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

Background/Objectives: The insula plays a role in various medical conditions, including eating disorders, addiction, and chronic pain. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising therapeutic avenue, yet few studies have investigated its modulation effects on the insula. Moreover, direct evidence of target engagement remains scarce. This study aimed to stimulate the insula with rTMS and assess BOLD signal modulation through concurrent functional magnetic resonance imaging (fMRI). Methods: Ten participants were recruited and six underwent a single session of 5 Hz high-frequency rTMS over the right insular cortex inside the MRI scanner, using a compatible MRI-B91 TMS coil. Stimulation consisted of 10 trains of 10 seconds, with 50-second 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 (significant cluster threshold of 10 voxels; False Discovery Rate at q < 0.01). Results: Increased activity was observed in the anterior, middle, and middle-inferior insula, while deactivations occurred in the ventral anterior and posterior insula. Two participants reported dysgeusia, providing further evidence of insular modulation. Conclusions: This study provides neuroimaging evidence for rTMS-induced insular modulation. Our results are highly relevant for future clinical applications, with potential therapeutic avenues in individuals with conditions where insular dysfunction plays a key role.