Comparison of coil placement approaches targeting dorsolateral prefrontal cortex in depressed adolescents receiving repetitive transcranial magnetic stimulation: an electric field modeling study

Background A promising treatment option for adolescents with treatment-resistant depression is high-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to the left dorsolateral prefrontal cortex (L-DLPFC). Conventional coil placement strategies for rTMS in adults include the 5-cm rule, the Beam F3 method, and the magnetic resonance imaging (MRI) neuronavigation method. The purpose of this study was to compare the three targeting approaches to a computational E-field optimization coil placement method in depressed adolescents. Methods Ten consenting and assenting depressed adolescents (4 females, age: 15.9 ± 1.1) participated in an open-label rTMS treatment study. Participants were offered MRI-guided rTMS 5 times per week over 6–8 weeks. To compute the induced E-field, a head model was generated based on MRI images, and a figure-8 TMS coil (Neuronetics) was placed over the L-DLPFC using the four targeting approaches. Results Results show that there was a significant difference in the induced E-field at the L-DLPFC between the four targeting methods ( χ 2 = 24.7, p < 0.001). Post hoc pairwise comparisons show that there was a significant difference between any two of the targeting methods (Holm adjusted p < 0.05), with the 5-cm rule producing the weakest E-field (46.0 ± 17.4 V/m), followed by the F3 method (87.4 ± 35.4 V/m), followed by the MRI-guided (112.1 ± 14.6 V/m), and followed by the computationally optimized method (130.1 ± 18.1 V/m). The Bartlett test of homogeneity of variances show that there was a significant difference in sample variance between the groups ( K 2 = 8.0, p < 0.05), with F3 having the largest variance. In participants who completed the full course of treatment, the median E-field strength in the L-DLPFC was correlated with the change in depression severity ( r = – 0.77, p < 0.05). Conclusions The E-field models revealed inadequacies of scalp-based targeting methods compared to MRI-guidance. Computational optimization may further enhance E-field dose delivery to the treatment target. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT01502033 ### Funding Statement Z.-D. Deng, P. Robins, and M. Dannhauer are supported by the National Institute of Mental Health (NIMH) Intramural Research Program (ZIAMH002955). P. Croarkin is supported by the NIMH R01MH113700 grant: Glutamatergic and GABAergic Biomarkers in TMS for Adolescent Depression. The study was also supported by the O'Shaughnessy (Woolls') Foundation. Neuronetics provided equipment support and Senstar shields through an investigator-initiated trial program to Dr. Croarkin. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This open-label rTMS study was conducted under an Investigational Device Exemption (#G110091) from the United States Food and Drug Administration and approved by the Mayo Clinic Institutional Review Board. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors