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

van Hattem, Timo; Chang, Kai-Yen; Tik, Martin; Taylor, Paul; Björklund, Jonas; Bulubas, Lucia; Padberg, Frank; Keeser, Daniel; Campana, Mattia (2025): Contralateral prefrontal and network engagement during left DLPFC 10 Hz rTMS: an interleaved TMS-fMRI study in healthy adults. NeuroImage: Clinical, 48: 103862. ISSN 22131582

Abstract

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.

• Doc-Type: Article (LMU Hospital)
• Organisational unit (Faculties): 07 Medicine > Medical Center of the University of Munich > Clinic and Polyclinic for Psychiatry and Psychotherapy
• DFG subject classification of scientific disciplines: Life sciences
• DFG: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 491502892