1. Introduction
CORTEX
Non-invasive brain stimulation techniques, particularly transcranial direct current stimulation (tDCS), have gained prominence in investigating the relationship between modulated brain regions and stimulation outcomes [The variability in tDCS responses can be attributed to anatomical and functional factors, including individual differences in fat thickness, skull thickness, cerebrospinal fluid volume, ongoing brain activity, and connectivity [To investigate the dose-response relationship and understand how tDCS-induced EFs influence brain functions, multiple modalities of magnetic resonance imaging (MRI) data, including structural and functional MRI, could be informative. Structural MRI is used to create individualized computational head models that predict the distribution patterns of EFs over the cortex. Functional MRI captures cortical functional activity in response to the injected current. Few studies have integrated computational head models with functional MRI data to explore dose-response relationships.Based on our systematic review, as of the end of Jun 2023, only twelve studies have integrated computational head models with fMRI data to measure dose-response associations in both healthy and clinical populations [This study aimed to examine the association between individualized received dose (EFs estimated using subject-specific computational head models) and brain response (changes in fMRI data) at multiple levels. Although these four levels of analysis are interconnected, we explored all four levels to determine which approach may be more effective for future dose-response analyses. By investigating the associations at different levels, we aimed to gain a comprehensive understanding of the dose-response relationship in tDCS and identify the most informative pipeline for studying the effects of stimulation. This analysis allows us to evaluate the relative strengths and limitations of each level, providing insights into which level of analysis may be more effective in elucidating the underlying mechanisms of tDCS-induced brain modulation. Given the highly interconnected nature of the brain, we hypothesize that associations between EFs and functional changes will be stronger at the network level compared to other levels of analysis. Here, we present the data from our pre-registered trial (NCT03382379) [