Are we really targeting and stimulating DLPFC by placing transcranial electrical stimulation (tES) electrodes over F3/F4?

Background In many clinical trials involving transcranial electrical stimulation (tES), target electrodes are typically placed over DLPFC with the assumption that this will primarily stimulate the underlying brain region. However, our study aimed to evaluate the electric fields (EF) that are actually delivered and identify prefrontal regions that may be inadvertently targeted in DLPFC tES. Methods Head models were generated from Human Connectome Project database’s T1+T2-weighted MRIs of 80 healthy adults. Two common DLPFC montages were simulated; symmetric-F4/F3, and asymmetric-F4/Fp1. Averaged EF was extracted from (1) the center of target electrode (F4), and (2) the top 1% of voxels showing the strongest EF in individualized EF maps. Inter-individual variabilities were quantified with standard deviation of EF peak location/value. Similar steps were repeated with 66 participants with methamphetamine use disorder (MUDs) as an independent clinical population. Results In healthy adults, the group-level location of EF peaks was situated in the medial-frontopolar, and the individualized EF peaks were positioned in a cube with a volume of 29cm3/46cm3 (symmetric/asymmetric montages). EFs in frontopolar area were significantly higher than EF “under” the target electrode in both symmetric (peak:0.41±0.06, F4:0.22±0.04) and asymmetric (peak:0.38±0.04, F4:0.2±0.04) montages (Heges’g>0.7). Similar results with slight between-group differences were found in MUDs. Conclusions We highlighted that in common DLPFC tES montages, in addition to inter-individual/inter-group variability, the frontopolar received the highest EFs rather than DLPFC as the main target. We specifically recommended considering the potential involvement of the frontopolar area as a mechanism underlying the effectiveness of DLPFC tES protocols. Highlights There are many published tES studies assuming targeting DLPFC with DLPFC tES montages In DLPFC tES montages, electric field peaks are not located under the electrodes The electric field peak in DLPFC montages is located in the medial frontopolar area An independent population showed between-group similarities and variations in electric field There is a large interindividual variation in both location and strength of the electric field peak