Standardized MNI-Guided TMS Yields Functional Similarity to Individualized T1-Guidance: Evidence from Behavioral, Anatomical, and Electromagnetic Levels

BackgroundNeuronavigation based on the standard MNI template (MNI-protocol) offers a cost-effective alternative to the gold-standard individualized T1-weighted MRI approach (T1-protocol). However, it remains unclear whether the reduced anatomical precision of the MNI-protocol compromises its functional efficacy, creating a critical need to verify protocol interchangeability. ObjectiveWe aimed to determine whether the MNI-protocol yields targeting efficacy comparable to the T1-protocol by specifically testing their functional and biophysical equivalence. MethodsWe employed a novel tri-level within-subject framework. The behavioral level assessed functional efficacy via the size congruity effect (SCE) during TMS to the right intraparietal sulcus (IPS). Anatomical accuracy (coil-to-cortex distances) and electromagnetic efficacy (E-field simulations) were evaluated across three distinct regions (right IPS, left dorsolateral prefrontal cortex, and left primary motor cortex) to assess regional generalizability. ResultsThe MNI-protocol demonstrated functional similarity to the T1-protocol, yielding behavioral outcomes that were statistically indistinguishable. This functional equivalence was corroborated by electromagnetic analyses, which revealed nearly identical induced E-field magnitudes and spatial distributions across all three target regions. Although the T1-protocol achieved significantly shorter coil-to-cortex distances, this anatomical advantage did not confer any measurable functional benefit. ConclusionThe MNI-protocol produced behavioral and electromagnetic outcomes equivalent to the T1-protocol. These findings validate the MNI-protocol as a scientifically sound and scalable alternative to individualized MRI-guided targeting, supporting its broader application in diverse research and clinical settings. HighlightsO_LIFunctional equivalence of MNI-vs. T1-guided TMS was systematically tested. C_LIO_LIA novel tri-level framework compared behavioral, anatomical, and E-field metrics. C_LIO_LIMNI- and T1-guided targeting yielded comparable behavioral and E-field outcomes. C_LIO_LIAnatomical proximity does not ensure better behavior or stronger E-field strength. C_LIO_LIMNI-guided targeting offers a robust, practical alternative to individual MRI. C_LI