Deep continuous theta burst stimulation of the operculo-insular cortex selectively affects Aδ-fibre heat pain

Previous studies have suggested a pivotal role of the insular cortex in nociception and pain perception. Using a double-cone coil designed for deep transcranial magnetic stimulation, our objective was to assess (1) whether continuous theta burst stimulation (cTBS) of the operculo-insular cortex affects differentially the perception of different types of thermal and mechanical somatosensory inputs, (2) whether the induced after-effects are lateralized relative to the stimulated hemisphere and (3) whether the after-effects are due to neuromodulation of the insula or neuromodulation of the more superficial opercular cortex. Seventeen participants took part in two experiments. In experiment 1, thresholds and perceived intensity of Aδ- and C-fiber heat pain elicited by laser stimulation, non-painful cool sensations elicited by contact cold stimulation and mechanical vibrotactile sensations were assessed at the left hand before, immediately after and 20 minutes after deep cTBS delivered over the right operculo-insular cortex. In experiment 2, Aδ-fiber heat pain and vibrotactile sensations elicited by stimulating the contralateral and ipsilateral hands were evaluated before and after deep cTBS or superficial cTBS delivered using a flat figure-ofeight coil. Only the threshold to detect Aδ-fiber heat pain was significantly increased 20 minutes after deep cTBS. This effect was present at both hands. No effect was observed after superficial cTBS. Neuromodulation of the operculo-insular cortex using deep cTBS induces a bilateral reduction of the ability to perceive Aδ-fiber heat pain, without concomitantly affecting the ability to perceive innocuous warm, cold or vibrotactile sensations