Brain Stimulation Lab, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, USADepartment of Psychology, LMU Munich, Germany; Department of Psychology, Universität Zürich, SwitzerlandDepartment of Psychiatry and Psychotherapy, University Hospital LMU, LMU Munich, Germany; Neuroimaging Core Unit Munich – NICUM, University Hospital LMU, LMU Munich, Germany; DZPG (German Center for Mental Health), partner site Munich-Augsburg, GermanyDepartment of Psychiatry and Psychotherapy, University Hospital LMU, LMU Munich, Germany; Neuroimaging Core Unit Munich – NICUM, University Hospital LMU, LMU Munich, Germany; DZPG (German Center for Mental Health), partner site Munich-Augsburg, GermanyDepartment of Psychiatry and Psychotherapy, University Hospital LMU, LMU Munich, Germany; Neuroimaging Core Unit Munich – NICUM, University Hospital LMU, LMU Munich, Germany; DZPG (German Center for Mental Health), partner site Munich-Augsburg, Germany; Corresponding author at: Department of Psychiatry and Psychotherapy, University Hospital LMU, LMU Munich, Germany.Department of Psychiatry and Psychotherapy, University Hospital LMU, LMU Munich, Germany; Neuroimaging Core Unit Munich – NICUM, University Hospital LMU, LMU Munich, Germany; DZPG (German Center for Mental Health), partner site Munich-Augsburg, Germany; Munich Center for Neurosciences (MCN), Ludwig Maximilian University LMU, Munich, GermanyDepartment of Psychiatry and Psychotherapy, University Hospital LMU, LMU Munich, Germany; LVR Hospital, Department of General Psychiatry 2, Clinic of the Heinrich Heine University, Düsseldorf, GermanyBackground: High-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) serves as an effective treatment for major depression and other psychiatric disorders. Despite its growing clinical application, the neural mechanisms by which prefrontal rTMS exerts its therapeutic effects remain incompletely understood. To address this gap, we investigated the immediate blood-oxygen-level-dependent (BOLD) activity during 600 stimuli of left DLPFC 10 Hz rTMS in healthy individuals using interleaved TMS-fMRI. Methods: In a crossover design, 17 healthy subjects received 10 Hz rTMS (60 trains with 9-second intertrain intervals) over the left DLPFC at 40 % and 80 % of their resting motor threshold (rMT) inside the MR scanner. Results: 10 Hz rTMS over the left DLPFC elicited BOLD responses in prefrontal regions, cingulate cortex, insula, striatum, thalamus, as well as auditory and somatosensory areas. Notably, our findings revealed that 10 Hz rTMS effects were lateralized towards the contralateral (right) DLPFC. Dose-response effects between 40 % vs. 80 % rMT were exclusively observed in the hippocampus. Conclusions: The 10 Hz rTMS protocol used in this study induced distinct target engagement and propagation patterns in the prefrontal cortex. These patterns differ from our previous interleaved TMS-fMRI findings using 600 stimuli of left DLPFC intermittent theta burst stimulation (iTBS) at the same intensities. Thus, interleaved TMS-fMRI emerges as a valuable method for comparing clinical prefrontal rTMS protocols regarding their immediate effect on brain circuits in order to differentiate their action mechanisms and to potentially inform clinical applications.http://www.sciencedirect.com/science/article/pii/S2213158225001329Interleaved TMS-fMRI10 Hz rTMSiTBSMajor depressionNeuromodulationNeuroimaging
spellingShingle Timo van Hattem
Kai-Yen Chang
Martin Tik
Paul Taylor
Jonas Björklund
Lucia Bulubas
Frank Padberg
Daniel Keeser
Mattia Campana
Contralateral prefrontal and network engagement during left DLPFC 10 Hz rTMS: an interleaved TMS-fMRI study in healthy adults
NeuroImage: Clinical
Interleaved TMS-fMRI
10 Hz rTMS
iTBS
Major depression
Neuromodulation
Neuroimaging
title Contralateral prefrontal and network engagement during left DLPFC 10 Hz rTMS: an interleaved TMS-fMRI study in healthy adults
title_full Contralateral prefrontal and network engagement during left DLPFC 10 Hz rTMS: an interleaved TMS-fMRI study in healthy adults
title_fullStr Contralateral prefrontal and network engagement during left DLPFC 10 Hz rTMS: an interleaved TMS-fMRI study in healthy adults
title_full_unstemmed Contralateral prefrontal and network engagement during left DLPFC 10 Hz rTMS: an interleaved TMS-fMRI study in healthy adults
title_short Contralateral prefrontal and network engagement during left DLPFC 10 Hz rTMS: an interleaved TMS-fMRI study in healthy adults
title_sort contralateral prefrontal and network engagement during left dlpfc 10 hz rtms an interleaved tms fmri study in healthy adults
topic Interleaved TMS-fMRI
10 Hz rTMS
iTBS
Major depression
Neuromodulation
Neuroimaging
url http://www.sciencedirect.com/science/article/pii/S2213158225001329
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