Identification of Personalized Transcranial Magnetic Stimulation Targets Based on Subgenual Cingulate Connectivity: An Independent Replication

Transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is commonly used to treat major depressive disorder. The most effective TMS targets are the DLPFC regions that are functionally anticorrelated with the subgenual cingulate (SGC) at the group level ( 1 Weigand A. Horn A. Caballero R. Cooke D. Stern A.P. Taylor S.F. et al. Prospective validation that subgenual connectivity predicts antidepressant efficacy of transcranial magnetic stimulation sites. Biol Psychiatry. 2018; 84: 28-37 Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar , 2 Fox M.D. Buckner R.L. White M.P. Greicius M.D. Pascual-Leone A. Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate. Biol Psychiatry. 2012; 72: 595-603 Abstract Full Text Full Text PDF PubMed Scopus (521) Google Scholar , 3 Cash R.F.H. Zalesky A. Thomson R.H. Tian Y. Cocchi L. Fitzgerald P.B. Subgenual functional connectivity predicts antidepressant treatment response to transcranial magnetic stimulation: Independent validation and evaluation of personalization. Biol Psychiatry. 2019; 86: e5-e7 Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar ). Based on this finding, multiple studies have attempted to personalize TMS targets using individualized connectivity to the SGC ( 4 Cole E.J. Stimpson K.H. Bentzley B.S. Gulser M. Cherian K. Tischler C. et al. Stanford Accelerated Intelligent Neuromodulation Therapy for treatment-resistant depression. Am J Psychiatry. 2020; 177: 716-726 Crossref PubMed Scopus (92) Google Scholar , 5 Ning L. Makris N. Camprodon J.A. Rathi Y. Limits and reproducibility of resting-state functional MRI definition of DLPFC targets for neuromodulation. Brain Stimul. 2019; 12: 129-138 Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar , 6 Fox M.D. Liu H. Pascual-Leone A. Identification of reproducible individualized targets for treatment of depression with TMS based on intrinsic connectivity. Neuroimage. 2013; 66: 151-160 Crossref PubMed Scopus (190) Google Scholar ). In a recent retrospective study (N = 26), antidepressant efficacy of each TMS site was correlated with its proximity to this personalized target and its connectivity to the SGC ( 7 Cash R.F.H. Cocchi L. Lv J. Fitzgerald P.B. Zalesky A. Functional magnetic resonance imaging–guided personalization of transcranial magnetic stimulation treatment for depression. JAMA Psychiatry. 2021; 78: 337-339 Crossref PubMed Scopus (25) Google Scholar ). However, this study was limited by relatively brief treatment course (3 weeks) and scan duration (6 minutes), which may limit the reproducibility of the results. We attempted to replicate this finding in 25 patients who received 6 weeks of TMS for major depressive disorder at an independent center.