Edge controllability is associated with treatment response to repetitive transcranial magnetic stimulation in depression

<jats:title>Abstract</jats:title> <jats:p>Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD), yet variability in treatment response remains a significant challenge. Network control theory provides a framework to quantify how brain networks facilitate state transitions, but prior work has focused primarily on node level metrics. Here, we investigate whether edge based controllability of the structural connectome is associated with rTMS outcomes. Twenty five patients with treatment-resistant depression underwent diffusion MRI prior to a 5 week course of high frequency rTMS targeting the dorsolateral prefrontal cortex. Structural connectomes were constructed using MRtrix3 and the Destrieux atlas, and edge based controllability metrics were computed at baseline. Controllability of specific middle frontal gyrus centered edges showed significant associations with changes in HAMD-24 scores, including connections to the superior frontal gyrus, hippocampus, angular gyrus, and orbital gyrus (r = 0.470–0.597, p &lt; 0.05). These findings suggest that edge based controllability captures circuit level properties relevant to treatment response and may inform personalized neuromodulation strategies.</jats:p>