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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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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