Personalized models of Beam/F3 targeting in transcranial magnetic stimulation for depression: Implications for precision clinical translation

Background: Clinical transcranial magnetic stimulation (TMS) for depression routinely relies on the scalp-based Beam/F3 targeting method to identify stimulation targets in the dorsolateral prefrontal cortex (dLPFC). Scalp-based targeting offers a low-cost and easily implemented method for TMS coil placement, enhancing treatment availability. However, limited anatomical and functional specificity of the Beam/F3 method may affect treatment outcomes, motivating assessment of the clinical standard. Methods: In a naturalistic clinical trial of TMS conduced at four Veterans Affairs hospitals, the authors evaluate the Beam/F3 method using neuroimaging incorporated before TMS, after five treatment sessions, and after all thirty sessions. Personalized anatomical and electric field (E-field) models were developed to assess target location and network engagement, as well as subsequent effects on clinical outcomes. Results: Anatomical models demonstrate that the Beam/F3 method produced reliable targets in the dLPFC across individuals and repeated treatment sessions. E-field models revealed that baseline anticorrelation between the stimulation center and the sgACC was associated with antidepressant symptom response after five TMS sessions (p=0.032,r²=0.100,N=46) and at the end of treatment (p=0.042,r²=0.107,N=39). Relatedly, E-field magnitude at the sgACC-anticorrelated peak in the prefrontal cortex correlated with symptom response throughout treatment (early treatment: p=0.001,r²=0.220,N=46; end of treatment: p=0.026,r²=0.127,N=39). Conclusions: This work establishes that scalp-based targeting can produce reliable targets in the dLPFC and be successfully evaluated using a combination of neuroimaging and E-field modeling in pragmatic, multisite applications. Importantly, this investigation also found that significant network effects occur early in treatment and that Beam/F3 targets can engage functional mechanisms in TMS.