Optimization of focal brain stimulation by individualized electric field simulations: Implementation and assessment of effects across sites and functional domains

已经开发了先进的计算建模方法来估计由脑刺激引起的电场的强度和分布。通过使用基于磁共振成像（MRI）的头部模型，这些方法允许电流的个性化模拟。先前的研究已经揭示了在大脑中诱导的电场的强度和分布的相当大的个体间变异性，并将其与刺激结果的变异性联系起来。类似地，刺激目标的功能和微观结构特性与可变的刺激效果有关。然而，人类大脑中的个体感应电场对行为和神经生理刺激结果及其变异性的预测值仍需要建立。此外，虽然正在开发用于tDCS电流优化的方法，但目前关于剂量-反应关系的知识是基本的，并且对皮质区域、功能域、健康人寿命期间的变化和其他调节因素之间的潜在差异知之甚少。这将首次通过研究部门（RU）实施的高度协调和优化的刺激方法来解决。为了应对这些挑战，RU的项目9（P9）将（A）通过提供可靠的个性化目标所需的方法来履行经验项目（P1-8）的服务功能。基于在实验项目中获得的结构MRI数据，我们将开发一种个性化的局灶性刺激方法，以实现RU P1-8的优化和协调刺激方案。此外，我们将通过使用假设驱动的方法在项目内和项目间检查行为和神经tDCS反应的变异性来源，来补充这些单独项目中的研究：（B.1）与P1-8合作，以特定领域的方式确定模拟电场对行为和神经元结果的影响（项目内），以及（B.2）研究效应的跨项目一致性，从而利用RU将获得的独特的大型协调数据集，以评估电场的个体间变异性与跨大脑部位和功能域的刺激效应之间的关系。从长远来看，该项目将使未来的研究能够系统地规划和实施单独优化的tDCS干预措施。此外，RU的潜在第二阶段将探索与年龄相关的大脑变化如何影响皮质剂量关系及其介质。因此，该项目的结果将为整个人类生命周期的个体优化刺激方案奠定基础，最终目标是优化个体的刺激结果。

Advanced computational modeling approaches have been developed to estimate the strength and distribution of the electric field induced by brain stimulation. By using magnetic resonance imaging (MRI) based head models, these approaches allow individualized simulations of current flow. Previous studies have revealed considerable inter-individual variability in the strength and distribution of the electric field induced in the brain and have linked it to the variability of the stimulation outcome. Similarly, functional and microstructural properties of the stimulation targets were linked to variable stimulation effects. However, the predictive value of individually induced electric fields in the human brain for behavioral and neurophysiological stimulation outcomes and their variability still needs to be established. Additionally, while methods for tDCS current flow optimization are being developed, current knowledge about dose-response relationships is rudimentary and little is known about potential differences between cortical areas, functional domains, changes across the healthy human lifespan and other modulating factors. This will be addressed for the first time by the highly coordinated and optimized stimulation approach implemented in the Research Unit (RU).To meet these challenges, Project 9 (P9) of the RU will (A) fulfill a service function for the empirical projects (P1-8) by providing the methodology required for a reliable personalized targeting. Based on structural MRI data acquired in the empirical projects, we will develop an individualized and focal stimulation approach to enable optimized and coordinated stimulation protocols in P1-8 of the RU. Further, we will complement research in these individual projects by examining sources of variability in behavioral and neural tDCS responses using a hypothesis-driven approach within and across projects: (B.1) collaborating with P1-8 to determine the effect of simulated electric fields on behavioral and neuronal outcomes in a domain specific way (within projects), and (B.2) investigating cross-project consistency of the effects, thereby leveraging the unique large and coordinated dataset that will be acquired by the RU, to assess the relationship between inter-individual variability in electric fields and stimulation effects across brain sites and functional domains. In the long run, this project will enable future studies to systematically plan and implement individually optimized tDCS interventions. Moreover, the potential second phase of the RU will explore how age-associated brain changes impact cortical-dose relationships as well as their mediators. Therefore, the results of the project will lay the foundation for individually optimized stimulation protocols across the human lifespan, with the ultimate goal to optimize stimulation outcome for the individual.