Brahma Tapasi, Guillen Alexander, Moreno Jeffrey, Datta Abhishek, Huang Yu
Soterix Medical Inc., Woodbridge, NJ 07095.
The City College of New York, New York, NY 10031.
bioRxiv. 2025 Jun 27:2025.01.13.632831. doi: 10.1101/2025.01.13.632831.
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.
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.
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 models.
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.
经颅颞叶干扰刺激（TI、TIS或tTIS），也称为干扰刺激（IFS），如果经过适当优化，能够对脑深部区域进行局部刺激。我们之前提出了一种使用两个电极阵列优化TI的算法，并表明与优化的高清经颅电刺激（HD-TES）和使用两对电极的传统优化TI相比，它可以实现更聚焦的刺激，特别是在海马体等脑深部区域。然而，那些建模研究仅在平均头部（MNI152模板）和三个个体头部上进行，没有探索个体间的变异性。文献中现有的TI研究大多在不同个体头部上使用两对电极的通用（可能是优化的）电极组合，而没有考虑个体间的变异性。
在这里，我们旨在通过对N = 25个头部使用其个性化头部模型应用相同的优化算法来研究优化TI的个体间变异性。具体来说，我们比较了在个体优化和未优化的电极组合下，不同刺激技术在六个不同感兴趣区域（ROI；右侧海马体、左侧背外侧前额叶皮质、左侧运动皮质、右侧杏仁核、右侧尾状核和左侧丘脑）所实现的聚焦性。我们还对个体优化进行了数值敏感性分析，并进行了模型记录以测试我们的模型。
正如预期的那样，由于头部解剖结构和组织电导率的个体差异，TI在同一ROI上跨受试者实现的聚焦性变化高达1.2厘米。我们表明，在6个ROI中的5个上，使用两个电极阵列的优化TI在相同调制强度水平下比优化的HD-TES具有更高的聚焦性。与使用从MNI152模板或文献中优化的通用电极组合相比，使用两对电极的个体优化TI可将聚焦性提高多达4.4厘米，使用两个电极阵列时可提高多达1.1厘米。个体优化所实现的聚焦性对随机变化敏感，由于TI物理的非线性，其变化可达9.3厘米。在头部模型上的实验记录证实了使用未优化电极组合时TI刺激强度的下降，正如我们的模型所预测的那样。
这项工作证明了对TI进行个体优化以靶向脑深部区域的必要性，并主张在TI建模和实验研究中不要使用通用头部模型和电极组合。
