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

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 x 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.