Journal article

White matter pathways mediating dorsolateral prefrontal TMS therapy for depression

C Seguin, S Mansour L, RF Betzel, EJ Chumin, MG Puxeddu, J Lv, L Parkes, PB Fitzgerald, RFH Cash, A Zalesky

Nature Neuroscience | Published : 2026

Abstract

We use connectome modeling to map polysynaptic fiber pathways underlying transcranial magnetic stimulation (TMS) therapy for depression. We propose putative cortical and subcortical routes that connect stimulation sites in the dorsolateral prefrontal cortex to the subgenual cingulate cortex via intermediate regions. Here we show that route length explains both TMS treatment response in two independent patient cohorts and the clinical efficacy of functional magnetic resonance imaging-guided TMS targeting. Our results illuminate the neuroanatomical basis of TMS therapy for depression.