Lack of Target Engagement Following Low-Frequency Deep Transcranial Magnetic Stimulation of the Anterior Insula

Abstract

Objective: To evaluate the safety and efficacy of low-frequency, inhibitory, deep rTMS with a novel H-coil specifically designed to stimulate the insula.

Methods: In a randomized, crossover order, 16 healthy volunteers underwent two sessions (sham; active) of 1 Hz repetitive TMS at an intensity of 120% of individual motor threshold, over the right anterior insular cortex localized using a neuronavigation system. Before, immediately after, and one hour after rTMS, subjects performed two tasks that have previously been shown in fMRI experiments to activate insular cortex: A blink suppression task and a forced-choice risk-taking task.

Results: No drop-outs or adverse events occurred. Active deep rTMS did not result in decreased urge to blink compared to sham. Similarly, no significant time × condition interaction on risk-taking behavior was found.

Conclusions: Low-frequency deep rTMS using a novel H8 coil was shown to be safe but did not affect any of the behavioral markers, also used to investigate modulation of insula activity. Our findings highlight the challenges of modulating the activity of deep brain regions with TMS. Further studies are necessary to identify effective stimulation parameters for deep targets, and to characterize the effects of deep TMS on overlying cortical regions.

Keywords: Deep transcranial magnetic stimulation; H-coil; insula; risk; urge.

Figure 1.

The H8 coil device contains two symmetric components designed to stimulate one or both hemispheres. Lateral (a) and frontal (b) view of H8 coil placement on subject’ head. Figure (c) shows the coil elements contained in the H8 device.

Figure 2.

Target area (right anterior insula) and its relationship with coil placement over the scalp. The target area, located at approximately 4 cm from the scalp surface, was mapped using an MRI-guided navigation system for TMS. Target location was marked on a cap wore by the participants during the experimental session. The center of the coil, where the magnetic field is at the maximum, was also marked on the inner surface of the right wing of the H8 coil, which was placed on the target.

Figure 3.

Relative changes from baseline for eye blinking rate (BR) and urge to blink (AUC) following sham and active rTMS.

Figure 4.

Correlations of the AUC to BR scores at each time point, following both active and sham TMS.

Figure 5.

Relative changes from baseline for risk choices following sham and active rTMS