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

Abstract

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.

Keywords: BOLD signal; concurrent rTMS-fMRI; dysgeusia; fMRI; high-frequency; insular cortex; neuromodulation; neuronavigation; neurostimulation; rTMS.

Figure 1

The MRI-B91 coil is attached to an MRI-compatible TMS support while the subject lies on the MRI table, with the coil positioned on the scalp (A). A 16-channel head antenna is placed over the participant’s head to optimize signal reception during the fMRI acquisition (B,C).

Figure 2

Change in BOLD activity during post-train intervals compared to the resting-state fMRI. Results are displayed at q < 0.01 or q < 0.001, FDR-corrected. The left side represents BOLD signal activation/excitation (SBJ1, SBJ3, and SBJ4) and the right side represents BOLD signal deactivation/inhibition (SBJ2, SBJ4, and SBJ6). From top to bottom, a sagittal view (right and left), followed by a coronal view. The coordinates are reported in MNI space. In the sagittal view, x = 0 corresponds to the midline. In the coronal view, y = 0 is the anterior commissure.