Subgenual Functional Connectivity Predicts Antidepressant Treatment Response to Transcranial Magnetic Stimulation: Independent Validation and Evaluation of Personalization

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) is an established therapy for refractory depression. However, treatment outcomes are variable and can depend on the precise stimulation loci targeted within the DLPFC. We therefore followed with interest the evidence presented in Biological Psychiatry by Fox et al. ( 1 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 (591) Google Scholar ) and Weigand et al. ( 2 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 (189) Google Scholar ) indicating that the extent of negatively (i.e., anti-) correlated functional connectivity (FC) with the subgenual cingulate cortex (SGC) at the precise DLPFC stimulation site predicts treatment outcome and can potentially facilitate FC-guided rTMS personalization. Thus, establishing the generalizability of these findings across different cohorts and magnetic resonance imaging (MRI) scanners is crucial, particularly given the increasing emphasis on reproducibility in neuroscience ( 3 Poldrack R.A. Baker C.I. Durnez J. Gorgolewski K.J. Matthews P.M. Munafo M.R. et al. Scanning the horizon: Towards transparent and reproducible neuroimaging research. Nat Rev Neurosci. 2017; 18: 115-126 Crossref PubMed Scopus (647) Google Scholar , 4 Button K.S. Ioannidis J.P. Mokrysz C. Nosek B.A. Flint J. Robinson E.S. et al. Power failure: Why small sample size undermines the reliability of neuroscience. Nat Rev Neurosci. 2013; 14: 365-376 Crossref PubMed Scopus (4082) Google Scholar ).