How Standardized Is Transcranial Magnetic Stimulation Treatment for Depression? Large-Cohort Modeling Reveals Systematic Dosimetric Variability.

INTRODUCTION

Repetitive transcranial magnetic stimulation (rTMS) is a widely utilized, noninvasive brain stimulation technique for treating neurological and psychiatric disorders worldwide. The efficacy of rTMS is influenced by individual head morphology, which shapes the induced electric field (E-field) in the brain. The standard practice for dosing rTMS involves adjusting the intensity to a defined percentage of the motor threshold (MT), a method exemplified by the globally adopted, US FDA-approved protocol of using 120% MT for depression. Since head morphology varies systematically across ethnic groups, current dosing protocols may lead to inconsistent cortical dosing.

METHODS

Here, we used large-scale computational modeling (N = 1,085) to systematically evaluate TMS dosage across "White," "Han Chinese," and "Black or African Am."

RESULTS

Our findings reveal striking ethnic disparities in the E-field ratio between the therapeutic target (left dorsolateral prefrontal cortex, DLPFC) and the calibration site (left primary motor cortex, M1). "Han Chinese" individuals exhibited a significantly higher E-field ratio (E-fieldDLPFC/E-fieldM1 = 1.226) compared to "White" individuals (E-fieldDLPFC/E-fieldM1 = 1.096). These differences are primarily driven by variations in scalp-to-cortex distance (SCD). Based on these findings, we derived both simplified population-level adjustment formulas and individualized SCD-based dosing equations and implemented them in a web-based tool for practical use.

CONCLUSION

Our results suggest that applying a uniform multiplier of MT to DLPFC stimulation may introduce systematic differences in delivered cortical dose across ethnic populations, highlighting that universal dosing conventions derived predominantly from specific demographic cohorts may embed bias, such that established safety and efficacy profiles may not be uniformly applicable across diverse global populations.