A new study is adding momentum to a more individualized approach to transcranial magnetic stimulation, suggesting that the amount of stimulation reaching the brain may matter more than a standardized machine setting. The research represents an important development in interventional psychiatry research by prospectively using real-time electric-field modeling to guide TMS intensity in adults with major depressive disorder.
Why Standard TMS Intensity May Miss Individual Differences
TMS dosing for depression has traditionally relied on resting motor threshold, or rMT. Clinicians first determine the stimulation intensity required to produce a motor response and then use that measurement to calculate treatment intensity at the left dorsolateral prefrontal cortex, or DLPFC.
For conventional high-frequency TMS, treatment is commonly delivered at 120% of motor threshold. The underlying assumption is that a percentage derived from motor cortex stimulation provides a reasonable proxy for the dose reaching a non-motor treatment target.
Anatomical differences complicate that assumption. Skull geometry, brain morphology, tissue conductivity, and coil-to-cortex relationships can influence the electric field, or E-Field, actually generated in cortical tissue. Previous modeling research has already demonstrated substantial variability in the prefrontal E-Field produced by standardized motor-threshold dosing.
Personalized TMS Dosing Moves Closer To The Actual Cortical Dose
Ganesh and colleagues examined whether real-time E-Field modeling could provide a more individualized measure of stimulation intensity. Their analysis included 28 participants with major depressive disorder who received a single-day accelerated intermittent theta-burst stimulation protocol consisting of 10 sessions with 1,800 pulses per session.
Rather than simply applying a uniform percentage of rMT, investigators used neuronavigation-based E-Field estimates to determine the intensity needed at the DLPFC to approximate the E-Field associated with each participant’s motor threshold.
The resulting differences between participants were substantial.
To achieve a motor-equivalent DLPFC E-Field, required intensity ranged from 49.7% to 150.4% rMT, with a mean of 99.7%. More than half of participants required less than 100% rMT, while only three required more than 120%.
Real-Time Modeling Improved Dosing Precision
The investigators also compared their real-time approach with conventional 120% rMT dosing.
Real-time E-Field-guided dosing produced a smaller deviation from the target motor-equivalent E-Field. The researchers calculated that the approach improved dosing precision by an average of 48.1% compared with the conventional method.
That finding supports a broader shift in neuromodulation research. Instead of defining dose only according to machine output, E-Field modeling attempts to estimate the electrical exposure occurring within the targeted cortex.
Lower Intensity Was Linked With Greater Symptom Improvement
Perhaps the most provocative finding involved clinical outcomes.
The percentage of rMT delivered was not significantly associated with improvement on the QIDS-SR16 depression scale. In contrast, both the DLPFC-to-M1 E-Field ratio and absolute DLPFC E-Field strength showed significant negative correlations with symptom improvement.
In other words, participants receiving lower modeled cortical E-Field strengths tended to experience greater reductions in depressive symptoms.
This does not establish that lower-intensity TMS is superior. The clinical analyses were exploratory, the sample included only 28 participants, and the study was not designed to randomly compare different E-Field doses. The authors explicitly caution that the results are not sufficient to change clinical practice.
Still, the finding challenges a relatively intuitive assumption that increasing stimulation intensity necessarily improves therapeutic effects.
A Different Model For Precision Neuromodulation
The mechanism may involve more than simply delivering greater energy to the DLPFC. Theta-burst stimulation is intended to influence neuroplasticity, and previous physiological research has demonstrated meaningful plastic effects at subthreshold stimulation intensities.
The new results therefore raise a more nuanced question: rather than asking how much stimulation a patient can tolerate, future research may need to determine the cortical E-Field range most likely to produce the desired biological response.
That distinction could eventually affect both efficacy and tolerability.
From Standardized Percentages To Individualized Brain Stimulation
The study does not provide a replacement dosing standard. Instead, it establishes a rationale for prospective trials directly comparing conventional 120% rMT treatment with multiple individualized E-Field doses.
If replicated in larger randomized studies, personalized TMS dosing could become another layer of precision neuromodulation alongside individualized targeting, neuronavigation, imaging, and connectivity-guided treatment planning.
For clinicians and researchers, the immediate message is more measured. A machine setting does not necessarily describe the cortical dose equally across patients, and more stimulation should not automatically be interpreted as better stimulation. The next phase of TMS research may depend on identifying not simply where to stimulate the brain, but how much stimulation that specific brain actually needs.
Citations
- Ganesh P, Kim H, Kweon J, Halko MA, Caulfield KA, Brown JC. “Depression Improvement Correlates With Lower TMS Intensity in a Randomized Trial With Real-Time E-Field Modeling.” Human Brain Mapping. Published August 4, 2026. https://doi.org/10.1002/hbm.70607
- Caulfield KA, et al. “A Reexamination of Motor and Prefrontal TMS in Tobacco Use Disorder: Time for Personalized Dosing Based on Electric Field Modeling?” Clinical Neurophysiology. 2021;132(9):2199-2207. https://doi.org/10.1016/j.clinph.2021.06.015
Explore more at https://www.interventionalpsychiatry.org/
