Author response: Insular and anterior cingulate cortex deep stimulation for central neuropathic pain: Disassembling the percept of pain

We thank Dr. Zugaib et al. for the interest in our work.1 It has been suggested that modeling electric fields within the deep cortical structures would provide more reliable, target-effect conclusions. So far, the use of linear projection to target1 the posterior superior insula (PSI) has provided antinociceptive effects as measured by increases in the heat-pain threshold in patients with central pain2 and in healthy volunteers.3o Importantly, in a unique study,4 direct cortical stimulation of the PSI during stereo-EEG showed exactly4 the same heat-pain changes described by the linear projection-targeted deep transcranial magnetic stimulation (TMS). Taken together, these are very strong arguments for the precision of such an approach. In addition, in the setups cited above, stimulation intensity was calculated using the anterior tibialis muscle as a parameter (with the leg representation buried medially within the primary motor cortex), which attests that a measurable amount of induced electric current was indeed delivered to the PSI. As pointed out by Zugaib and Souza,5 computing electric field would not solve the issue of intensity of stimulation. Because the linear projection-based deep TMS approach proved itself accurate on psychophysical terms, we propose a pragmatic “reverse-modeling” perspective that future electric-field models should take into account the data from linear projection in their algorithms because they have been validated against sham and active controls and provided information on the intensity of stimulation all at once.