On the need of individually optimizing temporal interference stimulation of human brains due to inter-individual variability.

Introduction: Transcranial temporal interference stimulation (TI, TIS, or tTIS), also known as interferential stimulation (IFS), is able to focally stimulate deep brain regions, provided it is properly optimized. We previously presented an algorithm for optimizing TI using two arrays of electrodes and showed that it can achieve more focal stimulation compared to optimized high-definition transcranial electrical stimulation (HD-TES) and conventional optimized TI using two pairs of electrodes, especially in the deep brain areas such as the hippocampus. However, those modeling studies were only performed on an averaged head (MNI152 template) and three individual heads without exploring inter-individual variability. Existing TI works in the literature mostly utilize a common (possibly optimized) montage of two pairs of electrodes on different individual heads without considering inter-individual variability.

Material and method: Here we aim to study the inter-individual variability of optimized TI by applying the same optimization algorithms on N = 25 heads using their individualized head models. Specifically, we compared the focality achieved by different stimulation techniques at six different regions of interest (ROI; right hippocampus, left dorsolateral prefrontal cortex, left motor cortex, right amygdala, right caudate, and left thalamus) under both individually optimized and unoptimized montages. We also conducted numerical sensitivity analysis on the individual optimization and performed phantom recordings to test our models.

Results: As expected, there is a variability in focality achieved by TI of up to 1.2 cm at the same ROI across subjects due to inter-individual differences in the head anatomy and tissue conductivity. We show that optimized TI using two arrays of electrodes achieves higher focality than that from optimized HD-TES at the same level of modulation intensity at 5 of the 6 ROIs. Compared to using a common montage either optimized from the MNI152 template or from the literature, individually optimized TI using two pairs of electrodes improves the focality by up to 4.4 cm, and by up to 1.1 cm if using two arrays of electrodes. Focality achieved by the individual optimization is sensitive to random changes and can vary up to 9.3 cm due to the non-lienarity of TI physics. Experimental recordings on a head phantom confirms the drop in TI stimulation strength when using unoptimized montages as predicted by our in silico models.

Conclusion: This work demonstrates the need of individually optimizing TI to target deep brain areas, and advocates against using a common head model and montage for TI modeling and experimental studies.