Depression Improvement Correlates With Lower TMS Intensity in a Randomized Trial With Real‐Time E‐Field Modeling

ABSTRACT

Current transcranial magnetic stimulation (TMS) practice uses fixed‐percentage motor threshold dosing, conventionally 120% rMT, for depression treatment. Individual anatomical variability may result in substantially different cortical electric‐Field (E‐Field) strengths across patients. We used prospective real‐time E‐Field modeling to characterize individual TMS intensity requirements and examine associations with clinical outcomes. Twenty‐eight subjects with major depressive disorder received single‐day accelerated intermittent theta‐burst stimulation (10 sessions, 1800 pulses/session) with real‐time E‐Field‐guided dosing targeting M1‐equivalent stimulation at left dorsolateral prefrontal cortex (DLPFC). Required %rMT for motor‐equivalent DLPFC E‐Field ranged from 49.7%–150.4% rMT (mean = 99.7% ± 18.9%), with 53.6% of subjects requiring less than 100% rMT. Real‐time E‐Field‐guided dosing achieved 48.1% better precision than conventional 120% rMT in approximating motor‐equivalent E‐Field delivery ( t (27) = 2.45, p  = 0.021). Three dosing frameworks were tested against change in QIDS‐SR16 scores: delivered %rMT was not significantly associated with outcomes ( ρ  = −0.15, p  = 0.436), while both the ratio of DLPFC to M1 E‐Field strength ( ρ  = −0.49, p  = 0.008) and absolute DLPFC E‐Field strength ( ρ  = −0.49, p  = 0.008) were significantly negatively correlated with greater symptom reduction. These findings demonstrate substantial interindividual variability in cortical E‐Field delivery under fixed‐percentage dosing, and that real‐time E‐Field guidance more precisely approximates motor‐equivalent stimulation than conventional 120% rMT. The association of lower absolute DLPFC E‐Field strength with greater symptom reduction challenges the assumption that higher stimulation intensity produces better clinical outcomes, and warrants systematic investigation in larger trials.