Exploring the capabilities of repetitive transcranial magnetic stimulation in major depressive disorder: Dynamic causal modeling of the neural network.

Repetitive transcranial magnetic stimulation (rTMS) of the left dorsal prefrontal cortex (DLPFC) has been utilized to manage treatment-resistant major depressive disorder (MDD). Understanding the biological basis of rTMS treatment in MDD is crucial for enhancing its clinical efficacy. Numerous brain regions functionally connected to the left DLPFC have been identified as a critical role in the pathophysiology of MDD, highlighting the significance of alterations in these neural circuits. We employed a dynamic causal modeling to estimate the causal relationships among depression-related regions functionally linked to the left DLPFC using a large-sample, multi-site resting-state functional magnetic resonance imaging dataset, comprising 270 healthy controls and 175 patients with MDD. We revealed aberrant causal connections from the left DLPFC, amygdala (AMY), nucleus accumbens (NAC), and thalamus (Thal) to the visual cortex (VIS) in MDD. We also found negative associations between depression severities and NAC-to-VIS connections, indicating that VIS plays an essential role in MDD. Furthermore, we identified aberrant causal connections between the ventromedial prefrontal cortex (VMPFC) and subcortical regions including, AMY, NAC, and subgenual anterior cingulate cortex (sgACC), and positive correlation between the depression severities and AMY-to-sgACC connection, suggesting the disruption in corticostriatal circuit is related to the aberrant emotional regulation in MDD. These aberrant connections may support the neural mechanisms of MDD and indicate rTMS may modulate these areas, potentially improving the disrupted function in MDD. Our study provides deeper insights into the pathophysiological mechanisms of MDD and the potential mechanisms of rTMS treatment.