Associations Between TMS-Induced Electric Fields and Craving and Consumption Outcomes in Substance Use Disorders: A Multimodal Dose-Response Meta-Analysis

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Abstract Background Transcranial magnetic stimulation (TMS) is a promising treatment for substance use disorders (SUDs), although heterogeneous stimulation parameters hinder the identification of optimal strategies. Using meta-modeling, we linked treatment effect sizes (Hedges’ g) to simulated electric field (E-field) distributions to identify brain regions associated with efficacy variability. Methods TMS trials in individuals with SUDs published through the end of 2025 were identified through a systematic PubMed search. Studies reporting craving or consumption outcomes with quantifiable effect sizes were included. Objectives were to (i) examine associations between study-level effect sizes and simulated local E-field strength in MNI space for craving and consumption outcomes; (ii) generate a combined E-field–effect size association map; and (iii) assess spatial overlap with fMRI drug cue–reactivity patterns in 60 individuals with SUDs. Results The analysis included 81 randomized controlled TMS studies, yielding 107 effect size estimates for craving and consumption (n = 75 and n = 32, respectively). Compared with sham stimulation, TMS produced small-to-moderate improvements in both outcomes. E-field modeling identified the pre-supplementary motor area (pre-SMA) and inferior frontal gyrus (IFG) as regions associated with variability in craving-related effect sizes, and the frontopolar cortex with variability in consumption-related effect sizes. Correlation maps were highly robust (mean leave-one-out similarity r = 0.996), and the frontopolar cluster showed significant spatial overlap with fMRI drug cue–reactivity patterns (Dice coefficient = 0.37). Conclusion These findings identify frontopolar, pre-SMA, and IFG regions where local E-field strength is associated with SUD treatment effects, supporting more precise neuromodulation strategies.

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